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is often considered a marker of thrombosis&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">3</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">Cardiovascular disease &#40;CVD&#41; is a major cause of death in patients with peripheral arterial disease &#40;PAD&#41;&#46; These patients also tend to suffer from complications when they have diabetes&#44; dyslipidemia and hypertension&#46; They may also develop severe systemic atherosclerosis&#44; leading to increased mortality due to coronary artery disease &#40;CAD&#41;&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">High Lp&#40;a&#41; is positively associated with coronary artery calcification&#44; CAD and PAD&#46;<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">4&#44;5</span></a> It also promotes thrombosis by binding to fibrin&#44; thus blocking the fibrinolytic action of plasmin&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">2</span></a> Lp&#40;a&#41; may be a predictor of peripheral and central CVD in younger men and women with dyslipidemia&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Several observations suggest that targeting Lp&#40;a&#41; could decrease total residual cardiovascular risk&#44; as increased plasma Lp&#40;a&#41; concentrations are significantly associated with higher risk of CAD&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">6</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">Lp&#40;a&#41; is a marker of particular risk for poor outcomes in terms of severity and progression of CVD&#46; Several prospective studies have correlated Lp&#40;a&#41; levels with vascular disease in general&#44; and plasma Lp&#40;a&#41; &#62;30 mg&#47;dl with increased cardiovascular risk&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">4</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">Studies with statins alone reveal that&#44; although they significantly reduce LDL and major adverse cardiovascular events &#40;MACE&#41;&#44; statins do not appear to reduce Lp&#40;a&#41; concentrations&#46; Almost all studies in this field have targeted total cholesterol &#40;TC&#41; and LDL&#44; as well as high-density lipoprotein cholesterol &#40;HDL&#41;&#44; but none has validated the use of HDL as a therapeutic target in the management of cardiovascular risk factors&#46; Furthermore&#44; in clinical practice cardiovascular risk scores are not usually applied to younger patients &#40;aged &#60;40 years&#41; with lower HDL levels&#44; even if they have other cardiovascular risk factors&#46; We therefore aimed to assess the possible relevance of all lipid fractions&#44; including HDL&#44; to cardiovascular risk factors&#44; regardless of age&#44; and following current clinical guidelines&#46;<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">7&#8211;9</span></a> In this study&#44; we assessed clinical and biochemical changes in randomly selected patients with two or more cardiovascular risk factors&#44; 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and had not suffered MACE&#46; The selection criteria were as follows&#58; at least two personal and&#47;or family cardiovascular risk factors&#44; regular attendance at a three-monthly consultation for a minimum of two years&#44; and an annual biochemical assessment&#44; including cardiovascular exams and clinical assessment&#46; Participants filled in a self-administered questionnaire and provided written informed consent for inclusion in the study&#44; which was approved by the Ethics Committee of S&#227;o Jo&#227;o Hospital Center&#44; Porto&#46; Patients were followed for both clinical and anthropometric changes during the observation period&#44; paying particular attention to lipid and metabolic profiles and variations in Lp&#40;a&#41; levels&#46; The disorders diagnosed were classified into the following nosological groups&#58; cardiovascular&#44; cerebrovascular&#44; metabolic and behavioral diseases&#46; Data were collected from the first medical consultation until the last or current appointment recorded on the patient&#39;s medical chart&#46; It was established that an individual patient&#39;s record could only be updated for specific reasons&#44; such as CVD&#44; dependency or immobility&#44; MACE or death&#46; Records were updated 19 times due to death and six times due to the patient being bedridden&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">Patients&#8217; sociodemographic characteristics were analyzed based on their clinical records&#46; Their clinical&#44; anthropometric&#44; biochemical and cardiovascular characteristics were also analyzed and recorded&#46; These assessments included cardiovascular exams&#44; including electrocardiogram &#40;ECG&#41;&#44; two-dimensional echocardiogram and Doppler ultrasound &#40;7&#46;5 mHz linear probe&#44; Sonos 1000&#44; Hewlett Packard&#44; Andover&#44; MA&#41; of the supra-aortic trunks to measure carotid intima-media thickness &#40;IMT&#41;&#44; as well as ambulatory blood pressure monitoring &#40;ABPM&#41;&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Assessment of both renal and liver function are essential to analysis of metabolic status and the effects of pharmaceutical therapy&#46; Renal function was therefore assessed in this study&#44; based on microalbuminuria and creatinine clearance estimated by the Cockcroft-Gault method&#44; and liver function and morphology were assessed by ultrasound&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">Cardiovascular risk was calculated based on the three most commonly used scores&#58; the Framingham risk score &#40;FRS&#41;&#44; the European Society of Cardiology&#39;s Systematic Coronary Risk Evaluation &#40;SCORE&#41;&#44; and the American College of Cardiology&#39;s atherosclerotic cardiovascular disease risk estimator &#40;ASCVD&#41;&#46; The resulting overall scores were analyzed by age-group&#46; Also&#44; due to the association between metabolic compensation and clinical improvement in patients with cardiovascular risk factors&#44; the study included assessment of patients&#8217; lifestyle behaviors&#44; including alcohol consumption &#40;classified as never&#44; occasional&#44; moderate &#91;one or two drinks daily&#93;&#44; excessive &#91;three or more drinks daily&#93;&#44; alcoholic&#44; or abstinent &#91;at least one year since the last drink&#93;&#41;&#44; smoking &#40;current smoker&#44; ex-smoker or never-smoker&#41;&#44; and exercise levels &#40;all aerobic exercise at least twice a week in addition to that arising from daily activities&#41;&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">Finally&#44; drug therapies administered during the observation period were classified into pharmacological groups&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Statistical analysis</span><p id="par0165" class="elsevierStylePara elsevierViewall">Quantitative variables were summarized using descriptive statistics&#58; mean&#44; median&#44; standard deviation and range &#40;minimum and maximum&#41;&#46; Categorical variables were expressed as absolute &#40;n&#41; and relative &#40;&#37;&#41; frequencies&#46; Associations between two categorical variables were tested using the chi-square test or Fisher&#39;s exact test&#46; The McNemar test for paired samples was used to compare the presence of a symptom before and after treatment or to compare the results of two diagnostic tests applied in the same group&#46; Quantitative variables in two independent groups were compared using the t test for independent samples or the Mann-Whitney &#40;MW&#41; non-parametric test&#44; according to whether the respective assumptions were validated&#46; The non-parametric Wilcoxon signed-rank &#40;WSR&#41; test and sign test &#40;ST&#41; were used for paired samples to compare clinical scores before and after treatment if the assumption of normality was not confirmed&#46; Statistical tests were two-tailed and the significance level was taken to be 5&#37;&#46; Multivariate linear regression analysis was performed to assess associations between variables of interest and changes in Lp&#40;a&#41; levels between the beginning and the end of the study period&#46; Stepwise optimization was used to choose the statistically significant variables for the model&#46; All statistical analyses were conducted using IBM<span class="elsevierStyleSup">&#174;</span> SPSS<span class="elsevierStyleSup">&#174;</span> Statistics version 19&#46;</p></span></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Results</span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Sociodemographic&#44; clinical and anthropometric characteristics of the study population</span><p id="par0170" class="elsevierStylePara elsevierViewall">Of the 516 patients&#44; 224 were male and 292 were female&#44; and 98&#46;6&#37; were Caucasian&#46; The mean observation time was 11&#46;35&#177;4&#46;32 years &#40;range&#58; 2-26&#41;&#44; median 11&#46;0 years&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">During the observation period&#44; patients&#8217; age increased from an initial median of 46 years to a final median of 58 years&#46; Thus&#44; age grouping was readjusted&#44; as the number of patients decreased drastically in the &#60;20 years &#40;initial&#58; 2&#46;2&#37;&#59; final&#58; 0&#46;2&#37;&#41; and 20-34 years &#40;initial&#58; 20&#46;2&#37;&#59; final&#58; 7&#46;0&#37;&#41; age groups&#44; changed slightly in the 34-50 years age group &#40;initial&#58; 34&#46;3&#37;&#59; final&#58; 22&#46;9&#37;&#41;&#44; and increased in the 50-64 years &#40;initial&#58; 27&#46;9&#37;&#59; final&#58; 35&#46;5&#37;&#41; and &#8805;65 years &#40;initial&#58; 14&#46;9&#37;&#59; final&#58; 34&#46;5&#37;&#41; age groups&#46; By the end of the observation period&#44; 23 patients had died &#40;4&#46;5&#37;&#41; and 41 patients were bedridden &#40;7&#46;9&#37;&#41;&#59; most of these events occurred after data collection&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">Changes in patients&#8217; clinical and anthropometric assessments between initial and final observations are detailed in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; Significant reductions were seen in waist circumference&#44; upper arm circumference and triceps skinfold &#40;p&#60;0&#46;001&#41;&#46; In addition&#44; there were considerable improvements in blood pressure control&#44; reflected in statistically significant differences in mean systolic and diastolic daytime and night-time blood pressure &#40;p&#60;0&#46;001&#41;&#46; The number of patients with controlled atrial fibrillation rose from nine to 18 patients during the study period&#44; while the number with non-controlled atrial fibrillation decreased from two to one&#46; No statistical differences were found regarding weight&#44; height or body mass index&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Lifestyle</span><p id="par0185" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> shows changes in patients&#8217; lifestyles&#46; The reduction in alcohol consumption and the unexpected increase in regular exercise should be noted&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Biochemical assessment</span><p id="par0190" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> reports the results of the biochemical assessments&#46; Significant differences were found in almost every metabolic variable studied&#44; including CRP&#44; glycated hemoglobin&#44; fructosamine&#44; TC&#44; HDL&#44; LDL&#44; very-low-density lipoprotein&#44; triglycerides&#44; fibrinogen&#44; homocysteine&#44; uric acid and microalbuminuria &#40;p&#60;0&#46;001&#41;&#46; In addition&#44; fasting insulin and C-peptide values decreased between the first and the final observation&#44; although without statistically significant differences&#46; Lp&#40;a&#41; levels were also significantly reduced&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Cardiovascular exams</span><p id="par0195" class="elsevierStylePara elsevierViewall">The cardiovascular exams performed included ECG&#44; echocardiogram&#44; IMT and ABPM&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">Some changes were found in the ECG assessment&#46; A normal exam was seen in 247 patients &#40;47&#46;2&#37;&#41; at the initial observation&#44; compared to 281 patients &#40;55&#46;6&#37;&#41; at the final visit&#46; Atrial fibrillation was present in four patients &#40;0&#46;8&#37;&#41; at the first consultation&#44; and in 22 &#40;4&#46;4&#37;&#41; at the last&#46; On echocardiographic study&#44; alterations were seen in 267 patients &#40;52&#46;5&#37;&#41; at baseline&#44; and in 273 patients &#40;54&#46;7&#37;&#41; at the end of the observation period&#46; These included mild aortic valve abnormalities &#40;mild regurgitation in two patients&#41; and left atrial dilatation &#40;four patients&#41;&#46; Nevertheless&#44; the overall improvement in these parameters should be noted&#46; Concerning the 347 hypertensive patients &#40;69&#46;2&#37;&#41; who underwent ABPM&#44; at the end 14 patients &#40;2&#46;9&#37;&#41; were found to have uncontrolled hypertension&#46; The absence of acute episodes&#44; such as MACE&#44; during the study period should be noted&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">Doppler ultrasound of the supra-aortic trunks showed an improvement in the number of patients with normal results from 82 patients &#40;16&#46;2&#37;&#41; to 100 &#40;19&#46;8&#37;&#41;&#46; IMT also improved&#44; from an initial median of 2&#46;90 mm to a final median of 1&#46;40 mm &#40;Wilcoxon signed-rank test&#44; p&#60;0&#46;001&#41;&#46; However&#44; there was no reduction in the number of cases of vascular stenosis &#40;McNemar test&#44; p&#61;0&#46;500&#41;&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">It should be noted that&#44; of the 435 patients &#40;85&#46;4&#37;&#41; with hepatic steatosis&#44; 208 &#40;40&#46;8&#37;&#41; presented hepatic steatosis with hepatomegaly &#40;non-alcoholic fatty liver disease &#91;NAFLD&#93;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">11</span></a> Nevertheless&#44; liver function was only altered in a small number of patients &#40;14&#46;5&#37;&#41;&#46;</p><p id="par0215" class="elsevierStylePara elsevierViewall">The kidney is one of the target organs of CVD&#46; Our assessment of renal function showed that overall&#44; 46&#46;7&#37; &#40;241&#47;516&#41; of patients had abnormal creatinine clearance &#40;mean 104&#46;13&#177;46&#46;18 ml&#47;min&#47;m<span class="elsevierStyleSup">2</span>&#44; median 98&#46;20&#59; range 11&#46;3-276&#46;3&#41;&#44; normal being defined as 70-135 ml&#47;min&#47;m<span class="elsevierStyleSup">2</span>&#46; Moreover&#44; creatinine levels were abnormal in 31&#46;8&#37; &#40;164&#47;516&#41; of patients&#44; with mean levels of 87&#177;0&#46;34 g&#47;dl &#40;median 0&#46;81&#59; range 0&#46;39-4&#46;5&#41;&#44; normal being defined as 0&#46;66-1&#46;25 g&#47;dl&#46; Mean creatinine level was 0&#46;87&#177;0&#46;34 g&#47;dl &#40;median 0&#46;81&#59; range 0&#46;39-4&#46;5&#41;&#46; Finally&#44; 31&#37; &#40;160&#47;516&#41; of patients were found to have abnormal urea levels&#44; normal being defined as 10-50 mg&#47;dl&#46; Mean urea level was 47&#46;09&#177;17&#46;41 mg&#47;dl &#40;median 41&#46;00 mg&#47;dl&#59; range 17&#46;0-259&#46;0&#41;&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Nosological groups</span><p id="par0220" class="elsevierStylePara elsevierViewall">Clinical diagnoses were classified into the following nosological groups&#58; 390 patients with cardiovascular disease &#40;75&#46;6&#37;&#41;&#44; 50 with cerebrovascular disease &#40;9&#46;7&#37;&#41;&#44; 491 with metabolic diseases &#40;95&#46;2&#37;&#41; and 301 with behavioral diseases &#40;58&#46;3&#37;&#41;&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Stratification of cardiovascular risk</span><p id="par0225" class="elsevierStylePara elsevierViewall">Initial and final cardiovascular risk was stratified by estimating 10-year risk according to the parameters of the FRS&#44; SCORE and ASCVD&#46; Differences between cardiovascular risk scores calculated before and after treatment were as follows&#58; FRS&#58; -15&#46;37 &#40;min-max&#58; -79&#46;20-28&#46;60&#41;&#44; high-risk SCORE&#58; -1&#46;08 &#40;min-max&#58; -26&#46;36-4&#46;31&#41;&#44; low-risk SCORE&#58; -0&#46;44 &#40;min-max&#58; -14&#46;50-2&#46;83&#41; and ASCVD&#58; -5&#46;83 &#40;min-max&#58; -87&#46;73-40&#46;12&#41;&#46; All improvements in cardiovascular risk scores between initial and final measures were statistically significant &#40;p&#60;0&#46;05&#41;&#44; regardless of the calculation method applied &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Pharmacological therapy</span><p id="par0230" class="elsevierStylePara elsevierViewall">The pharmacological therapies administered to the patients are presented in <a class="elsevierStyleCrossRef" href="#fig0010">Figure 2</a> and <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#44; divided into pharmacological groups&#46; The following therapies were used most in this patient group&#58; antidepressants &#40;particularly selective serotonin reuptake inhibitors &#91;SSRIs&#93;&#41;&#44; anxiolytics&#44; lipid-lowering therapy including statins&#44; and antiplatelets&#46; Allopurinol&#44; diuretics&#44; angiotensin-converting enzyme inhibitors &#40;ACEIs&#41; and angiotensin receptor blockers &#40;ARBs&#41; were also commonly used&#46; We also compared the efficacy of each of these therapies individually between patients who were receiving a particular treatment and those who were not&#44; based on final Lp&#40;a&#41; levels&#46; Results of the multiple regression analysis are shown in Supplementary <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; Briefly&#44; statins&#44; ACEIs&#44; ARBs&#44; oral antidiabetic drugs &#40;OADs&#41;&#44; antiplatelets&#44; calcium channel blockers &#40;CCBs&#41; and allopurinol showed statistically significant differences on bivariate analysis &#40;p&#60;0&#46;05&#41; and were selected to enter the final model&#46; This analysis excluded patients who died&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0235" class="elsevierStylePara elsevierViewall">Overall&#44; the use of statins&#44; ACEIs&#44; ARBs&#44; OADs&#44; antiplatelets&#44; CCBs and allopurinol was associated with greater reductions in Lp&#40;a&#41; values during the follow-up period&#46; The final optimized regression model showed that the regression coefficient for reduction in Lp&#40;a&#41; levels in patients under statins between the initial and the final measurement was more than 10&#46;635&#44; compared to those not under statins&#44; after adjustment for antiplatelets&#44; allopurinol and antidepressants &#40;final model variables&#41;&#46; Furthermore&#44; the regression coefficient for reduction in Lp&#40;a&#41; levels in patients under antiplatelets was more than 4&#46;786&#44; compared with those not under antiplatelets&#44; after adjustment for statins&#44; allopurinol and antidepressants&#46; The regression coefficient for reduction in Lp&#40;a&#41; levels in patients under allopurinol was more than 5&#46;376&#44; in comparison with those who were not under allopurinol&#44; after adjustment for statins&#44; antiplatelets and antidepressants&#46; Finally&#44; the regression coefficient for reduction in Lp&#40;a&#41; levels in patients under antidepressants was more than 4&#46;367 compared with those who were not under antidepressants&#44; after adjustment for statins&#44; antiplatelets and allopurinol&#46;</p></span></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Discussion</span><p id="par0240" class="elsevierStylePara elsevierViewall">In this retrospective observational study&#44; we appraised the effects of using combined drug therapies on changes in Lp&#40;a&#41; levels in patients with high cardiovascular risk&#44; without MACE&#46; Overall&#44; our results indicate significant clinical improvements between the initial and final measurements&#44; especially regarding blood pressure and metabolic risk factors&#46;</p><p id="par0245" class="elsevierStylePara elsevierViewall">Neither social nor demographic factors appeared to pose difficulties in following the proposed treatments and guidance for improving lifestyles&#46; The improvements in blood pressure control and significant reductions in waist circumference should be noted&#44; as these are important cardiovascular risk factors influencing the atherosclerotic process&#46;</p><p id="par0250" class="elsevierStylePara elsevierViewall">This study demonstrated a significant correlation between Lp&#40;a&#41; levels and cardiovascular risk scores in patients with high cardiovascular risk but without MACE&#46; In previous work&#44; we found that increased Lp&#40;a&#41; levels in these individuals were strongly associated with cardiovascular risk factors such as IMT&#44; LDL-C and homocysteine&#44; as well as with NAFLD&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">12</span></a> In addition&#44; for the same population&#44; a positive and significant correlation was found between Lp&#40;a&#41; and the risk scores used for CVD stratification &#40;p&#60;0&#46;001&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">12</span></a> These data suggest that guidelines for assessing the severity of the atherosclerotic process should be reviewed&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">13</span></a></p><p id="par0255" class="elsevierStylePara elsevierViewall">Until recently&#44; Lp&#40;a&#41; has been a recognized but under-appreciated cardiovascular risk factor&#44; largely because a therapeutic approach has yet to be established&#46;<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">14&#44;15</span></a> As specific treatments are lacking&#44; Lp&#40;a&#41; warrants further investigation&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">1</span></a> Early primary prevention is recommended&#44; with the introduction of available therapies in clinically stable patients&#44; regardless of vascular age risk &#40;personal&#44; family and lifestyle&#41; and metabolic alterations promoting the atherosclerosis process&#46; However&#44; currently used cardiovascular risk scores do not fit this interventional approach&#44; but rather delay the administration of combined drug treatments&#46; Patients&#8217; commitment to implementing changes&#44; including adopting healthier lifestyles&#44;<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">16&#8211;18</span></a> such as regular exercise&#44; is essential to the success of the treatment&#46;<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">8&#44;19</span></a></p><p id="par0260" class="elsevierStylePara elsevierViewall">Lp&#40;a&#41; acts as a marker of severity and progression of CVD in patients at particular risk for poor outcomes&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">20</span></a> In our study&#44; although there was a significant decrease in IMT&#44; cases of carotid stenosis persisted after the treatment period&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">20</span></a> Therefore&#44; although this was not evident in previous studies&#44; lipid-lowering therapy&#44; especially statins combined with other treatments&#44; appears to be involved in Lp&#40;a&#41; reduction&#46; Similar results were obtained with ACEIs&#44; diuretics&#44; ARBs&#44; CCBs and antiplatelets&#46; The effects of allopurinol&#44; OADs and proton pump inhibitors in combined drug therapy&#44; should also be highlighted&#46; On the other hand&#44; beta-blockers and insulin had less effect&#46;</p><p id="par0265" class="elsevierStylePara elsevierViewall">These results confirm that the role of Lp&#40;a&#41; as a biomarker of cardiovascular risk should be analyzed along with that of patients&#8217; lifestyles and biochemical parameters&#46; Lp&#40;a&#41; may thus be a crucial indicator for comprehensive early multidisciplinary treatment&#44; directed at all cardiovascular risk factors and associated comorbidities&#46;</p><p id="par0270" class="elsevierStylePara elsevierViewall">A large proportion of patients had moderate renal failure&#44; as expected since the kidney is a target organ for atherosclerotic disease&#44; and also due to cellular senescence&#46; This finding indicates that appropriate adjustments to therapy may be required&#46; We also observed a high number of patients with hepatic steatosis&#44; which indicates that this condition should be considered in the presence of NAFLD and&#44; as such&#44; may represent a way to contextualize the evolution and severity of atherosclerotic disease&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">11&#44;21</span></a></p><p id="par0275" class="elsevierStylePara elsevierViewall">In view of the clinically relevant and statistically significant reduction of Lp&#40;a&#41; seen in our study&#44;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">22</span></a> further research is required to establish a consistent therapeutic strategy to achieve this end&#44;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">23</span></a> as well as to improve upon the subjective calculation of cardiovascular risk with currently used algorithms&#46; Nonetheless&#44; we can state that first-line therapies should include statins&#44;<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">24&#44;25</span></a> allopurinol&#44; antiplatelets and antidepressant drugs&#46; In addition&#44; the atherogenicity of Lp&#40;a&#41; may be modified through substantial reductions in LDL levels&#46;</p><p id="par0280" class="elsevierStylePara elsevierViewall">Although clinically relevant&#44; our results should be interpreted in the light of the inherent methodological limitations of the study&#46; As it is based on data from a single center&#44; the results cannot be extrapolated to the Portuguese population in general&#46; Due to its retrospective nature&#44; the study could have been affected by information bias from data gathered from patients&#8217; charts&#44; including changes in therapeutic guidelines over the long follow-up period &#40;median 11&#46;0 years&#41;&#46; Furthermore&#44; it was not possible to establish temporal relationships between risk factors and CVD that demonstrate causation&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Conclusion</span><p id="par0285" class="elsevierStylePara elsevierViewall">Lp&#40;a&#41; is a key indicator of global cardiovascular risk and should be considered a therapeutic target&#46; According to the results obtained for our patients&#44; it may be important to initiate primary prevention&#44; including combined drug therapies&#44; while addressing all cardiovascular risk factors&#44; to delay the atherosclerotic process&#46; First-line therapy should include statins&#44; antiplatelets&#44; allopurinol and antidepressants&#44; particularly SSRIs&#46; Among other pharmacological therapies&#44; CCBs&#44; ACEIs&#44; OADs and ARBs should also be considered&#44; as well as lifestyle modifications&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Conflicts of interest</span><p id="par0290" class="elsevierStylePara elsevierViewall">The author has no conflicts of interest to declare&#46;</p></span></span>"
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            0 => "Lipoprote&#237;na&#40;a&#41;"
            1 => "Doen&#231;as cardiovasculares"
            2 => "Aterosclerose"
            3 => "Terap&#234;utica farmacol&#243;gica combinada"
            4 => "Risco cardiovascular"
            5 => "Doen&#231;a arterial perif&#233;rica"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction and Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Lipoprotein&#40;a&#41; &#91;Lp&#40;a&#41;&#93; is an independent cardiovascular risk factor but is closely associated with other similar risk factors that are manageable with appropriate treatment and guidance&#46; We aimed to study the impact of using combined therapy for managing Lp&#40;a&#41; levels in patients at high cardiovascular risk but without major adverse cardiovascular events&#44; in primary prevention&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">We conducted a retrospective observational study in 516 patients randomly selected from a group of 1677 patients who attended cardiovascular risk and metabolism consultations between 1995 and 2015&#46; The disorders observed and therapies used were classified into nosological and pharmacological groups&#44; respectively&#46; Cardiovascular risk was calculated based on the Framingham risk score&#44; the European Society of Cardiology&#39;s SCORE and the American College of Cardiology&#39;s ASCVD Risk Estimator&#44; and changes in patients&#8217; lifestyle were assessed&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Significant differences &#40;p&#60;0&#46;001&#41; were found in almost all metabolic variables&#44; except fasting insulin and C-peptide&#46; Lp&#40;a&#41; levels were also significantly reduced &#40;p&#60;0&#46;001&#41;&#46; Carotid intima-media thickness improved&#44; decreasing from 2&#46;90 mm to 1&#46;40 mm&#59; however&#44; there was no reduction in the number of cases of vascular stenosis&#46; Of patients with hepatic steatosis &#40;85&#46;5&#37;&#41;&#44; 40&#46;7&#37; presented hepatomegaly&#44; but liver function was only altered in a few patients &#40;14&#46;5&#37;&#41;&#46; Lipid-lowering therapy&#44; especially statins&#44; significantly decreased Lp&#40;a&#41;&#44; benefiting from synergy with other treatments&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Lp&#40;a&#41; is a key overall indicator of vascular risk and should be considered a therapeutic target&#46; Besides a healthy lifestyle&#44; primary prevention should include combined drug therapies to address all cardiovascular risk factors and to delay the atherosclerotic process&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Introduction and Objective"
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          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Methods"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Results"
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          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Conclusions"
          ]
        ]
      ]
      "pt" => array:3 [
        "titulo" => "Resumo"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introdu&#231;&#227;o e objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Lp&#40;a&#41; &#233; um fator de risco cardiovascular independente&#44; mas intrinsecamente associado a outros fatores de risco similares&#44; control&#225;veis com terap&#234;uticas e orienta&#231;&#245;es adequadas&#46; O nosso objetivo &#233; estudar o impacto do uso de terap&#234;uticas combinadas na gest&#227;o da evolu&#231;&#227;o da Lp&#40;a&#41; em doentes com elevado risco vascular&#44; sem ECVM em preven&#231;&#227;o prim&#225;ria&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Estudo observacional retrospetivo realizado em 516 doentes&#44; selecionados aleatoriamente de um universo de 1677 indiv&#237;duos&#44; que participaram regularmente em consultas de risco vascular e metabolismo entre 1995 e 2015&#46; As patologias observadas e terap&#234;uticas utilizadas foram distribu&#237;das em diferentes grupos nosol&#243;gicos e grupos farmacol&#243;gicos&#44; respetivamente&#46; Calculou-se o RV com base em FRS&#44; SCORE e ASCVD e avaliou-se tamb&#233;m a evolu&#231;&#227;o do estilo de vida dos doentes&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Encontraram-se diferen&#231;as significativas &#40;p&#60;0&#44;001&#41; em quase todas as vari&#225;veis metab&#243;licas&#44; exceto insulina &#40;jejum&#41; e p&#233;ptido-C&#46; Houve uma redu&#231;&#227;o significativa nos n&#237;veis de Lp&#40;a&#41; &#40;p&#60;0&#44;001&#41;&#46; A espessura &#237;ntima-m&#233;dia carot&#237;dea evoluiu favoravelmente&#44; diminuindo de 2&#44;90 mm para 1&#44;40 mm&#59; por&#233;m&#44; n&#227;o houve redu&#231;&#227;o do n&#250;mero de casos de estenose vascular&#46; Dos doentes com esteatose hep&#225;tica &#40;85&#44;5&#37;&#41;&#44; 40&#44;7&#37; apresentaram hepatomegalia&#46; Contudo&#44; poucos doentes &#40;14&#44;5&#37;&#41; apresentaram fun&#231;&#227;o hep&#225;tica alterada&#46; A terap&#234;utica antidislipid&#233;mica&#44; especialmente as estatinas&#44; diminuiu significativamente a Lp&#40;a&#41;&#44; beneficiando da sinergia com demais tratamentos&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclus&#245;es</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Lp&#40;a&#41; &#233; um indicador global e fundamental de risco vascular&#44; a considerar como alvo terap&#234;utico&#46; Al&#233;m de um estilo de vida saud&#225;vel&#44; a preven&#231;&#227;o prim&#225;ria deve incluir terap&#234;uticas farmacol&#243;gicas combinadas dirigidas aos fatores de risco cardiovasculares e&#44; consequentemente&#44; retardar o processo ateroscler&#243;tico&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Introdu&#231;&#227;o e objetivo"
          ]
          1 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "M&#233;todos"
          ]
          2 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Resultados"
          ]
          3 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Conclus&#245;es"
          ]
        ]
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        "seccion" => array:1 [
          0 => array:4 [
            "apendice" => "<p id="par0305" class="elsevierStylePara elsevierViewall">The following are the supplementary material to this article&#58;<elsevierMultimedia ident="upi0005"></elsevierMultimedia></p>"
            "etiqueta" => "Appendix A"
            "titulo" => "Supplementary material"
            "identificador" => "sec0085"
          ]
        ]
      ]
    ]
    "nomenclatura" => array:1 [
      0 => array:3 [
        "identificador" => "nom0005"
        "titulo" => "<span class="elsevierStyleSectionTitle" id="sect0065">List of abbreviations</span>"
        "listaDefinicion" => array:1 [
          0 => array:1 [
            "definicion" => array:21 [
              0 => array:2 [
                "termino" => "ACEI"
                "descripcion" => "<p id="par0005" class="elsevierStylePara elsevierViewall">angiotensin-converting enzyme inhibitor</p>"
              ]
              1 => array:2 [
                "termino" => "AMBP"
                "descripcion" => "<p id="par0010" class="elsevierStylePara elsevierViewall">ambulatory blood pressure monitoring</p>"
              ]
              2 => array:2 [
                "termino" => "ARB"
                "descripcion" => "<p id="par0015" class="elsevierStylePara elsevierViewall">angiotensin receptor blocker</p>"
              ]
              3 => array:2 [
                "termino" => "apoA"
                "descripcion" => "<p id="par0020" class="elsevierStylePara elsevierViewall">apolipoprotein A</p>"
              ]
              4 => array:2 [
                "termino" => "BMI"
                "descripcion" => "<p id="par0025" class="elsevierStylePara elsevierViewall">body mass index</p>"
              ]
              5 => array:2 [
                "termino" => "CAD"
                "descripcion" => "<p id="par0030" class="elsevierStylePara elsevierViewall">coronary artery disease</p>"
              ]
              6 => array:2 [
                "termino" => "CCB"
                "descripcion" => "<p id="par0035" class="elsevierStylePara elsevierViewall">calcium channel blocker</p>"
              ]
              7 => array:2 [
                "termino" => "CRP"
                "descripcion" => "<p id="par0040" class="elsevierStylePara elsevierViewall">C-reactive protein</p>"
              ]
              8 => array:2 [
                "termino" => "CVD"
                "descripcion" => "<p id="par0045" class="elsevierStylePara elsevierViewall">cardiovascular disease</p>"
              ]
              9 => array:2 [
                "termino" => "FRS"
                "descripcion" => "<p id="par0050" class="elsevierStylePara elsevierViewall">Framingham risk score</p>"
              ]
              10 => array:2 [
                "termino" => "HDL"
                "descripcion" => "<p id="par0055" class="elsevierStylePara elsevierViewall">high-density lipoprotein</p>"
              ]
              11 => array:2 [
                "termino" => "IMT"
                "descripcion" => "<p id="par0060" class="elsevierStylePara elsevierViewall">carotid intima-media thickness</p>"
              ]
              12 => array:2 [
                "termino" => "Lp&#40;a&#41;"
                "descripcion" => "<p id="par0065" class="elsevierStylePara elsevierViewall">lipoprotein&#40;a&#41;</p>"
              ]
              13 => array:2 [
                "termino" => "LDL"
                "descripcion" => "<p id="par0070" class="elsevierStylePara elsevierViewall">low-density lipoprotein</p>"
              ]
              14 => array:2 [
                "termino" => "MACE"
                "descripcion" => "<p id="par0075" class="elsevierStylePara elsevierViewall">major acute cardiovascular events</p>"
              ]
              15 => array:2 [
                "termino" => "NAFLD"
                "descripcion" => "<p id="par0080" class="elsevierStylePara elsevierViewall">non-alcoholic fatty liver disease</p>"
              ]
              16 => array:2 [
                "termino" => "OAD"
                "descripcion" => "<p id="par0085" class="elsevierStylePara elsevierViewall">oral antidiabetic</p>"
              ]
              17 => array:2 [
                "termino" => "PAD"
                "descripcion" => "<p id="par0090" class="elsevierStylePara elsevierViewall">peripheral arterial disease</p>"
              ]
              18 => array:2 [
                "termino" => "SCORE"
                "descripcion" => "<p id="par0095" class="elsevierStylePara elsevierViewall">Systematic Coronary Risk Evaluation</p>"
              ]
              19 => array:2 [
                "termino" => "SSRI"
                "descripcion" => "<p id="par0100" class="elsevierStylePara elsevierViewall">selective serotonin reuptake inhibitors</p>"
              ]
              20 => array:2 [
                "termino" => "TC"
                "descripcion" => "<p id="par0105" class="elsevierStylePara elsevierViewall">total cholesterol</p>"
              ]
            ]
          ]
        ]
      ]
    ]
    "multimedia" => array:7 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 1248
            "Ancho" => 2147
            "Tamanyo" => 63657
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        "descripcion" => array:1 [
          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Differences between after treatment and before treatment for VR score calculated by each reference model&#46; ASCVD&#58; atherosclerotic cardiovascular disease&#59; FRS&#58; Framingham risk score&#59; SCORE&#58; systematic coronary risk evaluation&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Figure 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 729
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            "Tamanyo" => 105082
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        "descripcion" => array:1 [
          "en" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Drug therapies by pharmacological group and percentages of patients under treatment&#46; ACEI&#58; angiotensin-converting enzyme inhibitor&#59; ARB&#58; angiotensin receptor blocker&#59; CCB&#58; calcium channel blocker&#59; OAD&#58; oral antidiabetic drug&#59; PPI&#58; proton pump inhibitor&#46;</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at1"
            "detalle" => "Table "
            "rol" => "short"
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">BMI&#58; body mass index&#59; DBP&#58; diastolic blood pressure&#59; SBP&#58; systolic blood pressure&#59; ST&#58; sign test&#59; WSR&#58; Wilcoxon signed-rank test&#46;</p>"
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">n&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Weight&#44; kg&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">516&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-0&#46;54&#177;9&#46;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">-0&#46;4500&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">-40&#46;00-57&#46;60&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#46;069 &#40;WSR&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Height&#44; cm&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">516&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">-0&#46;37&#177;4&#46;73&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">-6&#46;00-86&#46;00&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#46;700 &#40;ST&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">BMI&#44; kg&#47;m<span class="elsevierStyleSup">2</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">516&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">-0&#46;36&#177;3&#46;23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">-0&#46;19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">-15&#46;94-10&#46;61&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#46;077 &#40;ST&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">516&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">-2&#46;03&#177;8&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">-2&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-43&#46;00-45&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001 &#40;WSR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Upper arm circumference&#44; cm&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">516&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-1&#46;41&#177;2&#46;75&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-2&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-10&#46;00-10&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001 &#40;WSR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Triceps skinfold&#44; cm&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">516&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-0&#46;39&#177;0&#46;63&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-0&#46;35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-3&#46;00-1&#46;20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001 &#40;ST&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SBP&#44; mmHg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">516&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-19&#46;35&#177;25&#46;28&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-148&#46;00-56&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001 &#40;ST&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DBP&#44; mmHg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">516&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-13&#46;35&#177;25&#46;29&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&#46;72&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-80&#46;00-30&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001 &#40;ST&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Heart rate&#44; bpm&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">493&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-10&#46;30&#177;12&#46;90&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-104&#46;00-22&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001 &#40;ST&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Daytime SBP&#44; mmHg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">478&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-23&#46;24&#177;24&#46;80&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-22&#46;50&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-147&#46;00-29&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001 &#40;ST&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Daytime DBP&#44; mmHg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">478&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-21&#46;45&#177;17&#46;98&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-22&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-86&#46;00-24&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001 &#40;ST&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Night-time SBP&#44; mmHg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">478&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-17&#46;77&#177;19&#46;11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-17&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-127&#46;00-25&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001 &#40;ST&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Night-time DBP&#44; mmHg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">478&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-19&#46;07&#177;15&#46;89&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-18&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-81&#46;00-14&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001 &#40;ST&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2138892.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Changes in anthropometric and clinical assessments between initial and final visits&#46;</p>"
        ]
      ]
      3 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at2"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">n &#40;&#37;&#41;</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Initial&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Final&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Smoking</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Ex-smoker&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">60 &#40;11&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">90 &#40;17&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Never-smoker&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">389 &#40;75&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">402 &#40;77&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Current smoker&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">67 &#40;13&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24 &#40;4&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Alcohol consumption</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Never&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">107 &#40;20&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">161 &#40;31&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Regular&#47;moderate &#40;one or two drinks&#47;day&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">233 &#40;45&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">68 &#40;13&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Excessive &#40;more than two drinks&#47;day&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">80 &#40;15&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17 &#40;3&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Alcoholic &#40;more than three drinks daily&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">36 &#40;7&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8 &#40;1&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Abstinent &#40;no drinks for at least one year&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;0&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10 &#40;1&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Exercise</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Physically inactive&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">371 &#40;71&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">144 &#40;28&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Physically active&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">145 &#40;28&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">371 &#40;72&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t">-0&#46;10&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">484&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">-0&#46;40&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">-7&#46;6-3&#46;5&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Fructosamine&#44; mmol&#47;l</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">387&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">-71&#46;25&#177;103&#46;16&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">-22&#46;00&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-379-123&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Fasting insulin&#44; &#956;U&#47;ml</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">463&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-0&#46;53&#177;6&#46;08&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-30-37&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;188&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>No&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">337&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">143&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Yes&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>No&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">-70&#46;00-4&#46;10&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Yes&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">191&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Yes&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Yes&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-32&#46;34&#177;15&#46;60&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-30&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-71&#46;00-4&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                      "titulo" => "Lipoprotein&#40;a&#41;&#58; a unique risk factor for cardiovascular disease"
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                          "etal" => true
                          "autores" => array:3 [
                            0 => "E&#46; Anuurad"
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                        "tituloSerie" => "Clin Lab Med"
                        "fecha" => "2006"
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                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17110238"
                            "web" => "Medline"
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Original Article
Lipoprotein(a) as a key target in combined therapeutic approaches for cardiovascular disease
Lipoproteína(a) como alvo fundamental nas estratégias terapêuticas múltiplas para a doença cardiovascular
Joaquim A. Meireles Brandãoa,b,
Corresponding author
dr.meirelesbrandao@gmail.com

Corresponding author.
, Lúcia R. Meireles-Brandãob, Rui Coelhoa, Francisco Rocha-Gonçalvesa
a Faculdade de Medicina do Porto, Universidade do Porto (FMUP), Porto, Portugal
b Starmedica.Clinica, Paredes, Portugal
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            "entidad" => "Faculdade de Medicina do Porto&#44; Universidade do Porto &#40;FMUP&#41;&#44; Porto&#44; Portugal"
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            "entidad" => "Starmedica&#46;Clinica&#44; Paredes&#44; Portugal"
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        "titulo" => "Lipoprote&#237;na&#40;a&#41; como alvo fundamental nas estrat&#233;gias terap&#234;uticas m&#250;ltiplas para a doen&#231;a cardiovascular"
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          "en" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Drug therapies by pharmacological group and percentages of patients under treatment&#46; ACEI&#58; angiotensin-converting enzyme inhibitor&#59; ARB&#58; angiotensin receptor blocker&#59; CCB&#58; calcium channel blocker&#59; OAD&#58; oral antidiabetic drug&#59; PPI&#58; proton pump inhibitor&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Introduction</span><p id="par0110" class="elsevierStylePara elsevierViewall">Lipoprotein&#40;a&#41; &#91;Lp&#40;a&#41;&#93; is identical to low-density lipoprotein &#40;LDL&#41; except for the addition of apolipoprotein A &#40;apoA&#41;&#44; which is highly glycosylated&#46; There is a striking homology between the amino acid sequences of apoA and plasminogen&#44; which is recognized to be a cardiovascular risk factor&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">1</span></a> Thus&#44; Lp&#40;a&#41; may play an important role in the transition from atherosclerosis to thrombosis&#44; because it activates monocyte adhesion and migration of macrophage foam cells into the arterial wall&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">2</span></a> Lp&#40;a&#41; is often considered a marker of thrombosis&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">3</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">Cardiovascular disease &#40;CVD&#41; is a major cause of death in patients with peripheral arterial disease &#40;PAD&#41;&#46; These patients also tend to suffer from complications when they have diabetes&#44; dyslipidemia and hypertension&#46; They may also develop severe systemic atherosclerosis&#44; leading to increased mortality due to coronary artery disease &#40;CAD&#41;&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">High Lp&#40;a&#41; is positively associated with coronary artery calcification&#44; CAD and PAD&#46;<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">4&#44;5</span></a> It also promotes thrombosis by binding to fibrin&#44; thus blocking the fibrinolytic action of plasmin&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">2</span></a> Lp&#40;a&#41; may be a predictor of peripheral and central CVD in younger men and women with dyslipidemia&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Several observations suggest that targeting Lp&#40;a&#41; could decrease total residual cardiovascular risk&#44; as increased plasma Lp&#40;a&#41; concentrations are significantly associated with higher risk of CAD&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">6</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">Lp&#40;a&#41; is a marker of particular risk for poor outcomes in terms of severity and progression of CVD&#46; Several prospective studies have correlated Lp&#40;a&#41; levels with vascular disease in general&#44; and plasma Lp&#40;a&#41; &#62;30 mg&#47;dl with increased cardiovascular risk&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">4</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">Studies with statins alone reveal that&#44; although they significantly reduce LDL and major adverse cardiovascular events &#40;MACE&#41;&#44; statins do not appear to reduce Lp&#40;a&#41; concentrations&#46; Almost all studies in this field have targeted total cholesterol &#40;TC&#41; and LDL&#44; as well as high-density lipoprotein cholesterol &#40;HDL&#41;&#44; but none has validated the use of HDL as a therapeutic target in the management of cardiovascular risk factors&#46; Furthermore&#44; in clinical practice cardiovascular risk scores are not usually applied to younger patients &#40;aged &#60;40 years&#41; with lower HDL levels&#44; even if they have other cardiovascular risk factors&#46; We therefore aimed to assess the possible relevance of all lipid fractions&#44; including HDL&#44; to cardiovascular risk factors&#44; regardless of age&#44; and following current clinical guidelines&#46;<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">7&#8211;9</span></a> In this study&#44; we assessed clinical and biochemical changes in randomly selected patients with two or more cardiovascular risk factors&#44; in primary prevention&#44; with no known cardiovascular events&#44; and considering their social&#44; cultural and demographic characteristics&#44; before and after the patients underwent treatment and medical guidance&#44; and the impact on metabolism and lipid&#44; C-reactive protein &#40;CRP&#41;&#44; fibrinogen and homocysteine levels&#44; among other clinical parameters&#44; including Lp&#40;a&#41; profile according to the criteria of the BiomarCaRE consortium&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">10</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Methods</span><p id="par0140" class="elsevierStylePara elsevierViewall">This retrospective observational study was conducted in 516 patients randomly selected from a group of 1677 patients who attended cardiovascular risk and metabolism consultations between 1995 and 2015&#44; in primary prevention&#44; and had not suffered MACE&#46; The selection criteria were as follows&#58; at least two personal and&#47;or family cardiovascular risk factors&#44; regular attendance at a three-monthly consultation for a minimum of two years&#44; and an annual biochemical assessment&#44; including cardiovascular exams and clinical assessment&#46; Participants filled in a self-administered questionnaire and provided written informed consent for inclusion in the study&#44; which was approved by the Ethics Committee of S&#227;o Jo&#227;o Hospital Center&#44; Porto&#46; Patients were followed for both clinical and anthropometric changes during the observation period&#44; paying particular attention to lipid and metabolic profiles and variations in Lp&#40;a&#41; levels&#46; The disorders diagnosed were classified into the following nosological groups&#58; cardiovascular&#44; cerebrovascular&#44; metabolic and behavioral diseases&#46; Data were collected from the first medical consultation until the last or current appointment recorded on the patient&#39;s medical chart&#46; It was established that an individual patient&#39;s record could only be updated for specific reasons&#44; such as CVD&#44; dependency or immobility&#44; MACE or death&#46; Records were updated 19 times due to death and six times due to the patient being bedridden&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">Patients&#8217; sociodemographic characteristics were analyzed based on their clinical records&#46; Their clinical&#44; anthropometric&#44; biochemical and cardiovascular characteristics were also analyzed and recorded&#46; These assessments included cardiovascular exams&#44; including electrocardiogram &#40;ECG&#41;&#44; two-dimensional echocardiogram and Doppler ultrasound &#40;7&#46;5 mHz linear probe&#44; Sonos 1000&#44; Hewlett Packard&#44; Andover&#44; MA&#41; of the supra-aortic trunks to measure carotid intima-media thickness &#40;IMT&#41;&#44; as well as ambulatory blood pressure monitoring &#40;ABPM&#41;&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Assessment of both renal and liver function are essential to analysis of metabolic status and the effects of pharmaceutical therapy&#46; Renal function was therefore assessed in this study&#44; based on microalbuminuria and creatinine clearance estimated by the Cockcroft-Gault method&#44; and liver function and morphology were assessed by ultrasound&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">Cardiovascular risk was calculated based on the three most commonly used scores&#58; the Framingham risk score &#40;FRS&#41;&#44; the European Society of Cardiology&#39;s Systematic Coronary Risk Evaluation &#40;SCORE&#41;&#44; and the American College of Cardiology&#39;s atherosclerotic cardiovascular disease risk estimator &#40;ASCVD&#41;&#46; The resulting overall scores were analyzed by age-group&#46; Also&#44; due to the association between metabolic compensation and clinical improvement in patients with cardiovascular risk factors&#44; the study included assessment of patients&#8217; lifestyle behaviors&#44; including alcohol consumption &#40;classified as never&#44; occasional&#44; moderate &#91;one or two drinks daily&#93;&#44; excessive &#91;three or more drinks daily&#93;&#44; alcoholic&#44; or abstinent &#91;at least one year since the last drink&#93;&#41;&#44; smoking &#40;current smoker&#44; ex-smoker or never-smoker&#41;&#44; and exercise levels &#40;all aerobic exercise at least twice a week in addition to that arising from daily activities&#41;&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">Finally&#44; drug therapies administered during the observation period were classified into pharmacological groups&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Statistical analysis</span><p id="par0165" class="elsevierStylePara elsevierViewall">Quantitative variables were summarized using descriptive statistics&#58; mean&#44; median&#44; standard deviation and range &#40;minimum and maximum&#41;&#46; Categorical variables were expressed as absolute &#40;n&#41; and relative &#40;&#37;&#41; frequencies&#46; Associations between two categorical variables were tested using the chi-square test or Fisher&#39;s exact test&#46; The McNemar test for paired samples was used to compare the presence of a symptom before and after treatment or to compare the results of two diagnostic tests applied in the same group&#46; Quantitative variables in two independent groups were compared using the t test for independent samples or the Mann-Whitney &#40;MW&#41; non-parametric test&#44; according to whether the respective assumptions were validated&#46; The non-parametric Wilcoxon signed-rank &#40;WSR&#41; test and sign test &#40;ST&#41; were used for paired samples to compare clinical scores before and after treatment if the assumption of normality was not confirmed&#46; Statistical tests were two-tailed and the significance level was taken to be 5&#37;&#46; Multivariate linear regression analysis was performed to assess associations between variables of interest and changes in Lp&#40;a&#41; levels between the beginning and the end of the study period&#46; Stepwise optimization was used to choose the statistically significant variables for the model&#46; All statistical analyses were conducted using IBM<span class="elsevierStyleSup">&#174;</span> SPSS<span class="elsevierStyleSup">&#174;</span> Statistics version 19&#46;</p></span></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Results</span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Sociodemographic&#44; clinical and anthropometric characteristics of the study population</span><p id="par0170" class="elsevierStylePara elsevierViewall">Of the 516 patients&#44; 224 were male and 292 were female&#44; and 98&#46;6&#37; were Caucasian&#46; The mean observation time was 11&#46;35&#177;4&#46;32 years &#40;range&#58; 2-26&#41;&#44; median 11&#46;0 years&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">During the observation period&#44; patients&#8217; age increased from an initial median of 46 years to a final median of 58 years&#46; Thus&#44; age grouping was readjusted&#44; as the number of patients decreased drastically in the &#60;20 years &#40;initial&#58; 2&#46;2&#37;&#59; final&#58; 0&#46;2&#37;&#41; and 20-34 years &#40;initial&#58; 20&#46;2&#37;&#59; final&#58; 7&#46;0&#37;&#41; age groups&#44; changed slightly in the 34-50 years age group &#40;initial&#58; 34&#46;3&#37;&#59; final&#58; 22&#46;9&#37;&#41;&#44; and increased in the 50-64 years &#40;initial&#58; 27&#46;9&#37;&#59; final&#58; 35&#46;5&#37;&#41; and &#8805;65 years &#40;initial&#58; 14&#46;9&#37;&#59; final&#58; 34&#46;5&#37;&#41; age groups&#46; By the end of the observation period&#44; 23 patients had died &#40;4&#46;5&#37;&#41; and 41 patients were bedridden &#40;7&#46;9&#37;&#41;&#59; most of these events occurred after data collection&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">Changes in patients&#8217; clinical and anthropometric assessments between initial and final observations are detailed in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; Significant reductions were seen in waist circumference&#44; upper arm circumference and triceps skinfold &#40;p&#60;0&#46;001&#41;&#46; In addition&#44; there were considerable improvements in blood pressure control&#44; reflected in statistically significant differences in mean systolic and diastolic daytime and night-time blood pressure &#40;p&#60;0&#46;001&#41;&#46; The number of patients with controlled atrial fibrillation rose from nine to 18 patients during the study period&#44; while the number with non-controlled atrial fibrillation decreased from two to one&#46; No statistical differences were found regarding weight&#44; height or body mass index&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Lifestyle</span><p id="par0185" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> shows changes in patients&#8217; lifestyles&#46; The reduction in alcohol consumption and the unexpected increase in regular exercise should be noted&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Biochemical assessment</span><p id="par0190" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> reports the results of the biochemical assessments&#46; Significant differences were found in almost every metabolic variable studied&#44; including CRP&#44; glycated hemoglobin&#44; fructosamine&#44; TC&#44; HDL&#44; LDL&#44; very-low-density lipoprotein&#44; triglycerides&#44; fibrinogen&#44; homocysteine&#44; uric acid and microalbuminuria &#40;p&#60;0&#46;001&#41;&#46; In addition&#44; fasting insulin and C-peptide values decreased between the first and the final observation&#44; although without statistically significant differences&#46; Lp&#40;a&#41; levels were also significantly reduced&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Cardiovascular exams</span><p id="par0195" class="elsevierStylePara elsevierViewall">The cardiovascular exams performed included ECG&#44; echocardiogram&#44; IMT and ABPM&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">Some changes were found in the ECG assessment&#46; A normal exam was seen in 247 patients &#40;47&#46;2&#37;&#41; at the initial observation&#44; compared to 281 patients &#40;55&#46;6&#37;&#41; at the final visit&#46; Atrial fibrillation was present in four patients &#40;0&#46;8&#37;&#41; at the first consultation&#44; and in 22 &#40;4&#46;4&#37;&#41; at the last&#46; On echocardiographic study&#44; alterations were seen in 267 patients &#40;52&#46;5&#37;&#41; at baseline&#44; and in 273 patients &#40;54&#46;7&#37;&#41; at the end of the observation period&#46; These included mild aortic valve abnormalities &#40;mild regurgitation in two patients&#41; and left atrial dilatation &#40;four patients&#41;&#46; Nevertheless&#44; the overall improvement in these parameters should be noted&#46; Concerning the 347 hypertensive patients &#40;69&#46;2&#37;&#41; who underwent ABPM&#44; at the end 14 patients &#40;2&#46;9&#37;&#41; were found to have uncontrolled hypertension&#46; The absence of acute episodes&#44; such as MACE&#44; during the study period should be noted&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">Doppler ultrasound of the supra-aortic trunks showed an improvement in the number of patients with normal results from 82 patients &#40;16&#46;2&#37;&#41; to 100 &#40;19&#46;8&#37;&#41;&#46; IMT also improved&#44; from an initial median of 2&#46;90 mm to a final median of 1&#46;40 mm &#40;Wilcoxon signed-rank test&#44; p&#60;0&#46;001&#41;&#46; However&#44; there was no reduction in the number of cases of vascular stenosis &#40;McNemar test&#44; p&#61;0&#46;500&#41;&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">It should be noted that&#44; of the 435 patients &#40;85&#46;4&#37;&#41; with hepatic steatosis&#44; 208 &#40;40&#46;8&#37;&#41; presented hepatic steatosis with hepatomegaly &#40;non-alcoholic fatty liver disease &#91;NAFLD&#93;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">11</span></a> Nevertheless&#44; liver function was only altered in a small number of patients &#40;14&#46;5&#37;&#41;&#46;</p><p id="par0215" class="elsevierStylePara elsevierViewall">The kidney is one of the target organs of CVD&#46; Our assessment of renal function showed that overall&#44; 46&#46;7&#37; &#40;241&#47;516&#41; of patients had abnormal creatinine clearance &#40;mean 104&#46;13&#177;46&#46;18 ml&#47;min&#47;m<span class="elsevierStyleSup">2</span>&#44; median 98&#46;20&#59; range 11&#46;3-276&#46;3&#41;&#44; normal being defined as 70-135 ml&#47;min&#47;m<span class="elsevierStyleSup">2</span>&#46; Moreover&#44; creatinine levels were abnormal in 31&#46;8&#37; &#40;164&#47;516&#41; of patients&#44; with mean levels of 87&#177;0&#46;34 g&#47;dl &#40;median 0&#46;81&#59; range 0&#46;39-4&#46;5&#41;&#44; normal being defined as 0&#46;66-1&#46;25 g&#47;dl&#46; Mean creatinine level was 0&#46;87&#177;0&#46;34 g&#47;dl &#40;median 0&#46;81&#59; range 0&#46;39-4&#46;5&#41;&#46; Finally&#44; 31&#37; &#40;160&#47;516&#41; of patients were found to have abnormal urea levels&#44; normal being defined as 10-50 mg&#47;dl&#46; Mean urea level was 47&#46;09&#177;17&#46;41 mg&#47;dl &#40;median 41&#46;00 mg&#47;dl&#59; range 17&#46;0-259&#46;0&#41;&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Nosological groups</span><p id="par0220" class="elsevierStylePara elsevierViewall">Clinical diagnoses were classified into the following nosological groups&#58; 390 patients with cardiovascular disease &#40;75&#46;6&#37;&#41;&#44; 50 with cerebrovascular disease &#40;9&#46;7&#37;&#41;&#44; 491 with metabolic diseases &#40;95&#46;2&#37;&#41; and 301 with behavioral diseases &#40;58&#46;3&#37;&#41;&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Stratification of cardiovascular risk</span><p id="par0225" class="elsevierStylePara elsevierViewall">Initial and final cardiovascular risk was stratified by estimating 10-year risk according to the parameters of the FRS&#44; SCORE and ASCVD&#46; Differences between cardiovascular risk scores calculated before and after treatment were as follows&#58; FRS&#58; -15&#46;37 &#40;min-max&#58; -79&#46;20-28&#46;60&#41;&#44; high-risk SCORE&#58; -1&#46;08 &#40;min-max&#58; -26&#46;36-4&#46;31&#41;&#44; low-risk SCORE&#58; -0&#46;44 &#40;min-max&#58; -14&#46;50-2&#46;83&#41; and ASCVD&#58; -5&#46;83 &#40;min-max&#58; -87&#46;73-40&#46;12&#41;&#46; All improvements in cardiovascular risk scores between initial and final measures were statistically significant &#40;p&#60;0&#46;05&#41;&#44; regardless of the calculation method applied &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Pharmacological therapy</span><p id="par0230" class="elsevierStylePara elsevierViewall">The pharmacological therapies administered to the patients are presented in <a class="elsevierStyleCrossRef" href="#fig0010">Figure 2</a> and <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#44; divided into pharmacological groups&#46; The following therapies were used most in this patient group&#58; antidepressants &#40;particularly selective serotonin reuptake inhibitors &#91;SSRIs&#93;&#41;&#44; anxiolytics&#44; lipid-lowering therapy including statins&#44; and antiplatelets&#46; Allopurinol&#44; diuretics&#44; angiotensin-converting enzyme inhibitors &#40;ACEIs&#41; and angiotensin receptor blockers &#40;ARBs&#41; were also commonly used&#46; We also compared the efficacy of each of these therapies individually between patients who were receiving a particular treatment and those who were not&#44; based on final Lp&#40;a&#41; levels&#46; Results of the multiple regression analysis are shown in Supplementary <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; Briefly&#44; statins&#44; ACEIs&#44; ARBs&#44; oral antidiabetic drugs &#40;OADs&#41;&#44; antiplatelets&#44; calcium channel blockers &#40;CCBs&#41; and allopurinol showed statistically significant differences on bivariate analysis &#40;p&#60;0&#46;05&#41; and were selected to enter the final model&#46; This analysis excluded patients who died&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0235" class="elsevierStylePara elsevierViewall">Overall&#44; the use of statins&#44; ACEIs&#44; ARBs&#44; OADs&#44; antiplatelets&#44; CCBs and allopurinol was associated with greater reductions in Lp&#40;a&#41; values during the follow-up period&#46; The final optimized regression model showed that the regression coefficient for reduction in Lp&#40;a&#41; levels in patients under statins between the initial and the final measurement was more than 10&#46;635&#44; compared to those not under statins&#44; after adjustment for antiplatelets&#44; allopurinol and antidepressants &#40;final model variables&#41;&#46; Furthermore&#44; the regression coefficient for reduction in Lp&#40;a&#41; levels in patients under antiplatelets was more than 4&#46;786&#44; compared with those not under antiplatelets&#44; after adjustment for statins&#44; allopurinol and antidepressants&#46; The regression coefficient for reduction in Lp&#40;a&#41; levels in patients under allopurinol was more than 5&#46;376&#44; in comparison with those who were not under allopurinol&#44; after adjustment for statins&#44; antiplatelets and antidepressants&#46; Finally&#44; the regression coefficient for reduction in Lp&#40;a&#41; levels in patients under antidepressants was more than 4&#46;367 compared with those who were not under antidepressants&#44; after adjustment for statins&#44; antiplatelets and allopurinol&#46;</p></span></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Discussion</span><p id="par0240" class="elsevierStylePara elsevierViewall">In this retrospective observational study&#44; we appraised the effects of using combined drug therapies on changes in Lp&#40;a&#41; levels in patients with high cardiovascular risk&#44; without MACE&#46; Overall&#44; our results indicate significant clinical improvements between the initial and final measurements&#44; especially regarding blood pressure and metabolic risk factors&#46;</p><p id="par0245" class="elsevierStylePara elsevierViewall">Neither social nor demographic factors appeared to pose difficulties in following the proposed treatments and guidance for improving lifestyles&#46; The improvements in blood pressure control and significant reductions in waist circumference should be noted&#44; as these are important cardiovascular risk factors influencing the atherosclerotic process&#46;</p><p id="par0250" class="elsevierStylePara elsevierViewall">This study demonstrated a significant correlation between Lp&#40;a&#41; levels and cardiovascular risk scores in patients with high cardiovascular risk but without MACE&#46; In previous work&#44; we found that increased Lp&#40;a&#41; levels in these individuals were strongly associated with cardiovascular risk factors such as IMT&#44; LDL-C and homocysteine&#44; as well as with NAFLD&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">12</span></a> In addition&#44; for the same population&#44; a positive and significant correlation was found between Lp&#40;a&#41; and the risk scores used for CVD stratification &#40;p&#60;0&#46;001&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">12</span></a> These data suggest that guidelines for assessing the severity of the atherosclerotic process should be reviewed&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">13</span></a></p><p id="par0255" class="elsevierStylePara elsevierViewall">Until recently&#44; Lp&#40;a&#41; has been a recognized but under-appreciated cardiovascular risk factor&#44; largely because a therapeutic approach has yet to be established&#46;<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">14&#44;15</span></a> As specific treatments are lacking&#44; Lp&#40;a&#41; warrants further investigation&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">1</span></a> Early primary prevention is recommended&#44; with the introduction of available therapies in clinically stable patients&#44; regardless of vascular age risk &#40;personal&#44; family and lifestyle&#41; and metabolic alterations promoting the atherosclerosis process&#46; However&#44; currently used cardiovascular risk scores do not fit this interventional approach&#44; but rather delay the administration of combined drug treatments&#46; Patients&#8217; commitment to implementing changes&#44; including adopting healthier lifestyles&#44;<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">16&#8211;18</span></a> such as regular exercise&#44; is essential to the success of the treatment&#46;<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">8&#44;19</span></a></p><p id="par0260" class="elsevierStylePara elsevierViewall">Lp&#40;a&#41; acts as a marker of severity and progression of CVD in patients at particular risk for poor outcomes&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">20</span></a> In our study&#44; although there was a significant decrease in IMT&#44; cases of carotid stenosis persisted after the treatment period&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">20</span></a> Therefore&#44; although this was not evident in previous studies&#44; lipid-lowering therapy&#44; especially statins combined with other treatments&#44; appears to be involved in Lp&#40;a&#41; reduction&#46; Similar results were obtained with ACEIs&#44; diuretics&#44; ARBs&#44; CCBs and antiplatelets&#46; The effects of allopurinol&#44; OADs and proton pump inhibitors in combined drug therapy&#44; should also be highlighted&#46; On the other hand&#44; beta-blockers and insulin had less effect&#46;</p><p id="par0265" class="elsevierStylePara elsevierViewall">These results confirm that the role of Lp&#40;a&#41; as a biomarker of cardiovascular risk should be analyzed along with that of patients&#8217; lifestyles and biochemical parameters&#46; Lp&#40;a&#41; may thus be a crucial indicator for comprehensive early multidisciplinary treatment&#44; directed at all cardiovascular risk factors and associated comorbidities&#46;</p><p id="par0270" class="elsevierStylePara elsevierViewall">A large proportion of patients had moderate renal failure&#44; as expected since the kidney is a target organ for atherosclerotic disease&#44; and also due to cellular senescence&#46; This finding indicates that appropriate adjustments to therapy may be required&#46; We also observed a high number of patients with hepatic steatosis&#44; which indicates that this condition should be considered in the presence of NAFLD and&#44; as such&#44; may represent a way to contextualize the evolution and severity of atherosclerotic disease&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">11&#44;21</span></a></p><p id="par0275" class="elsevierStylePara elsevierViewall">In view of the clinically relevant and statistically significant reduction of Lp&#40;a&#41; seen in our study&#44;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">22</span></a> further research is required to establish a consistent therapeutic strategy to achieve this end&#44;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">23</span></a> as well as to improve upon the subjective calculation of cardiovascular risk with currently used algorithms&#46; Nonetheless&#44; we can state that first-line therapies should include statins&#44;<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">24&#44;25</span></a> allopurinol&#44; antiplatelets and antidepressant drugs&#46; In addition&#44; the atherogenicity of Lp&#40;a&#41; may be modified through substantial reductions in LDL levels&#46;</p><p id="par0280" class="elsevierStylePara elsevierViewall">Although clinically relevant&#44; our results should be interpreted in the light of the inherent methodological limitations of the study&#46; As it is based on data from a single center&#44; the results cannot be extrapolated to the Portuguese population in general&#46; Due to its retrospective nature&#44; the study could have been affected by information bias from data gathered from patients&#8217; charts&#44; including changes in therapeutic guidelines over the long follow-up period &#40;median 11&#46;0 years&#41;&#46; Furthermore&#44; it was not possible to establish temporal relationships between risk factors and CVD that demonstrate causation&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Conclusion</span><p id="par0285" class="elsevierStylePara elsevierViewall">Lp&#40;a&#41; is a key indicator of global cardiovascular risk and should be considered a therapeutic target&#46; According to the results obtained for our patients&#44; it may be important to initiate primary prevention&#44; including combined drug therapies&#44; while addressing all cardiovascular risk factors&#44; to delay the atherosclerotic process&#46; First-line therapy should include statins&#44; antiplatelets&#44; allopurinol and antidepressants&#44; particularly SSRIs&#46; Among other pharmacological therapies&#44; CCBs&#44; ACEIs&#44; OADs and ARBs should also be considered&#44; as well as lifestyle modifications&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Conflicts of interest</span><p id="par0290" class="elsevierStylePara elsevierViewall">The author has no conflicts of interest to declare&#46;</p></span></span>"
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              "titulo" => "Sociodemographic&#44; clinical and anthropometric characteristics of the study population"
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            1 => "Cardiovascular disease"
            2 => "Atherosclerosis"
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            5 => "Peripheral arterial disease"
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            0 => "Lipoprote&#237;na&#40;a&#41;"
            1 => "Doen&#231;as cardiovasculares"
            2 => "Aterosclerose"
            3 => "Terap&#234;utica farmacol&#243;gica combinada"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction and Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Lipoprotein&#40;a&#41; &#91;Lp&#40;a&#41;&#93; is an independent cardiovascular risk factor but is closely associated with other similar risk factors that are manageable with appropriate treatment and guidance&#46; We aimed to study the impact of using combined therapy for managing Lp&#40;a&#41; levels in patients at high cardiovascular risk but without major adverse cardiovascular events&#44; in primary prevention&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">We conducted a retrospective observational study in 516 patients randomly selected from a group of 1677 patients who attended cardiovascular risk and metabolism consultations between 1995 and 2015&#46; The disorders observed and therapies used were classified into nosological and pharmacological groups&#44; respectively&#46; Cardiovascular risk was calculated based on the Framingham risk score&#44; the European Society of Cardiology&#39;s SCORE and the American College of Cardiology&#39;s ASCVD Risk Estimator&#44; and changes in patients&#8217; lifestyle were assessed&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Significant differences &#40;p&#60;0&#46;001&#41; were found in almost all metabolic variables&#44; except fasting insulin and C-peptide&#46; Lp&#40;a&#41; levels were also significantly reduced &#40;p&#60;0&#46;001&#41;&#46; Carotid intima-media thickness improved&#44; decreasing from 2&#46;90 mm to 1&#46;40 mm&#59; however&#44; there was no reduction in the number of cases of vascular stenosis&#46; Of patients with hepatic steatosis &#40;85&#46;5&#37;&#41;&#44; 40&#46;7&#37; presented hepatomegaly&#44; but liver function was only altered in a few patients &#40;14&#46;5&#37;&#41;&#46; Lipid-lowering therapy&#44; especially statins&#44; significantly decreased Lp&#40;a&#41;&#44; benefiting from synergy with other treatments&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Lp&#40;a&#41; is a key overall indicator of vascular risk and should be considered a therapeutic target&#46; Besides a healthy lifestyle&#44; primary prevention should include combined drug therapies to address all cardiovascular risk factors and to delay the atherosclerotic process&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introdu&#231;&#227;o e objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Lp&#40;a&#41; &#233; um fator de risco cardiovascular independente&#44; mas intrinsecamente associado a outros fatores de risco similares&#44; control&#225;veis com terap&#234;uticas e orienta&#231;&#245;es adequadas&#46; O nosso objetivo &#233; estudar o impacto do uso de terap&#234;uticas combinadas na gest&#227;o da evolu&#231;&#227;o da Lp&#40;a&#41; em doentes com elevado risco vascular&#44; sem ECVM em preven&#231;&#227;o prim&#225;ria&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Estudo observacional retrospetivo realizado em 516 doentes&#44; selecionados aleatoriamente de um universo de 1677 indiv&#237;duos&#44; que participaram regularmente em consultas de risco vascular e metabolismo entre 1995 e 2015&#46; As patologias observadas e terap&#234;uticas utilizadas foram distribu&#237;das em diferentes grupos nosol&#243;gicos e grupos farmacol&#243;gicos&#44; respetivamente&#46; Calculou-se o RV com base em FRS&#44; SCORE e ASCVD e avaliou-se tamb&#233;m a evolu&#231;&#227;o do estilo de vida dos doentes&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Encontraram-se diferen&#231;as significativas &#40;p&#60;0&#44;001&#41; em quase todas as vari&#225;veis metab&#243;licas&#44; exceto insulina &#40;jejum&#41; e p&#233;ptido-C&#46; Houve uma redu&#231;&#227;o significativa nos n&#237;veis de Lp&#40;a&#41; &#40;p&#60;0&#44;001&#41;&#46; A espessura &#237;ntima-m&#233;dia carot&#237;dea evoluiu favoravelmente&#44; diminuindo de 2&#44;90 mm para 1&#44;40 mm&#59; por&#233;m&#44; n&#227;o houve redu&#231;&#227;o do n&#250;mero de casos de estenose vascular&#46; Dos doentes com esteatose hep&#225;tica &#40;85&#44;5&#37;&#41;&#44; 40&#44;7&#37; apresentaram hepatomegalia&#46; Contudo&#44; poucos doentes &#40;14&#44;5&#37;&#41; apresentaram fun&#231;&#227;o hep&#225;tica alterada&#46; A terap&#234;utica antidislipid&#233;mica&#44; especialmente as estatinas&#44; diminuiu significativamente a Lp&#40;a&#41;&#44; beneficiando da sinergia com demais tratamentos&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclus&#245;es</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Lp&#40;a&#41; &#233; um indicador global e fundamental de risco vascular&#44; a considerar como alvo terap&#234;utico&#46; Al&#233;m de um estilo de vida saud&#225;vel&#44; a preven&#231;&#227;o prim&#225;ria deve incluir terap&#234;uticas farmacol&#243;gicas combinadas dirigidas aos fatores de risco cardiovasculares e&#44; consequentemente&#44; retardar o processo ateroscler&#243;tico&#46;</p></span>"
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            "etiqueta" => "Appendix A"
            "titulo" => "Supplementary material"
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                "termino" => "ACEI"
                "descripcion" => "<p id="par0005" class="elsevierStylePara elsevierViewall">angiotensin-converting enzyme inhibitor</p>"
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              1 => array:2 [
                "termino" => "AMBP"
                "descripcion" => "<p id="par0010" class="elsevierStylePara elsevierViewall">ambulatory blood pressure monitoring</p>"
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                "termino" => "ARB"
                "descripcion" => "<p id="par0015" class="elsevierStylePara elsevierViewall">angiotensin receptor blocker</p>"
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                "termino" => "apoA"
                "descripcion" => "<p id="par0020" class="elsevierStylePara elsevierViewall">apolipoprotein A</p>"
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                "termino" => "BMI"
                "descripcion" => "<p id="par0025" class="elsevierStylePara elsevierViewall">body mass index</p>"
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                "termino" => "CAD"
                "descripcion" => "<p id="par0030" class="elsevierStylePara elsevierViewall">coronary artery disease</p>"
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                "termino" => "CCB"
                "descripcion" => "<p id="par0035" class="elsevierStylePara elsevierViewall">calcium channel blocker</p>"
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                "termino" => "CRP"
                "descripcion" => "<p id="par0040" class="elsevierStylePara elsevierViewall">C-reactive protein</p>"
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                "descripcion" => "<p id="par0045" class="elsevierStylePara elsevierViewall">cardiovascular disease</p>"
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                "termino" => "FRS"
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                "termino" => "Lp&#40;a&#41;"
                "descripcion" => "<p id="par0065" class="elsevierStylePara elsevierViewall">lipoprotein&#40;a&#41;</p>"
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                "termino" => "LDL"
                "descripcion" => "<p id="par0070" class="elsevierStylePara elsevierViewall">low-density lipoprotein</p>"
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                "termino" => "MACE"
                "descripcion" => "<p id="par0075" class="elsevierStylePara elsevierViewall">major acute cardiovascular events</p>"
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              15 => array:2 [
                "termino" => "NAFLD"
                "descripcion" => "<p id="par0080" class="elsevierStylePara elsevierViewall">non-alcoholic fatty liver disease</p>"
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                "termino" => "OAD"
                "descripcion" => "<p id="par0085" class="elsevierStylePara elsevierViewall">oral antidiabetic</p>"
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                "termino" => "PAD"
                "descripcion" => "<p id="par0090" class="elsevierStylePara elsevierViewall">peripheral arterial disease</p>"
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              18 => array:2 [
                "termino" => "SCORE"
                "descripcion" => "<p id="par0095" class="elsevierStylePara elsevierViewall">Systematic Coronary Risk Evaluation</p>"
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                "termino" => "SSRI"
                "descripcion" => "<p id="par0100" class="elsevierStylePara elsevierViewall">selective serotonin reuptake inhibitors</p>"
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              20 => array:2 [
                "termino" => "TC"
                "descripcion" => "<p id="par0105" class="elsevierStylePara elsevierViewall">total cholesterol</p>"
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Differences between after treatment and before treatment for VR score calculated by each reference model&#46; ASCVD&#58; atherosclerotic cardiovascular disease&#59; FRS&#58; Framingham risk score&#59; SCORE&#58; systematic coronary risk evaluation&#46;</p>"
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Range &#40;min-max&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Weight&#44; kg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">516&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-0&#46;54&#177;9&#46;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-0&#46;4500&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-40&#46;00-57&#46;60&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;069 &#40;WSR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Height&#44; cm&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">516&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-0&#46;37&#177;4&#46;73&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-6&#46;00-86&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;700 &#40;ST&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">BMI&#44; kg&#47;m<span class="elsevierStyleSup">2</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">516&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-0&#46;36&#177;3&#46;23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-0&#46;19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-15&#46;94-10&#46;61&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;077 &#40;ST&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Waist circumference&#44; cm&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">516&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-2&#46;03&#177;8&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-2&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-43&#46;00-45&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001 &#40;WSR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Upper arm circumference&#44; cm&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">516&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-1&#46;41&#177;2&#46;75&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-2&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-10&#46;00-10&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001 &#40;WSR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Triceps skinfold&#44; cm&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">516&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-0&#46;39&#177;0&#46;63&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-0&#46;35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-3&#46;00-1&#46;20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001 &#40;ST&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SBP&#44; mmHg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">516&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-19&#46;35&#177;25&#46;28&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-148&#46;00-56&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001 &#40;ST&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DBP&#44; mmHg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">516&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-13&#46;35&#177;25&#46;29&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&#46;72&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-80&#46;00-30&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001 &#40;ST&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Heart rate&#44; bpm&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">493&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-10&#46;30&#177;12&#46;90&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-104&#46;00-22&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001 &#40;ST&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Daytime SBP&#44; mmHg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">478&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-23&#46;24&#177;24&#46;80&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-22&#46;50&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-147&#46;00-29&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001 &#40;ST&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Daytime DBP&#44; mmHg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">478&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-21&#46;45&#177;17&#46;98&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-22&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-86&#46;00-24&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001 &#40;ST&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Night-time SBP&#44; mmHg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">478&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-17&#46;77&#177;19&#46;11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-17&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-127&#46;00-25&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001 &#40;ST&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Night-time DBP&#44; mmHg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">478&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-19&#46;07&#177;15&#46;89&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-18&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-81&#46;00-14&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001 &#40;ST&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">n &#40;&#37;&#41;</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Initial&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Final&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Smoking</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Ex-smoker&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">60 &#40;11&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">90 &#40;17&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Never-smoker&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">389 &#40;75&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">402 &#40;77&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Current smoker&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">67 &#40;13&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24 &#40;4&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Never&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">57 &#40;11&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">251 &#40;48&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Occasional&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">107 &#40;20&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">161 &#40;31&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Regular&#47;moderate &#40;one or two drinks&#47;day&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">233 &#40;45&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">68 &#40;13&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Excessive &#40;more than two drinks&#47;day&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">80 &#40;15&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17 &#40;3&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Alcoholic &#40;more than three drinks daily&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">36 &#40;7&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8 &#40;1&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Abstinent &#40;no drinks for at least one year&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;0&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10 &#40;1&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Exercise</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Physically inactive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">371 &#40;71&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">144 &#40;28&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Physically active&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">145 &#40;28&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">371 &#40;72&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">n&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Mean difference&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Median difference&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Range &#40;min-max&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p &#40;WSR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">222&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-27&#46;89&#177;14&#46;87&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-25&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-68&#46;00-4&#46;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001 &#40;MW&#41;</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">259&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-35&#46;33&#177;15&#46;05&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-34&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-71&#46;00-0&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">ARBs</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">274&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-29&#46;35&#177;14&#46;35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-27&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-68&#46;00-4&#46;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001 &#40;MW&#41;</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">207&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-35&#46;27&#177;16&#46;12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-34&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-71&#46;00-0&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">OADs</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">337&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-30&#46;04&#177;15&#46;39&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-27&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-71&#46;00-4&#46;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001 &#40;MW&#41;</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">143&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-36&#46;20&#177;14&#46;62&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-36&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-71&#46;00--8&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Antiplatelets</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">217&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-27&#46;31&#177; 14&#46;84&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-24&#46;40&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-70&#46;00-4&#46;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001 &#40;MW&#41;</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">263&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-35&#46;73&#177; 14&#46;84&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-36&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-71&#46;00-0&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">CCBs</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">290&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-29&#46;00&#177;14&#46;74&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-27&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-70&#46;00-4&#46;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001 &#40;MW&#41;</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">191&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-36&#46;29&#177;15&#46;39&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-35&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-71&#46;00-0&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Allopurinol</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">242&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-27&#46;85&#177;14&#46;11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-25&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-68&#46;00-4&#46;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001 &#40;MW&#41;</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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ISSN: 21742049
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Revista Portuguesa de Cardiologia (English edition)
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