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Changes in albumin-to-creatinine ratio at 12-month follow-up in patients undergoing renal denervation
Rácio albumina-creatinina aos 12 meses de seguimento após desnervação renal
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Of the total number of patients observed in an outpatient hypertension clinic (n=318), 253 were excluded for various reasons (see main text) and 65 underwent renal denervation. Of these 65, complete 12-month follow-up with ambulatory blood pressure monitoring and transthoracic echocardiographic data were available in 31 patients. 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"referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 7 => array:3 [ "nombre" => "Maria João" "apellidos" => "Andrade" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 8 => array:3 [ "nombre" => "Nuno" "apellidos" => "Neuparth" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 9 => array:3 [ "nombre" => "Ana" "apellidos" => "Aleixo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 10 => array:3 [ "nombre" => "Miguel" "apellidos" => "Mendes" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 11 => array:3 [ "nombre" => "José Diogo" "apellidos" => "Barata" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Hospital de Santa Cruz, CHLO, Lisbon, Portugal" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Hospital da Luz, Lisbon, Portugal" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "CEDOC-Nova Medical School, Lisbon, Portugal" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Rácio albumina-creatinina aos 12 meses de seguimento após desnervação renal" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1555 "Ancho" => 2333 "Tamanyo" => 91158 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Values of albumin-to-creatinine ratio and estimated glomerular filtration rate at 12 months after renal denervation. There was a significant reduction in the median values of ACR and the percentage of patients with ACR >30 mg/g, without significant changes in eGFR. ACR: albumin-to-creatinine ratio; eGFR: estimated glomerular filtration rate.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Cardiovascular disease is the leading cause of morbidity and mortality in developed countries and hypertension is one of its most important risk factors.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">1</span></a> Some hypertensive patients have drug-resistant hypertension and are at a higher risk of events.<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">2,3</span></a> Besides clinical events, assessment of target organ damage can provide earlier insights into the biological impact of hypertension. For several years, albuminuria has been recognized as an indicator of cardiovascular risk, although the pathophysiology behind this association is still not fully understood.<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">4–6</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">In recent years sympathetic renal denervation (RDN) has been developed as a treatment for the management of patients with resistant hypertension<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">7,8</span></a> and it may have a positive impact on hypertension-related target organ damage. An example is recently published reports of reductions in left ventricular hypertrophy after RDN.<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">9–11</span></a> The kidney is also an important organ in this context, but evidence on the effect of RDN on proteinuria is still limited and results are conflicting.<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">12,13</span></a> The aim of the present study was to assess the impact of RDN on the albumin-to-creatinine ratio (ACR) at 12-month follow-up.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Study design and patient population</span><p id="par0015" class="elsevierStylePara elsevierViewall">From a single-center prospective registry including 318 patients with resistant hypertension referred for RDN between July 2011 and April 2015, we included for the purpose of the present study 31 patients with complete information on blood pressure (BP) measurements (both office and 24-h ambulatory blood pressure monitoring [ABPM]) at baseline and 12 months, transthoracic echocardiogram and renal function (creatinine clearance and ACR), out of 65 patients who were considered good candidates and underwent RDN (<a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">The details of this patient population have been previously described.<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">11,14</span></a> Briefly, all patients who underwent RDN were aged over 18 years, with persistent office systolic blood pressure (SBP) above 160 mmHg even after optimal antihypertensive therapy (at least three drugs, including a diuretic). Before RDN all patients were studied for secondary causes of hypertension and visited regularly (for at least six weeks) in order to ensure drug regime optimization and full compliance with medical treatment.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Demographic, clinical, anthropometric, laboratory and procedural data were recorded and stored in a dedicated database and written informed consent was obtained from all patients. The study was approved by the ethics committee of Hospital de Santa Cruz and Nova Medical School, Lisbon, Portugal.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Blood pressure measurement and definition of responders</span><p id="par0030" class="elsevierStylePara elsevierViewall">Office BP readings were measured in a seated position, after a 5 min rest (in accordance with the European guidelines for the management of arterial hypertension), using an Omron HEM-907 semiautomatic oscillometric sphygmomanometer (Omron Healthcare, USA).</p><p id="par0035" class="elsevierStylePara elsevierViewall">At baseline, before RDN, BP measurements were taken in both arms and the arm with the higher BP was selected for all subsequent readings. The mean of three measurements was used for analysis. An ABM monitor (Spacelabs Healthcare, USA) was used for 24-h ABPM assessment.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Patients with a decrease of 10 mmHg or more in office SBP or of 2 mmHg or more in 24-h ABPM SBP at 12-month follow-up were considered to be BP responders to RDN.<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">11,15</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Renal function and albuminuria measurement</span><p id="par0045" class="elsevierStylePara elsevierViewall">Creatinine clearance was estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. Albuminuria was obtained in spot urine and measured using the ACR, expressed in mg/g, which is equivalent to 24-h albumin excretion in mg/day. ACR values were acquired before RDN (at baseline) and at 12-month follow-up.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Renal denervation procedure</span><p id="par0050" class="elsevierStylePara elsevierViewall">RDN procedures were performed using mild anesthesia (propofol and remifentanil) for sedation and pain control. An activated clotting time of 250-300 s was obtained with unfractionated heparin. After femoral artery access, abdominal aortography and selective renal artery angiography were performed to confirm anatomic eligibility. In all cases, the femoral access site was closed using a sealing device (Angio-Seal<span class="elsevierStyleSup">®</span>, St. Jude Medical, USA).</p><p id="par0055" class="elsevierStylePara elsevierViewall">Denervation was performed using the following radiofrequency systems: Symplicity<span class="elsevierStyleSup">®</span> (n=25), EnligHTN<span class="elsevierStyleSup">®</span> (n=4) and OneShot<span class="elsevierStyleSup">®</span> (n=2), in accordance with standard techniques.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Statistical analysis</span><p id="par0060" class="elsevierStylePara elsevierViewall">Continuous variables are reported as mean ± standard deviation. Normality was tested with the Kolmogorov-Smirnov test and/or visual assessment of a Q-Q plot. Normally distributed variables were compared between baseline and 12-month follow-up using a paired Student's t test, or a Wilcoxon matched-pairs test if not normally distributed. Discrete variables are expressed as frequencies and percentages. Statistical comparisons of characteristics at baseline and at follow-up were performed using the chi-square test or Fisher's exact test, as appropriate, for categorical variables and the paired Student's t test for continuous variables. A two-tailed p value <0.05 was considered as statistically significant.</p><p id="par0065" class="elsevierStylePara elsevierViewall">SPSS<span class="elsevierStyleSup">®</span> version 21.0 (IBM SPSS Inc, Chicago, IL) was used for data processing and statistical analysis.</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Results</span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Patient characteristics</span><p id="par0070" class="elsevierStylePara elsevierViewall">A total of 318 patients were observed in an outpatient hypertension clinic between 2011 and 2015. Of these, 253 were excluded due to: (a) BP control being achieved after dose and/or drug changes (n=139); (b) a secondary cause of hypertension (n=31); (c) renal anatomy considered unsuitable for RDN on computed tomography angiography; (d) estimated glomerular filtration rate (eGFR) <30 ml/min/1.73 m<span class="elsevierStyleSup">2</span>; (e) patient refusal after discussion of the expected benefits and risks. A total of 65 patients were considered good candidates and underwent RDN. Of these, the first 31 with complete data on blood and urine samples, office BP and 24-h ABPM, and transthoracic echocardiogram at both baseline and 12-month follow-up were included in the present analysis (<a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>). Data on left ventricular mass and function have been reported elsewhere.<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">11</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">Mean age was 65±7 years, all patients were Caucasian and 48% (n=14) were male. Regarding cardiovascular risk factors, 71% had type 2 diabetes, 68% were obese (mean body mass index 32±6 kg/m<span class="elsevierStyleSup">2</span>), 68% had dyslipidemia and only one patient was an active smoker. Ten patients (33%) had manifestations of vascular disease (mainly coronary artery disease). Mean eGFR was 76.4±24.7 ml/min/1.73 m<span class="elsevierStyleSup">2</span> and five patients had chronic kidney disease (eGFR <60 ml/min/1.73 m<span class="elsevierStyleSup">2</span>) (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). At baseline, median ACR was 25.8 (interquartile range [IQR] 9.0-574.0) and 15 (48%) patients had ACR >30 mg/g.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">Most patients (90%) had known hypertension for at least 10 years and were treated at baseline with a mean of 5.8 anti-hypertensive drugs, corresponding to a mean of 5.5 different drug classes. Of note, 74% were treated with spironolactone. Details on antihypertensive medication at baseline and follow-up are presented in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>.</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Blood pressure control</span><p id="par0085" class="elsevierStylePara elsevierViewall">Mean office SBP and diastolic BP (DBP) at baseline were 176±24 mmHg and 90±14 mmHg, respectively, and mean heart rate was 73±11 bpm. On 24-h ABPM, mean SBP and DBP were 150±20 mmHg and 83±10 mmHg, respectively (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>).</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">At 12-month follow-up mean SBP had decreased from 176±24 to 149±13 mmHg (p<0.001) and DBP from 90±14 to 79±11 mmHg (p<0.001). These changes were consistent with the results of 24-h ABPM, in which mean SBP decreased from 150±20 to 132±14 mmHg (p<0.001) and mean DBP from 83±10 to 74±9 mmHg (p=0.001). At 12-month follow-up, 71% of patients were considered office SBP responders and 84% were considered ABPM SBP responders (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>). During this period there was also a reduction in the number of antihypertensive drugs and classes taken; the number of drugs decreased from 5.8±1.1 to 5.0±1.2 (p=0.002) and drug classes from 5.5±0.9 to 4.9±1.1 (p=0.02) (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Changes in albumin-to-creatinine ratio after renal denervation and relation with blood pressure control</span><p id="par0095" class="elsevierStylePara elsevierViewall">At baseline, median ACR was 25.8 mg/g (IQR 9.0-574.0 mg/g) and 48.4% of patients (n=15) had an ACR >30 mg/g. We found a significant reduction at 12-month follow-up to a median of 14.8 mg/g (IQR 4.5-61.0 mg/g, p=0.007) (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>).</p><p id="par0100" class="elsevierStylePara elsevierViewall">Interestingly, we also found a significant reduction in the percentage of patients with ACR >30 mg/g between baseline and 12-month follow-up (<a class="elsevierStyleCrossRef" href="#fig0010">Figure 2</a>). Considering patients with any ACR reduction as ACR responders, 77.4% (n=24) of patients were ACR responders. The distribution of patients across the different classes of urinary albumin excretion also demonstrated a favorable effect (<a class="elsevierStyleCrossRef" href="#fig0015">Figure 3</a>).</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0105" class="elsevierStylePara elsevierViewall">When the results were split according to ABPM SBP responder status, we found a significant reduction in responders (from 25.6 mg/g [IQR 8.7-382.8 mg/g] to 15.9 mg/g [IQR 4.4-55.0 mg/g], p=0.009), and a numerical decrease in non-responders (from 165.0 mg/g [IQR 8.8-1423.5 mg/g] to 13.6 mg/dl [IQR 5.7-1417.0 mg/g], p=0.345), probably due to the small number of patients in this subgroup (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> and <a class="elsevierStyleCrossRef" href="#fig0020">Figure 4</a>). The same analysis was performed according to dipper status and the results were similar, with a significant reduction in patients with dipper status on baseline ABPM (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> and <a class="elsevierStyleCrossRef" href="#fig0025">Figure 5</a>).</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia><elsevierMultimedia ident="fig0025"></elsevierMultimedia><p id="par0110" class="elsevierStylePara elsevierViewall">With regard to diabetic status, patients with diabetes had a higher median baseline ACR and showed a statistically significant decrease (from 48.9 mg/g [IQR 9.1-1116.3 mg/g] to 23.1 mg/g [IQR 4.3-123.8 mg/g], p=0.028); there was also a numerical decrease in ACR in non-diabetic patients (from 25.4 mg/g (IQR 5.3-68.6 mg/g) to 10.9 mg/dl (IQR 3.4-20.8 mg/g), p=0.066), probably also due to the small patient sample in this subgroup (n=9) (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> and <a class="elsevierStyleCrossRef" href="#fig0030">Figure 6</a>).</p><elsevierMultimedia ident="fig0030"></elsevierMultimedia></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Safety</span><p id="par0115" class="elsevierStylePara elsevierViewall">There were four vascular access complications: three hematomas and one femoral pseudoaneurysm. No significant changes in eGFR were seen (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> and <a class="elsevierStyleCrossRef" href="#fig0010">Figure 2</a>).</p></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Discussion</span><p id="par0120" class="elsevierStylePara elsevierViewall">The main findings of our study are: (1) RDN was associated with a significant BP reduction at 12-month follow-up; (2) there was a significant decrease in median ACR, without significant changes in eGFR, and a significant reduction in the percentage of patients with ACR >30 mg/g between baseline and 12-month follow-up; (3) the reduction in ACR was observed in both BP responders and non-responders.</p><p id="par0125" class="elsevierStylePara elsevierViewall">Although the initial results with catheter-based RDN were very promising,<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">7,8,16</span></a> the most recent and largest randomized trial, SYMPLICITY HTN-3,<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">15</span></a> failed to meet its primary efficacy endpoint, raising doubts about the real biological effect of this treatment. The unexpected negative results of HTN-3 have been extensively discussed and many possible reasons have been put forward, both clinical (mainly related to patient selection) and technical (procedure-related, particularly the number and pattern of radiofrequency applications).<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">17</span></a> Another possible factor is how the efficacy of RDN is currently measured, and examining target organ damage may provide a better assessment than BP values. In line with this are the recent results in LV mass and function after RDN, for which several groups have published positive results at six-month follow-up based on both transthoracic echocardiography<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">11,18</span></a> and cardiac magnetic resonance imaging (MRI).<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">10</span></a> Our group recently reported a significant reduction in left ventricular mass at 12-month follow-up, without correlation with changes in systolic ABPM.<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">11</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">Another approach to monitoring hypertension-related target organ damage is to calculate ACR, a recognized marker which has been linked to cardiovascular outcomes in several studies on hypertension.<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">4–6</span></a> Ott et al.<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">19</span></a> found a significant reduction in ACR at six-month follow-up in 59 patients with resistant hypertension (mean 24-h ABPM SBP 156 mmHg, treated with a mean of 5.5 antihypertensive drugs). In contrast with the latter study, we also included patients with normal (<30 mg/g) baseline ACR and therefore our median values are lower that those reported by Ott et al. Of note, even among this mixed population of different ACR baseline profiles, half of whom had normal urinary albumin excretion (51.6% with ACR <30 mg/dl), the mean age (65 years), baseline ABPM SBP (150 mmHg) and mean number of drugs (5.8) were very similar to the study by Ott et al. Our study also included a higher percentage of patients with type 2 diabetes (71%, compared to 51% in Ott et al.’s study). In another recently published single-center study, Verloop et al.<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">13</span></a> failed to demonstrate any significant decrease in either LV mass (by cardiac MRI) or urinary albumin excretion, and found only a modest impact on blood pressure. These results are in contrast with previous studies and our results, and may have been due to differences in patient populations. In the study by Verloop et al.,<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">13</span></a> the mean age was lower (58 years) and so was the mean number of drugs (4, as opposed to 5.5 in Ott et al. and 5.8 in our study). Other important differences are the much lower prevalence of diabetes (only 15%) and the fact that the authors did not exclude patients with eGFR <45 ml/min/1.73 m<span class="elsevierStyleSup">2</span>.</p><p id="par0135" class="elsevierStylePara elsevierViewall">One interesting observation in our study is the fact that the reduction in ACR was also found in BP non-responders, although this did not reach statistical significance, probably due to the small size of this patient subgroup. This raises the question of whether RDN, by reducing sympathetic hyperactivity, might have a positive direct effect on glomerular endothelial function independent of the hemodynamic effect derived from blood pressure reduction, since there is a close association between urinary albumin excretion and glomerular endothelium dysfunction and glycocalyx loss.<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">5,20</span></a> These two factors may be modulated by autonomic nervous system tone and, in theory, this positive impact on endothelial physiology could be linked to the expected decrease in overall cardiovascular risk that is the ultimate goal of RDN. On the other hand, endothelial dysfunction is only one of several effects of increased sympathetic activity, a common denominator in cardiovascular and renal pathophysiology.<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">21</span></a> Finally, the ACR reduction seen in our study should be interpreted in the context of the high cardiovascular risk of patients with resistant hypertension,<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">2,3</span></a> and this reduction is expected to help to lower this risk, although no prospective studies have been published on the prognostic impact of RDN on clinical outcomes.</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Limitations</span><p id="par0140" class="elsevierStylePara elsevierViewall">The present study has some limitations that should be mentioned: (1) it is a single-center prospective registry with a small sample size; (2) the physicians following patients after RDN were not blinded, although the most important outcome measurements (24-h ABPM and ACR) were performed by cardiac and laboratory technicians unaware of treatment status; (3) there was no control group or sham procedure; (4) changes were made in antihypertensive therapy during follow-up, which could have influenced reductions in blood pressure and ACR (but the mean number of drugs actually decreased during follow-up, which could lead to underestimation of the benefit of RDN in this daily practice setting).</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Conclusions</span><p id="par0145" class="elsevierStylePara elsevierViewall">In this single-center unblinded study of patients with resistant hypertension undergoing RDN, we found a significant reduction in both office BP and 24-h ABPM which was associated with a significant decrease in median ACR, without significant changes in eGFR. At 12-month follow-up, there was a reduction in the percentage of patients with pathological urinary albumin excretion, and this reduction was independent of BP responder status.</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Ethical disclosures</span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Protection of human and animal subjects</span><p id="par0150" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals for this study.</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Confidentiality of data</span><p id="par0155" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appear in this article.</p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Right to privacy and informed consent</span><p id="par0160" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appear in this article.</p></span></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Conflicts of interest</span><p id="par0165" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:13 [ 0 => array:3 [ "identificador" => "xres851856" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Objective" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Methods and Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec846465" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres851857" "titulo" => "Resumo" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introdução" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Objetivo" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Métodos e resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusão" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec846466" "titulo" => "Palavras-chave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Methods" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Study design and patient population" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Blood pressure measurement and definition of responders" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Renal function and albuminuria measurement" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Renal denervation procedure" ] 4 => array:2 [ "identificador" => "sec0035" "titulo" => "Statistical analysis" ] ] ] 6 => array:3 [ "identificador" => "sec0040" "titulo" => "Results" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0045" "titulo" => "Patient characteristics" ] 1 => array:2 [ "identificador" => "sec0050" "titulo" => "Blood pressure control" ] 2 => array:2 [ "identificador" => "sec0055" "titulo" => "Changes in albumin-to-creatinine ratio after renal denervation and relation with blood pressure control" ] 3 => array:2 [ "identificador" => "sec0060" "titulo" => "Safety" ] ] ] 7 => array:2 [ "identificador" => "sec0065" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0070" "titulo" => "Limitations" ] 9 => array:2 [ "identificador" => "sec0075" "titulo" => "Conclusions" ] 10 => array:3 [ "identificador" => "sec0080" "titulo" => "Ethical disclosures" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0085" "titulo" => "Protection of human and animal subjects" ] 1 => array:2 [ "identificador" => "sec0090" "titulo" => "Confidentiality of data" ] 2 => array:2 [ "identificador" => "sec0095" "titulo" => "Right to privacy and informed consent" ] ] ] 11 => array:2 [ "identificador" => "sec0100" "titulo" => "Conflicts of interest" ] 12 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-07-22" "fechaAceptado" => "2016-09-26" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec846465" "palabras" => array:4 [ 0 => "Resistant hypertension" 1 => "Renal denervation" 2 => "Albuminuria" 3 => "Blood pressure" ] ] ] "pt" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palavras-chave" "identificador" => "xpalclavsec846466" "palabras" => array:4 [ 0 => "Hipertensão arterial resistente" 1 => "Desnervação renal" 2 => "Albuminúria" 3 => "Pressão arterial" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Sympathetic renal denervation (RDN) was developed as a treatment for the management of patients with resistant hypertension. This procedure may have a positive impact on hypertension-related target organ damage, particularly renal disease, but the evidence is still limited.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objective</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">To assess the impact of RDN on the albumin-to-creatinine ratio (ACR) at 12-month follow-up.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Methods and Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">From a single-center prospective registry including 65 patients with resistant hypertension undergoing renal denervation, 31 patients with complete baseline and 12-month follow-up blood pressure (BP) measurements (both office and 24-h ambulatory blood pressure monitoring [ABPM]) and ACR were included in the present study. Mean age was 65±7 years, 52% were female, most (90%) had been diagnosed with hypertension for more than 10 years, 71% had type 2 diabetes and 33% had vascular disease in at least one territory. Mean estimated glomerular filtration rate was 73.6±25.1 ml/min/1.73 m<span class="elsevierStyleSup">2</span> and 15 patients (48%) had an ACR >30 mg/g. After 12 months, 22 patients were considered BP responders (73%). ACR decreased significantly from a median of 25.8 mg/g (interquartile range [IQR] 9.0-574.0 mg/g) to 14.8 mg/g (IQR 4.5-61.0 mg/g, p=0.007). When the results were split according to systolic BP responder status on ABPM, we found a significant reduction in responders (from 25.6 mg/g [IQR 8.7-382.8 mg/g] to 15.9 mg/g [IQR 4.4-55.0 mg/g], p=0.009), and a numerical decrease in the non-responder subgroup (from 165.0 mg/g [IQR 8.8-1423.5 mg/g] to 13.6 mg/dl [IQR 5.7-1417.0 mg/g], p=0.345).</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Besides significant reductions in blood pressure (both office and 24-h ABPM), renal denervation was associated with a significant reduction in ACR, a recognized marker of target organ damage.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Objective" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Methods and Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "pt" => array:3 [ "titulo" => "Resumo" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introdução</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">A desnervação simpática renal (RDN) foi desenvolvida como uma forma de tratamento para os doentes com hipertensão arterial resistente (R-HTN). Este procedimento poderá ter um impacto favorável nas lesões de órgão alvo relacionadas com a hipertensão, nomeadamente a doença renal, no entanto, a evidência disponível ainda é escassa.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Objetivo</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Avaliar o impacto da RDN no rácio albumina-creatinina (ACR) aos 12 meses de seguimento após RDN.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Métodos e resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Registo prospetivo de centro único incluindo 65 doentes com R-HTN submetidos a RDN, dos quais 31 doentes com avaliação basal e a um ano completa da pressão arterial (na consulta e na monitorização ambulatória [ABPM]) e da ACR foram incluídos no presente estudo. A idade média foi de 65±7 anos, 52% do sexo feminino. A maioria da população tinha diagnóstico de HTN há >10 anos, 71% tinha diabetes tipo 2 e 33% tinham doença vascular em pelo menos um território. A taxa de filtração glomerular estimada foi de 73,6±25,1 ml/min/1,73 m<span class="elsevierStyleSup">2</span> e 48% (15 doentes) tinham uma ACR>30 mg/g. Aos 12 meses de seguimento, 22 doentes foram considerados respondedores na pressão arterial (73%). A ACR teve uma descida significativa de uma mediana de 25,8 mg/g (IQR 9,0-574,0 mg/g) para 14,8 mg/g (IQR 4,5-61,0 mg/g, p=0,007). Quando os resultados foram divididos em subgrupos, de acordo com o estado de respondedor à pressão arterial na ABPM, verificou-se uma redução significativa nos respondedores (de 25,6 mg/g [IQR 8,7-382,8 mg/g] para 15,9 mg/g [IQR 4,4-55,0 mg/g], p=0,009), e uma tendência no subgrupo de não respondedores (de 165,0 mg/g [IQR 8,8-1423,5 mg/g] para 13,6 mg/dl [IQR 5,7-1417,0 mg/g], p=0,345).</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusão</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Para além da descida significativa da pressão arterial (quer na consulta quer na monitorização ambulatória de 24 h), a desnervação renal associou-se a uma redução significativa da ACR, um reconhecido marcador de lesão de órgão alvo na hipertensão arterial.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introdução" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Objetivo" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Métodos e resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusão" ] ] ] ] "multimedia" => array:9 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1145 "Ancho" => 1628 "Tamanyo" => 125341 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Flowchart of patient selection. Of the total number of patients observed in an outpatient hypertension clinic (n=318), 253 were excluded for various reasons (see main text) and 65 underwent renal denervation. Of these 65, complete 12-month follow-up with ambulatory blood pressure monitoring and transthoracic echocardiographic data were available in 31 patients. ABPM: 24-h ambulatory blood pressure monitoring; ACR: albumin-to-creatinine ratio; BP: blood pressure; eGFR: estimated glomerular filtration rate; RDN: renal denervation.</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" => 1555 "Ancho" => 2333 "Tamanyo" => 91158 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Values of albumin-to-creatinine ratio and estimated glomerular filtration rate at 12 months after renal denervation. There was a significant reduction in the median values of ACR and the percentage of patients with ACR >30 mg/g, without significant changes in eGFR. ACR: albumin-to-creatinine ratio; eGFR: estimated glomerular filtration rate.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1336 "Ancho" => 1625 "Tamanyo" => 58910 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Percentages of patients in the different albumin-to-creatinine ratio subgroups. There was a numerical decrease in the percentage of patients with an ACR >300 mg/g and an increase in patients with normal urinary albumin excretion between baseline and 12-month follow-up. ACR: albumin-to-creatinine ratio.</p>" ] ] 3 => array:7 [ "identificador" => "fig0020" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1535 "Ancho" => 2275 "Tamanyo" => 76478 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Values of albumin-to-creatinine ratio at 12 months after renal denervation in 24-h ambulatory blood pressure monitoring responder subgroups. There was a significant reduction in median ACR in the BP responder subgroup, and a numerical decrease in non-responders. ACR: albumin-to-creatinine ratio; BP: blood pressure.</p>" ] ] 4 => array:7 [ "identificador" => "fig0025" "etiqueta" => "Figure 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr5.jpeg" "Alto" => 1503 "Ancho" => 2245 "Tamanyo" => 66736 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Values of albumin-to-creatinine ratio at 12 months after renal denervation according to dipper status on 24-h ambulatory blood pressure monitoring. There was a significant reduction in median ACR in the dipper subgroup, and a numerical decrease in non-dippers. ACR: albumin-to-creatinine ratio.</p>" ] ] 5 => array:7 [ "identificador" => "fig0030" "etiqueta" => "Figure 6" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr6.jpeg" "Alto" => 1489 "Ancho" => 2292 "Tamanyo" => 71388 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Values of albumin-to-creatinine ratio at 12 months after renal denervation according to diabetic status. There was a significant reduction in median ACR in patients with diabetes, and a numerical decrease in the smaller subgroup of patients without diabetes. ACR: albumin-to-creatinine ratio.</p>" ] ] 6 => 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" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">BMI: body mass index; CKD: chronic kidney disease (eGFR <60 ml/min/1.73 m<span class="elsevierStyleSup">2</span>); eGFR: estimated glomerular filtration rate; RDN: renal denervation; RF: radiofrequency.</p>" "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=""><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Demographic and clinical variables</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Age (years) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">65±7 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Male (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">15 (48.4) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Caucasian (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">31 (100) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Weight (kg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">86±16 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Height (m) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.65±0.1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>BMI (kg/m<span class="elsevierStyleSup">2</span>) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">31.8±5.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Obesity (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">21 (67.7) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Atrial fibrillation (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 (3.2) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Previous stroke (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 (6.5) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Type 2 diabetes (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">22 (71) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Dyslipidemia (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">21 (67.7) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Smoking (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 (3.2) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Sleep apnea (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5 (19.1) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>eGFR (ml/min/1.73 m<span class="elsevierStyleSup">2</span>) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">76.4±24.7 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>CKD (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5 (16.1) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Hypertension >10 years (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">28 (90.3) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Coronary artery disease (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10 (32.3) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Any vascular disease (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">11 (35.5) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">RDN procedure</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Mean no. of RF applications, right renal artery \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5.1±1.3 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Mean no. of RF applications, left renal artery \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5.7±1.1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Mean no. of RF applications per patient \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10.8±2.3 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1438173.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Baseline characteristics and renal denervation procedures.</p>" ] ] 7 => 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:2 [ "leyenda" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">ACE: angiotensin-converting enzyme; ARB: angiotensin receptor blockers.</p>" "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="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Baseline \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">12 months \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">p \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Mean no. of antihypertensive drugs \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5.8±1.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5.0±1.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.002 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Mean no. of drug classes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5.5±0.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4.9±1.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.015 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ACE inhibitors \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">19 (61.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">17 (54.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.688 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ARBs (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">19 (61.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">18 (58.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Beta-blockers (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">26 (83.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">27 (87.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Calcium channel blockers (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">30 (96.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">21 (67.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.012 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Diuretics (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">27 (87.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">24 (77.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.727 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Spironolactone (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">23 (74.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">26 (83.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.453 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sympatholytics (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">22 (71) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">19 (61.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.508 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Aliskiren \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4 (12.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.046 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1438174.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Antihypertensive medication.</p>" ] ] 8 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "<p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">ABPM: 24-h ambulatory blood pressure; ACR: albumin to creatinine ratio; BP: blood pressure; bpm: beats per minute; DBP: diastolic blood pressure; eGFR: estimated glomerular filtration rate; SBP: systolic blood pressure.</p>" "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="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Baseline \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">12 months \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">p \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Office SBP (mmHg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">176±24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">149±13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Office DBP (mmHg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">90±14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">79±11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Heart rate (bpm) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">73±11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">70±11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.261 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ABPM SBP (mmHg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">150±20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">132±14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ABPM DBP (mmHg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">83±10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">74±9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ABPM pulse pressure (mmHg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">67±18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">58±13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ABPM mean BP (mmHg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">105±9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">95.3±8.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ABPM heart rate (bpm) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">67.6±9.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">65.5±9.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.090 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ABPM SBP responders<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">- \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">26 (83.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">- \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Office SBP responders<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">- \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">22 (71) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">- \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">eGFR (ml/min/1.73 m<span class="elsevierStyleSup">2</span>) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">73.6±25.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">72.5±25.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.711 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ACR (mg/g) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">25.8 (9.0-574.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">14.8 (4.5-61.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.007 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ACR in ABPM BP responders (mg/g) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">25.6 (8.7-382.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">15.9 (4.4-55.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.009 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ACR in ABPM BP non-responders (mg/g) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">165.0 (8.8-1423.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">13.6 (5.7-1417.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.345 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ACR in ABPM dippers (mg/g) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">20.8 (6.8-290.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">9.4 (3.7-41.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.028 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ACR in ABPM non-dippers (mg/g) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">62.3 (9.1-852.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">20.8 (9.3-197.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.096 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ACR in diabetic patients (mg/g) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">48.9 (9.1-1116.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">23.1 (4.3-123.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.028 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ACR in non-diabetic patients (mg/g) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">25.4 (5.2-68.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10.9 (3.4-20.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.066 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1438175.png" ] ] ] "notaPie" => array:2 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Decrease of 2 mmHg between baseline ABPM SBP and at 12 months.</p>" ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "b" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Decrease of 10 mmHg between baseline office SBP and at 12 months.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">Blood pressure, heart rate and albumin-to-creatinine ratio before and 12 months after renal denervation.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:21 [ 0 => array:3 [ "identificador" => "bib0110" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC)" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "G. Mancia" 1 => "R. Fagard" 2 => "K. Narkiewicz" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/01.hjh.0000431740.32696.cc" "Revista" => array:6 [ "tituloSerie" => "J Hypertens" "fecha" => "2013" "volumen" => "31" "paginaInicial" => "1281" "paginaFinal" => "1357" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23817082" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0115" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Resistant hypertension: diagnosis, evaluation, and treatment. A scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "D.A. Calhoun" 1 => "D. Jones" 2 => "S. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 11 | 2 | 13 |
| 2024 October | 41 | 32 | 73 |
| 2024 September | 54 | 26 | 80 |
| 2024 August | 42 | 26 | 68 |
| 2024 July | 37 | 25 | 62 |
| 2024 June | 29 | 19 | 48 |
| 2024 May | 28 | 20 | 48 |
| 2024 April | 26 | 20 | 46 |
| 2024 March | 45 | 21 | 66 |
| 2024 February | 32 | 25 | 57 |
| 2024 January | 33 | 29 | 62 |
| 2023 December | 27 | 23 | 50 |
| 2023 November | 40 | 24 | 64 |
| 2023 October | 34 | 16 | 50 |
| 2023 September | 21 | 22 | 43 |
| 2023 August | 30 | 14 | 44 |
| 2023 July | 27 | 9 | 36 |
| 2023 June | 25 | 10 | 35 |
| 2023 May | 39 | 23 | 62 |
| 2023 April | 25 | 9 | 34 |
| 2023 March | 31 | 22 | 53 |
| 2023 February | 35 | 17 | 52 |
| 2023 January | 34 | 16 | 50 |
| 2022 December | 26 | 15 | 41 |
| 2022 November | 32 | 19 | 51 |
| 2022 October | 34 | 18 | 52 |
| 2022 September | 26 | 34 | 60 |
| 2022 August | 44 | 36 | 80 |
| 2022 July | 37 | 42 | 79 |
| 2022 June | 27 | 16 | 43 |
| 2022 May | 22 | 28 | 50 |
| 2022 April | 37 | 34 | 71 |
| 2022 March | 30 | 50 | 80 |
| 2022 February | 23 | 32 | 55 |
| 2022 January | 24 | 19 | 43 |
| 2021 December | 18 | 36 | 54 |
| 2021 November | 40 | 35 | 75 |
| 2021 October | 37 | 42 | 79 |
| 2021 September | 40 | 24 | 64 |
| 2021 August | 50 | 27 | 77 |
| 2021 July | 17 | 25 | 42 |
| 2021 June | 41 | 28 | 69 |
| 2021 May | 39 | 36 | 75 |
| 2021 April | 43 | 37 | 80 |
| 2021 March | 60 | 25 | 85 |
| 2021 February | 44 | 21 | 65 |
| 2021 January | 31 | 12 | 43 |
| 2020 December | 35 | 7 | 42 |
| 2020 November | 23 | 15 | 38 |
| 2020 October | 16 | 20 | 36 |
| 2020 September | 43 | 5 | 48 |
| 2020 August | 18 | 9 | 27 |
| 2020 July | 34 | 7 | 41 |
| 2020 June | 25 | 14 | 39 |
| 2020 May | 28 | 9 | 37 |
| 2020 April | 21 | 4 | 25 |
| 2020 March | 30 | 8 | 38 |
| 2020 February | 46 | 14 | 60 |
| 2020 January | 34 | 5 | 39 |
| 2019 December | 30 | 9 | 39 |
| 2019 November | 22 | 10 | 32 |
| 2019 October | 40 | 6 | 46 |
| 2019 September | 22 | 15 | 37 |
| 2019 August | 19 | 8 | 27 |
| 2019 July | 28 | 13 | 41 |
| 2019 June | 17 | 6 | 23 |
| 2019 May | 30 | 14 | 44 |
| 2019 April | 19 | 14 | 33 |
| 2019 March | 17 | 10 | 27 |
| 2019 February | 38 | 11 | 49 |
| 2019 January | 54 | 5 | 59 |
| 2018 December | 70 | 8 | 78 |
| 2018 November | 76 | 14 | 90 |
| 2018 October | 139 | 19 | 158 |
| 2018 September | 42 | 12 | 54 |
| 2018 August | 30 | 18 | 48 |
| 2018 July | 16 | 1 | 17 |
| 2018 June | 25 | 8 | 33 |
| 2018 May | 20 | 4 | 24 |
| 2018 April | 30 | 2 | 32 |
| 2018 March | 35 | 6 | 41 |
| 2018 February | 11 | 1 | 12 |
| 2018 January | 24 | 11 | 35 |
| 2017 December | 26 | 10 | 36 |
| 2017 November | 26 | 12 | 38 |
| 2017 October | 35 | 9 | 44 |
| 2017 September | 46 | 18 | 64 |
| 2017 August | 49 | 13 | 62 |
| 2017 July | 32 | 17 | 49 |
| 2017 June | 44 | 18 | 62 |
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