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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Every year cardiovascular disease &#40;CVD&#41; causes 3&#46;9 million deaths in Europe and over 1&#46;8 million deaths in the European Union &#40;EU&#41;&#44; accounting for 37&#37; of all deaths in the EU&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">1</span></a> In Portugal and in Europe as a whole&#44; CVD is the leading cause of death&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Despite recent decreases in mortality rates in many countries&#44; CVD is still responsible for almost half of all deaths in Europe&#44;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">2</span></a> and constitutes a major public health challenge in western Europe&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Of all behavioral components&#44; dietary factors pose the greatest risk for CVD mortality and reduced CVD disability-adjusted life years in the European population&#46; High systolic blood pressure and smoking represent other major risk factors&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Several European countries have implemented measures to tackle CVD mortality&#44; from disease prevention by tackling major risk factors to improvements in disease management and treatment&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">As part of this effort&#44; in recent years Portugal has instituted a set of health policies that directly or indirectly tackle CVD mortality&#44; including a smoking ban in 2009&#44; a salt reduction regulation in 2010 and the coronary fast-track system &#40;FTS&#41; for acute coronary syndrome &#40;ACS&#41;&#46; The latter policy&#44; which was more directed linked to reducing mortality&#44; was launched in 2000&#44; but was not fully implemented throughout the country until 2007&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">There is growing evidence-based data worldwide on the effectiveness of these health policies and public health initiatives&#59; however&#44; reports on the effectiveness of similar policies in Portugal is scarce&#46; More importantly&#44; there has been no analysis of the cumulative effect of the three major polices recently implemented in Portugal&#46; In the context of increasingly limited resources for health care&#44; investment in population-wide policy strategies needs to show an appropriate return&#44; in this case a decline in CVD mortality&#46; It is therefore important to assess the influence of these policies on observed coronary heart disease &#40;CHD&#41; mortality&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Our aim was thus to analyze the impact of the three health policies implemented in Portugal in reducing ACS case-fatality rates&#44; namely the FTS for primary angioplasty&#44; the smoking ban and the salt reduction regulation&#44; using case-fatality rates from 2000 to 2016&#46;</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">Data</span><p id="par0040" class="elsevierStylePara elsevierViewall">Data were obtained from the national Diagnosis-Related Group database&#44; which collects information on all admissions to public hospitals in mainland Portugal&#44; including primary diagnosis&#44; demographic variables such as gender and age&#44; and the geographic region of the admission&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">4</span></a> Approval to access the data was previously obtained from the Ministry of Health&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">All admissions between 2002 and 2016 of individuals &#8805;20 years of age with a primary diagnosis of ACS&#44; as coded by the International Classification of Diseases&#44; Ninth Revision &#40;ICD-9&#41;&#44; were extracted&#46; Codes 410&#46;00-410&#46;xx were used to identify admission diagnoses of acute myocardial infarction &#40;MI&#41; and 413 codes were used to identify unstable angina&#46; All participants with missing data were excluded from the analysis&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Health policies and public health initiatives</span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Coronary fast-track system</span><p id="par0050" class="elsevierStylePara elsevierViewall">The FTS was implemented in all regions of Portugal by 2007&#46; We therefore had available for analysis seven years of data before the implementation of the regulation &#40;January 2000-December 2007&#41; and nine years of data after implementation &#40;January 2008-December 2016&#41;&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">The aim of the FTS was to create a priority system that would facilitate access to clinical&#44; therapeutic and diagnostic resources for ACS patients&#46; Direct admission to the catheterization laboratory for primary angioplasty is essential since the time between symptom onset and treatment in MI is crucial to reducing morbidity and mortality&#46; The system is triggered by patients calling the emergency number &#40;112&#41;&#46; The National Institute for Emergency Medicine &#40;INEM&#41; can then initiate diagnosis and treatment earlier by transferring the patient to a hospital unit specializing in ACS treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">5</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">INEM has the capacity to intervene early&#44; and after clinical diagnosis and electrocardiogram&#44; decides jointly with the Referral Center for Emergency Patients &#40;CODU&#41; on pre-hospital treatment and hospital referral&#44; increasing the likelihood of therapeutic success&#46; CODU contacts the hospital unit to organize the patient&#39;s admission and treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">6</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Smoking ban</span><p id="par0065" class="elsevierStylePara elsevierViewall">The smoking ban was implemented in January 2008&#46; We therefore had available for analysis six years of data before the implementation of the ban &#40;January 2002-December 2007&#41; and nine years of data after implementation &#40;January 2008-December 2016&#41;&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Portugal is a signatory of the World Health Organization &#40;WHO&#41;&#8217;s Framework Convention on Tobacco Control&#44;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">7</span></a> which led to implementation in January 2008 of the most recent anti-smoking measure&#44; Law no&#46; 37&#47;2007&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">8</span></a> This legislation introduced a new framework to protect individuals from passive &#40;second-hand&#41; smoking and to promote smoking reduction and cessation&#46;<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">8&#44;9</span></a> The law banned smoking in all enclosed public places&#44; including hospitals&#44; public transport&#44; and workplaces&#46; In addition&#44; it established further regulations regarding information provided on tobacco products&#44; their packaging and labeling&#44; as well as further restrictions on advertising&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">10</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Salt reduction policy</span><p id="par0075" class="elsevierStylePara elsevierViewall">The salt reduction policy was implemented in September 2010&#46; We therefore had available for analysis eight years of data before the implementation of the regulation &#40;January 2002-September 2010&#41; and six years of data after implementation &#40;October 2010-December 2016&#41;&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Even small reductions in the prevalence of high blood pressure can lead to major health gains&#46; In view of the importance of these approaches&#44; the WHO created a set of recommendations to reduce dietary salt intake to 5 g&#47;day&#44; in order to prevent chronic disease and improve health&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">11</span></a> In the WHO European Region&#44; 26 out of the 53 member states&#44; including Portugal&#44; have implemented operational salt reduction policies&#44; including those aimed at reducing salt intake&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Notably&#44; bread accounts for about one-sixth of daily salt intake&#44;<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">12&#44;13</span></a> with Portugal&#44; Poland and Japan having the highest levels of salt in bread&#46;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">14&#44;15</span></a> The policy introduced in Portugal aimed to reduce salt to 1&#46;4 g per 100 g bread&#46; It also mandated clear salt content labeling of packaged products&#46;</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Statistical analysis</span><p id="par0090" class="elsevierStylePara elsevierViewall">The main outcome in our study was monthly case-fatality rates&#44; subsequently stratified by age and gender&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">ACS case-fatality rates were calculated for each month&#44; using the total number of patients admitted to public hospitals as the denominator and the number of ACS deaths as the numerator&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">The impact of the three policies was studied individually&#44; using a binary covariable indicating the start of the policy&#44; as well as a continuous covariable to account for the effect of the policy after its implementation&#46; A segmented multiple linear regression model was implemented to assess changes over time&#46; These models are useful when the relationship between the response and the independent variables is piecewise linear&#44; i&#46;e&#46; represented by two or more straight lines connected at unknown values &#40;breakpoints&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">16</span></a> In this study&#44; the segmented model was implemented to test for significant changes in case-fatality rates after the introduction of the three policies&#46; The Davies test was used to assess whether the differences between the slopes before and after the breakpoint were significant&#46; The model was fitted in R version 2&#46;5&#46;1 software using the &#8220;segmented&#8221; library&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">17</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">For all models created&#44; the case-fatality rate was the response variable&#46; Four models were created in total&#44; one for each of the policies and one used subsequently to test which year showed a significant difference in case-fatality rate&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">All analyses were stratified by gender and age&#46; Two age categories were used&#44; &#60;65 and &#8805;65 years&#46; Short-term autocorrelation between monthly estimates was incorporated into the model by applying a first-order autoregressive process to the residuals&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Although we were aware that there might be short-term temporal differences in case-fatality rates&#44; related for example to the day of the week&#44; or weekends vs&#46; weekdays&#44; we did not adjust for this in our models&#46; Other studies have shown a steady reduction in differences between weekends and weekdays in the time of CVD events&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">18</span></a> There have also been studies showing that after accounting for mode of arrival at the hospital&#44; there was no difference in case-fatality rates between weekdays and weekends&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">19</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">Statistical significance was assessed through p-values&#44; assuming &#60;5&#37; as significant&#44; and 95&#37; confidence intervals &#40;CI&#41; were calculated for each of the regression coefficients&#46; Models were fitted in R software&#44; version 2&#46;5&#46;1&#46;</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Results</span><p id="par0125" class="elsevierStylePara elsevierViewall">A total of 20&#160;849 in-hospital deaths from ACS were recorded in mainland Portugal from 2000 to 2016&#44; out of a total of 203&#160;040 admissions for ACS&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Of the models created individually&#44; one for each policy&#44; the FTS showed an immediate decrease in case fatalities &#40;beta&#61;-1&#46;27&#44; p&#61;0&#46;003&#41;&#59; however&#44; it did not impact case-fatality trends after 2007&#44; which remained steady&#46; Similarly&#44; the smoking ban resulted in an immediate decrease in case fatalities after its implementation &#40;p&#61;-0&#46;861&#44; p&#61;0&#46;05&#41;&#44; but no significant decrease in trends was observed after 2008 &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> and <a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0135" class="elsevierStylePara elsevierViewall">By contrast&#44; the salt reduction policy did not have any significant effect on case fatalities &#40;beta&#61;0&#46;012&#44; p&#61;0&#46;189&#41;&#44; or any immediate impact after its implementation &#40;beta&#61;0&#46;421&#44; p&#61;0&#46;365&#59; <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Using a model applying segmented regression&#44; 2009 was identified as a year in which there was a difference in case-fatality rates&#46; Slope trends both before &#40;beta&#61;-0&#46;004&#59; 95&#37; CI -0&#46;005 to -0&#46;004&#41; and after 2009 &#40;p&#61;-0&#46;003&#59; 95&#37; CI -0&#46;003 to -0&#46;002&#41; showed a decrease&#59; however&#44; after 2009 this was less pronounced &#40;beta&#61;0&#46;002&#44; p&#61;0&#46;004&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0145" class="elsevierStylePara elsevierViewall">All four models were stratified for ACS case-fatality rates by gender and age&#46; For females &#40;beta&#61;-1&#46;306&#44; p&#61;0&#46;020&#41; and individuals aged &#8805;65 years &#40;beta&#61;-1&#46;169&#44; p&#61;0&#46;029&#41;&#44; there was a significant decrease in case-fatality rates after the smoking ban&#46; For the FTS&#44; both sexes presented a significant decrease in case-fatality rates&#59; however&#44; there was no difference in trends between age groups &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Figure 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0150" class="elsevierStylePara elsevierViewall">In the segmented model&#44; the year found to have a differential rate of case fatalities was consistent with the model including all the data &#40;2009&#41;&#46; Both trends&#44; before and after 2009&#44; were decreasing&#44; though after 2009 the decrease was not as marked as for the period before 2009&#44; as observed for the model including all the patients&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">The differences in case-fatality rates before and after 2009 were higher for women &#40;beta&#61;0&#46;003&#44; p&#61;0&#46;029&#41; than for men&#44; and for individuals aged &#8805;65 years &#40;beta&#61;0&#46;003&#44; p&#61;0&#46;008&#59; <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">The seasonal pattern was consistent with that reported elsewhere&#44;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">20</span></a> with higher admission rates in winter and lower rates during the summer&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Discussion</span><p id="par0165" class="elsevierStylePara elsevierViewall">In the last 11 years&#44; a set of health policies have been implemented in Portugal to help decrease CVD mortality&#46; The first initiative was the FTS in 2007&#44; followed by the smoking ban in 2008 and the salt reduction regulation in mid-2010&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">We created a series of statistical models&#44; four to assess the individual impact of each of the policies&#44; and then one to determine if there was any year during the study that could indicate a difference between trends&#44; suggesting a possible impact of the policies in the country&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">The FTS and the smoking ban led to an immediate decrease in case-fatality rates&#46; Previous national and international studies have shown that an FTS&#44; by substantially shortening the time between symptom onset and treatment&#44; directly influences survival&#46; It has been demonstrated that a symptom onset-treatment time of more than 120 min leads to increased in-hospital mortality in an almost linear fashion&#46;<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">21&#8211;23</span></a> However&#44; the FTS in Portugal is mainly aimed at ST-elevation MI&#44; which accounts for around 40&#37; of all ACS&#44; and so it would not be expected to affect non-ST-elevation MI&#44; meaning that around 60&#37; of ACS patients are not covered by this service&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">The relationship between smoking and CVD mortality has been extensively demonstrated&#46; Smoking worsens atherosclerotic alterations&#44; including narrowing the vascular lumen and inducing a hypercoagulable state&#46; Such changes increase the risk of acute thrombosis and thus mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">24</span></a> The results of the current study were very encouraging regarding the smoking ban&#44; as an immediate decrease in case fatalities was found after the ban was implemented&#46; Since the ban targets both smokers and those exposed to second-hand smoke&#44; case-fatality rates should decrease for both groups&#46; Smoking cessation&#44; and even small reductions in consumption&#44; have been linked to decreases in CVD events and in mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">25</span></a></p><p id="par0185" class="elsevierStylePara elsevierViewall">Few studies have analyzed the effect of tobacco control on CVD mortality&#46; Of those available&#44; most focus on how regulations affect hospital admissions<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">26</span></a>&#59; however&#44; the impact on mortality is equally important&#46; Nevertheless&#44; we are not the first to analyze the impact on mortality&#46; A recent study similarly found a reduction of up to 11&#37; in MI mortality one year after a smoking ban was implemented&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">27</span></a> Another study found a 13&#37; decrease in all-cause mortality&#44; with a decrease of up to 26&#37; in ischemic heart disease &#40;IHD&#41; mortality&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">In the current study&#44; we found that 2009 was a breakpoint in our observed trends&#44; which supported the results from the individual models&#46; Up to 2009 the trends were significantly impacted by the policies&#44; leading to a significant decrease in case-fatality rates&#46; After that year&#44; although the trend continued to decrease it was less marked&#46; The impact of the salt regulation in mid-2010 showed a similar effect&#44; with no change in trends after that year&#46; A similar pattern was observed when the impact of this policy on ACS admissions was analyzed&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">28</span></a></p><p id="par0195" class="elsevierStylePara elsevierViewall">We hypothesised that although the salt regulation was an important initiative&#44; it was highly dependent on individual adherence&#46; The way the regulation was implemented may not have produced the desired effect on the population&#44; perhaps due to the low level of health literacy observed in Portugal&#44; and the fact that the policy envisioned a maximum salt content of bread of 1&#46;4 g of salt per 100 g of bread&#44; while other countries set lower limits&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">When stratified by gender and age&#44; our results showed that the smoking ban led to an immediate decrease in case-fatality rates for women and individuals aged &#8805;65 years&#46; Although the number of women who smoke has increased in recent years&#44; the number of men smoking was even higher&#44; and their length of time smoking was also greater&#46; As a consequence&#44; men will have increased mortality from CVD&#44; even if they quit smoking or reduce their tobacco consumption&#46; Older people are more vulnerable to exposure to second-hand smoke&#44; and so reducing it could lead to a decrease in case-fatalities in this group&#46; Our findings were also consistent with another study in which post-ban reductions in IHD mortality were seen in those aged &#8805;65 years&#44; but not in younger subjects&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">29</span></a></p><p id="par0205" class="elsevierStylePara elsevierViewall">Analyzing the impact of the FTS by groups&#44; we found similarly decreasing case-fatality rates for men and women&#44; an effect previously observed in other studies in which the rate of decrease in CHD mortality was similar in both sexes&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">30</span></a> In addition&#44; no immediate change in case-fatality rates was observed after implementation of the FTS for either younger or older patients&#46; For both groups&#44; there were significant changes in trend&#59; however&#44; the trends observed were increasing&#46; The prevalence of obesity and diabetes<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">31</span></a> is rising in Portugal&#44; which could have weakened any reduction in the younger group&#46; This effect has been observed in other studies<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">30&#44;32</span></a> in which increases in obesity lead to lower reductions in mortality for younger groups&#46; A similar pattern was observed for the older group&#44; which has previously been found in other datasets&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">32</span></a></p><p id="par0210" class="elsevierStylePara elsevierViewall">Our results for age stratification when using segmented regression showed significant differences between trends before and after 2009&#44; for females and older subjects&#46; As for the non-stratified model&#44; the decrease in trends observed before 2009 was steeper than the decrease observed afterward&#46; These results were consistent with those observed when studying the smoking ban with age stratification&#44; in which a significant decrease in case-fatality rates was observed for older but not for younger individuals&#46; For the gender stratification&#44; although the FTS analysis showed a significant decrease after 2007 for men&#44; this was an immediate effect and not a trend&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Limitations</span><p id="par0215" class="elsevierStylePara elsevierViewall">As in any ecological study&#44; it is not possible to directly prove any association between policy implementation and the reduction in case-fatality rates from ACS&#46;</p><p id="par0220" class="elsevierStylePara elsevierViewall">One of the strengths of our study is the use of a well-validated and standardized database&#44; enabling easy comparison with other studies in different countries&#44; particularly in other European countries&#46; In addition to the availability of information on gender and age&#44; this enabled us to assess the robustness of our findings among different subgroups&#46; The time-series method is preferred over the simpler pre- and post-proportion comparison method&#44; because it does not take pre-intervention trends into account and also enables corrections to be made for autocorrelation&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">33</span></a></p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Conclusions</span><p id="par0225" class="elsevierStylePara elsevierViewall">This study extends the existing literature on the patterns of ACS mortality over time&#44; and assesses whether public health interventions to reduce mortality by ACS were successful&#46; Furthermore&#44; it indicates that to decrease case-fatality rates a multifactorial strategy was needed&#44; rather than a single approach&#46;</p><p id="par0230" class="elsevierStylePara elsevierViewall">Strategies such as the smoking ban and the FTS led to an immediate decrease in case-fatality rates&#59; however&#44; after 2009 no major decreases in ACS trends were found&#46;</p><p id="par0235" class="elsevierStylePara elsevierViewall">Considering that CHD constitutes an immense public health problem&#44;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">34</span></a> it is crucial for different stakeholders&#44; including decision-makers&#44; public health authorities&#44; medical societies and the cardiology community&#44; to keep working together to reduce ACS mortality rates&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Conflicts of interest</span><p id="par0240" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction and Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Every year cardiovascular disease &#40;CVD&#41; causes 3&#46;9 million deaths in Europe&#46; Portugal has implemented a set of public health policies to tackle CVD mortality&#58; a smoking ban in 2008&#44; a salt reduction regulation in 2010 and the coronary fast-track system &#40;FTS&#41; for acute coronary syndrome &#40;ACS&#41; in 2007&#46; Our goal in this study was to analyze the impact of these three public health policies in reducing case-fatality rates from ACS between 2000 and 2016&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">The impact of these policies on monthly ACS case-fatalities was assessed by creating individual models for each of the initiatives and implementing multiple linear regression analysis&#44; using standard methods for interrupted time series&#46; We also implemented segmented regression analysis to test which year showed a significant difference in the case-fatality slopes&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Separate modeling showed that the smoking ban &#40;beta&#61;-0&#46;861&#44; p&#61;0&#46;050&#41; and the FTS &#40;beta&#61;-1&#46;27&#44; p&#61;0&#46;003&#41; had an immediate impact after implementation&#44; but did not have a significant impact on ACS trends&#46; The salt reduction regulation did not have a significant impact&#46; For the segmented model&#44; we found significant differences between case-fatality trends before and after 2009&#44; with rates before 2009 showing a steeper decrease&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The smoking ban and the FTS led to an immediate decrease in case-fatality rates&#59; however&#44; after 2009 no major decrease in case-fatality trends was found&#46; Coronary heart disease constitutes an immense public health problem and it remains essential for decision-makers&#44; public health authorities and the cardiology community to keep working to reduce ACS mortality rates&#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">A doen&#231;a cardiovascular &#40;DCV&#41; causa 3&#44;9 milh&#245;es de mortes na Europa anualmente&#46; Portugal implementou um conjunto de pol&#237;ticas de sa&#250;de p&#250;blica que abordam a mortalidade por DCV&#44; a lei do tabaco em 2008&#44; a lei de redu&#231;&#227;o do sal em 2010 e a via verde coron&#225;ria &#40;VVC&#41; em 2007&#46; O objetivo deste estudo foi analisar o impacto destas tr&#234;s pol&#237;ticas de sa&#250;de na redu&#231;&#227;o das taxas de letalidade por s&#237;ndrome coron&#225;ria aguda &#40;SCA&#41; entre 2000 e 2016&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">O impacto destas pol&#237;ticas na taxa letalidade foi avaliado atrav&#233;s da cria&#231;&#227;o de modelos individuais para cada uma das iniciativas&#46; Foi tamb&#233;m implementada uma regress&#227;o segmentada para testar qual o ano em que houve uma diferen&#231;a significativa na letalidade&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Os modelos individuais mostraram que a lei do tabaco &#40;&#946;&#61;-0&#44;861&#44; p-valor&#61;0&#44;050&#41; e a VVC &#40;&#946;&#61;-1&#44;27&#44; p-valor&#61;0&#44;003&#41; tiveram impacto imediato ap&#243;s a sua implementa&#231;&#227;o&#46; A estrat&#233;gia de redu&#231;&#227;o do sal n&#227;o teve impacto significativo&#46; Para o modelo segmentado&#44; encontramos diferen&#231;as significativas entre as tend&#234;ncias de letalidade antes e depois de 2009&#44; com taxas anteriores a 2009 mostrando uma queda mais acentuada&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclus&#227;o</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">A lei do tabaco e a VVC levaram a uma diminui&#231;&#227;o imediata da taxa de letalidade&#59; no entanto&#44; depois de 2009&#44; n&#227;o houve redu&#231;&#227;o significativa&#46; A doen&#231;a coron&#225;ria constitui um grande problema de sa&#250;de p&#250;blica&#44; &#233; cr&#237;tico que as autoridades de sa&#250;de p&#250;blica e a comunidade de cardiologia continuem a trabalhar para reduzir as taxas de mortalidade por SCA&#46;</p></span>"
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Longitudinal trends for case-fatality rates from acute coronary syndrome &#40;percentages&#41; for January 2000-December 2016&#46; The vertical lines mark when the coronary fast-track system was fully implemented throughout Portugal &#40;2007&#41;&#44; the implementation of the smoking ban &#40;2008&#41;&#44; and the implementation of the salt reduction regulation &#40;mid-2010&#41;&#46; ACS&#58; acute coronary syndrome&#46;</p>"
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        "figura" => array:1 [
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          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Gender- and age-stratified longitudinal trends for case-fatality rates from acute coronary syndrome &#40;percentage&#41; for January 2000-December 2016&#46; &#40;A&#41; Males&#59; &#40;B&#41; females&#59; &#40;C&#41; individuals aged &#60;65 years&#59; &#40;D&#41; individuals aged &#8805;65 years&#46; The vertical lines mark the years the policies were implemented&#46; ACS&#58; acute coronary syndrome&#46;</p>"
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                  \t\t\t\t">Time of breakpoint<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> time interaction&nbsp;\t\t\t\t\t\t\n
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Original Article
Impact of public health initiatives on acute coronary syndrome fatality rates in Portugal
Impacto das medidas de saúde pública na mortalidade intra-hospitalar por síndrome coronária aguda em Portugal
Daisy Abreua,b,
Corresponding author
da.abreu@ensp.unl.pt

Corresponding author.
, Paulo Sousaa,b,c, Carlos Matias-Diasa,b,c, Fausto Pintod,e
a Escola Nacional de Saúde Pública, Universidade Nova de Lisboa, Lisboa, Portugal
b Department of Epidemiology of the Instituto Nacional de Saúde Doutor Ricardo Jorge, Lisboa, Portugal
c Centro de Investigação em Saúde Pública – ENSP-UNL, Lisboa, Portugal
d Serviço de Cardiologia, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte – EPE, Centro Académico Medicina de Lisboa, Lisboa, Portugal
e Centro Cardiovascular da Universidade de Lisboa, Lisboa, Portugal
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Longitudinal trends for case-fatality rates from acute coronary syndrome &#40;percentages&#41; for January 2000-December 2016&#46; The vertical lines mark when the coronary fast-track system was fully implemented throughout Portugal &#40;2007&#41;&#44; the implementation of the smoking ban &#40;2008&#41;&#44; and the implementation of the salt reduction regulation &#40;mid-2010&#41;&#46; ACS&#58; acute coronary syndrome&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Every year cardiovascular disease &#40;CVD&#41; causes 3&#46;9 million deaths in Europe and over 1&#46;8 million deaths in the European Union &#40;EU&#41;&#44; accounting for 37&#37; of all deaths in the EU&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">1</span></a> In Portugal and in Europe as a whole&#44; CVD is the leading cause of death&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Despite recent decreases in mortality rates in many countries&#44; CVD is still responsible for almost half of all deaths in Europe&#44;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">2</span></a> and constitutes a major public health challenge in western Europe&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Of all behavioral components&#44; dietary factors pose the greatest risk for CVD mortality and reduced CVD disability-adjusted life years in the European population&#46; High systolic blood pressure and smoking represent other major risk factors&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Several European countries have implemented measures to tackle CVD mortality&#44; from disease prevention by tackling major risk factors to improvements in disease management and treatment&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">As part of this effort&#44; in recent years Portugal has instituted a set of health policies that directly or indirectly tackle CVD mortality&#44; including a smoking ban in 2009&#44; a salt reduction regulation in 2010 and the coronary fast-track system &#40;FTS&#41; for acute coronary syndrome &#40;ACS&#41;&#46; The latter policy&#44; which was more directed linked to reducing mortality&#44; was launched in 2000&#44; but was not fully implemented throughout the country until 2007&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">There is growing evidence-based data worldwide on the effectiveness of these health policies and public health initiatives&#59; however&#44; reports on the effectiveness of similar policies in Portugal is scarce&#46; More importantly&#44; there has been no analysis of the cumulative effect of the three major polices recently implemented in Portugal&#46; In the context of increasingly limited resources for health care&#44; investment in population-wide policy strategies needs to show an appropriate return&#44; in this case a decline in CVD mortality&#46; It is therefore important to assess the influence of these policies on observed coronary heart disease &#40;CHD&#41; mortality&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Our aim was thus to analyze the impact of the three health policies implemented in Portugal in reducing ACS case-fatality rates&#44; namely the FTS for primary angioplasty&#44; the smoking ban and the salt reduction regulation&#44; using case-fatality rates from 2000 to 2016&#46;</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">Data</span><p id="par0040" class="elsevierStylePara elsevierViewall">Data were obtained from the national Diagnosis-Related Group database&#44; which collects information on all admissions to public hospitals in mainland Portugal&#44; including primary diagnosis&#44; demographic variables such as gender and age&#44; and the geographic region of the admission&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">4</span></a> Approval to access the data was previously obtained from the Ministry of Health&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">All admissions between 2002 and 2016 of individuals &#8805;20 years of age with a primary diagnosis of ACS&#44; as coded by the International Classification of Diseases&#44; Ninth Revision &#40;ICD-9&#41;&#44; were extracted&#46; Codes 410&#46;00-410&#46;xx were used to identify admission diagnoses of acute myocardial infarction &#40;MI&#41; and 413 codes were used to identify unstable angina&#46; All participants with missing data were excluded from the analysis&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Health policies and public health initiatives</span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Coronary fast-track system</span><p id="par0050" class="elsevierStylePara elsevierViewall">The FTS was implemented in all regions of Portugal by 2007&#46; We therefore had available for analysis seven years of data before the implementation of the regulation &#40;January 2000-December 2007&#41; and nine years of data after implementation &#40;January 2008-December 2016&#41;&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">The aim of the FTS was to create a priority system that would facilitate access to clinical&#44; therapeutic and diagnostic resources for ACS patients&#46; Direct admission to the catheterization laboratory for primary angioplasty is essential since the time between symptom onset and treatment in MI is crucial to reducing morbidity and mortality&#46; The system is triggered by patients calling the emergency number &#40;112&#41;&#46; The National Institute for Emergency Medicine &#40;INEM&#41; can then initiate diagnosis and treatment earlier by transferring the patient to a hospital unit specializing in ACS treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">5</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">INEM has the capacity to intervene early&#44; and after clinical diagnosis and electrocardiogram&#44; decides jointly with the Referral Center for Emergency Patients &#40;CODU&#41; on pre-hospital treatment and hospital referral&#44; increasing the likelihood of therapeutic success&#46; CODU contacts the hospital unit to organize the patient&#39;s admission and treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">6</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Smoking ban</span><p id="par0065" class="elsevierStylePara elsevierViewall">The smoking ban was implemented in January 2008&#46; We therefore had available for analysis six years of data before the implementation of the ban &#40;January 2002-December 2007&#41; and nine years of data after implementation &#40;January 2008-December 2016&#41;&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Portugal is a signatory of the World Health Organization &#40;WHO&#41;&#8217;s Framework Convention on Tobacco Control&#44;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">7</span></a> which led to implementation in January 2008 of the most recent anti-smoking measure&#44; Law no&#46; 37&#47;2007&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">8</span></a> This legislation introduced a new framework to protect individuals from passive &#40;second-hand&#41; smoking and to promote smoking reduction and cessation&#46;<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">8&#44;9</span></a> The law banned smoking in all enclosed public places&#44; including hospitals&#44; public transport&#44; and workplaces&#46; In addition&#44; it established further regulations regarding information provided on tobacco products&#44; their packaging and labeling&#44; as well as further restrictions on advertising&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">10</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Salt reduction policy</span><p id="par0075" class="elsevierStylePara elsevierViewall">The salt reduction policy was implemented in September 2010&#46; We therefore had available for analysis eight years of data before the implementation of the regulation &#40;January 2002-September 2010&#41; and six years of data after implementation &#40;October 2010-December 2016&#41;&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Even small reductions in the prevalence of high blood pressure can lead to major health gains&#46; In view of the importance of these approaches&#44; the WHO created a set of recommendations to reduce dietary salt intake to 5 g&#47;day&#44; in order to prevent chronic disease and improve health&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">11</span></a> In the WHO European Region&#44; 26 out of the 53 member states&#44; including Portugal&#44; have implemented operational salt reduction policies&#44; including those aimed at reducing salt intake&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Notably&#44; bread accounts for about one-sixth of daily salt intake&#44;<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">12&#44;13</span></a> with Portugal&#44; Poland and Japan having the highest levels of salt in bread&#46;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">14&#44;15</span></a> The policy introduced in Portugal aimed to reduce salt to 1&#46;4 g per 100 g bread&#46; It also mandated clear salt content labeling of packaged products&#46;</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Statistical analysis</span><p id="par0090" class="elsevierStylePara elsevierViewall">The main outcome in our study was monthly case-fatality rates&#44; subsequently stratified by age and gender&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">ACS case-fatality rates were calculated for each month&#44; using the total number of patients admitted to public hospitals as the denominator and the number of ACS deaths as the numerator&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">The impact of the three policies was studied individually&#44; using a binary covariable indicating the start of the policy&#44; as well as a continuous covariable to account for the effect of the policy after its implementation&#46; A segmented multiple linear regression model was implemented to assess changes over time&#46; These models are useful when the relationship between the response and the independent variables is piecewise linear&#44; i&#46;e&#46; represented by two or more straight lines connected at unknown values &#40;breakpoints&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">16</span></a> In this study&#44; the segmented model was implemented to test for significant changes in case-fatality rates after the introduction of the three policies&#46; The Davies test was used to assess whether the differences between the slopes before and after the breakpoint were significant&#46; The model was fitted in R version 2&#46;5&#46;1 software using the &#8220;segmented&#8221; library&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">17</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">For all models created&#44; the case-fatality rate was the response variable&#46; Four models were created in total&#44; one for each of the policies and one used subsequently to test which year showed a significant difference in case-fatality rate&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">All analyses were stratified by gender and age&#46; Two age categories were used&#44; &#60;65 and &#8805;65 years&#46; Short-term autocorrelation between monthly estimates was incorporated into the model by applying a first-order autoregressive process to the residuals&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Although we were aware that there might be short-term temporal differences in case-fatality rates&#44; related for example to the day of the week&#44; or weekends vs&#46; weekdays&#44; we did not adjust for this in our models&#46; Other studies have shown a steady reduction in differences between weekends and weekdays in the time of CVD events&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">18</span></a> There have also been studies showing that after accounting for mode of arrival at the hospital&#44; there was no difference in case-fatality rates between weekdays and weekends&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">19</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">Statistical significance was assessed through p-values&#44; assuming &#60;5&#37; as significant&#44; and 95&#37; confidence intervals &#40;CI&#41; were calculated for each of the regression coefficients&#46; Models were fitted in R software&#44; version 2&#46;5&#46;1&#46;</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Results</span><p id="par0125" class="elsevierStylePara elsevierViewall">A total of 20&#160;849 in-hospital deaths from ACS were recorded in mainland Portugal from 2000 to 2016&#44; out of a total of 203&#160;040 admissions for ACS&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Of the models created individually&#44; one for each policy&#44; the FTS showed an immediate decrease in case fatalities &#40;beta&#61;-1&#46;27&#44; p&#61;0&#46;003&#41;&#59; however&#44; it did not impact case-fatality trends after 2007&#44; which remained steady&#46; Similarly&#44; the smoking ban resulted in an immediate decrease in case fatalities after its implementation &#40;p&#61;-0&#46;861&#44; p&#61;0&#46;05&#41;&#44; but no significant decrease in trends was observed after 2008 &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> and <a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0135" class="elsevierStylePara elsevierViewall">By contrast&#44; the salt reduction policy did not have any significant effect on case fatalities &#40;beta&#61;0&#46;012&#44; p&#61;0&#46;189&#41;&#44; or any immediate impact after its implementation &#40;beta&#61;0&#46;421&#44; p&#61;0&#46;365&#59; <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Using a model applying segmented regression&#44; 2009 was identified as a year in which there was a difference in case-fatality rates&#46; Slope trends both before &#40;beta&#61;-0&#46;004&#59; 95&#37; CI -0&#46;005 to -0&#46;004&#41; and after 2009 &#40;p&#61;-0&#46;003&#59; 95&#37; CI -0&#46;003 to -0&#46;002&#41; showed a decrease&#59; however&#44; after 2009 this was less pronounced &#40;beta&#61;0&#46;002&#44; p&#61;0&#46;004&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0145" class="elsevierStylePara elsevierViewall">All four models were stratified for ACS case-fatality rates by gender and age&#46; For females &#40;beta&#61;-1&#46;306&#44; p&#61;0&#46;020&#41; and individuals aged &#8805;65 years &#40;beta&#61;-1&#46;169&#44; p&#61;0&#46;029&#41;&#44; there was a significant decrease in case-fatality rates after the smoking ban&#46; For the FTS&#44; both sexes presented a significant decrease in case-fatality rates&#59; however&#44; there was no difference in trends between age groups &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Figure 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0150" class="elsevierStylePara elsevierViewall">In the segmented model&#44; the year found to have a differential rate of case fatalities was consistent with the model including all the data &#40;2009&#41;&#46; Both trends&#44; before and after 2009&#44; were decreasing&#44; though after 2009 the decrease was not as marked as for the period before 2009&#44; as observed for the model including all the patients&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">The differences in case-fatality rates before and after 2009 were higher for women &#40;beta&#61;0&#46;003&#44; p&#61;0&#46;029&#41; than for men&#44; and for individuals aged &#8805;65 years &#40;beta&#61;0&#46;003&#44; p&#61;0&#46;008&#59; <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">The seasonal pattern was consistent with that reported elsewhere&#44;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">20</span></a> with higher admission rates in winter and lower rates during the summer&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Discussion</span><p id="par0165" class="elsevierStylePara elsevierViewall">In the last 11 years&#44; a set of health policies have been implemented in Portugal to help decrease CVD mortality&#46; The first initiative was the FTS in 2007&#44; followed by the smoking ban in 2008 and the salt reduction regulation in mid-2010&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">We created a series of statistical models&#44; four to assess the individual impact of each of the policies&#44; and then one to determine if there was any year during the study that could indicate a difference between trends&#44; suggesting a possible impact of the policies in the country&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">The FTS and the smoking ban led to an immediate decrease in case-fatality rates&#46; Previous national and international studies have shown that an FTS&#44; by substantially shortening the time between symptom onset and treatment&#44; directly influences survival&#46; It has been demonstrated that a symptom onset-treatment time of more than 120 min leads to increased in-hospital mortality in an almost linear fashion&#46;<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">21&#8211;23</span></a> However&#44; the FTS in Portugal is mainly aimed at ST-elevation MI&#44; which accounts for around 40&#37; of all ACS&#44; and so it would not be expected to affect non-ST-elevation MI&#44; meaning that around 60&#37; of ACS patients are not covered by this service&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">The relationship between smoking and CVD mortality has been extensively demonstrated&#46; Smoking worsens atherosclerotic alterations&#44; including narrowing the vascular lumen and inducing a hypercoagulable state&#46; Such changes increase the risk of acute thrombosis and thus mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">24</span></a> The results of the current study were very encouraging regarding the smoking ban&#44; as an immediate decrease in case fatalities was found after the ban was implemented&#46; Since the ban targets both smokers and those exposed to second-hand smoke&#44; case-fatality rates should decrease for both groups&#46; Smoking cessation&#44; and even small reductions in consumption&#44; have been linked to decreases in CVD events and in mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">25</span></a></p><p id="par0185" class="elsevierStylePara elsevierViewall">Few studies have analyzed the effect of tobacco control on CVD mortality&#46; Of those available&#44; most focus on how regulations affect hospital admissions<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">26</span></a>&#59; however&#44; the impact on mortality is equally important&#46; Nevertheless&#44; we are not the first to analyze the impact on mortality&#46; A recent study similarly found a reduction of up to 11&#37; in MI mortality one year after a smoking ban was implemented&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">27</span></a> Another study found a 13&#37; decrease in all-cause mortality&#44; with a decrease of up to 26&#37; in ischemic heart disease &#40;IHD&#41; mortality&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">In the current study&#44; we found that 2009 was a breakpoint in our observed trends&#44; which supported the results from the individual models&#46; Up to 2009 the trends were significantly impacted by the policies&#44; leading to a significant decrease in case-fatality rates&#46; After that year&#44; although the trend continued to decrease it was less marked&#46; The impact of the salt regulation in mid-2010 showed a similar effect&#44; with no change in trends after that year&#46; A similar pattern was observed when the impact of this policy on ACS admissions was analyzed&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">28</span></a></p><p id="par0195" class="elsevierStylePara elsevierViewall">We hypothesised that although the salt regulation was an important initiative&#44; it was highly dependent on individual adherence&#46; The way the regulation was implemented may not have produced the desired effect on the population&#44; perhaps due to the low level of health literacy observed in Portugal&#44; and the fact that the policy envisioned a maximum salt content of bread of 1&#46;4 g of salt per 100 g of bread&#44; while other countries set lower limits&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">When stratified by gender and age&#44; our results showed that the smoking ban led to an immediate decrease in case-fatality rates for women and individuals aged &#8805;65 years&#46; Although the number of women who smoke has increased in recent years&#44; the number of men smoking was even higher&#44; and their length of time smoking was also greater&#46; As a consequence&#44; men will have increased mortality from CVD&#44; even if they quit smoking or reduce their tobacco consumption&#46; Older people are more vulnerable to exposure to second-hand smoke&#44; and so reducing it could lead to a decrease in case-fatalities in this group&#46; Our findings were also consistent with another study in which post-ban reductions in IHD mortality were seen in those aged &#8805;65 years&#44; but not in younger subjects&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">29</span></a></p><p id="par0205" class="elsevierStylePara elsevierViewall">Analyzing the impact of the FTS by groups&#44; we found similarly decreasing case-fatality rates for men and women&#44; an effect previously observed in other studies in which the rate of decrease in CHD mortality was similar in both sexes&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">30</span></a> In addition&#44; no immediate change in case-fatality rates was observed after implementation of the FTS for either younger or older patients&#46; For both groups&#44; there were significant changes in trend&#59; however&#44; the trends observed were increasing&#46; The prevalence of obesity and diabetes<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">31</span></a> is rising in Portugal&#44; which could have weakened any reduction in the younger group&#46; This effect has been observed in other studies<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">30&#44;32</span></a> in which increases in obesity lead to lower reductions in mortality for younger groups&#46; A similar pattern was observed for the older group&#44; which has previously been found in other datasets&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">32</span></a></p><p id="par0210" class="elsevierStylePara elsevierViewall">Our results for age stratification when using segmented regression showed significant differences between trends before and after 2009&#44; for females and older subjects&#46; As for the non-stratified model&#44; the decrease in trends observed before 2009 was steeper than the decrease observed afterward&#46; These results were consistent with those observed when studying the smoking ban with age stratification&#44; in which a significant decrease in case-fatality rates was observed for older but not for younger individuals&#46; For the gender stratification&#44; although the FTS analysis showed a significant decrease after 2007 for men&#44; this was an immediate effect and not a trend&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Limitations</span><p id="par0215" class="elsevierStylePara elsevierViewall">As in any ecological study&#44; it is not possible to directly prove any association between policy implementation and the reduction in case-fatality rates from ACS&#46;</p><p id="par0220" class="elsevierStylePara elsevierViewall">One of the strengths of our study is the use of a well-validated and standardized database&#44; enabling easy comparison with other studies in different countries&#44; particularly in other European countries&#46; In addition to the availability of information on gender and age&#44; this enabled us to assess the robustness of our findings among different subgroups&#46; The time-series method is preferred over the simpler pre- and post-proportion comparison method&#44; because it does not take pre-intervention trends into account and also enables corrections to be made for autocorrelation&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">33</span></a></p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Conclusions</span><p id="par0225" class="elsevierStylePara elsevierViewall">This study extends the existing literature on the patterns of ACS mortality over time&#44; and assesses whether public health interventions to reduce mortality by ACS were successful&#46; Furthermore&#44; it indicates that to decrease case-fatality rates a multifactorial strategy was needed&#44; rather than a single approach&#46;</p><p id="par0230" class="elsevierStylePara elsevierViewall">Strategies such as the smoking ban and the FTS led to an immediate decrease in case-fatality rates&#59; however&#44; after 2009 no major decreases in ACS trends were found&#46;</p><p id="par0235" class="elsevierStylePara elsevierViewall">Considering that CHD constitutes an immense public health problem&#44;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">34</span></a> it is crucial for different stakeholders&#44; including decision-makers&#44; public health authorities&#44; medical societies and the cardiology community&#44; to keep working together to reduce ACS mortality rates&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Conflicts of interest</span><p id="par0240" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare&#46;</p></span></span>"
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              "titulo" => "Health policies and public health initiatives"
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                  "titulo" => "Coronary fast-track system"
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                  "titulo" => "Smoking ban"
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    "fechaRecibido" => "2018-12-31"
    "fechaAceptado" => "2019-05-26"
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          "clase" => "keyword"
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          "palabras" => array:4 [
            0 => "Public health"
            1 => "Cardiovascular health"
            2 => "Acute coronary syndrome"
            3 => "Case-fatality rate"
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          "palabras" => array:4 [
            0 => "Sa&#250;de p&#250;blica"
            1 => "Doen&#231;a cardiovascular"
            2 => "S&#237;ndrome coron&#225;ria aguda"
            3 => "Letalidade"
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    "resumen" => array:2 [
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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">Every year cardiovascular disease &#40;CVD&#41; causes 3&#46;9 million deaths in Europe&#46; Portugal has implemented a set of public health policies to tackle CVD mortality&#58; a smoking ban in 2008&#44; a salt reduction regulation in 2010 and the coronary fast-track system &#40;FTS&#41; for acute coronary syndrome &#40;ACS&#41; in 2007&#46; Our goal in this study was to analyze the impact of these three public health policies in reducing case-fatality rates from ACS between 2000 and 2016&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">The impact of these policies on monthly ACS case-fatalities was assessed by creating individual models for each of the initiatives and implementing multiple linear regression analysis&#44; using standard methods for interrupted time series&#46; We also implemented segmented regression analysis to test which year showed a significant difference in the case-fatality slopes&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Separate modeling showed that the smoking ban &#40;beta&#61;-0&#46;861&#44; p&#61;0&#46;050&#41; and the FTS &#40;beta&#61;-1&#46;27&#44; p&#61;0&#46;003&#41; had an immediate impact after implementation&#44; but did not have a significant impact on ACS trends&#46; The salt reduction regulation did not have a significant impact&#46; For the segmented model&#44; we found significant differences between case-fatality trends before and after 2009&#44; with rates before 2009 showing a steeper decrease&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The smoking ban and the FTS led to an immediate decrease in case-fatality rates&#59; however&#44; after 2009 no major decrease in case-fatality trends was found&#46; Coronary heart disease constitutes an immense public health problem and it remains essential for decision-makers&#44; public health authorities and the cardiology community to keep working to reduce ACS mortality rates&#46;</p></span>"
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            "titulo" => "Methods"
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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">A doen&#231;a cardiovascular &#40;DCV&#41; causa 3&#44;9 milh&#245;es de mortes na Europa anualmente&#46; Portugal implementou um conjunto de pol&#237;ticas de sa&#250;de p&#250;blica que abordam a mortalidade por DCV&#44; a lei do tabaco em 2008&#44; a lei de redu&#231;&#227;o do sal em 2010 e a via verde coron&#225;ria &#40;VVC&#41; em 2007&#46; O objetivo deste estudo foi analisar o impacto destas tr&#234;s pol&#237;ticas de sa&#250;de na redu&#231;&#227;o das taxas de letalidade por s&#237;ndrome coron&#225;ria aguda &#40;SCA&#41; entre 2000 e 2016&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">O impacto destas pol&#237;ticas na taxa letalidade foi avaliado atrav&#233;s da cria&#231;&#227;o de modelos individuais para cada uma das iniciativas&#46; Foi tamb&#233;m implementada uma regress&#227;o segmentada para testar qual o ano em que houve uma diferen&#231;a significativa na letalidade&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Os modelos individuais mostraram que a lei do tabaco &#40;&#946;&#61;-0&#44;861&#44; p-valor&#61;0&#44;050&#41; e a VVC &#40;&#946;&#61;-1&#44;27&#44; p-valor&#61;0&#44;003&#41; tiveram impacto imediato ap&#243;s a sua implementa&#231;&#227;o&#46; A estrat&#233;gia de redu&#231;&#227;o do sal n&#227;o teve impacto significativo&#46; Para o modelo segmentado&#44; encontramos diferen&#231;as significativas entre as tend&#234;ncias de letalidade antes e depois de 2009&#44; com taxas anteriores a 2009 mostrando uma queda mais acentuada&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclus&#227;o</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">A lei do tabaco e a VVC levaram a uma diminui&#231;&#227;o imediata da taxa de letalidade&#59; no entanto&#44; depois de 2009&#44; n&#227;o houve redu&#231;&#227;o significativa&#46; A doen&#231;a coron&#225;ria constitui um grande problema de sa&#250;de p&#250;blica&#44; &#233; cr&#237;tico que as autoridades de sa&#250;de p&#250;blica e a comunidade de cardiologia continuem a trabalhar para reduzir as taxas de mortalidade por SCA&#46;</p></span>"
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Longitudinal trends for case-fatality rates from acute coronary syndrome &#40;percentages&#41; for January 2000-December 2016&#46; The vertical lines mark when the coronary fast-track system was fully implemented throughout Portugal &#40;2007&#41;&#44; the implementation of the smoking ban &#40;2008&#41;&#44; and the implementation of the salt reduction regulation &#40;mid-2010&#41;&#46; ACS&#58; acute coronary syndrome&#46;</p>"
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          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Gender- and age-stratified longitudinal trends for case-fatality rates from acute coronary syndrome &#40;percentage&#41; for January 2000-December 2016&#46; &#40;A&#41; Males&#59; &#40;B&#41; females&#59; &#40;C&#41; individuals aged &#60;65 years&#59; &#40;D&#41; individuals aged &#8805;65 years&#46; The vertical lines mark the years the policies were implemented&#46; ACS&#58; acute coronary syndrome&#46;</p>"
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Time of breakpoint<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> time interaction&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;019 &#40;0&#46;001 to 0&#46;038&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;051&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  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Age &#60;65 years</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">Time of breakpoint&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;141 &#40;-0&#46;362 to 0&#46;645&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;583&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">Time of breakpoint<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> time interaction&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;012 &#40;0&#46;003 to 0&#46;020&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;009&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  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Age &#8805;65 years</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">Time of breakpoint&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-1&#46;169 &#40;-2&#46;209 to -0&#46;129&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;029&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">Time of breakpoint<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> time interaction&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;019 &#40;0&#46;001 to 0&#46;037&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;045&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="4" 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="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Salt reduction regulation</span></td></tr><tr title="table-row"><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"><span class="elsevierStyleHsp" style=""></span>Overall</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">Time of breakpoint&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;421 &#40;-0&#46;488 to 1&#46;295&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;365&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">Time of breakpoint<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> time interaction&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;012 &#40;-0&#46;006 to 0&#46;031&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;190&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  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Male</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">Time of breakpoint&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;538 &#40;-0&#46;319 to 1&#46;395&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;220&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">Time of breakpoint<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> time interaction&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;008 &#40;-0&#46;009 to 0&#46;026&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;341&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  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Female</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">Time of breakpoint&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;243 &#40;-0&#46;921 to 1&#46;408&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;683&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">Time of breakpoint<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> time interaction&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;023 &#40;0&#46;0001 to 0&#46;046&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;052&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  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Age &#60;65 years</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">Time of breakpoint&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;557 &#40;0&#46;061 to 1&#46;053&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;029&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">Time of breakpoint<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> time interaction&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;005 &#40;-0&#46;005 to 0&#46;015&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;320&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  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Age &#8805;65 years</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">Time of breakpoint&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;711 &#40;-0&#46;404 to 1&#46;826&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;213&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">Time of breakpoint<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> time interaction&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;016 &#40;-0&#46;007 to 0&#46;039&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;170&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="4" 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="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">FTS</span></td></tr><tr title="table-row"><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"><span class="elsevierStyleHsp" style=""></span>Overall<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a></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">FTS implemented&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-1&#46;270 &#40;-2&#46;101 to -0&#46;436&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;003&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">FTS implemented<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> time interaction&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;005 &#40;-0&#46;011 to 0&#46;020&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;565&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  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Male<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a></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">FTS implemented&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-1&#46;064 &#40;-1&#46;869 to -0&#46;258&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;01&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
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Revista Portuguesa de Cardiologia (English edition)
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