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For example&#44; the European SCORE risk chart is mainly aimed at middle-aged individuals and its use is recommended for those who are 40&#8211;65 years of age<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a>&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Moreover&#44; observational studies in the elderly have shown that risk estimation in people older than 70 years is problematic because the predictive power of CVRF declines with age&#46; The Leiden 85-plus study showed that the Framingham score is not useful for people older than 70 because of its low power of discrimination<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a>&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Several studies have reported that the association between hypertension and mortality is attenuated in older adults and thus&#44; age might make hypertension a poor determinant of CVD risk in the elderly<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#8211;10</span></a>&#46; However&#44; measures of frailty and function may better identify older adults at risk of adverse consequences of hypertension&#46; It has been reported that systolic blood pressure &#40;SBP&#41; is associated with an increased risk of mortality in elderly individuals with reduced walking speed<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a>&#46; In addition&#44; the effects of some classical CVRF such as total cholesterol &#40;TC&#41; on CVD risk become nebulous or even invert among elderly individuals<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a>&#46; Therefore&#44; a more adequate assessment of CVD risk in the old and very old is desirable in order to target and optimize prevention and treatment&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">The aim of this study was to determine the major predictors of total CVD risk in the elderly population in Spain and to develop specific CVD risk charts for this age group&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Methods</span><p id="par0025" class="elsevierStylePara elsevierViewall">The EPICARDIAN study is a multicenter&#44; population-based&#44; cohort study of people 65 years of age and older from three geographical areas of Spain&#58; the city of Madrid&#44; the municipality of Ar&#233;valo &#40;&#193;vila province&#41;&#44; and the municipality of Begonte &#40;Lugo province&#41;&#46; The study design and methods have previously been published elsewhere<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13&#44;14</span></a>&#46; In summary&#44; a total of 3&#44;729 individuals older than 64 years participated in the baseline examination&#46; Two hundred fifty-five patients &#40;6&#46;8&#37;&#41; showed overt clinical CVD at baseline&#46; Only individuals without CVD at baseline were included in the analyses&#46; Therefore&#44; the initial cohort comprised 3&#44;474 individuals &#40;1&#44;462 men and 2&#44;012 women&#41;&#46; All participants were followed until occurrence of a first cardiovascular event&#44; death&#44; or for ten years&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Variables were measured at baseline and the risk formula included age&#59; sex&#59; SBP&#59; smoking&#59; TC&#59; fasting blood glucose&#59; and a medical diagnosis of hypertension&#44; hypercholesterolemia&#44; diabetes mellitus&#44; or specific drug treatment for these conditions&#46; Serum TC was determined by enzymatic methods<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a>&#46; LDL cholesterol was not measured in the cohort because only a small proportion of participants had HDL cholesterol values available&#46; Blood glucose was determined by means of a glucose-oxidase assay<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a>&#46; For the Cox proportional hazards model&#44; variables were grouped using the Framingham risk factor categories<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a>&#58; age was grouped in five-year categories starting from 65 to 69 years&#44; SBP was classified into three categories&#44; and TC was classified into four categories&#46; Participants were categorized either as smokers &#40;those who smoked at baseline or quit smoking within six months of baseline&#41; or non-smokers&#47;ex-smokers &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; Hypertension was considered present if SBP&#160;&#8805;&#160;140&#160;mmHg&#44; diastolic blood pressure &#40;DBP&#41;&#160;&#8805;&#160;90&#160;mmHg&#44; or if the subject received antihypertensive treatment<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a>&#46; Hypercholesterolemia was considered present if TC&#160;&#8805;&#160;5&#46;1&#160;mmol&#47;L or if the subject received lipid-lowering treatment<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a>&#46; Diabetes was considered present if fasting plasma glucose&#160;&#8805;&#160;7&#46;0&#160;mmol&#47;L or if the subject received antidiabetic treatment<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">A search was conducted for data on CVD events in the initial cohort using primary care and hospital medical records&#44; information from primary care physicians&#44; postal mail&#44; and telephone calls to the subject or relatives&#46; The date and cause of death of deceased individuals in the cohort were confirmed through the Spanish National Death Index and the death records of each healthcare district&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">The International Classification of Diseases &#40;ICD-9 and ICD-10&#41; was used for recording coronary heart disease &#40;ICD-9&#58; 410&#8211;414&#44; ICD-10&#58; I20-I25&#41; and other cardiovascular conditions &#40;ICD-9&#58; 797&#8211;799&#59; ICD-10&#58; I46&#44; R96&#44; R98&#44; I50&#41;&#46; Coronary events were confirmed using the WHO-MONICA algorithm<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a>&#46; The CVD outcome was defined as a composite of first coronary event &#40;fatal or non-fatal definite myocardial infarction &#40;MI&#41; and fatal possible MI&#41;&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">In order to describe the selected data&#44; the arithmetic mean with standard deviation &#40;SD&#41; was calculated for continuous variables and relative frequency distribution was calculated for categorical variables&#46; In order to compare proportions&#44; Pearson&#8217;s chi-square &#40;&#967;<span class="elsevierStyleSup">2</span>&#41; test and Somers&#8217; D were calculated in the case of ordinal variables&#46; To compare groups&#44; Student&#8217;s <span class="elsevierStyleItalic">t</span>-test was used in the case of independent binary measures and analysis of variance for variables with more than two categories&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">The aforementioned independent variables were included in the multivariate models using the Enter method&#46; We created separate models for men and women&#46; In the first step&#44; we treated SBP and TC as continuous variables in order to assess interactions between antihypertensive treatment and SBP values and between lipid-lowering drug and TC levels&#46; In the second step&#44; SBP and TC were categorized&#46; In the third step&#44; the interactions were removed&#46; Finally&#44; in order to simplify the model&#44; the lipid-lowering treatment variable was eliminated because it was not statistically significant&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Bivariate and multivariate associations between each independent variable in the model and the outcome were assessed&#46; The &#223;-coefficient associated with each potential CVRF and the first recorded CVD event were estimated by means of Cox proportional hazards model separately for men and women&#46; Ten-year Kaplan-Meier survival curves for the first fatal&#47;non-fatal CVD event were determined in order to calculate the mean cumulative incidence&#46; The estimate of survival function was calculated using a Cox model adjusted for competing 10-year mortality from non-CVD using the Fine-Gray model&#44; and stratified according to sex&#46; The omnibus test was used to validate the model &#40;<span class="elsevierStyleItalic">p</span>&#160;&#60;&#160;&#46;05&#41;&#46; Sex-specific risk scores for the prediction of fatal and non-fatal CVD using categorical variables were calculated from the &#946;-coefficients of the Cox proportional hazards models&#46; The observed total 10-year CVD risk was categorized as low risk &#40;&#60;20&#37;&#41;&#44; mild risk &#40;20&#37;&#8211;29&#37;&#41;&#44; moderate risk &#40;30&#37;&#8211;39&#37;&#41;&#44; moderate high risk &#40;40&#37;&#8211;49&#37;&#41;&#44; high risk &#40;50&#37;&#8211;59&#37;&#41;&#44; or very high risk &#40;&#8805;60&#37;&#41;&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">All statistical analyses were performed using R statistics software &#40;<a href="http://www.R-project.org">http&#58;&#47;&#47;www&#46;R-project&#46;org</a>&#41;&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Additional statistical analyses&#8212;including the calculation of &#223;-coefficients for different risk factors in the typical 10-year CVD risk model and afterwards using age as a time-scale variable&#8212;calibration&#44; discrimination of the risk functions&#44; and comparisons of mean ten-year cardiovascular risk according to the SCORE-OP charts and the EPICARDIAN score by sex are shown in the <a class="elsevierStyleCrossRef" href="#sec0045">Appendix A supplementary material</a>&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">The study was conducted in compliance with the Declaration of Helsinki &#40;<a href="http://www.wma.net/e/policy/b3.htm">http&#58;&#47;&#47;www&#46;wma&#46;net&#47;e&#47;policy&#47;b3&#46;htm</a>&#41;&#46; Written informed consent was obtained from all participants during the baseline examination&#46; The study protocol was approved by the Ethics Committee of La Princesa University Hospital&#44; Madrid&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Results</span><p id="par0075" class="elsevierStylePara elsevierViewall">A total of 3&#44;474 participants were included&#44; which yielded 27&#44;749 person-years of follow-up&#46; At baseline&#44; 42&#46;5&#37; of the sample had hypertension&#44; 28&#46;4&#37; had hypercholesterolemia&#44; 11&#46;5&#37; had diabetes mellitus&#44; 11&#46;9&#37; smoked&#44; and 52&#37; were on antihypertensive treatment&#46; Follow-up information was obtained on 3&#44;474 individuals &#40;99&#46;8&#37;&#59; 1&#44;462 men and 2&#44;012 women&#41;&#46; There were a total of 1&#44;340 deaths &#40;38&#46;6&#37;&#41; in the entire cohort during the follow-up period &#40;702 deaths in men and 638 in women&#41;&#44; of which 457 were fatal CVD deaths &#40;222 in men and 235 in women&#41;&#46; In total&#44; 768 CVD events &#40;457 fatal CVD events and 311 non-fatal CVD events&#41; were observed&#46; <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the distribution of CVRF and CVD events by sex&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> shows the multivariate Cox proportional hazards model of mean 10-year first fatal or non-fatal CVD for men &#40;panel A&#41; and women &#40;panel B&#41;&#46; Age was the strongest predictor of CVD in both men and women&#46; In men&#44; the variables most strongly associated with CVD were high blood pressure treatment &#40;HR&#58; 1&#46;35&#59; 95&#37; CI&#58; 1&#46;067&#8211;1&#46;710&#41;&#44; diabetes &#40;HR&#58; 1&#46;359&#59; 95&#37; CI&#58; 0&#46;997&#8211;1&#46;852&#41;&#44; and smoking &#40;HR&#58; 1&#46;207&#59; 95&#37; CI&#58; 0&#46;945&#8211;1&#46;541&#41;&#46; In women&#44; the variables most strongly associated with CVD were smoking &#40;HR&#58; 1&#46;881&#59; 95&#37; CI&#58; 1&#46;356&#8211;2&#46;609&#41; and diabetes &#40;HR&#58; 1&#46;285&#59; 95&#37; CI&#58; 0&#46;967&#8211;1&#46;707&#41;&#46; The model showed a discriminative power &#40;C-statistic&#41; of 0&#46;656 &#40;95&#37; CI 0&#46;601&#8722;0&#46;701&#41; in men&#44; and 0&#46;702 &#40;95&#37; CI 0&#46;669&#8722;0&#46;723&#41; in women&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0085" class="elsevierStylePara elsevierViewall">In a second stage of the analysis&#44; we used age as a time-scale variable rather than a typical independent variable&#46; The Cox proportional hazards model significantly improved for diabetes as a predictive variable&#46; The HR of diabetes increased from 1&#46;37 to 1&#46;48 in men and from 1&#46;28 to 1&#46;34 in women &#40;data shown in the <a class="elsevierStyleCrossRef" href="#sec0045">Appendix A supplementary material</a>&#41;&#46; The HR of other variables included in the Cox proportional hazards model &#40;serum TC&#44; smoking&#44; SBP&#44; and antihypertensive treatment&#41; did not increase when age was treated as a time-scale variable&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> shows the individual absolute 10-year cardiovascular risk specifically for men who do not smoke &#40;panel A&#41; and men who smoke &#40;panel B&#41;&#46; <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a> shows the corresponding values for women who do not smoke &#40;panel A&#41; and women who smoke &#40;panel B&#41;&#46; This visual format facilitates the interpretation of individual absolute 10-year total cardiovascular risk &#40;fatal and non-fatal CVD&#41; for each individual&#8217;s sex and smoking status while also taking into account his or her antihypertensive treatment&#44; diabetes status&#44; age&#44; TC&#44; and SBP&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Discussion</span><p id="par0095" class="elsevierStylePara elsevierViewall">The EPICARDIAN score is based on a large cohort of 3&#44;474 elderly Spanish citizens&#46; Previous scores&#44; such as the Framingham score and the European SCORE risk chart&#44; are based on populations recruited before the 1980s&#44; when the prevalence of risk factors in the population was lower&#46; In contrast&#44; the EPICARDIAN cohort was assembled more recently and provides a risk estimation for people who receive or do not receive antihypertensives or other cardiovascular drugs&#46; The EPICARDIAN score also overcomes the problem of applying &#223;-coefficients derived from studies on middle-aged populations to older adults&#44; which may lead to an inadequate risk estimation in the elderly&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Age is the strongest predictor of cardiovascular risk in older men and women&#46; When using age as a time-scale variable rather than as a standard variable&#44; the performance of the Cox proportional hazards model improved&#44; particularly for women&#46; For example&#44; diabetes emerged as an independent predictor in women &#40;in the original model diabetes was borderline&#41;&#46; For example&#44; diabetes emerged as an independent predictor in women &#40;in the original model diabetes was borderline&#41;&#44; though the finding was not statistically significant&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">A different CVRF pattern was observed in men versus women&#46; In men&#44; diabetes was the strongest predictive factor and high blood pressure treatment had a greater impact than it did in women&#46; Smoking also showed a significant association with CVD&#44; which was stronger in women than in men&#46; Similar to previous studies<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">21&#44;22</span></a>&#44; the contribution of TC to CVD acts in an inverse manner in those older than 70 years compared to in those younger than 70 years&#46; The absence of a positive predictive value of TC raises the question of whether risk estimation in the elderly may warrant a different approach than in middle-aged individuals and confirms that the predictive power of certain classic risk factors such as hypercholesterolemia diminish with age&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Current scores used to predict CVD in the elderly mainly rely on calibrated risk equations based on the original Framingham<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> and European SCORE risk charts<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a>&#46; Important limitations of these scores include the small number of participants older than 70 years of age&#44; the occupational origin of some cohorts&#44; and the consideration of CVD mortality as the only main outcome in the predictive model&#46; In contrast&#44; the EPICARDIAN score includes a significant proportion of individuals older than 75 years of age and indicates total CVD risk&#44; which is a more comprehensive estimate of individual total risk in a Mediterranean country such as Spain&#44; which has low rates of coronary heart disease &#40;CHD&#41;&#46; Moreover&#44; previous European scores for the elderly do not include diabetes or&#44; as is the case in the Framingham study&#44; the prediction is based on a sample with a small proportion of individuals with diabetes &#40;4&#37;&#41; whose diagnoses were not made using the current international definition of diabetes&#46; Finally&#44; a unique feature of the EPICARDIAN score is that it accounts for the use of antihypertensive drugs&#8212;the most common treatment in older adults&#8212;which addresses a major gap in previous risk assessment tools<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a>&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Recently&#44; a new European SCORE risk chart for elderly individuals&#44; SCORE-OP&#44; has been published<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a>&#46; We applied the SCORE-OP to our population and found that mean 10-year CVD risk was significantly lower in men and women than what was obtained with the EPICARDIAN charts<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a>&#46; This is most likely due to the fact that the mean age of the EPICARDIAN study population is older and the prevalence of diabetes and smoking is higher than in the cohorts included in the SCORE-OP&#44; which mainly came from Northern and Central Europe&#46; Also&#44; the two equations do not include exactly the same parameters&#46; For instance&#44; the EPICARDIAN equation includes hypertension treatment as a variable in the model whereas the SCORE-OP includes c-HDL values&#46; We have also found that the SCORE-OP identifies fewer patients 65 years of age and older as being at high or very high risk than the original SCORE risk chart for low-risk countries&#44; which includes Spain<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a>&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">The EPICARDIAN charts consider only the major CVRF&#46; Other factors such as family history of CVD&#44; fibrinogen levels&#44; physical activity&#44; waist circumference&#44; or C-reactive protein levels can theoretically modulate the CVD risk in the elderly&#46; In contrast&#44; as mentioned above&#44; the predictive value of classic risk factors such as hypercholesterolemia or systolic hypertension weakens with age<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#44;21</span></a>&#46; Therefore&#44; the absolute risk estimations in some boxes&#44; particularly in groups of older adults with few individuals with very high levels of TC and SBP&#44; could be less accurate as a result&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Our findings are in line with a recently published systematic review<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> showing the inconsistency of predictive values of traditional CVD risk factors such as cholesterol fractions&#44; blood pressure&#44; smoking&#44; or BMI in elderly individuals&#46; These findings justify the development of new risk models like the EPICARDIAN score&#44; which consider competing causes of death&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Our study has several strengths&#46; The sample included individuals recruited from urban and rural settings&#44; from different geographical locations&#44; from a wide age range within the segment of the population defined as elderly&#44; and included a high proportion of individuals with diabetes&#46; The availability of information on CVRF treatment&#44; particularly antihypertensive treatment&#44; is another strength of this study&#46; It provides useful information for clinicians when it comes to adjusting estimated CVD risk in patients already receiving antihypertensive treatment&#46; The EPICARDIAN cohort provides the first prospective association between total CVD and multiple CVRF for the elderly in Spain&#44; a country with low incidence of CVD&#46; The EPICARDIAN score allows for the direct estimation of total CVD risk based on the current background risk of the elderly population rather than based on foreign scores calibrated for low-risk European populations&#46; Predictions based on these calibrations may not be accurate if a long time has passed and a marked change in CVD mortality has occurred between when the risk score was designed and when it is applied to different populations&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Conclusions</span><p id="par0135" class="elsevierStylePara elsevierViewall">Our results allow for adjusting the degree to which some specific CVRF&#44; such as cholesterol levels&#44; may affect the specific population they were drawn from&#46; It is expected that this risk score will be validated in the future&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">The EPICARDIAN score offers a novel estimation of total CVD risk by incorporating hypertensive treatment to the risk calculation&#46; CVD risk is significantly higher in elderly men with diabetes&#44; elderly men who receive antihypertensive treatment&#44; and elderly women who smoke&#46; The score is a practical tool that clinicians can use to estimate the total individual CVD risk in Spanish individuals older than 70 years of age&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Funding</span><p id="par0145" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleGrantNumber" refid="gs0005">FIS 93&#47;012&#59;</span><span class="elsevierStyleGrantNumber" refid="gs0005">FIS 96&#47;1993&#59;</span><span class="elsevierStyleGrantNumber" refid="gs0005">FIS 02&#47;0896</span> from <span class="elsevierStyleGrantSponsor" id="gs0005">Instituto de Salud Carlos III</span> and <span class="elsevierStyleGrantSponsor" id="gs0010">DGICyT</span><span class="elsevierStyleGrantNumber" refid="gs0010">PB&#47;255-Co4&#46;</span> Spain&#46; The funder&#40;s&#41; had no role in study but funding&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Conflicts of interests</span><p id="par0150" class="elsevierStylePara elsevierViewall">The authors declare that they do not have any conflicts of interests&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background and objectives</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Cardiovascular risk estimation in people over 70 years of age is problematic&#46; Most scores have been created based on cohorts of middle-aged people&#44; with an underrepresentation of older adults&#46; The predictive power of classical cardiovascular risk factors declines with age&#46; The aim of this work is to develop a specific score for estimating cardiovascular risk among the elderly population in Spain&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">This work is a population-based cohort established in 1995&#46; Setting&#58; Three geographical areas of Spain &#40;Madrid&#44; &#193;vila&#44; and Lugo&#41;&#46; Participants&#58; 3&#44;729 people older than 64 years with no cardiovascular diseases &#40;CVD&#41; at baseline&#46; Measurements&#58; Suspected fatal and nonfatal CVD &#40;both coronary heart disease and stroke&#41; were investigated annually and confirmed using the WHO-MONICA criteria&#46; All participants were followed-up on until occurrence of a first CVD event&#44; until death&#44; or until December 31&#44; 2015&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Age was the strongest predictor of CVD at 10 years in both men and women&#46; In men&#44; variables associated with CVD were high blood pressure treatment &#40;HR&#58; 1&#46;35&#59; 95&#37; CI&#58; 1&#46;067&#8211;1&#46;710&#41;&#44; diabetes &#40;HR&#58; 1&#46;359&#59; 95&#37; CI&#58; 0&#46;997&#8211;1&#46;852&#41;&#44; and smoking &#40;HR&#58; 1&#46;207&#59; 95&#37; CI&#58; 0&#46;945&#8211;1&#46;541&#41; and in women&#44; the variables were smoking &#40;HR&#58; 1&#46;881&#59; 95&#37; CI&#58; 1&#46;356&#8211;2&#46;609&#41; and diabetes &#40;HR&#58; 1&#46;285&#59; 95&#37; CI&#58; 0&#46;967&#8211;1&#46;707&#41;&#46; Total cholesterol did not increase the risk of CVD in men or women&#46; However&#44; total cholesterol levels &#62;200&#160;mg&#47;dL were inversely associated with 10-year risk of CVD in men and women&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">In elderly Spanish men&#44; total CVD at 10 years is significantly increased by age&#44; diabetes&#44; and antihypertensive treatment and in elderly Spanish women by diabetes and smoking&#46; Total cholesterol levels did not increase the risk of CVD&#44; particularly in males&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Background and objectives"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Methods"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Results"
          ]
          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Conclusions"
          ]
        ]
      ]
      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Antecedentes y objetivos</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">La estimaci&#243;n del riesgo cardiovascular en personas mayores de 70 a&#241;os es problem&#225;tica&#46; La mayor&#237;a de las escalas se han creado bas&#225;ndose en cohortes de personas de mediana edad&#44; con una representaci&#243;n insuficiente de los adultos de m&#225;s edad&#46; El poder predictivo de los factores de riesgo cardiovascular cl&#225;sicos disminuye con la edad&#46; El objetivo de este estudio es desarrollar una escala espec&#237;fica para estimar el riesgo cardiovascular de la poblaci&#243;n anciana espa&#241;ola&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Este estudio se realiz&#243; en una cohorte poblacional establecida en 1995&#46; Marco&#58; tres zonas geogr&#225;ficas de Espa&#241;a &#40;Madrid&#44; &#193;vila y Lugo&#41;&#46; Participantes&#58; 3&#46;729 personas mayores de 64 a&#241;os sin enfermedades cardiovasculares &#40;ECV&#41; al inicio del seguimiento&#46; Mediciones&#58; Se investigaron anualmente las sospechas de ECV mortal y no mortal &#40;cardiopat&#237;a coronaria e ictus&#41; y se confirmaron usando los criterios del proyecto MONICA de la OMS&#46; Se sigui&#243; a todos los participantes hasta que apareci&#243; el primer episodio de ECV&#44; hasta su muerte o hasta el 31 de diciembre de 2015&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">La edad fue el factor predictivo m&#225;s potente de ECV a los 10 a&#241;os en ambos sexos&#46; Las variables asociadas con ECV en los varones fueron el tratamiento de la hipertensi&#243;n arterial &#40;HR&#58; 1&#44;35&#59; IC al 95&#37;&#58; 1&#44;067&#8722;1&#44;710&#41;&#44; la diabetes &#40;HR&#58; 1&#44;359&#59; IC al 95&#37;&#58; 0&#44;997&#8722;1&#44;852&#41; y el tabaquismo &#40;HR&#58; 1&#44;207&#59; IC al 95&#37;&#58; 0&#44;945&#8722;1&#44;541&#41; y en las mujeres&#44; el tabaquismo &#40;HR&#58; 1&#44;881&#59; IC al 95&#37;&#58; 1&#44;356&#8722;2&#44;609&#41; y la diabetes &#40;HR&#58; 1&#44;285&#59; IC al 95&#37;&#58; 0&#44;967&#8722;1&#44;707&#41;&#46; El colesterol-total no aument&#243; el riesgo de ECV&#44; ni en varones ni en mujeres&#46; Sin embargo&#44; las concentraciones de colesterol total &#62;&#160;200&#160;mg&#47;dL se asociaron inversamente al riesgo de ECV a los 10 a&#241;os&#44; tanto en varones como en mujeres&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">La ECV total a los 10 a&#241;os aumenta significativamente en los varones espa&#241;oles de edad avanzada con la edad&#44; la diabetes y el tratamiento antihipertensivo y en las mujeres con la diabetes y el tabaquismo&#46; Los niveles de colesterol total no aumentaron el riesgo de ECV&#44; sobre todo en los varones&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Antecedentes y objetivos"
          ]
          1 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "M&#233;todos"
          ]
          2 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Resultados"
          ]
          3 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Conclusiones"
          ]
        ]
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0030">Please cite this article as&#58; Gabriel R&#44; Mu&#241;iz J&#44; Vega S&#44; Moral I&#44; P&#233;rez Castro TR&#44; Rodriguez-Salvan&#233;s F&#44; et al&#46;&#44; Riesgo cardiovascular en la poblaci&#243;n anciana espa&#241;ola&#46; Escala de riesgo EPICARDIAN&#46; Rev Cl&#237;n Esp&#46; 2022&#59;222&#58;13&#8211;21&#46;</p>"
      ]
    ]
    "apendice" => array:1 [
      0 => array:1 [
        "seccion" => array:1 [
          0 => array:4 [
            "apendice" => "<p id="par0165" class="elsevierStylePara elsevierViewall">The following is Supplementary data to this article&#58;<elsevierMultimedia ident="upi0005"></elsevierMultimedia></p>"
            "etiqueta" => "Appendix A"
            "titulo" => "Supplementary data"
            "identificador" => "sec0045"
          ]
        ]
      ]
    ]
    "multimedia" => array:7 [
      0 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0005"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:3 [
          "leyenda" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Number of cases and their corresponding percentages &#40;&#37;&#41;&#46;</p>"
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Lower&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Upper&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Age &#40;ref&#46; 65&#8722;69 years-old&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">168&#46;745&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&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
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>70&#8722;74 years&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&#46;324&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">2&#46;488&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>75&#8722;79 years&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;971&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">35&#46;104&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">2&#46;639&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&#46;915&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">3&#46;639&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>80&#8722;84 years&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">66&#46;284&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#8805;&#160;85 years&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Systolic blood pressure &#40;ref&#46; &#60;&#160;140&#160;mmHg&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>140&#8722;149&#160;mmHg&nbsp;\t\t\t\t\t\t\n
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Original article
Cardiovascular risk in the elderly population of Spain. The EPICARDIAN risk score
Riesgo cardiovascular en la población anciana española. Escala de riesgo EPICARDIAN
R. Gabriela,
Corresponding author
rgabriel@isciii.es

Corresponding author.
, J. Muñizb, S. Vegac, I. Morald, T.R. Pérez Castrob, F. Rodriguez-Salvanése, C. Suáreze, B. Novellae, C. Brotonsd, on behalf of the EPICARDIAN Study Group
a Departamento de Salud Internacional, Escuela Nacional de Sanidad, Instituto de Salud Carlos III, Madrid, Spain
b Instituto Universitario de Ciencias de la Salud, Universidad de La Coruña, A Coruña, Spain
c Centro de Salud de Arévalo, SACyL, Arévalo, Ávila, Spain
d Unidad de Investigación, EAP Sardenya-IIB, Barcelona, Spain
e Instituto de Investigación Sanitaria Hospital Universitario de La Princesa, Madrid, Spain
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However&#44; measures of frailty and function may better identify older adults at risk of adverse consequences of hypertension&#46; It has been reported that systolic blood pressure &#40;SBP&#41; is associated with an increased risk of mortality in elderly individuals with reduced walking speed<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a>&#46; In addition&#44; the effects of some classical CVRF such as total cholesterol &#40;TC&#41; on CVD risk become nebulous or even invert among elderly individuals<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a>&#46; Therefore&#44; a more adequate assessment of CVD risk in the old and very old is desirable in order to target and optimize prevention and treatment&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">The aim of this study was to determine the major predictors of total CVD risk in the elderly population in Spain and to develop specific CVD risk charts for this age group&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Methods</span><p id="par0025" class="elsevierStylePara elsevierViewall">The EPICARDIAN study is a multicenter&#44; population-based&#44; cohort study of people 65 years of age and older from three geographical areas of Spain&#58; the city of Madrid&#44; the municipality of Ar&#233;valo &#40;&#193;vila province&#41;&#44; and the municipality of Begonte &#40;Lugo province&#41;&#46; The study design and methods have previously been published elsewhere<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13&#44;14</span></a>&#46; In summary&#44; a total of 3&#44;729 individuals older than 64 years participated in the baseline examination&#46; Two hundred fifty-five patients &#40;6&#46;8&#37;&#41; showed overt clinical CVD at baseline&#46; Only individuals without CVD at baseline were included in the analyses&#46; Therefore&#44; the initial cohort comprised 3&#44;474 individuals &#40;1&#44;462 men and 2&#44;012 women&#41;&#46; All participants were followed until occurrence of a first cardiovascular event&#44; death&#44; or for ten years&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Variables were measured at baseline and the risk formula included age&#59; sex&#59; SBP&#59; smoking&#59; TC&#59; fasting blood glucose&#59; and a medical diagnosis of hypertension&#44; hypercholesterolemia&#44; diabetes mellitus&#44; or specific drug treatment for these conditions&#46; Serum TC was determined by enzymatic methods<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a>&#46; LDL cholesterol was not measured in the cohort because only a small proportion of participants had HDL cholesterol values available&#46; Blood glucose was determined by means of a glucose-oxidase assay<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a>&#46; For the Cox proportional hazards model&#44; variables were grouped using the Framingham risk factor categories<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a>&#58; age was grouped in five-year categories starting from 65 to 69 years&#44; SBP was classified into three categories&#44; and TC was classified into four categories&#46; Participants were categorized either as smokers &#40;those who smoked at baseline or quit smoking within six months of baseline&#41; or non-smokers&#47;ex-smokers &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; Hypertension was considered present if SBP&#160;&#8805;&#160;140&#160;mmHg&#44; diastolic blood pressure &#40;DBP&#41;&#160;&#8805;&#160;90&#160;mmHg&#44; or if the subject received antihypertensive treatment<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a>&#46; Hypercholesterolemia was considered present if TC&#160;&#8805;&#160;5&#46;1&#160;mmol&#47;L or if the subject received lipid-lowering treatment<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a>&#46; Diabetes was considered present if fasting plasma glucose&#160;&#8805;&#160;7&#46;0&#160;mmol&#47;L or if the subject received antidiabetic treatment<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">A search was conducted for data on CVD events in the initial cohort using primary care and hospital medical records&#44; information from primary care physicians&#44; postal mail&#44; and telephone calls to the subject or relatives&#46; The date and cause of death of deceased individuals in the cohort were confirmed through the Spanish National Death Index and the death records of each healthcare district&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">The International Classification of Diseases &#40;ICD-9 and ICD-10&#41; was used for recording coronary heart disease &#40;ICD-9&#58; 410&#8211;414&#44; ICD-10&#58; I20-I25&#41; and other cardiovascular conditions &#40;ICD-9&#58; 797&#8211;799&#59; ICD-10&#58; I46&#44; R96&#44; R98&#44; I50&#41;&#46; Coronary events were confirmed using the WHO-MONICA algorithm<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a>&#46; The CVD outcome was defined as a composite of first coronary event &#40;fatal or non-fatal definite myocardial infarction &#40;MI&#41; and fatal possible MI&#41;&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">In order to describe the selected data&#44; the arithmetic mean with standard deviation &#40;SD&#41; was calculated for continuous variables and relative frequency distribution was calculated for categorical variables&#46; In order to compare proportions&#44; Pearson&#8217;s chi-square &#40;&#967;<span class="elsevierStyleSup">2</span>&#41; test and Somers&#8217; D were calculated in the case of ordinal variables&#46; To compare groups&#44; Student&#8217;s <span class="elsevierStyleItalic">t</span>-test was used in the case of independent binary measures and analysis of variance for variables with more than two categories&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">The aforementioned independent variables were included in the multivariate models using the Enter method&#46; We created separate models for men and women&#46; In the first step&#44; we treated SBP and TC as continuous variables in order to assess interactions between antihypertensive treatment and SBP values and between lipid-lowering drug and TC levels&#46; In the second step&#44; SBP and TC were categorized&#46; In the third step&#44; the interactions were removed&#46; Finally&#44; in order to simplify the model&#44; the lipid-lowering treatment variable was eliminated because it was not statistically significant&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Bivariate and multivariate associations between each independent variable in the model and the outcome were assessed&#46; The &#223;-coefficient associated with each potential CVRF and the first recorded CVD event were estimated by means of Cox proportional hazards model separately for men and women&#46; Ten-year Kaplan-Meier survival curves for the first fatal&#47;non-fatal CVD event were determined in order to calculate the mean cumulative incidence&#46; The estimate of survival function was calculated using a Cox model adjusted for competing 10-year mortality from non-CVD using the Fine-Gray model&#44; and stratified according to sex&#46; The omnibus test was used to validate the model &#40;<span class="elsevierStyleItalic">p</span>&#160;&#60;&#160;&#46;05&#41;&#46; Sex-specific risk scores for the prediction of fatal and non-fatal CVD using categorical variables were calculated from the &#946;-coefficients of the Cox proportional hazards models&#46; The observed total 10-year CVD risk was categorized as low risk &#40;&#60;20&#37;&#41;&#44; mild risk &#40;20&#37;&#8211;29&#37;&#41;&#44; moderate risk &#40;30&#37;&#8211;39&#37;&#41;&#44; moderate high risk &#40;40&#37;&#8211;49&#37;&#41;&#44; high risk &#40;50&#37;&#8211;59&#37;&#41;&#44; or very high risk &#40;&#8805;60&#37;&#41;&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">All statistical analyses were performed using R statistics software &#40;<a href="http://www.R-project.org">http&#58;&#47;&#47;www&#46;R-project&#46;org</a>&#41;&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Additional statistical analyses&#8212;including the calculation of &#223;-coefficients for different risk factors in the typical 10-year CVD risk model and afterwards using age as a time-scale variable&#8212;calibration&#44; discrimination of the risk functions&#44; and comparisons of mean ten-year cardiovascular risk according to the SCORE-OP charts and the EPICARDIAN score by sex are shown in the <a class="elsevierStyleCrossRef" href="#sec0045">Appendix A supplementary material</a>&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">The study was conducted in compliance with the Declaration of Helsinki &#40;<a href="http://www.wma.net/e/policy/b3.htm">http&#58;&#47;&#47;www&#46;wma&#46;net&#47;e&#47;policy&#47;b3&#46;htm</a>&#41;&#46; Written informed consent was obtained from all participants during the baseline examination&#46; The study protocol was approved by the Ethics Committee of La Princesa University Hospital&#44; Madrid&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Results</span><p id="par0075" class="elsevierStylePara elsevierViewall">A total of 3&#44;474 participants were included&#44; which yielded 27&#44;749 person-years of follow-up&#46; At baseline&#44; 42&#46;5&#37; of the sample had hypertension&#44; 28&#46;4&#37; had hypercholesterolemia&#44; 11&#46;5&#37; had diabetes mellitus&#44; 11&#46;9&#37; smoked&#44; and 52&#37; were on antihypertensive treatment&#46; Follow-up information was obtained on 3&#44;474 individuals &#40;99&#46;8&#37;&#59; 1&#44;462 men and 2&#44;012 women&#41;&#46; There were a total of 1&#44;340 deaths &#40;38&#46;6&#37;&#41; in the entire cohort during the follow-up period &#40;702 deaths in men and 638 in women&#41;&#44; of which 457 were fatal CVD deaths &#40;222 in men and 235 in women&#41;&#46; In total&#44; 768 CVD events &#40;457 fatal CVD events and 311 non-fatal CVD events&#41; were observed&#46; <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the distribution of CVRF and CVD events by sex&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> shows the multivariate Cox proportional hazards model of mean 10-year first fatal or non-fatal CVD for men &#40;panel A&#41; and women &#40;panel B&#41;&#46; Age was the strongest predictor of CVD in both men and women&#46; In men&#44; the variables most strongly associated with CVD were high blood pressure treatment &#40;HR&#58; 1&#46;35&#59; 95&#37; CI&#58; 1&#46;067&#8211;1&#46;710&#41;&#44; diabetes &#40;HR&#58; 1&#46;359&#59; 95&#37; CI&#58; 0&#46;997&#8211;1&#46;852&#41;&#44; and smoking &#40;HR&#58; 1&#46;207&#59; 95&#37; CI&#58; 0&#46;945&#8211;1&#46;541&#41;&#46; In women&#44; the variables most strongly associated with CVD were smoking &#40;HR&#58; 1&#46;881&#59; 95&#37; CI&#58; 1&#46;356&#8211;2&#46;609&#41; and diabetes &#40;HR&#58; 1&#46;285&#59; 95&#37; CI&#58; 0&#46;967&#8211;1&#46;707&#41;&#46; The model showed a discriminative power &#40;C-statistic&#41; of 0&#46;656 &#40;95&#37; CI 0&#46;601&#8722;0&#46;701&#41; in men&#44; and 0&#46;702 &#40;95&#37; CI 0&#46;669&#8722;0&#46;723&#41; in women&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0085" class="elsevierStylePara elsevierViewall">In a second stage of the analysis&#44; we used age as a time-scale variable rather than a typical independent variable&#46; The Cox proportional hazards model significantly improved for diabetes as a predictive variable&#46; The HR of diabetes increased from 1&#46;37 to 1&#46;48 in men and from 1&#46;28 to 1&#46;34 in women &#40;data shown in the <a class="elsevierStyleCrossRef" href="#sec0045">Appendix A supplementary material</a>&#41;&#46; The HR of other variables included in the Cox proportional hazards model &#40;serum TC&#44; smoking&#44; SBP&#44; and antihypertensive treatment&#41; did not increase when age was treated as a time-scale variable&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> shows the individual absolute 10-year cardiovascular risk specifically for men who do not smoke &#40;panel A&#41; and men who smoke &#40;panel B&#41;&#46; <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a> shows the corresponding values for women who do not smoke &#40;panel A&#41; and women who smoke &#40;panel B&#41;&#46; This visual format facilitates the interpretation of individual absolute 10-year total cardiovascular risk &#40;fatal and non-fatal CVD&#41; for each individual&#8217;s sex and smoking status while also taking into account his or her antihypertensive treatment&#44; diabetes status&#44; age&#44; TC&#44; and SBP&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Discussion</span><p id="par0095" class="elsevierStylePara elsevierViewall">The EPICARDIAN score is based on a large cohort of 3&#44;474 elderly Spanish citizens&#46; Previous scores&#44; such as the Framingham score and the European SCORE risk chart&#44; are based on populations recruited before the 1980s&#44; when the prevalence of risk factors in the population was lower&#46; In contrast&#44; the EPICARDIAN cohort was assembled more recently and provides a risk estimation for people who receive or do not receive antihypertensives or other cardiovascular drugs&#46; The EPICARDIAN score also overcomes the problem of applying &#223;-coefficients derived from studies on middle-aged populations to older adults&#44; which may lead to an inadequate risk estimation in the elderly&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Age is the strongest predictor of cardiovascular risk in older men and women&#46; When using age as a time-scale variable rather than as a standard variable&#44; the performance of the Cox proportional hazards model improved&#44; particularly for women&#46; For example&#44; diabetes emerged as an independent predictor in women &#40;in the original model diabetes was borderline&#41;&#46; For example&#44; diabetes emerged as an independent predictor in women &#40;in the original model diabetes was borderline&#41;&#44; though the finding was not statistically significant&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">A different CVRF pattern was observed in men versus women&#46; In men&#44; diabetes was the strongest predictive factor and high blood pressure treatment had a greater impact than it did in women&#46; Smoking also showed a significant association with CVD&#44; which was stronger in women than in men&#46; Similar to previous studies<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">21&#44;22</span></a>&#44; the contribution of TC to CVD acts in an inverse manner in those older than 70 years compared to in those younger than 70 years&#46; The absence of a positive predictive value of TC raises the question of whether risk estimation in the elderly may warrant a different approach than in middle-aged individuals and confirms that the predictive power of certain classic risk factors such as hypercholesterolemia diminish with age&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Current scores used to predict CVD in the elderly mainly rely on calibrated risk equations based on the original Framingham<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> and European SCORE risk charts<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a>&#46; Important limitations of these scores include the small number of participants older than 70 years of age&#44; the occupational origin of some cohorts&#44; and the consideration of CVD mortality as the only main outcome in the predictive model&#46; In contrast&#44; the EPICARDIAN score includes a significant proportion of individuals older than 75 years of age and indicates total CVD risk&#44; which is a more comprehensive estimate of individual total risk in a Mediterranean country such as Spain&#44; which has low rates of coronary heart disease &#40;CHD&#41;&#46; Moreover&#44; previous European scores for the elderly do not include diabetes or&#44; as is the case in the Framingham study&#44; the prediction is based on a sample with a small proportion of individuals with diabetes &#40;4&#37;&#41; whose diagnoses were not made using the current international definition of diabetes&#46; Finally&#44; a unique feature of the EPICARDIAN score is that it accounts for the use of antihypertensive drugs&#8212;the most common treatment in older adults&#8212;which addresses a major gap in previous risk assessment tools<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a>&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Recently&#44; a new European SCORE risk chart for elderly individuals&#44; SCORE-OP&#44; has been published<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a>&#46; We applied the SCORE-OP to our population and found that mean 10-year CVD risk was significantly lower in men and women than what was obtained with the EPICARDIAN charts<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a>&#46; This is most likely due to the fact that the mean age of the EPICARDIAN study population is older and the prevalence of diabetes and smoking is higher than in the cohorts included in the SCORE-OP&#44; which mainly came from Northern and Central Europe&#46; Also&#44; the two equations do not include exactly the same parameters&#46; For instance&#44; the EPICARDIAN equation includes hypertension treatment as a variable in the model whereas the SCORE-OP includes c-HDL values&#46; We have also found that the SCORE-OP identifies fewer patients 65 years of age and older as being at high or very high risk than the original SCORE risk chart for low-risk countries&#44; which includes Spain<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a>&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">The EPICARDIAN charts consider only the major CVRF&#46; Other factors such as family history of CVD&#44; fibrinogen levels&#44; physical activity&#44; waist circumference&#44; or C-reactive protein levels can theoretically modulate the CVD risk in the elderly&#46; In contrast&#44; as mentioned above&#44; the predictive value of classic risk factors such as hypercholesterolemia or systolic hypertension weakens with age<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#44;21</span></a>&#46; Therefore&#44; the absolute risk estimations in some boxes&#44; particularly in groups of older adults with few individuals with very high levels of TC and SBP&#44; could be less accurate as a result&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Our findings are in line with a recently published systematic review<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> showing the inconsistency of predictive values of traditional CVD risk factors such as cholesterol fractions&#44; blood pressure&#44; smoking&#44; or BMI in elderly individuals&#46; These findings justify the development of new risk models like the EPICARDIAN score&#44; which consider competing causes of death&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Our study has several strengths&#46; The sample included individuals recruited from urban and rural settings&#44; from different geographical locations&#44; from a wide age range within the segment of the population defined as elderly&#44; and included a high proportion of individuals with diabetes&#46; The availability of information on CVRF treatment&#44; particularly antihypertensive treatment&#44; is another strength of this study&#46; It provides useful information for clinicians when it comes to adjusting estimated CVD risk in patients already receiving antihypertensive treatment&#46; The EPICARDIAN cohort provides the first prospective association between total CVD and multiple CVRF for the elderly in Spain&#44; a country with low incidence of CVD&#46; The EPICARDIAN score allows for the direct estimation of total CVD risk based on the current background risk of the elderly population rather than based on foreign scores calibrated for low-risk European populations&#46; Predictions based on these calibrations may not be accurate if a long time has passed and a marked change in CVD mortality has occurred between when the risk score was designed and when it is applied to different populations&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Conclusions</span><p id="par0135" class="elsevierStylePara elsevierViewall">Our results allow for adjusting the degree to which some specific CVRF&#44; such as cholesterol levels&#44; may affect the specific population they were drawn from&#46; It is expected that this risk score will be validated in the future&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">The EPICARDIAN score offers a novel estimation of total CVD risk by incorporating hypertensive treatment to the risk calculation&#46; CVD risk is significantly higher in elderly men with diabetes&#44; elderly men who receive antihypertensive treatment&#44; and elderly women who smoke&#46; The score is a practical tool that clinicians can use to estimate the total individual CVD risk in Spanish individuals older than 70 years of age&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Funding</span><p id="par0145" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleGrantNumber" refid="gs0005">FIS 93&#47;012&#59;</span><span class="elsevierStyleGrantNumber" refid="gs0005">FIS 96&#47;1993&#59;</span><span class="elsevierStyleGrantNumber" refid="gs0005">FIS 02&#47;0896</span> from <span class="elsevierStyleGrantSponsor" id="gs0005">Instituto de Salud Carlos III</span> and <span class="elsevierStyleGrantSponsor" id="gs0010">DGICyT</span><span class="elsevierStyleGrantNumber" refid="gs0010">PB&#47;255-Co4&#46;</span> Spain&#46; The funder&#40;s&#41; had no role in study but funding&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Conflicts of interests</span><p id="par0150" class="elsevierStylePara elsevierViewall">The authors declare that they do not have any conflicts of interests&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background and objectives</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Cardiovascular risk estimation in people over 70 years of age is problematic&#46; Most scores have been created based on cohorts of middle-aged people&#44; with an underrepresentation of older adults&#46; The predictive power of classical cardiovascular risk factors declines with age&#46; The aim of this work is to develop a specific score for estimating cardiovascular risk among the elderly population in Spain&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">This work is a population-based cohort established in 1995&#46; Setting&#58; Three geographical areas of Spain &#40;Madrid&#44; &#193;vila&#44; and Lugo&#41;&#46; Participants&#58; 3&#44;729 people older than 64 years with no cardiovascular diseases &#40;CVD&#41; at baseline&#46; Measurements&#58; Suspected fatal and nonfatal CVD &#40;both coronary heart disease and stroke&#41; were investigated annually and confirmed using the WHO-MONICA criteria&#46; All participants were followed-up on until occurrence of a first CVD event&#44; until death&#44; or until December 31&#44; 2015&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Age was the strongest predictor of CVD at 10 years in both men and women&#46; In men&#44; variables associated with CVD were high blood pressure treatment &#40;HR&#58; 1&#46;35&#59; 95&#37; CI&#58; 1&#46;067&#8211;1&#46;710&#41;&#44; diabetes &#40;HR&#58; 1&#46;359&#59; 95&#37; CI&#58; 0&#46;997&#8211;1&#46;852&#41;&#44; and smoking &#40;HR&#58; 1&#46;207&#59; 95&#37; CI&#58; 0&#46;945&#8211;1&#46;541&#41; and in women&#44; the variables were smoking &#40;HR&#58; 1&#46;881&#59; 95&#37; CI&#58; 1&#46;356&#8211;2&#46;609&#41; and diabetes &#40;HR&#58; 1&#46;285&#59; 95&#37; CI&#58; 0&#46;967&#8211;1&#46;707&#41;&#46; Total cholesterol did not increase the risk of CVD in men or women&#46; However&#44; total cholesterol levels &#62;200&#160;mg&#47;dL were inversely associated with 10-year risk of CVD in men and women&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">In elderly Spanish men&#44; total CVD at 10 years is significantly increased by age&#44; diabetes&#44; and antihypertensive treatment and in elderly Spanish women by diabetes and smoking&#46; Total cholesterol levels did not increase the risk of CVD&#44; particularly in males&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Background and objectives"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Methods"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Results"
          ]
          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Conclusions"
          ]
        ]
      ]
      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Antecedentes y objetivos</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">La estimaci&#243;n del riesgo cardiovascular en personas mayores de 70 a&#241;os es problem&#225;tica&#46; La mayor&#237;a de las escalas se han creado bas&#225;ndose en cohortes de personas de mediana edad&#44; con una representaci&#243;n insuficiente de los adultos de m&#225;s edad&#46; El poder predictivo de los factores de riesgo cardiovascular cl&#225;sicos disminuye con la edad&#46; El objetivo de este estudio es desarrollar una escala espec&#237;fica para estimar el riesgo cardiovascular de la poblaci&#243;n anciana espa&#241;ola&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Este estudio se realiz&#243; en una cohorte poblacional establecida en 1995&#46; Marco&#58; tres zonas geogr&#225;ficas de Espa&#241;a &#40;Madrid&#44; &#193;vila y Lugo&#41;&#46; Participantes&#58; 3&#46;729 personas mayores de 64 a&#241;os sin enfermedades cardiovasculares &#40;ECV&#41; al inicio del seguimiento&#46; Mediciones&#58; Se investigaron anualmente las sospechas de ECV mortal y no mortal &#40;cardiopat&#237;a coronaria e ictus&#41; y se confirmaron usando los criterios del proyecto MONICA de la OMS&#46; Se sigui&#243; a todos los participantes hasta que apareci&#243; el primer episodio de ECV&#44; hasta su muerte o hasta el 31 de diciembre de 2015&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">La edad fue el factor predictivo m&#225;s potente de ECV a los 10 a&#241;os en ambos sexos&#46; Las variables asociadas con ECV en los varones fueron el tratamiento de la hipertensi&#243;n arterial &#40;HR&#58; 1&#44;35&#59; IC al 95&#37;&#58; 1&#44;067&#8722;1&#44;710&#41;&#44; la diabetes &#40;HR&#58; 1&#44;359&#59; IC al 95&#37;&#58; 0&#44;997&#8722;1&#44;852&#41; y el tabaquismo &#40;HR&#58; 1&#44;207&#59; IC al 95&#37;&#58; 0&#44;945&#8722;1&#44;541&#41; y en las mujeres&#44; el tabaquismo &#40;HR&#58; 1&#44;881&#59; IC al 95&#37;&#58; 1&#44;356&#8722;2&#44;609&#41; y la diabetes &#40;HR&#58; 1&#44;285&#59; IC al 95&#37;&#58; 0&#44;967&#8722;1&#44;707&#41;&#46; El colesterol-total no aument&#243; el riesgo de ECV&#44; ni en varones ni en mujeres&#46; Sin embargo&#44; las concentraciones de colesterol total &#62;&#160;200&#160;mg&#47;dL se asociaron inversamente al riesgo de ECV a los 10 a&#241;os&#44; tanto en varones como en mujeres&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">La ECV total a los 10 a&#241;os aumenta significativamente en los varones espa&#241;oles de edad avanzada con la edad&#44; la diabetes y el tratamiento antihipertensivo y en las mujeres con la diabetes y el tabaquismo&#46; Los niveles de colesterol total no aumentaron el riesgo de ECV&#44; sobre todo en los varones&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Antecedentes y objetivos"
          ]
          1 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "M&#233;todos"
          ]
          2 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Resultados"
          ]
          3 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Conclusiones"
          ]
        ]
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0030">Please cite this article as&#58; Gabriel R&#44; Mu&#241;iz J&#44; Vega S&#44; Moral I&#44; P&#233;rez Castro TR&#44; Rodriguez-Salvan&#233;s F&#44; et al&#46;&#44; Riesgo cardiovascular en la poblaci&#243;n anciana espa&#241;ola&#46; Escala de riesgo EPICARDIAN&#46; Rev Cl&#237;n Esp&#46; 2022&#59;222&#58;13&#8211;21&#46;</p>"
      ]
    ]
    "apendice" => array:1 [
      0 => array:1 [
        "seccion" => array:1 [
          0 => array:4 [
            "apendice" => "<p id="par0165" class="elsevierStylePara elsevierViewall">The following is Supplementary data to this article&#58;<elsevierMultimedia ident="upi0005"></elsevierMultimedia></p>"
            "etiqueta" => "Appendix A"
            "titulo" => "Supplementary data"
            "identificador" => "sec0045"
          ]
        ]
      ]
    ]
    "multimedia" => array:7 [
      0 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0005"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:3 [
          "leyenda" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Number of cases and their corresponding percentages &#40;&#37;&#41;&#46;</p>"
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Lower&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Upper&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Age &#40;ref&#46; 65&#8722;69 years-old&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">168&#46;745&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&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
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>70&#8722;74 years&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&#46;324&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">2&#46;488&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>75&#8722;79 years&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;971&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">35&#46;104&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">2&#46;639&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&#46;915&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">3&#46;639&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>80&#8722;84 years&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">66&#46;284&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#8805;&#160;85 years&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Systolic blood pressure &#40;ref&#46; &#60;&#160;140&#160;mmHg&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>140&#8722;149&#160;mmHg&nbsp;\t\t\t\t\t\t\n
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