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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">Current demographic trends in developed countries show growth and an increasing importance of the older adult population group&#46; In most developed countries worldwide&#44; the proportion of the total population 65 years of age or older is already greater than 10&#37;&#46; In many&#44; such as Great Britain and Spain&#44; this age group represents more than 15&#37; of the population<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a>&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Individuals 80 years of called &#8220;aging of the aged&#46;&#8221; Indeed&#44; according to the most recent forecasts from Spain&#39;s National Institute of Statistics &#40;INE&#44; for its initials in Spanish&#41;&#44; 11&#46;6&#37; of the population of Spain will be 80 years or older by 2050<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a>&#46; age or more&#8212;or very elderly patients &#40;VEP&#41;&#8212;are the fastest growing population segment in developed countries&#46; In Spain&#44; they already represent 6&#46;1&#37; of the population and their proportion among older adults will continue to rise in a process</p><p id="par0015" class="elsevierStylePara elsevierViewall">Age is the most important independent risk factor &#40;RF&#41; for stroke&#46; For every ten years after age 55&#44; the rate of stroke &#62; doubles in both men and women<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a>&#46; More than 50&#37; of all strokes occur in patients older than 75 years and 88&#37; of deaths due to stroke occur in patients older than 65 years<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a>&#46; What&#8217;s more&#44; old age is an independent factor for recurrence of stroke after an ischemic cerebrovascular event or transient ischemic attack &#40;TIA&#41;&#46; Individuals older than 65 years have a three times greater risk of having a vascular event in the ten years after a stroke or TIA compared to younger patients<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;3</span></a>&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">The general population aging in developed countries and the improvement in survival of patients with stroke has created a large population of older adults who have had a stroke who require secondary prevention measures<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a>&#46; At present&#44; more than 5&#37; of individuals from 65 to 74 years of age and more than 10&#37; of those older than 75 years have had a prior stroke<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a>&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">When considering who to treat&#44; it could be argued that a patient should have a life expectancy of at least five years in order to benefit from preventive therapies&#46; However&#44; nearly all women up to 80 years of age and men up to 75 years of age have a life expectancy of more than five years&#44; regardless of their health status&#59; it is even expected that those in fair health at 80 years of age live will live for more than five years<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a>&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Unfortunately&#44; older adult patients have been systematically excluded from the majority of multicenter&#44; randomized&#44; prospective studies&#46; Therefore&#44; there is a paucity of evidence to serve as a guide for determining what medical interventions&#44; such as reducing blood pressure or prescribing statins&#44; would be most beneficial&#44; especially among those older than 80 years<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a>&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Nevertheless&#44; in recent decades&#44; evidence has emerged which suggests that older adults with a previous stroke or TIA may benefit enormously from secondary stroke prevention measures<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#8211;5</span></a>&#44; such as the use of antihypertensive or lipid-lowering drugs&#59; this may possibly have translated into a change in clinical practice&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">In this regard&#44; this study proposes to evaluate how pharmacological treatment for secondary ischemic stroke prevention in VEP in routine clinical practice has changed in recent decades&#44; focusing on changes in antihypertensive&#44; lipid-lowering&#44; and antithrombotic prescribing in these patients when they are discharged from the hospital&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Materials and methods</span><p id="par0045" class="elsevierStylePara elsevierViewall">In order to evaluate changes in drug prescribing in VEP with a recent ischemic stroke&#44; a retrospective&#44; observational study was conducted among patients who were discharged with a diagnosis of ischemic stroke from the Virgen Macarena&#44; Virgen del Roc&#237;o&#44; and Virgen de Valme University Hospitals in Seville&#44; Spain&#46; VEP were defined as patients aged &#8805;80 years&#44; in line with the literature<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a>&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Cerebral infarction was defined as a sudden-onset focal neurological deficit that persisted beyond 24&#8239;h documented by a computed tomography &#40;CT&#41; scan or magnetic resonance imaging &#40;MRI&#41; test of the head that indicates its presence&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">There were no exclusion criteria&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Three study periods were chosen&#58; a baseline &#40;less affected by the COVID-19 pandemic overload&#41; from 2019 to 2020&#59; five years previously&#44; from 2014 to 2016&#59; and 20 years previously&#44; from 1999 to 2001&#46; A random sample was selected &#40;consecutive patients during a certain period of several months chosen at random&#41; of said periods&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Various demographic variables&#44; such as age and sex&#44; and clinical variables&#44; such as a history of cardiovascular RF &#40;hypertension&#44; hypercholesterolemia&#44; tobacco use&#44; atrial fibrillation &#40;AF&#41;&#41; or established cardiovascular disease &#40;ischemic heart disease&#44; stroke&#44; or peripheral arterial disease&#41;&#44; among others&#44; as well as the type of drug and dose prescribed upon the patient&#8217;s discharge were gathered and tabulated <a class="elsevierStyleCrossRef" href="#tbl0005">Table1</a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">The study focused on drugs used in the secondary prevention of ischemic stroke&#58; antihypertensives&#44; statins&#44; and antithrombotic therapy<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a>&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">In regard to statins&#44; the criteria of the American College of Cardiology&#47;American Heart Association &#40;ACC&#47;AHA&#41; guidelines were used to define high-intensity statin therapy&#58; those that on average achieved a decrease in LDL cholesterol &#62;50&#37; and which include a daily dose of 20 and 40&#8239;mg of rosuvastatin and 40 and 80&#8239;mg of atorvastatin<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a>&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Statistical analysis</span><p id="par0080" class="elsevierStylePara elsevierViewall">The IBM SPSS v22&#46;0 program was used for the statistical analysis&#46; Continuous variables were expressed as means and standard deviation&#46; Categorical variables were expressed as percentages&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Afterwards&#44; a study of the association between patients&#8217; clinical characteristics and the use of statins and high-intensity statin therapy was performed&#46; Continuous variables were compared using Student&#39;s <span class="elsevierStyleItalic">t</span>-test for non-paired samples&#46; Categorical variables were compared using the chi-square test&#46; For all statistical hypothesis tests&#44; the level of statistical significance was <span class="elsevierStyleItalic">p</span>&#8239;&#60;&#8239;0&#46;05&#46;</p></span></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Results</span><p id="par0090" class="elsevierStylePara elsevierViewall">A total population of 1806 patients discharged due to ischemic stroke was analyzed&#59; this population included 349 VEP&#44; 19&#46;3&#37; of the total&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">The average VEP included in the study was a woman &#40;61&#46;9&#37; of the total&#41; who was 84 &#40;&#177;3&#41; years old&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">In regard to the proportion of VEP in each period&#44; it was observed that the percentage of VEP increased over the years &#40;13&#46;5&#37; vs&#46; 25&#46;9&#37; vs&#46; 28&#37; <span class="elsevierStyleItalic">p</span> &#61; 0&#46;0001&#41;&#44; as did their mean age &#40;83&#46;3&#8239;&#177;&#8239;3 vs 84&#46;1&#8239;&#177;&#8239;3 vs 85&#46;2&#8239;&#177;&#8239;4&#59; <span class="elsevierStyleItalic">p</span> &#61; 0&#46;001&#41;&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Focusing on the VEP&#44; upon comparing the three periods&#44; patients now have a greater frequency of hypertension &#40;HT&#41; &#40;69&#46;9&#37; vs&#46; 84&#46;8&#37; vs&#46; 84&#46;6&#37;&#59; <span class="elsevierStyleItalic">p</span> &#61; 0&#46;0001&#41; and dyslipidemia &#40;12&#37; vs&#46; 41&#46;7&#37; vs&#46; 52&#46;3&#37;&#59; <span class="elsevierStyleItalic">p</span> &#61; 0&#46;0001&#41;&#44; with no differences in the frequency of other risk factors or clinical cardiovascular disease&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Progressively more antihypertensive drugs &#40;in 69&#46;1&#37; vs&#46; 86&#46;7&#37; vs&#46; 92&#46;3&#37; of patients&#44; respectively&#44; <span class="elsevierStyleItalic">p</span> &#61; 0&#46;0001&#41;&#44; statins &#40;in 5&#46;3&#37; vs&#46; 78&#37; vs&#46; 81&#46;5&#37;&#44; <span class="elsevierStyleItalic">p</span> &#61; 0&#46;0001&#41;&#44; and anticoagulants &#40;in 16&#46;5&#37; vs&#46; 19&#46;4&#37; vs&#46; 53&#46;1&#37; <span class="elsevierStyleItalic">p</span> &#61; 0&#46;001&#41; were used upon discharge&#46; A progressive increase was noted in the number of antihypertensive drugs &#40;mean of 1&#8239;&#177;&#8239;0&#46;9 vs&#46; 1&#46;6&#8239;&#177;&#8239;0&#46;9 vs&#46; 1&#46;9&#8239;&#177;&#8239;0&#46;8 drugs&#44; <span class="elsevierStyleItalic">p</span> &#61; 0&#46;0001&#41; and high-intensity statins &#40;2&#46;3&#37; vs&#46; 42&#46;7&#37; vs&#46; 69&#46;2&#37; <span class="elsevierStyleItalic">p</span> &#61; 0&#46;0001&#41;&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">The demographic data&#44; risk factors&#44; and treatments in the population studied are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Upon evaluating differences in the use of drugs in secondary prevention among VEP and among those younger than 80 years&#44; it can be observed how the differences have disappeared with the passing of time&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">In regard to antithrombotic treatment&#44; there were only differences in the use of acetylsalicylic acid &#40;ASA&#41; and anticoagulants &#40;<a class="elsevierStyleCrossRefs" href="#fig0005">Figs&#46; 1 and 2</a>&#41; during the first study period &#40;ASA&#58; 58&#46;6&#37; of VEP vs&#46; 44&#46;8&#37; of those younger than 80 years&#44; <span class="elsevierStyleItalic">p</span> &#61; 0&#46;021&#59; anticoagulants&#58; 16&#46;5&#37; of VEP vs&#46; 24&#46;5&#37; of those younger than 80 years&#44; <span class="elsevierStyleItalic">p</span>&#8239;&#60;&#8239;0&#46;001&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0130" class="elsevierStylePara elsevierViewall">Upon comparing lipid-lowering treatment&#44; fewer statins were used among VEP in the first and second period &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41; &#40;first period&#58; 5&#46;3&#37; of VEP vs&#46; 20&#46;8&#37; of those younger than 80 years&#44; <span class="elsevierStyleItalic">p</span>&#8239;&#60;&#8239;0&#46;001&#59; second period&#58; 78&#37; of VEP vs&#46; 90&#37; of those younger than 80 years&#44; <span class="elsevierStyleItalic">p</span>&#8239;&#60;&#8239;0&#46;001&#41; whereas the differences in the use of high-intensity statins remained steady during the three periods analyzed &#40;first period&#58; 2&#46;3&#37; of VEP vs&#46; 12&#46;5&#37; of those younger than 80 years&#44; <span class="elsevierStyleItalic">p</span>&#8239;&#60;&#8239;0&#46;001&#59; second period&#58; 42&#46;7&#37; of VEP vs&#46; 59&#46;8&#37; of those younger than 80 years&#44; <span class="elsevierStyleItalic">p</span>&#8239;&#60;&#8239;0&#46;001&#59; third period&#58; 69&#46;2&#37; of VEP vs&#46; 81&#46;2&#37; of those younger than 80 years&#44; <span class="elsevierStyleItalic">p</span> &#61; 0&#46;048&#41;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0135" class="elsevierStylePara elsevierViewall">On the contrary&#44; there were no differences in the three periods studied in antihypertensive treatment among VEP and those younger than 80 years or in the percentage of patients treated with antihypertensive drugs &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#41; or the number of antihypertensive drugs used &#40;first period&#58; 1&#8239;&#177;&#8239;0&#46;9 of VEP vs&#46; 0&#46;9&#8239;&#177;&#8239;0&#46;8 of those younger than 80 years&#44; <span class="elsevierStyleItalic">p</span> &#61; 0&#46;225&#59; second period&#58; 1&#46;6&#8239;&#177;&#8239;0&#46;9 of VEP vs&#46; 1&#46;6&#8239;&#177;&#8239;1 of those younger than 80 years&#44; <span class="elsevierStyleItalic">p</span> &#61; 0&#46;906&#59; third period&#58; 1&#46;9&#8239;&#177;&#8239;0&#46;8 of VEP vs&#46; 1&#46;8&#8239;&#177;&#8239;0&#46;8 of those younger than 80 years&#44; <span class="elsevierStyleItalic">p</span> &#61; 0&#46;552&#41;&#46;</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Discussion</span><p id="par0140" class="elsevierStylePara elsevierViewall">Although recent studies indicate that the decline in the mortality rate due to cerebrovascular disease has decelerated or even come to a standstill in Spain&#44; the absolute number of deaths&#44; patients disabled&#44; and patients who have survived a stroke have increased significantly&#46; What&#8217;s more&#44; it is expected that the incidence of stroke will rise in upcoming decades as a result of population aging and an increased prevalence of the main modifiable risk factors<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#44;9</span></a>&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">The data from this study reflect this trend and the progressive increase in the proportion of VEP who are discharged due to ischemic stroke&#46; This study observed that the percentage of VEP has doubled in the last 20 years&#44; from 14&#37; to 28&#37;&#44; and that the mean age of these VEP has also progressively increased&#44; reaching 85 years&#46; These results confirm that in clinical practice&#44; the proportion of VEP in the global burden of cerebrovascular disease is increasingly relevant&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">A systematic review of the incidence of stroke in VEP which included 16 studies reported values similar to this study&#8217;s results and concluded that at present&#44; around one-third &#40;29&#46;9&#37;&#41; of strokes occur in subjects older than 80 years&#58; 15&#46;2&#37; in those between 80 and 84 years and 16&#46;7&#37; in those older than 85 years<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a>&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">In fact&#44; international stroke guidelines have promoted the use of systemic thrombolysis in older adult patients given that these treatments&#44; which were initially not recommended in those older than 80 years&#44; are now perceived as safe in this population&#46; The percentage of VEP who receive treatment with recombinant tissue plasminogen activator &#40;rt-PA&#41; has clearly increased in recent years<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11&#44;12</span></a>&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">Along these lines&#44; in regard to treatment for blood pressure in VEP with a previous stroke&#44; although physicians have traditionally been reticent to aggressively reduce blood pressure levels among older adults out of fear of adverse effects such as falls or syncope<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a>&#44; this study shows that there are no significant differences when prescribing antihypertensive medication in patients with a recent stroke based on whether or not they are VEP and&#44; what&#8217;s more&#44; this approach has not changed in the last two decades&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">Indeed&#44; this concern has been reflected in various guidelines&#8217; recommendations on hypertension&#58; the 2017 American Heart Association &#40;AHA&#41; guidelines recommend a cautious approach to controlling blood pressure in very old&#44; frail patients<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a>&#59; the 2018 European Society of Hypertension and the European Society of Cardiology &#40;ESH&#47;ESC&#41;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> guidelines recommend individualized targets for this population based on the individual&#8217;s functional status instead of just age&#59; and the 2019 National Institute for Health and Care Excellence &#40;NICE&#41; guidelines recommend a target BP of &#60;150&#47;90&#8239;mmHg in those older than 80 years and an individualized decision for those who are frail or who have multimorbidity<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a>&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">In fact&#44; observational evidence seems to indicate that older adults in general may have a greater risk of adverse effects related to a reduction in blood pressure&#44; including falls and even greater mortality&#46; This seems to be due to age-related factors&#44; such as greater arterial stiffness and reduced baroreceptor reflexes which are not present in younger individuals<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a>&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">Nevertheless&#44; in a recent meta-analysis which included seven trials on the secondary prevention of stroke with 38&#44;596 participants&#44; of which 2336 &#40;6&#46;1&#37;&#41; were &#8805;80 years of age&#44; VEP had a greater risk of hypotension&#44; but there was no statistical increase in risk of falls&#44; syncope&#44; or mortality<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a>&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">Regarding the use of statins in VEP with recent stroke&#44; it must be taken into account that the evidence on treatment with statins for the prevention of new strokes and other cardiovascular events after a stroke is fundamentally based on trials that were not specifically designed for this population&#46; Indeed&#44; the mean age in the main trials on statins in secondary stroke prevention&#44; such as the Stroke Prevention by Aggressive Reduction in Cholesterol Levels &#40;SPARCL&#41;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a>&#44; the Japan Statin Treatment Against Recurrent Stroke &#40;J-STARS&#41;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a>&#44; or the Treat Stroke to Target &#40;TST&#41; studies<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a>&#44; were 63&#44; 66&#44; and 66 years&#44; respectively&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">It is true that there are specific subanalyses on the older population&#46; A posterior analysis of the SPARCL study<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> corroborates the effectiveness of statins in older adult patients &#40;&#8805;65 years&#41; with a recent ischemic stroke&#46; The study included 2249 patients in the older adult group with a mean age of 72&#46;4 years&#44; although only 4&#46;6&#37; were &#8805;80 years&#46; The risk of stroke and TIA &#40;hazard ratio &#40;HR&#41;&#58; 0&#46;79&#59; <span class="elsevierStyleItalic">p</span> &#61; 0&#46;01&#41; and major coronary events &#40;HR&#58; 0&#46;68&#59; <span class="elsevierStyleItalic">p</span> &#61; 0&#46;035&#41; were also clearly reduced in the group of older adult patients&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">In addition&#44; in a meta-analysis<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> of 28 randomized controlled trials in patients with an indication of secondary prevention with statins&#44; starting statins was associated with a 20&#37; reduction in the risk of cardiovascular disease in all age groups&#44; including in those older than 75 years&#44; although neither stroke nor overall mortality were reduced in this subgroup&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">Recently&#44; in an observational study<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> of 3157 patients &#8805;80 years&#44; starting statins following an ischemic stroke was associated with a reduction in the risk of new vascular events &#40;which included nonfatal myocardial infarction&#44; nonfatal stroke&#44; and cardiovascular mortality&#58; &#40;relative risk &#40;RR&#41;&#58; 0&#46;80 &#40;95&#37; CI 0&#46;62&#8211;1&#46;02&#41;&#41; and all-cause mortality &#40;RR 0&#46;67 &#40;95&#37; CI 0&#46;57&#8211;0&#46;80&#41;&#41;&#46; The number needed to treat for the primary outcome measure was 64 patients during a mean follow-up time of 3&#46;9 years and 19 patients for all-cause mortality&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">Therefore&#44; although there is no clear indication in this age group&#44; there is a growing body of evidence in favor of the use of statins in this population&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">This is reflected in results based on clinical practice&#46; There has been a very significant increase in the use of statins in VEP&#44; from an initial value of 5&#37; to more than 80&#37; in the last period&#44; and in particular in high-intensity statins&#44; which are used in nearly 70&#37; of cases&#46; Therefore&#44; although there were differences in the prescribing of statins between VEP and the group of those younger than 80 years in the first two periods&#44; these differences disappeared in the last period analyzed&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">In regard to the use of antithrombotic therapy&#44; this study showed how differences in the use of these drugs due to the patient&#8217;s age have disappeared over the years&#46;</p><p id="par0215" class="elsevierStylePara elsevierViewall">It is well known that AF plays an increasingly important role in the etiopathogenesis of ischemic stroke with age&#46; In fact&#44; the results from this cohort coincide with other studies which indicate that AF and hypertension are the only vascular risk factors that are more common among VEP if compared to other age groups<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11&#44;12</span></a>&#46; Indeed&#44; AF is an older adult&#8217;s disease&#44; with a prevalence and incidence that increase with age&#58; it affects 10&#37; of the general population &#8805;80 years and increases exponentially among the oldest patients<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a>&#46;</p><p id="par0220" class="elsevierStylePara elsevierViewall">Therefore&#44; the use of anticoagulants is going to be more necessary in VEP&#46; Nevertheless&#44; anticoagulants have traditionally been underused in VEP for various reasons&#58; first&#44; due to a lack of evidence in this population &#40;older adult patients were underrepresented in historical randomized clinical trials on AF in the last two decades&#41; and second&#44; because physicians are concerned about safety problems such as risk of bleeding or disability in VEP&#44; especially in light of the fact that these patients would have to periodically control of their international normalized ratio &#40;INR&#41; levels&#44; which may be a burden for these patients<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a>&#46;</p><p id="par0225" class="elsevierStylePara elsevierViewall">On the contrary&#44; numerous more recent studies have demonstrated the efficacy and safety of anticoagulants in VEP&#46; The Birmingham Atrial Fibrillation Treatment of the Aged &#40;BAFTA&#41;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> study&#44; which specifically investigated 973 older adult patients &#40;&#8805;75 years&#41; with AF who were randomly assigned to receive warfarin or aspirin 75&#8239;mg&#44; demonstrated that warfarin reduced thromboembolism by &#62;50&#37; with no significant differences in major bleeding or intracranial hemorrhage&#46;</p><p id="par0230" class="elsevierStylePara elsevierViewall">In the small trial Warfarin Versus Aspirin for Stroke Prevention in Octogenarians With AF &#40;WASPO&#41;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a>&#44; conducted in octogenarians&#44; there were no numerical differences in the number of strokes between warfarin and aspirin&#44; but there was a significantly greater rate of adverse safety effects &#40;including bleeding&#41; in patients treated with aspirin&#46;</p><p id="par0235" class="elsevierStylePara elsevierViewall">A recent nationwide cohort study in Taiwan<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> which investigated the risk of ischemic stroke and intracranial hemorrhage &#40;ICH&#41; and the net clinical benefit of treatment with anticoagulants in 15&#44;756 patients with AF aged &#8805;90 years demonstrated that the use of warfarin was associated with a lower risk of ischemic cerebrovascular accident with no differences in the risk of ICH compared to treatment without warfarin &#40;receiving antiplatelet therapy or not receiving therapy&#41;&#46;</p><p id="par0240" class="elsevierStylePara elsevierViewall">In this regard&#44; and in line with the new evidence&#44; our study shows how the use of anticoagulants in VEP also increased significantly in the last 20 years from 16&#46;5&#37; to 53&#46;1&#37; &#40;<span class="elsevierStyleItalic">p</span> &#61; 0&#46;001&#41;&#44; with their use in VEP and younger patients becoming equal over time&#46;</p><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Limitations of the study</span><p id="par0245" class="elsevierStylePara elsevierViewall">The possible limitations of this study are those inherent to retrospective studies&#44; such as&#44; for example&#44; the under-recording of disease or possible variability among professionals and patients&#44; given the observational design&#46; In addition&#44; as it was not included in the majority of medical records&#44; a functional&#44; social&#44; or cognitive evaluation of patients was not able to be recorded&#46; These data could add further nuance to the lack of use of some specific therapies in this population of VEP&#46;</p><p id="par0250" class="elsevierStylePara elsevierViewall">Nevertheless&#44; this study has multiple strengths&#58; it is a multicenter study which included the three main hospitals in Seville&#44; Spain&#59; the number of patients studied&#59; and the comprehensive registry of the medication prescribed&#44; among others&#46; It is a faithful reflection of what has occurred in routine clinical practice&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Conclusions</span><p id="par0255" class="elsevierStylePara elsevierViewall">At present&#44; VEP represent one-fourth of all patients with stroke discharged from the hospitals included in the study&#46; It is known that compared to younger patients&#44; VEP have a higher mortality rate and a greater risk of recurrent cardiovascular disease&#46; However&#44; secondary prevention therapies have been shown to be effective in this age group&#46;</p><p id="par0260" class="elsevierStylePara elsevierViewall">This study confirms that there is a progressive increase in the proportion of VEP in the total number of patients with stroke&#46; In addition&#44; there has been clear improvement in the prescribing of drugs for secondary stroke prevention in VEP in the last two decades and it approaches the measures used in younger patients&#46;</p><p id="par0265" class="elsevierStylePara elsevierViewall">Although additional studies are needed to evaluate how these changes translate into an improvement in clinical outcomes or quality of life for patients&#44; these results also show that there is still room for improvement in preventive therapy&#46;</p><p id="par0270" class="elsevierStylePara elsevierViewall">Therefore&#44; given the increasing contribution of VEP to the burden of disease of stroke and that this will require a greater effort from healthcare systems&#44; it is necessary to continue improving secondary prevention measures in this population segment&#44; which will surely benefit public health&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Funding</span><p id="par0275" class="elsevierStylePara elsevierViewall">No type of funding was received for the creation of this article&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Conflicts of interest</span><p id="par0280" class="elsevierStylePara elsevierViewall">The authors declare that they do not have any conflicts of interest&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Population aging has caused an increase in strokes in very elderly patients &#40;VEP&#41;&#46; We assess how secondary prevention of ischemic stroke has changed in VEP in recent decades&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Method</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Retrospective study of discharges due to ischemic stroke in the Virgen Macarena&#44; Virgen del Rocio and Valme hospitals in Seville &#40;Spain&#41;&#44; during the periods 1999&#8211;2001&#44; 2014&#8722;16 and 2019&#8722;2020&#46; VEP were considered those with &#8805;80 years&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Result</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">We studied 1806 patients&#44; 349 &#40;19&#46;3&#37;&#41; were VEP&#46; Over the years&#44; VEPs have doubled &#40;13&#46;5&#37; vs&#46; 25&#46;9&#37; and 28&#37; <span class="elsevierStyleItalic">p</span> &#61; 0&#46;0001&#41; and age has increased &#40;83&#46;3&#8239;&#177;&#8239;3 vs&#46; 84&#46;1&#8239;&#177;&#8239;3 vs&#46; 85&#46;2&#8239;&#177;&#8239;4 <span class="elsevierStyleItalic">p</span> &#61; 0&#46;001&#41;&#46; Comparing the periods&#44; the VEPs have more hypertension &#40;69&#46;9&#37; vs&#46; 84&#46;8&#37; vs&#46; 84&#46;6&#37;&#59; <span class="elsevierStyleItalic">p</span> &#61; 0&#46;0001&#41; and dyslipidemia &#40;12&#37; vs&#46; 41&#46;7&#37; vs&#46; 52&#46;3&#37;&#59; p&#8239;&#61;&#8239;0&#46;0001&#41; and have prescribed more antihypertensives &#40;69&#46;1&#37; vs&#46; 86&#46;7&#37; vs&#46; 92&#46;3&#37;&#59; <span class="elsevierStyleItalic">p</span> &#61; 0&#46;0001&#41;&#44; statins &#40;5&#46;3&#37; vs&#46; 78&#37; vs&#46; 81&#46;5&#37;&#59; <span class="elsevierStyleItalic">p</span> &#61; 0&#46;0001&#41; and anticoagulants &#40;16&#46;5&#37; vs&#46; 19&#46;4&#37; vs&#46; 53&#46;1&#37;&#59; <span class="elsevierStyleItalic">p</span> &#61; 0&#46;001&#41;&#44; increasing the number of antihypertensives &#40;1&#8239;&#177;&#8239;0&#46;9 vs&#46; 1&#46;6&#8239;&#177;&#8239;0&#44; 9 vs&#46; 1&#46;9&#8239;&#177;&#8239;0&#46;8 drugs <span class="elsevierStyleItalic">p</span> &#61; 0&#46;0001&#41;&#44; and high-intensity statins &#40;2&#46;3&#37; vs&#46; 42&#46;7 vs&#46; 69&#46;2&#37; <span class="elsevierStyleItalic">p</span> &#61; 0&#46;0001&#41;&#46; Comparing the VEPs with the younger ones&#44; there were no differences in antihypertensive treatment in any period&#44; there were differences in antithrombotic treatment in the first period&#44; and with statins the differences were maintained until the end&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">In the last 20 years the number of VEPs has doubled&#44; exceeding a quarter of the discharges&#46; Although there is improvement in secondary stroke prevention in VEPs&#44; there is room for improvement&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducci&#243;n</span><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">El envejecimiento poblacional ha provocado un aumento de los ictus en los pacientes muy ancianos &#40;PMA&#41;&#46; Valoramos c&#243;mo ha cambiado la prevenci&#243;n secundaria del ictus isqu&#233;mico en PMA en las &#250;ltimas d&#233;cadas&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todo</span><p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Estudio retrospectivo de las altas por ictus isqu&#233;mico en los hospitales Virgen Macarena&#44; Virgen del Roc&#237;o y Virgen de Valme de Sevilla &#40;Espa&#241;a&#41;&#44; durante los per&#237;odos 1999-2001&#44; 2014-2016 y 2019-2020&#46; Se consider&#243; PMA&#8239;&#8805;&#8239;80 a&#241;os&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultado</span><p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Estudiamos a 1&#46;806 pacientes&#44; de los cuales 349 &#40;19&#44;3&#37;&#41; eran PMA&#46; Con los a&#241;os se han duplicado los PMA &#40;13&#44;5&#37; vs&#46; 25&#44;9&#37; y 28&#37;&#59; <span class="elsevierStyleItalic">p</span> &#61; 0&#44;0001&#41; y aumentado la edad &#40;83&#44;3&#8239;&#177;&#8239;3 vs&#46; 84&#44;1&#8239;&#177;&#8239;3 vs&#46; 85&#44;2&#8239;&#177;&#8239;4&#59; <span class="elsevierStyleItalic">p</span> &#61; 0&#44;001&#41;&#46; Comparando los per&#237;odos&#44; los PMA tienen m&#225;s hipertensi&#243;n &#40;69&#44;9 vs&#46; 84&#44;8&#37; vs&#46; 84&#44;6&#37;&#59; <span class="elsevierStyleItalic">p</span> &#61; 0&#44;0001&#41; y dislipidemia &#40;12 vs&#46; 41&#44;7&#37; vs&#46; 52&#44;3&#37;&#59; <span class="elsevierStyleItalic">p</span> &#61; 0&#44;0001&#41; y tienen prescritos m&#225;s antihipertensivos &#40;69&#44;1&#37; vs&#46; 86&#44;7&#37; vs&#46; 92&#44;3&#37;&#59; <span class="elsevierStyleItalic">p</span> &#61; 0&#44;0001&#41;&#44; estatinas &#40;5&#44;3&#37; vs&#46; 78&#37; vs&#46; 81&#44;5&#37;&#59; <span class="elsevierStyleItalic">p</span> &#61; 0&#44;0001&#41; y anticoagulantes &#40;16&#44;5&#37; vs&#46; 19&#44;4&#37; vs&#46; 53&#44;1&#37;&#59; <span class="elsevierStyleItalic">p</span> &#61; 0&#44;001&#41;&#59; tambi&#233;n ha aumentado el n&#250;mero de antihipertensivos &#40;1&#8239;&#177;&#8239;0&#44;9 vs&#46; 1&#44;6&#8239;&#177;&#8239;0&#44;9 vs&#46; 1&#44;9&#8239;&#177;&#8239;0&#44;8 f&#225;rmacos&#59; <span class="elsevierStyleItalic">p</span> &#61; 0&#44;0001&#41; y de estatinas de alta intensidad &#40;2&#44;3&#37; vs&#46; 42&#44;7&#37; vs&#46; 69&#44;2&#37;&#59; <span class="elsevierStyleItalic">p</span> &#61; 0&#44;0001&#41;&#46; Comparando los PMA con pacientes m&#225;s j&#243;venes&#44; no hubo diferencias en el tratamiento antihipertensivo en ning&#250;n per&#237;odo&#44; aunque s&#237; hubo diferencias en el tratamiento antitromb&#243;tico en el primer per&#237;odo y con las estatinas las diferencias se mantuvieron hasta el final&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">En los &#250;ltimos 20 a&#241;os el n&#250;mero de PMA se ha duplicado y supera la cuarta parte de las altas&#46; Aunque existe mejor&#237;a en la prevenci&#243;n secundaria del ictus en los PMA&#44; existe margen de mejora&#46;</p></span>"
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">25&#46;9&#37;&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
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                  \t\t\t\t">28&#46;0&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#46;0001</span>&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="elsevierStyleBold">Age &#40;SD&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">83&#46;3&#8239;&#177;&#8239;3&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">84&#46;1&#8239;&#177;&#8239;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">85&#46;2&#8239;&#177;&#8239;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleBold">0&#46;001</span>&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>Sex &#40;female&#41;&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">63&#46;8&#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">60&#46;3&#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">61&#46;5&#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#46;828&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="elsevierStyleBold">Hypertension</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">69&#46;9&#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">84&#46;8&#37;&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
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                  \t\t\t\t">74&#46;6&#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleBold">0&#46;0004</span>&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>Diabetes&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">39&#46;8&#37;&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
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                  \t\t\t\t">38&#46;4&#37;&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
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                  \t\t\t\t">35&#46;4&#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">0&#46;832&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="elsevierStyleBold">Hypercholesterolemia</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">12&#46;0&#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">41&#46;7&#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">52&#46;3&#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleBold">0&#46;0001</span>&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>Tobacco use&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">6&#46;0&#37;&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">10&#46;5&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">6&#46;2&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#46;327&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>Atrial fibrillation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">36&#46;8&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">34&#46;4&#37;&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
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                  \t\t\t\t">27&#46;7&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#46;442&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>Ischemic heart disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">22&#46;6&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">15&#46;9&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">23&#46;1&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#46;282&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>Stroke&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">33&#46;1&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">30&#46;5&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">32&#46;3&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#46;456&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>Peripheral arterial disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">2&#46;9&#37;&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
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                  \t\t\t\t">3&#46;3&#37;&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
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                  \t\t\t\t">3&#46;1&#37;&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
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                  \t\t\t\t">0&#46;845&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="elsevierStyleBold">Acetylsalicylic acid</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">58&#46;6&#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">53&#46;7&#37;&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
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                  \t\t\t\t">41&#46;5&#37;&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
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                  \t\t\t\t"><span class="elsevierStyleBold">0&#46;002</span>&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="elsevierStyleBold">Oral anticoagulants</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16&#46;5&#37;&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
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">19&#46;4&#37;&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
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                  \t\t\t\t">53&#46;1&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#46;0001</span>&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="elsevierStyleBold">Statins</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#46;3&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">78&#46;0&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">81&#46;5&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#46;0001</span>&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="elsevierStyleBold">High-intensity statins</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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