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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Rheumatoid arthritis &#40;RA&#41; is a chronic autoimmune disease characterized by systemic inflammation with a prevalence of 0&#46;5&#8211;1&#37; in the adult population&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">1</span></a> It is characterized by excess morbidity and mortality from cardiovascular disease&#46;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">2&#8211;4</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Multiple mechanisms have been proposed to explain the increased cardiovascular risk observed in the RA population&#46;<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">5&#44;6</span></a> An increased prevalence of traditional cardiovascular risk factors is found in RA patients&#46; In addition&#44; the inflammatory process through mediators such as cytokines implicated in RA would play an important role in the development of atherosclerosis&#46; Likewise&#44; the action of autoantibodies &#91;i&#46;e&#46; anti-citrullinated protein antibodies &#40;ACPA&#41; and rheumatoid factor &#40;RF&#41;&#93; on the arterial wall would also explain in part the increased cardiovascular risk&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">However&#44; the estimation of cardiovascular risk in subjects with RA has some peculiarities&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">7</span></a> The classical risk scores used to calculate cardiovascular risk have limitations&#44; due to the fact that they were not developed specifically for RA&#46; Most traditional cardiovascular risk prediction models developed for the general population do not include non-traditional cardiovascular risk factors such as autoantibodies or systemic inflammation&#46; Then&#44; when applied to patients with RA these classic scores have been found to significantly underestimate the true risk of cardiovascular disease&#46; Inadequate screening for risk factors or cardiovascular disease would aggravate the situation&#46; The low frequency of statins indication &#40;or the administration of a lower dose&#41; may be the result of this poor risk assessment&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Several strategies have been proposed to optimize cardiovascular risk stratification in RA subjects&#46; One of them&#44; recommended by the Consensus of Argentine Society of Cardiology and the European League Against Rheumatism &#40;EULAR&#41;&#44; is to adjust the risk calculated by a multiplying factor &#40;1&#46;5&#215;&#41; and follow the general recommendations for statin therapy&#46;<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">8&#44;9</span></a> Following The National Institute for Health and Care Excellence &#40;NICE&#41; recommendations&#44; another option is to use the QRISK-3 score&#44; which includes in addition to traditional risk factors&#44; the history of RA&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">10</span></a> Considering RA as a clinical situation that favors the indication of statins in intermediate risk subjects is proposed by a third strategy recommended by the American College of Cardiology&#47;American Heart Association &#40;ACC&#47;AHA&#41; guidelines for cholesterol management&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">11</span></a> Finally&#44; a recent position paper of the Working Group on Cardiovascular Pharmacotherapy of the European Society of Cardiology &#40;ESC&#41; introduces for the first time a new algorithm for estimation of cardiovascular risk in RA patients and sets therapeutic goals for low-density lipoprotein cholesterol &#40;LDL-C&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">12</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Therefore&#44; the objectives of the present study were&#58; &#40;1&#41; to estimate the cardiovascular risk by different strategies in patients with RA&#59; &#40;2&#41; to analyze which proportion of patients would be candidates to receive statin therapy and determine the reasons why they should receive them according to different strategies&#59; &#40;3&#41; to identify how many patients meet the recommended lipid goals according to ESC algorithm&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Material and methods</span><p id="par0030" class="elsevierStylePara elsevierViewall">A cross-sectional study from a secondary database was performed&#46; All patients older than 18 years with a diagnosis of RA &#40;fulfilling ACR&#47;EULAR 2010 criteria&#41;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">13</span></a> from January 1st&#44; 2010 to December 30th&#44; 2019 were included&#46; Date of diagnosis was considered when first fulfilling ACR&#47;EULAR 2010 criteria&#46; For those patients diagnosed previously to this criteria publication date&#44; we retrospectively reviewed their medical history identifying date of criteria fulfillment&#46; The sample was obtained from two university hospitals and a network of 21 associated peripheral centers distributed in Buenos Aires City&#44; Argentina&#46; The medical histories of the patients included were revised&#44; obtaining information about RA characteristics&#44; cardiovascular risk factors and medication received at the time of the last registered rheumatologic visit&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Colorimetric and turbidimetric assays were used to measure non-fasting plasma levels of triglycerides&#44; cholesterol bound to high-density lipoproteins &#40;HDL-C&#41; and total cholesterol&#46; The Friedewald equation was used to calculate LDL-C&#46; The blood levels of glucose&#44; creatinine&#44; glycated hemoglobin A1C and estimated glomerular filtration rate &#40;eGFR&#41; were measured according to standardized tests&#46; All patients performed the tests in a single laboratory with the same methodology&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Familial hypercholesterolaemia was diagnosed using clinical characteristics &#40;Dutch score &#8805;8 points&#41;&#46; Moderate or severe chronic renal failure was defined when eGFR was between 30 and 59 or less than 30<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&#44; respectively&#46; Diabetes was diagnosed by one of the following criteria&#58; fasting blood glucose level<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>126<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#44; oral glucose tolerance test &#40;2<span class="elsevierStyleHsp" style=""></span>h&#41;<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>200<span class="elsevierStyleHsp" style=""></span>mg&#47;dl or glycated hemoglobin A1C test<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>6&#46;5&#37; high blood pressure was diagnosed when systolic blood pressure was &#8805;140<span class="elsevierStyleHsp" style=""></span>mmHg or diastolic blood pressure was &#8805;90<span class="elsevierStyleHsp" style=""></span>mmHg&#46; A history of cardiovascular disease was considered when the patient had coronary disease &#40;acute myocardial infarction&#44; unstable angina&#44; stable chronic angina&#44; myocardial revascularization surgery&#44; coronary angioplasty&#41;&#44; stroke&#44; or peripheral arterial disease&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Four cardiovascular 10-years risk scores were calculated in subjects without cardiovascular disease&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">1&#46;</span><p id="par0050" class="elsevierStylePara elsevierViewall">The QRISK-3 score estimates the risk of atherosclerotic cardiovascular events used by NICE guidelines&#44; defining the population &#8220;at risk&#8221; when the calculated risk is &#8805;10&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">10&#44;14</span></a></p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">2&#46;</span><p id="par0055" class="elsevierStylePara elsevierViewall">The Framingham score for atherosclerotic cardiovascular disease events&#44; defining low&#44; moderate&#44; and high risk as values &#60;10&#37;&#44; between 10&#37; and 19&#37;&#44; and &#8805;20&#37;&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">15</span></a> The risk values calculated by the Framingham score ware adjusted by a multiplication factor of 1&#46;5&#44; following the Argentine recommendations&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">9</span></a></p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">3&#46;</span><p id="par0060" class="elsevierStylePara elsevierViewall">The atherosclerotic cardiovascular disease &#40;ASCVD&#41; calculator used by the ACC&#47;AHA guidelines&#44; defining low&#44; borderline&#44; moderate and high risk as values &#60;5&#37;&#44; between 5&#37; and 7&#46;5&#37;&#44; between 7&#46;5&#37; and 19&#37; and &#8805;20&#37;&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">11</span></a></p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">4&#46;</span><p id="par0065" class="elsevierStylePara elsevierViewall">The Systematic Coronary Risk Evaluation &#40;SCORE&#41; estimates the risk of cardiovascular fatal events used by the 2019 ESC guidelines&#46; Risk &#60;1&#37;&#44; between 1 and 4&#46;9&#37;&#44; 5 and 9&#46;9&#37; or &#8805;10&#37; was classified as low&#44; moderate&#44; high or very high&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">16</span></a></p></li></ul></p><p id="par0070" class="elsevierStylePara elsevierViewall">Applying recommendations of NICE guidelines&#44; patients with a QRISK-3<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>10&#37; should receive statins&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">14</span></a> Also statins should be indicated in patients with chronic renal failure &#40;eGFR less than 60<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&#41;&#44; familial hypercholesterolemia or type I diabetes&#44; despite their calculated risk score&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Considering the Argentine Consensuses&#44; the following patient groups were considered candidates for statin therapy&#58; &#40;a&#41; patients with diabetes&#59; &#40;b&#41; patients with an LDL-C level &#62;190<span class="elsevierStyleHsp" style=""></span>mg&#47;dl &#40;with or without familial hypercholesterolemia&#41;&#59; &#40;c&#41; subjects with a calculated Framingham score &#8805;20&#37;&#59; &#40;d&#41; patients with a calculated Framingham score &#8805;10&#37; and &#60;20&#37; with one or more risk factors&#59; &#40;e&#41; subjects with moderate to severe chronic renal insufficiency &#40;eGFR between 30 and 59 or less than 30<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&#44; respectively&#41; without hemodialysis&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">9</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">Applying the 2018 ACC&#47;AHA guidelines&#44; the following patient groups were considered candidates for statin therapy&#58; &#40;a&#41; patients 40&#8211;75 years of age with diabetes and LDL-C &#8805;70<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#59; &#40;b&#41; patients 20&#8211;75 years of age with an LDL-C level &#62;190<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#59; &#40;c&#41; adults 40&#8211;75 years of age without diabetes and ASCVD risk &#8805;20&#37;&#59; &#40;d&#41; adults 40&#8211;75 years of age without diabetes and ASCVD risk of 7&#46;5&#8211;19&#46;9&#37; &#40;intermediate risk&#41; with a risk-enhancing factors&#46; Risk-enhancing factors include RA&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">11</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">Following the ESC position paper&#44; the population was classified into 4 risk categories&#58; low risk &#40;SCORE &#60;1&#37;&#41;&#59; moderate risk &#40;SCORE &#8805;1&#37; and &#60;5&#37;&#41;&#59; high risk &#40;SCORE &#8805;5&#37; and &#60;10&#37;&#44; diabetes without target organ damage or other major cardiovascular risk factor&#44; moderate chronic kidney disease&#44; markedly elevated single cardiovascular risk factor&#41; and very high risk &#40;SCORE &#8805;10&#44; diabetes with target organ damage or other major cardiovascular risk factor&#44; severe chronic kidney disease or history of cardiovascular disease&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">12</span></a> Additionally&#44; the proposed algorithm by this Working Group stratifies RA according to RA-related characteristics influencing cardiovascular risk&#46; &#8220;Low-risk RA&#8221; &#40;LR-RA&#41; is defined as seronegative&#44; non-erosive RA in patients without extra-articular manifestations&#44; in long-term &#40;&#62;1 year&#41; remission &#40;CDAI<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>2&#46;8 or SDAI<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>3&#46;3 or DAS28-ESR<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>2&#46;6&#41;&#44; without active arthritis or persistently elevated C-reactive protein or erythrocyte sedimentation rate&#44; with well-preserved physical function &#40;HAQ-DI<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>0&#46;5&#41;&#44; without high cumulative disease activity&#44; not currently using glucocorticoids and without high cumulative glucocorticoid dose&#46; All other patients are classified as &#8220;High-risk RA&#8221; &#40;HR-RA&#41;&#46; Patients with cardiovascular risk-enhancing RA-related factors &#40;HR-RA&#41; should be considered as having cardiovascular risk-category that is one level higher compared to the general population&#46; For the low and moderate risk categories the recommended LDL-C goal is &#60;115<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#46; If the patient is classified as &#8220;HR-RA&#8221;&#44; the proposed LDL-C goal is &#60;100<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#46; For the high-risk category&#44; the recommended LDL-C goal is &#60;100<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#46; If the patient is classified as &#8220;HR-RA&#8221;&#44; the proposed LDL-C goal is &#60;70<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#46; Finally&#44; for the very high-risk category the recommended LDL-C goal is &#60;70<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Following the recommendations of all strategies&#44; we consider for the present analysis that patients in secondary prevention should receive high intensity statins&#46; It was defined as high intensity statins if they were able to reduce &#8805;50&#37; the LDL-C level &#40;atorvastatin 40&#8211;80<span class="elsevierStyleHsp" style=""></span>mg or rosuvastatin 20&#8211;40<span class="elsevierStyleHsp" style=""></span>mg per day&#41;&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Finally&#44; those patients already receiving statin therapy were considered as subjects with appropriate prescription according to all guidelines&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Statistical analysis</span><p id="par0100" class="elsevierStylePara elsevierViewall">Continuous data were compared between groups using the t test for normal distribution or the Mann&#8211;Whitney&#8211;Wilcoxon test for non-normal distribution&#46; The analysis of categorical data was performed using the chi-square test&#46; Continuous variables are given as mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>standard deviation or median &#91;25&#8211;75 interquartile range &#40;IQR&#41;&#93; according to the distribution of the variables&#44; while categorical variables are given as percentages&#46; The agreement between different lipid management strategies in selecting patients with statin indication was analyzed&#44; using the Cohen kappa index&#46; Mild&#44; discrete&#44; moderate&#44; significant&#44; or almost perfect agreement was defined if the kappa value was &#60;0&#46;20&#44; between 0&#46;21 and 0&#46;40&#44; 0&#46;41 and 0&#46;60&#44; 0&#46;61 and 0&#46;80&#44; and 0&#46;81 and 1&#44; respectively&#46; A value of <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05 was considered statistically significant&#46; STATA 13&#46;0 software packages were used for statistical analysis&#46;</p></span></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Results</span><p id="par0105" class="elsevierStylePara elsevierViewall">A total of 420 patients &#40;mean age 69&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>13&#46;8 years&#44; 85&#46;5&#37; women&#41; were included in the study&#46; Globally&#44; the prevalence of type 2 diabetes mellitus in the population was 7&#46;6&#37; and 51&#46;4&#37; of patients were hypertensive&#46; The prevalence of current smoking was 6&#46;4&#37; and 18&#46;1&#37; of the population showed history of cardiovascular disease&#46; The average time from RA diagnosis was 12&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#46;7 years&#46; The baseline characteristics of the population are described in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0110" class="elsevierStylePara elsevierViewall">The median adjusted Framingham score was 12&#46;0&#37; &#40;IQR 8&#46;0&#8211;21&#46;9&#37;&#41;&#46; According to Argentinean Consensus&#44; 22&#46;1&#37;&#44; 23&#46;7&#37;&#44; and 54&#46;2&#37; of the population was classified at low&#44; moderate&#44; or high risk&#46; Likewise&#44; the median ASCVD risk calculator was 8&#46;2&#37; &#40;IQR 3&#46;1&#8211;12&#46;3&#37;&#41;&#44; and 20&#46;6&#37;&#44; 6&#46;9&#37;&#44; 27&#46;0&#37;&#44; and 45&#46;5&#37; of the subjects were classified at low&#44; borderline&#44; moderate&#44; or high risk according to AHA&#47;ACC guidelines&#46; The median QRISK-3 values were 17&#46;6&#37; &#40;IQR 9&#46;5&#8211;29&#46;4&#37;&#41; and 79&#46;2&#37; of subjects were classified &#8220;at risk&#8221; following the recommendations of the NICE guidelines&#46; The median SCORE risk was 1&#46;0&#37; &#40;IQR 0&#46;5&#8211;1&#46;0&#37;&#41;&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">In total&#44; 88&#46;4&#37; were considered HR-RA patients&#46; Patients with high rheumatological risk were younger &#40;68&#46;9 vs&#46; 75&#46;4 years&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;002&#41;&#44; although no significant differences were observed in the prevalence of high blood pressure &#40;51&#46;5&#37; vs&#46; 54&#46;2&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;72&#41;&#44; current smoking &#40;6&#46;8&#37; vs&#46; 2&#46;1&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;38&#41;&#44; diabetes &#40;8&#46;2&#37; vs&#46; 4&#46;2&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;33&#41; or obesity &#40;22&#46;7&#37; vs&#46; 18&#46;6&#37;&#41;&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">When considering cardiovascular and rheumatological risks according to the ESC guidelines&#44; 3&#46;0&#37;&#44; 37&#46;4&#37;&#44; and 59&#46;6&#37; of patients were stratified at low-moderate&#44; high&#44; or very high risk&#44; respectively&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Increased use of statins was observed in patients in secondary prevention&#44; compared to subjects in primary prevention &#40;48&#46;7&#37; vs&#46; 24&#46;7&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; However&#44; only 19&#46;4&#37; of patients with cardiovascular history received high intensity statins&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">In those RA patients not taking statins&#44; several strategies in cardiovascular prevention were analyzed&#46; Applying the ACC&#47;AHA guidelines &#40;based on ASCVD score&#41; and the Argentine Consensuses &#40;based on adjusted Framingham score&#41;&#44; 26&#46;9&#37; and 26&#46;5&#37; of the population were eligible for statin therapy&#44; respectively&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">According to the NICE guidelines and based on the QRISK-3 score&#44; the use of statins was recommended in 41&#46;1&#37; of cases&#46; When the ESC guidelines were applied &#40;based on SCORE risk calculator and rheumatological risk&#41;&#44; statins were recommended in 18&#46;2&#37; of patients&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">The graphical representation of expected and observed statin use by four strategies is shown in <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0145" class="elsevierStylePara elsevierViewall">The concordance between four strategies in selecting patients with statin indication was variable &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0150" class="elsevierStylePara elsevierViewall">In patients without lipid-lowering treatment&#44; the main reason for the indication of statin treatment was the history of cardiovascular disease when we applied Argentine Consensuses&#44; ESC guidelines or ACC&#47;AHA recommendations&#46; However&#44; the main reason for the indication of statin treatment was the &#8220;at risk&#8221; categorization of the population when we applied NICE guidelines&#46; The reasons why statin therapy should be indicated using different strategies are shown in <a class="elsevierStyleCrossRefs" href="#fig0010">Figs&#46; 2 and 3</a>&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0155" class="elsevierStylePara elsevierViewall">Finally&#44; following the recommendations of the Working Group of the ESC&#44; and considering the cardiovascular and rheumatological risks estimated&#44; we analyzed the achievement of the recommended LDL-C goals in the total population &#40;treated or not with statins&#41;&#46; Then&#44; 50&#46;0&#37;&#44; 46&#46;2&#37; and 15&#46;9&#37; of the patients with low-moderate&#44; high or very high risk achieved the suggested lipid goals &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#41;&#46;</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Discussion</span><p id="par0160" class="elsevierStylePara elsevierViewall">This work evaluated four different strategies for cardiovascular stratification and statin indication in a population with RA&#46; Also&#44; we analyzed the application of a new algorithm that established LDL-C goals for the first time in this population&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">All current guidelines on the prevention of cardiovascular disease in clinical practice recommend the assessment of cardiovascular risk&#46; Patients with a higher cardiovascular risk should receive more intense interventions&#46; However&#44; cardiovascular risk algorithms developed for the general population are not accurate in RA patients&#46; These predictive tools were not specifically developed in patients with RA and the performance is suboptimal because traditional cardiovascular risk factors do not fully explain the increased cardiovascular risk&#46; Inflammation contributes to atherosclerosis plaque vulnerability and clinical atherothrombotic events&#44; but current risk functions do not represent this contributing factor&#46; Consequently&#44; cardiovascular risk is often underestimated&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">17</span></a></p><p id="par0170" class="elsevierStylePara elsevierViewall">Various strategies have been proposed to deal with this problem&#46; One of them uses a correction factor to adjust the estimated risk&#46; Another of them includes in addition to the variables commonly used in most risk scores&#44; the history of RA&#46; Considering RA as a potentiating factor in intermediate risk subjects is proposed by a third strategy&#46; Finally&#44; establishing cardiovascular and rheumatological risks jointly to determine lipid goals is a novel recommendation&#46; In this study&#44; we evaluate all the different strategies proposed&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">Our data shows that cardiovascular stratification varies according to the strategies used&#46; However&#44; the proportion of subjects classified as &#8220;at risk&#8221;&#44; high risk or very high risk was considerable&#44; regardless of the strategy used&#46; Previous reports have shown that the concordance between the different scores was variable in this population&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">18</span></a> Similarly&#44; Jafri et al&#46; showed that approximately 10&#37; of RA subjects had discordant 10-year cardiovascular risk scores when comparing the Framingham score with ACC&#47;AHA score&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">19</span></a> These findings did not significantly change when a 1&#46;5 multiplier was applied to the Framingham score&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">Strong evidence shows that the reduction of LDL-C using statin treatment leads to a significant decrease in the cardiovascular risk&#46; However&#44; the evidence in RA patients is limited&#46; A post hoc analysis of two prospective trials of statins showed that those subjects with and without inflammatory joint disease experience comparable lipid-lowering effects and cardiovascular risk reduction after intensive treatment with statins&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">20</span></a> Likewise&#44; Schoenfeld et al&#46; conducted an incident user cohort study with time-stratified propensity score matching using a general population database&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">21</span></a> In this study&#44; statin initiation was associated with a 21&#37; lower risk of all-cause mortality&#46; In the same way&#44; Rollefstad et al&#46; showed that intensive lipid-lowering treatment with rosuvastatin induced atherosclerotic regression in patients with inflammatory joint disease&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">22</span></a></p><p id="par0185" class="elsevierStylePara elsevierViewall">A single randomized clinical trial developed to assess the impact of statins on cardiovascular risk in RA patients has been published to date&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">23</span></a> Atorvastatin 40<span class="elsevierStyleHsp" style=""></span>mg daily was safe and results in a significantly greater reduction of LDL-C level than placebo&#46; The unexpectedly low event rate and resulting limited statistical power to detect cardiovascular end-points effect during the planned 5 years of follow up led to premature termination of the trial&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">The statin indication also varied according to the analyzed strategy&#46; The greatest indication was observed when applying the NICE guidelines &#40;about half&#41;&#44; followed by the Argentine and North American recommendations &#40;about a quarter&#41; and the European guidelines &#40;about a fifth&#41;&#46; The agreement between the different strategies in selecting subjects with an indication of statins was highly variable&#46; The best concordance was observed between the Argentine Consensus and the ACC&#47;AHA guidelines and the worst agreement was demonstrated between the European recommendations and the NICE guidelines&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">Tournadre et al&#46; calculated the proportion of patients eligible for statins according to ESC guidelines&#44; the Adult Treatment Panel III &#40;ATP-III&#41;&#44; and the ACC&#47;AHA in a French cohort of statin-na&#239;ve RA patients&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">24</span></a> A marked discordance in risk assessment and cholesterol treatment was observed between the three sets of guidelines&#46; Similarly&#44; another small Mexican study showed fair statin eligibility agreement &#40;<span class="elsevierStyleItalic">k</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;242&#41; between ACC&#47;AHA 2013 and ATP-III guidelines&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">25</span></a> Another study showed that in a group of 335 patients with inflammatory joint diseases &#40;including 201 subjects with RA&#41;&#44; 183 and 159 patients had a calculated cardiovascular risk by SCORE and ACC&#47;AHA &#60;5&#37;&#44; indicating no need of lipid lowering treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">26</span></a></p><p id="par0200" class="elsevierStylePara elsevierViewall">These findings were reported in other chronic inflammatory diseases&#46; Masson et al&#46; showed that not all patients with psoriasis should receive statins&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">27</span></a> The lipid-lowering therapy indication was similar when applying the ACC&#47;AHA and ESC guidelines but the concordance was moderate&#46; On the other hand&#44; another study reported that a large proportion of patients with systemic lupus erythematosus should receive statins after applying the strategies based on the Framingham score and the QRISK-3&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">28</span></a></p><p id="par0205" class="elsevierStylePara elsevierViewall">In the present study&#44; when analyzing patients who were not receiving lipid-lowering therapy&#44; the main reason for the indication of statin treatment was the history of cardiovascular disease&#46; However&#44; in subjects in primary prevention&#44; the presence of diabetes or moderate-high cardiovascular risk &#40;calculated with the scoring method&#41; were also important reasons for its recommendations&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">The position paper of the Working Group of the ESC introduces for the first time a new algorithm for estimation of cardiovascular risk &#40;considering cardiovascular and rheumatological risk&#41; in RA patients and sets therapeutic goals for LDL-C&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">12</span></a> Our results showed that the majority of RA patients were classified as &#8220;high-risk rheumatology&#8221;&#46; Consequently&#44; a large number of patients were reclassified&#44; establishing lower LDL-C goals&#46; Therefore&#44; a great proportion of patients did not achieve the recommended lipid goals&#46;</p><p id="par0215" class="elsevierStylePara elsevierViewall">Age is a determining factor when estimating cardiovascular risk&#46; Consequently&#44; cardiovascular risk is frequently underestimated in younger patients&#46; Our study showed that the age was lower in HR-RA patients compared to LR-RA patients&#46; Therefore&#44; many young patients with RA&#44; despite showing characteristics of the disease that place them in a category of higher cardiovascular risk&#44; would be classified as &#8220;low risk&#8221; if we only applied tools based on traditional risk factors&#46; The low frequency of statins indication may be the result of this deficient risk assessment&#46; This fact constitutes a major point of concern in RA&#44; a condition associated with early atherosclerotic disease&#46; In this sense&#44; one study found that RA significantly elevated the risk of cardiovascular disease in the young population&#44; relative to non-RA controls&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">29</span></a> Even without comorbidity at baseline&#44; patients with RA still had a greater risk&#46; Similarly&#44; a meta-analysis showed that the rate of cardiovascular events was significantly higher in young patients with RA compared with controls&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">30</span></a> We consider that a comprehensive evaluation of young patients&#44; considering the classical risk factors and the &#8220;rheumatological risk&#8221; constitutes the best option&#46;</p><p id="par0220" class="elsevierStylePara elsevierViewall">In everyday practice a number of patients with RA do not receive adequate treatment regardless of developed atherosclerosis&#46; Unfortunately&#44; despite high risk for cardiovascular disease mortality&#44; screening and treatment of hyperlipidemia in patients with RA is suboptimal&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">31</span></a></p><p id="par0225" class="elsevierStylePara elsevierViewall">Guideline recommended treatment to targets of cardiovascular risk is inadequate in patients with inflammatory joint diseases&#46; A study that included 2277 patients with chronic inflammatory diseases &#40;1376 with RA&#41; showed that the lipid-lowering treatment and antihypertensive medication were only indicated in 36&#46;1&#37; and 52&#46;6&#37; of cases&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">32</span></a> The LDL-C and blood pressure targets were obtained in 26&#46;2&#37; and 26&#46;3&#37;&#44; respectively&#46; Guideline recommended treatment and&#47;or corresponding treatment targets were not initiated or obtained in approximately 50&#37;&#46; Another study showed that one of the main barriers for rheumatologists to manage cardiovascular risk in RA subjects is lack of time&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">33</span></a> Rheumatologists also perceived conflict regarding of hyperlipidemia management and that they lack training and knowledge of hyperlipidemia guidelines&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">34</span></a> Similarly&#44; some studies demonstrated low patient awareness of cardiovascular risk with RA and low rates of patient-reported counseling by physicians&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">35</span></a></p><p id="par0230" class="elsevierStylePara elsevierViewall">In addition to optimal management of the underlying inflammatory condition according to current guidelines&#44; individual cardiovascular risk factors&#44; particularly dyslipidaemia&#44; should be assessed regularly and guide risk stratification and requirement for treatment&#46; In our opinion it is necessary to reach an agreement between rheumatologists&#44; cardiologists and general practitioners for screening of cardiovascular diseases in patients with RA&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Conclusion</span><p id="par0235" class="elsevierStylePara elsevierViewall">Stratification of cardiovascular risk in RA patients can be a real challenge&#46; Applying four strategies for lipid management in our population&#44; the indication for statins was considerably different&#46; However&#44; a significant gap was observed when comparing the expected and observed statin indication&#44; with very few patients achieving the LDL-C goals&#46; Interdisciplinary work between rheumatologists&#44; cardiologists and clinicians could improve these results&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Authors&#8217; contributions</span><p id="par0240" class="elsevierStylePara elsevierViewall">Masson Walter was the main coordinator of the project and was responsible for the study design&#46; Masson Walter&#44; Rossi Emiliano and Scolnik Marina drafted the manuscript of the present paper&#46; Cornejo-Pe&#241;a Guillermo&#44; Mora-Crespo Lorena&#44; Fiorini Norberto&#44; Alvarado Rodolfo&#44; Damonte Juan and Tobar-Jaramillo Mayra were involved in the supervising of data collection and stratification&#46; Masson Walter and Rossi Emiliano contributed to data assembly and analysis&#46; Scolnik Marina and Masson Walter contributed with manuscript revision&#46; All authors contributed intellectually to this manuscript and have approved this final version&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Ethics approval</span><p id="par0245" class="elsevierStylePara elsevierViewall">The study was conducted in compliance with the recommendations for medical research&#46; The protocol was reviewed and approved by the Ethical Board of the Institution&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Funding</span><p id="par0250" class="elsevierStylePara elsevierViewall">This research did not receive any specific grant from funding agencies in the public&#44; commercial&#44; or not-for-profit sectors&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Conflicts of interest</span><p id="par0255" class="elsevierStylePara elsevierViewall">None&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Different strategies have been proposed for the cardiovascular risk management of patients with rheumatoid arthritis &#40;RA&#41;&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objectives</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">&#40;1&#41; To estimate the cardiovascular risk by different strategies in RA patients&#44; analyzing which proportion of patients would be candidates to receive statin therapy&#59; &#40;2&#41; to identify how many patients meet the recommended lipid goals&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A cross-sectional study was performed from a secondary database&#46; The QRISK-3 score&#44; the Framingham score &#40;adjusted for a multiplying factor<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>1&#46;5&#41;&#44; the ASCVD calculator and the SCORE calculator were estimated&#46; The indications for statin therapy according to NICE&#44; Argentine Consensus&#44; ACC&#47;AHA&#44; and new European guidelines were analyzed&#46; The recommended LDL-C goals were analyzed&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">A total of 420 patients were included&#46; In total&#44; 24&#46;7&#37; and 48&#46;7&#37; of patients in primary and secondary prevention were receiving statins&#44; respectively&#46; Only 19&#46;4&#37; of patients with cardiovascular history received high intensity statins&#46; Applying the ACC&#47;AHA guidelines &#40;based on ASCVD score&#41;&#44; the Argentine Consensuses &#40;based on adjusted Framingham score&#41;&#44; the NICE guidelines &#40;based on QRISK-3&#41; and European recommendations &#40;based on SCORE&#41;&#44; 26&#46;9&#37;&#44; 26&#46;5&#37;&#44; 41&#46;1&#37; and 18&#46;2&#37; of the population were eligible for statin therapy&#44; respectively&#46; Following the new European recommendations&#44; 50&#46;0&#37;&#44; 46&#46;2&#37; and 15&#46;9&#37; of the patients with low-moderate&#44; high or very high risk achieved the suggested lipid goals&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusion</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Applying four strategies for lipid management in our population&#44; the cardiovascular risk stratification and the indication for statins were different&#46; A significant gap was observed when comparing the expected and observed statin indication&#44; with few patients achieving the LDL-C goals&#46;</p></span>"
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        "resumen" => "<span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Antecedentes</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Se han propuesto diferentes estrategias para el manejo del riesgo cardiovascular en pacientes con artritis reumatoide &#40;AR&#41;&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Objetivos</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">&#40;1&#41; estimar el riesgo cardiovascular mediante diferentes estrategias en pacientes con AR&#44; analizando qu&#233; proporci&#243;n de pacientes deber&#237;an recibir estatinas&#59; &#40;2&#41; identificar cu&#225;ntos pacientes alcanzaron los objetivos lip&#237;dicos recomendados&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">M&#233;todos</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Estudio de corte transversal&#46; Se estimaron los puntajes QRISK-3&#44; Framingham &#40;ajustado por un factor multiplicador &#215; 1&#44;5&#41;&#44; ASCVD y SCORE&#46; Se analizaron las indicaciones de estatinas&#44; seg&#250;n las gu&#237;as NICE&#44; el Consenso Argentino&#44; las gu&#237;as ACC&#47;AHA 2018 y las nuevas directrices europeas&#46; Se analizaron los objetivos de C-LDL&#46;</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Resultados</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Se incluyeron 420 pacientes&#59; 24&#44;7 y 48&#44;7&#37; de los pacientes en prevenci&#243;n primaria y secundaria recib&#237;an estatinas&#44; respectivamente&#46; El 19&#44;4&#37; de los pacientes con antecedentes cardiovasculares recib&#237;an estatinas de alta intensidad&#46; Aplicando las gu&#237;as ACC&#47;AHA &#40;basadas en el puntaje ASCVD&#41;&#44; el Consenso Argentino &#40;basado en el puntaje ajustado de Framingham&#41;&#44; las pautas NICE &#40;basadas en el QRISK-3&#41; y las recomendaciones europeas &#40;basadas en el SCORE&#41;&#44; 26&#44;9&#44; 26&#44;5&#44; 41&#44;1 y el 18&#44;2&#37; de la poblaci&#243;n eran elegibles para el tratamiento con estatinas&#44; respectivamente&#46; Siguiendo las nuevas recomendaciones europeas&#44; 50&#44; 46&#44;2 y 15&#44;9&#37; de los pacientes con riesgo bajo-moderado&#44; alto o muy alto lograron los objetivos lip&#237;dicos recomendados&#46;</p></span> <span id="abst0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conclusi&#243;n</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Aplicando varias estrategias para el manejo de los l&#237;pidos en nuestra poblaci&#243;n&#44; la estratificaci&#243;n del riesgo cardiovascular y la indicaci&#243;n de estatinas fueron diferentes&#46; Se observ&#243; una brecha significativa entre la indicaci&#243;n de estatinas esperada y observada&#44; logrando los objetivos de C-LDL muy pocos pacientes&#46;</p></span>"
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">HDL-C&#44; mg&#47;dl</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">55&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12&#46;8&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><span class="elsevierStyleItalic">Triglycerides&#44; mg&#47;dl</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">116&#46;7 &#40;54&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Body mass index&#44; kg&#47;m</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">2</span></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">26&#46;5 &#40;5&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Time from rheumatoid arthritis diagnosis&#44; years</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">12&#46;6 &#40;7&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">CDAI</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">7&#46;4 &#40;7&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">SDAI</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">7&#46;9 &#40;9&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">DAS28</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">2&#46;9 &#40;1&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">HAQ</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">0&#46;8 &#40;0&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Categorical variables&#44; &#37;</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Female gender</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">85&#46;5&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><span class="elsevierStyleItalic">Current smokers</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">6&#46;4&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><span class="elsevierStyleItalic">Arterial hypertension</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">51&#46;4&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><span class="elsevierStyleItalic">History of vascular disease</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">18&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Type 2 diabetes mellitus</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">7&#46;6&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><span class="elsevierStyleItalic">Chronic renal insufficiency</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">10&#46;0&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><span class="elsevierStyleItalic">Atria fibrillation</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">4&#46;3&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><span class="elsevierStyleItalic">Obesity</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">22&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Therapy</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Corticosteroids&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">46&#46;9&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><span class="elsevierStyleHsp" style=""></span>Conventional synthetic DMARDs&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">72&#46;6&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><span class="elsevierStyleHsp" style=""></span>Biological DMARDs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30&#46;7&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><span class="elsevierStyleHsp" style=""></span>Statins&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">29&#46;0&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Aspirin&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&#46;0&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><span class="elsevierStyleHsp" style=""></span>Antihypertensive therapy&nbsp;\t\t\t\t\t\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">47&#46;9&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><span class="elsevierStyleHsp" style=""></span>Antidiabetic therapy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#46;2&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><span class="elsevierStyleItalic">Extra articular manifestations</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">9&#46;8&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><span class="elsevierStyleItalic">Erosive disease</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">25&#46;2&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><span class="elsevierStyleItalic">Positive cyclic citrullinated peptide</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">81&#46;9&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><span class="elsevierStyleItalic">Positive rheumatoid factor</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">66&#46;6&nbsp;\t\t\t\t\t\t\n
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          "leyenda" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Concordance was evaluated using the kappa index&#46;</p><p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">ACC&#47;AHA&#58; American College of Cardiology&#47;American Heart Association&#59; ESC&#58; European Society of Cardiology&#59; NICE&#58; The National Institute for Health and Care Excellence&#46;</p>"
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">NICE&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">ACC&#47;AHA&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">NICE&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">ACC&#47;AHA&nbsp;\t\t\t\t\t\t\n
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