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          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Distribution of atheromatous plaques depending on the affected territory and vascular load &#40;number of atheromatous plaques&#41; for each population&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Background</span><p id="par0005" class="elsevierStylePara elsevierViewall">Chronic hepatitis C virus &#40;HCV&#41; infection is a global health problem&#44; with a worldwide prevalence of approximately 71 million individuals with the infection and 399&#44;000 deaths every year&#46; In Spain&#44; HCV affects almost 500&#44;000 individuals&#44; although this rate has changed in recent years since the use of new interferon-free therapies&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">1&#44;2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">HCV infection is one of the main causes of chronic liver disease and hepatocellular carcinoma and is associated with extrahepatic manifestations and significant metabolic disorders&#46;<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">3&#44;4</span></a> Recent reports have indicated an increase in subclinical atheromatosis and a higher rate of cardiovascular events in patients with HCV&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">5&#44;6</span></a> A number of studies have shown that chronic HCV infection is an independent risk factor for carotid atheromatosis&#44; coronary artery disease and stroke&#59; however&#44; the results of the various studies are inconclusive&#46;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">7&#8211;11</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">HCV infection increases the secretion of proinflammatory cytokine and alters the activity of the immune system&#46; This sustained inflammatory condition can promote atherogenesis in patients with the infection&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">12</span></a> Additionally&#44; HCV and liver disease are known to cause lipid and lipoprotein modification&#44; especially of apolipoprotein B&#44; using them as hosts for the replication and dissemination of HCV&#46; The virus circulates bound to low-density lipoproteins &#40;LDL&#41; and very low-density lipoproteins &#40;VLDL&#41; and interacts with LDL cell receptors&#44; penetrating the artery wall&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">13</span></a> In vivo studies have demonstrated HCV RNA colonizing and reproducing in cholesterol-rich atheromatous plaques&#46;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">14&#44;15</span></a> This cardiovascular risk can be increased by other HCV-associated disorders such as hyperhomocysteinemia&#44; hypoadiponectinemia and&#44; especially&#44; insulin resistance&#46; Despite the lack of consensus on particular aspects of the relationship between HCV infection and the formation of atheromatous plaques&#44; cardiovascular disease is an emerging problem in patients infected by this virus&#46;<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">16&#8211;20</span></a> Therefore&#44; although there are currently effective antiviral treatments for curing the viral infection&#44; a better understanding is needed of how HCV infection affects cardiovascular risk&#46; In this study&#44; we investigated whether HCV is an independent risk factor for subclinical atheromatosis&#44; whether there are differences in the lipid profile of patients with HCV infection&#44; with or without atheromatous plaques&#44; and its association with viral load and progression of liver disease as measured by the degree of fibrosis&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Patients and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Study design and patients</span><p id="par0020" class="elsevierStylePara elsevierViewall">This observational and cross-sectional study included outpatients with chronic HCV infection &#40;HCV<span class="elsevierStyleSup">&#43;</span>&#41; and a control group of patients without infection &#40;HCV<span class="elsevierStyleSup">&#8722;</span>&#41; followed-up in 2 university hospitals between March 2015 and June 2016&#46; The HCV<span class="elsevierStyleSup">&#43;</span> group consisted of patients with serologically confirmed &#40;i&#46;e&#46;&#44; positive for HCV antibodies and detectable viral load&#41; chronic HCV infection of any genotype and degree of hepatic fibrosis&#46; The patients were recruited from the hepatology units of the university hospitals Arnau de Vilanova and Santa Mar&#237;a &#40;Lleida&#44; Spain&#41; and entered the study before starting treatment with direct-acting antivirals&#46; The control group included HCV<span class="elsevierStyleSup">&#8722;</span> patients with moderate-low cardiovascular risk &#40;Systematic Coronary Risk Evaluation &#91;SCORE&#93; index &#60;5&#37;&#44; SCORE charts for Low-Risk European populations&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">21</span></a> The control patients were recruited from a cardiovascular risk unit where they underwent arterial ultrasonography to diagnose subclinical atheromatosis &#40;Detection and Treatment of Atherothrombotic Diseases Unit &#91;UDETMA&#93; of University Hospital Arnau de Vilanova of Lleida&#41;&#46; The exclusion criteria for both groups were as follows&#58; &#40;1&#41; age &#60;30 or &#62;75 years&#59; &#40;2&#41; decompensated cirrhosis&#59; &#40;3&#41; presence of hepatocellular carcinoma or other tumors&#59; &#40;4&#41; chronic non-HCV liver disease &#40;due to alcohol&#44; hepatitis B virus&#44; autoimmune disease or iron deposit&#41;&#59; &#40;5&#41; HIV infection&#59; &#40;6&#41; inflammatory disease or acute or chronic infection&#59; &#40;7&#41; previous history of cardiovascular events according to the International Classification of Diseases-10th edition-Clinical Modification&#44; &#40;ICD10-CM&#41; &#91;&#40;a&#41; cerebrovascular disease&#58; transient ischemic attack and&#47;or stable stroke&#59; &#40;b&#41; ischemic heart disease&#58; acute myocardial infarction&#44; unstable angina pectoris&#44; arrhythmias and&#47;or congestive heart failure&#59; &#40;c&#41; peripheral arterial disease of the legs or aortic aneurysm&#93;&#59; &#40;8&#41; chronic renal failure &#40;Chronic Kidney Disease Epidemiology Collaboration equation &#60;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;&#59; &#40;9&#41; diagnosis of diabetes mellitus&#59; &#40;10&#41; dyslipidemia treated with hypolipidemic agents&#59; and &#40;11&#41; history of arterial hypertension undergoing treatment&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">All patients signed an informed consent form before entering the study&#44; which was approved by the ethics committee of the 2 hospitals involved&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Clinical and laboratory data</span><p id="par0030" class="elsevierStylePara elsevierViewall">Clinical data were collected in a standardized interview in the follow-up consultation visit&#46; We used blood samples under fasting conditions to measure the following serum parameters&#58; glucose&#44; total cholesterol &#40;TC&#41;&#44; LDL and HDL cholesterol&#44; triglycerides&#44; creatinine and C-reactive protein &#40;CRP&#41;&#46; We calculated the following lipid coefficients&#58; non-HDL cholesterol &#40;total cholesterol<span class="elsevierStyleHsp" style=""></span>&#8722;<span class="elsevierStyleHsp" style=""></span>HDL cholesterol&#41;&#44; TG&#47;HDL cholesterol &#40;indicator of insulin resistance&#41; and TC&#47;HDL cholesterol &#40;atherogenic index&#41;&#44; performing all measurements in the same laboratory&#46; The anthropometric measurements &#40;weight and height&#41; for calculating the body mass index &#40;BMI&#41; and blood pressure were recorded in the UDETMA before performing the arterial ultrasonography&#46; Systolic and diastolic blood pressure was measured on 3 occasions in the seated position and after 10<span class="elsevierStyleHsp" style=""></span>min of rest&#44; using an automatic pressure monitor &#40;OMRON HEM-705 CP<span class="elsevierStyleSup">&#174;</span>&#41;&#46; We recorded the mean of the last 2 measurements&#46; The patients were also classified according to their history of tobacco use as smokers&#44; former smokers or nonsmokers&#46; The cardiovascular risk was calculated using SCORE risk charts&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">21</span></a> In the patient group with chronic hepatitis&#44; we analyzed the HCV RNA viral load using reverse transcription-polymerase chain reaction &#40;RT-PCR&#41;&#44; with a detection limit of 12<span class="elsevierStyleHsp" style=""></span>IU&#47;mL&#46; We performed transient elastography &#40;Fibroscan<span class="elsevierStyleSup">&#174;</span> &#91;FS&#93;&#44; Echosens&#44; Paris&#44; France&#41; to assess the degree of hepatic fibrosis and classify it as follows&#58; &#60;7&#46;5<span class="elsevierStyleHsp" style=""></span>kPa<span class="elsevierStyleHsp" style=""></span>s &#8211; no fibrosis &#40;F0&#8211;1&#41;&#59; 7&#46;6&#8211;9&#46;5<span class="elsevierStyleHsp" style=""></span>kPa<span class="elsevierStyleHsp" style=""></span>s &#8211; moderate fibrosis &#40;F2&#41;&#59; 9&#46;6&#8211;12&#46;5<span class="elsevierStyleHsp" style=""></span>kPa<span class="elsevierStyleHsp" style=""></span>s &#8211; significant fibrosis &#40;F3&#41;&#59; and &#62;12&#46;5<span class="elsevierStyleHsp" style=""></span>kPa<span class="elsevierStyleHsp" style=""></span>s &#8211; hepatic cirrhosis &#40;F4&#41;&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Assessment of subclinical arterial atheromatosis</span><p id="par0035" class="elsevierStylePara elsevierViewall">We determined the presence of atheromatous plaques in carotid and femoral territories using a General Electronic ultrasound &#40;model Vivid-I<span class="elsevierStyleSup">&#174;</span>&#41; with a 12L-SR vascular probe following a previously described standardized method&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">22</span></a> All images were captured and read by a single team&#44; consisting of previously certified practitioners&#46; The Kappa coefficient for intraobserver reliability was set at 1&#46; Atheromatous plaque is defined as a focal structure that protrudes into the vascular lumen or an intima-media thickness &#40;IMT&#41; &#62;1&#46;5<span class="elsevierStyleHsp" style=""></span>mm&#44; according to the Mannheim consensus&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">23</span></a> We analyzed 12 vascular territories to diagnose the presence of atheromatous plaques&#46; We examined carotid arteries &#40;common&#44; bifurcation&#44; internal and external&#41; and femoral arteries &#40;common and superficial&#41; bilaterally&#44; using a single axial and longitudinal plane&#44; with mode-B and color Doppler ultrasound&#46; We defined subclinical atheromatosis as the presence of 1 or more plaques in any of the studied territories&#46; In the patients without atheromatous plaques&#44; we measured the carotid IMT &#40;CIMT&#41; in the distal segment of the artery&#44; with the final value equal to the mean of the carotid territory&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Statistical analysis</span><p id="par0040" class="elsevierStylePara elsevierViewall">The categorical variables are listed as frequencies and percentages and were compared using Pearson&#39;s chi-squared test&#46; The quantitative variables are listed as median and interquartile range &#40;IQR&#41; or mean and standard deviation &#40;SD&#41;&#44; depending on their distribution&#46; We compared the normally distributed variables with Student&#39;s <span class="elsevierStyleItalic">t</span>-test and compared the non-normally distributed variables with the nonparametric Mann&#8211;Whitney <span class="elsevierStyleItalic">U</span> test&#46; The variables that showed significant differences between the patients with and without atheromatous plaques were included in a backward stepwise conditional multiple logistic regression to predict the presence of atheromatous plaques&#46; We employed a receiver operating characteristic &#40;ROC&#41; analysis to establish an age limit and determine the presence of plaques according to the study population&#39;s age&#44; transforming the quantitative variable into a dichotomous variable according to the obtained cutoff values&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">We studied the association of the changes in lipid profile according to the degree of hepatic fibrosis using an analysis of variance &#40;ANOVA&#41; and the presence of a correlation between the viral load and lipid levels using Spearman&#39;s <span class="elsevierStyleItalic">R</span>&#46; Statistical significance was established by a bilateral <span class="elsevierStyleItalic">&#945;</span> value &#60;0&#46;05&#44; and all analyses were performed using SPSS software &#40;IBM Statistics for Windows&#44; version 20&#46;0&#59; IBM Corp&#46;&#44; Armonk&#44; NY&#41;&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Results</span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Study population characteristics</span><p id="par0050" class="elsevierStylePara elsevierViewall">The study sample included 204 patients&#58; 102 in the HCV<span class="elsevierStyleSup">&#43;</span> group and 102 in the control group&#46; <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> lists the clinical and laboratory data for both populations&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">The study groups presented no statistically significant differences in terms of sex&#44; age or history of tobacco use&#46; The control group presented significantly higher values in most of the classical cardiovascular risk factors&#44; including BMI&#44; systolic and diastolic blood pressure and serum lipid profile&#46; There were no significant differences in terms of glucose and triglyceride levels&#44; TG&#47;HDL coefficient or the indicator of insulin resistance&#44; although the levels were&#44; in all cases&#44; higher for the control patients &#40;96&#46;5 vs&#46; 94&#46;2<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;888&#59; 121&#46;5 vs&#46; 102&#46;9<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;070&#59; and 2&#46;3 vs&#46; 2&#46;1&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;449&#41;&#46; Additionally&#44; the control patients presented significantly higher levels of serum creatinine and CRP and a higher cardiovascular risk index &#40;SCORE&#41;&#44; although the risk was low to moderate for both groups&#46; Almost 55&#37; of the patients with chronic HCV infection presented advanced liver disease &#40;29&#46;4&#37; of whom had grade 4 cirrhosis or fibrosis measured by hepatic elastography&#41;&#46; Some 67&#46;2&#37;&#44; 6&#46;7&#37;&#44; 9&#46;7&#37; and 16&#46;4&#37; were genotypes 1&#44; 2&#44; 3 and 4&#44; respectively&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">The percentage of patients with atheromatosis was significantly greater in the HCV<span class="elsevierStyleSup">&#43;</span> group than in the control group &#40;58&#46;8 vs&#46; 28&#46;4&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#44; with no significant differences in the CIMT measured in the patients without atheromatosis &#40;0&#46;76 vs&#46; 0&#46;89<span class="elsevierStyleHsp" style=""></span>mm&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;18&#41;&#44; although the CIMT was greater in the patients with infection&#46; In the control group&#44; the plaques were distributed 35&#37; in the carotid territory&#44; 23&#46;9&#37; in the femoral territory and 41&#46;1&#37; in both territories&#44; while the patients with HCV infection had a distribution of 45&#46;3&#37; in the carotid territory&#44; 19&#46;8&#37; in the femoral territory and 34&#46;9&#37; in both vascular areas&#46; The mean number of atheromatous plaques was 2&#46;95 &#40;1&#8211;10&#41; in the patients with infection compared with 2&#46;44 &#40;1&#8211;8&#41; in the patients without infection&#46; There were no significant differences between the populations in terms of affected vascular territory &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;710&#41; or in the mean number of detected plaques &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;420&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> analyzes the factors associated with the presence of atheromatous plaques in each of the study populations&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">The presence of atheromatous plaques in both groups &#40;with and without HCV infection&#41; was associated in a statistically significant manner with the male sex&#44; higher blood pressure readings&#44; high triglyceride levels and a greater cardiovascular risk according to the SCORE charts&#46; In terms of age&#44; there was no association with the presence of atheromatous plaques in the patients with infection&#46; In the control group&#44; however&#44; there was an association&#44; such that the presence of plaques was associated with an older age &#40;51&#46;8 years in the control patients without atheromatosis vs&#46; 67&#46;3 years in the control patients with atheromatosis&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#46; In terms of smoking&#44; an association was detected in the patients with HCV &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;003&#41;&#44; with plaques more frequent in the smokers and ex-smokers &#40;81&#46;6&#37;&#41; but not in the control group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;499&#41;&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">In terms of the lipid profile&#44; the patients with HCV and plaques presented lower HDL cholesterol readings &#40;57&#46;6 vs&#46; 50&#46;9<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;023&#41; and higher triglyceride levels &#40;89&#46;3 vs&#46; 112&#46;6<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;029&#41;&#44; TG&#47;HDL coefficient &#40;1&#46;7 vs&#46; 2&#46;3&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;026&#41; and TC&#47;HDL coefficient &#40;3 vs&#46; 3&#46;4&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;035&#41; than the patients with infection but no plaques&#46; There was no significance for these lipid factors between the control patients with or without atheromatous plaques&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">In terms of the viral factors in the patients with HCV infection&#44; we found no association between the presence of plaques and the viral load quantified by RNA &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;936&#41;&#44; but there were significant differences with the degree of hepatic fibrosis&#44; with the presence of plaques occurring more frequently in the patients with advanced fibrosis &#40;F4 without atheromatosis &#91;23&#46;8&#37;&#93; vs&#46; F4 with atheromatosis &#91;33&#46;3&#37;&#93;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;016&#41;&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">We analyzed the age&#44; according to the ROC analysis&#44; and an age older than 54 years was the best cut-off for predicting the presence of atheromatous plaques &#40;AUC&#44; 0&#46;682&#59; standard error&#44; 0&#46;039&#59; 95&#37; CI 0&#46;6&#8211;0&#46;7&#59; 67&#37; sensitivity&#59; 60&#37; specificity&#41;&#46; Below this cutoff &#40;&#60;54 years&#41;&#44; the percentage of patients with atheromatous plaques was 57&#37; in the HCV<span class="elsevierStyleSup">&#43;</span> group and 4&#37; in the control group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#46; In the patients 54 years of age or older&#44; the rate of atheromatosis increased to 61&#37; in the HCV<span class="elsevierStyleSup">&#43;</span> group and to 50&#37; in the control group&#44; without significant differences in this age group between the populations &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;252&#41;&#46; In the age group younger than 54 years&#44; the HCV<span class="elsevierStyleSup">&#43;</span> patients had a much higher probability of atheromatosis than the control group &#40;OR&#44; 30&#59; 95&#37; CI 6&#46;58&#8211;136&#46;67&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Factors associated with subclinical atheromatosis</span><p id="par0090" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> lists the clinical characteristics of the patients with and without subclinical atheromatosis&#46; Chronic HCV infection was significantly associated with the presence of subclinical atheromatosis&#44; as were the classical cardiovascular risk factors such as male sex&#44; advanced age&#44; systolic blood pressure&#44; high scores on SCORE&#44; low serum HDL cholesterol levels and higher triglyceride levels&#46; Chronic HCV infection was also associated with increased TG&#47;HDL quotients&#46; The presence of atheromatous plaques was not associated with BMI&#44; glucose levels or CRP values&#46; There was also no association with the lipid profile consisting of total cholesterol&#44; LDL and non-HDL cholesterol nor with the atherogenic index &#40;TC&#47;HDL&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0095" class="elsevierStylePara elsevierViewall">The multivariate analysis revealed a much higher probability of atheromatosis in the HCV<span class="elsevierStyleSup">&#43;</span> patients than in the control group &#40;OR&#44; 14&#46;37&#59; 95&#37; CI 5&#46;5&#8211;37&#46;5&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46; Other independent risk factors for subclinical atheromatosis included male sex&#44; advanced age and an increased TG&#47;HDL coefficient or indirect indicator of insulin resistance&#46; Neither systolic blood pressure nor the lipid profile contributed to the predictive model for the presence of atheromatous plaques&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Description of the lipid profile according to the degree of hepatic fibrosis in the patients with HCV in terms of the presence of atheromatous plaques</span><p id="par0100" class="elsevierStylePara elsevierViewall">We analyzed the lipid profile of the patients with HCV and with and without atheromatosis&#44; taking into account the degree of hepatic fibrosis measured by elastography&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">In the patients with HCV without atheromatosis&#44; there were no significant differences in any of the classical lipid profile values&#44; the coefficients indicative of insulin resistance &#40;TG&#47;HDL&#41; or the atherogenic factor &#40;TC&#47;HDL&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>a and b&#41;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0110" class="elsevierStylePara elsevierViewall">In the patients with HCV and atheromatosis &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>c and d&#41;&#44; there were significant differences in total cholesterol &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;018&#41;&#44; non-HDL cholesterol &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;002&#41; and LDL cholesterol levels &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;002&#41;&#44; as well as in the atherogenic index &#40;TC&#47;HDL&#41; &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#44; with an increasing trend as the hepatic fibrosis progressed and decreasing significantly in the presence of cirrhosis&#46; There were no changes in HDL cholesterol or triglyceride levels&#44; TG&#47;HDL coefficient or the degree of fibrosis in the presence of atheromatous plaques&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">When analyzing the correlation between the viral load and lipid profile&#44; we detected only a slight association between HCV RNA and non-HDL cholesterol levels &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;219&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;04&#41; and no association with any other analytical parameter&#46;</p></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Discussion</span><p id="par0120" class="elsevierStylePara elsevierViewall">This observational study analyzed the presence of atheromatosis in patients with and without chronic HCV infection and found that the patients with infection had a greater presence of subclinical atheromatosis and at a younger age than the controls&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Our results agree with those recently published in 2 meta-analyses that reported a greater presence of atheromatosis in populations with HCV infection &#40;between 38&#37; and 65&#37;&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">5&#44;6</span></a> In these studies&#44; the atheromatous plaques were identified by vascular Doppler ultrasonography&#44; and the diagnosis was established with a CIMT value &#62;1&#46;3<span class="elsevierStyleHsp" style=""></span>mm&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">20</span></a> In our study&#44; we followed the Mannheim criteria for diagnosing atheromatosis&#44; defining the plaque as an CIMT &#62;1&#46;5<span class="elsevierStyleHsp" style=""></span>mm&#46; One of the possible reasons for our higher rates was the expansion of the femoral study&#44; which increased the probability of detecting atheromatosis&#46; The presence of atheromatosis in the femoral territory in the absence of carotid plaques has been reported in the general population&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">24</span></a> We also analyzed various viral genotypes that have not been evaluated in previously published studies&#44;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">20</span></a> although genotype 3 is known to produce more metabolic disorders than the other genotypes&#46;<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">25&#44;26</span></a> Although the presence of plaques was greater in the patients with infection&#44; these patients had a low cardiovascular risk index according to the SCORE European Risk Charts&#46; Several populational studies have shown an association between the presence of plaques in peripheral arteries and the incidence of cardiovascular events&#44; even in patients without previous events &#40;1&#46;8-fold increased risk of coronary events and 4&#46;1-fold increased risk of cardiovascular events&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">27&#44;28</span></a> In line with these publications&#44; the presence of atheromatous plaques in our population was not associated with classical cardiovascular risk factors such as BMI&#44; blood glucose and dyslipidemia&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Our study involved the first Spanish patient cohort monoinfected with chronic HCV&#44; although it has a number of limitations intrinsic to a cross-sectional design and a selection bias in the control patients&#44; given that they belonged to a patient group from a cardiovascular risk office&#46; To minimize this bias&#44; we limited the selection criteria to patients with a low to moderate risk &#40;&#60;5&#37; probability of experiencing cardiovascular events at 10 years&#41;&#44; with no previous cardiovascular disease and who were not taking drugs for hypertension or dyslipidemia&#46; We excluded patients with diabetes and chronic kidney disease to avoid confounding factors&#46; A number of publications have indicated that HCV promotes the development of diabetes and chronic renal failure&#44; which predisposes patients to the presence of atheromatous lesions&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">16</span></a> Another confounding factor could be the larger presence of ex-smokers and active smokers among those patients with HCV<span class="elsevierStyleSup">&#43;</span> plaques&#44; as could the differences between the degree of hepatic fibrosis in the patients with and without plaques&#46; As shown by the multivariate analysis&#44; however&#44; neither tobacco nor fibrosis affected the development of atheromatous plaques&#46; There was&#44; however&#44; a high association &#40;OR&#44; 14&#46;37&#41; of HCV per se&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Based on these results&#44; we identified chronic HCV infection as an independent risk factor for atheromatosis&#44; with no influence from other classical cardiovascular factors&#44; which suggests a direct role of HCV in the development of atheromatous lesions&#46; Recent studies have shown the presence of HCV RNA in carotid plaques<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">14&#44;15</span></a> and due to the proinflammatory environment that the virus induces&#46;<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">4&#8211;12</span></a> In our study&#44; CRP levels &#40;a widely accepted marker of cardiovascular risk and systemic inflammation for the population<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">22</span></a>&#41; showed no significant differences between the two groups&#44; although hepatic synthesis proteins such as CRP can be altered in patients with chronic liver disease&#46; We also detected the presence of atheromatosis in the population with HCV&#44; which develops at an earlier age than in the group without HCV infection&#46; Below 54 years of age&#44; there were significant differences in the presence of plaques in the patients with infection compared with the controls &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; This finding suggests that the patients with HCV infection have accelerated atheromatosis or premature vascular aging&#44; similar to that observed in other chronic inflammatory and autoimmune diseases&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">29</span></a> In addition to age and HCV infection&#44; the male sex and TG&#47;HDL coefficient &#40;indirect marker of insulin-resistance&#41; were the only factors significantly associated with the presence of atheromatosis&#46; This coefficient is a predictive indicator of cardiovascular disease&#44; used as a marker of atherogenesis in the general population&#46; Although there are few data&#44; its predictive value in heart disease is high&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">30</span></a> The coefficient is also a good marker of atherogenesis in the population with infection&#44; because it does not change significantly with the progression of the liver disease or with the viral load&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">In this study&#44; we analyzed the changes in lipid profile in the various stages of liver disease progression measured by elastography &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41; and detected that&#44; in the patients with infection but without atheromatous plaques&#44; there were no differences in terms of serum lipid levels and hepatic fibrosis&#46; In the patients with HCV and atheromatosis&#44; the most atherogenic particles &#40;composed of LDL and VLDL&#41;&#44; which are the main transporters of HCV in plasma&#44; increased as the fibrosis progressed and decreased significantly once hepatic cirrhosis was established&#46; These more atherogenic particles are weakly correlated with the viral load&#44; without no association with the development of atheromatous plaques&#44; which could be due to the fluctuation in the viremia time or to the fact that these values depend on the progression of the hepatic fibrosis&#44; decreasing in stages of cirrhosis&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">In summary&#44; our results show that the patients with chronic HCV infection had a greater prevalence of subclinical atheromatosis than the population without infection&#44; with an early age at onset &#40;accelerated atheromatosis&#41;&#46; The metabolic profile and cardiovascular risk assessment using classical charts are not good predictors&#44; because most of these patients had low risk SCORES and a &#8220;low-risk&#8221; lipid profile &#40;lower non-HDL cholesterol and LDL cholesterol readings&#41;&#46; These results support the need for additional noninvasive cardiovascular tests for routine use&#44; such as arterial ultrasonography&#44; which could improve the risk stratification for this population&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Conflicts of interest</span><p id="par0150" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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              "titulo" => "Assessment of subclinical arterial atheromatosis"
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              "titulo" => "Description of the lipid profile according to the degree of hepatic fibrosis in the patients with HCV in terms of the presence of atheromatous plaques"
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            0 => "Hepatitis C virus &#40;HCV&#41;"
            1 => "Atheromatous plaque"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The association between subclinical atheromatosis and chronic hepatitis C virus &#40;HCV&#41; infection is unknown but is relevant now that antivirals are improving the survival of patients with the infection&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objectives</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">To determine whether HCV is an independent risk factor for subclinical atheromatosis and to analyze the changes in lipid profiles according to viral RNA levels and hepatic fibrosis&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Patients and methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">We conducted an observational&#44; cross-sectional study that included 102 HCV-positive patients and 102 HCV-negative patients with parity in terms of sex and age&#44; with no history of cardiovascular or kidney disease or diabetes&#46; Atheromatosis &#40;the presence of atheromatous plaques&#41; and the carotid intima-media thickness &#40;CIMT&#41; were assessed using ultrasonography of the carotid and femoral arteries&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">There was a greater presence of atheromatosis in any vascular territory in HCV-positive patients than in the patients without infection &#40;58&#46;8&#37; vs&#46; 28&#46;4&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;0001&#41;&#46; In the multivariate analysis&#44; the factors significantly associated with atheromatosis included HCV infection &#40;OR&#44; 14&#46;37 &#91;5&#46;5&#8211;37&#46;3&#93;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#44; age &#40;OR&#44; 1&#46;12 &#91;1&#46;1&#8211;1&#46;2&#93;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#44; male sex &#40;OR&#44; 4&#46;32 &#91;1&#46;9&#8211;9&#46;5&#93;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41; and the triglyceride&#47;HDL cholesterol coefficient &#40;TG&#47;HDL-indirect indicator of insulin resistance&#41; &#40;OR&#44; 1&#46;34 &#91;1&#46;1&#8211;1&#46;6&#93;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;007&#41;&#46; The HCV-positive patients with atheromatous plaques had a higher TG&#47;HDL coefficient but no significant differences in terms of the viral load or degree of hepatic fibrosis and with a &#8216;low risk&#8217; lipid profile&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusions</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">HCV infection is an independent risk factor for subclinical atheromatosis&#46; Systemic arterial ultrasonography for this population improves the cardiovascular risk assessment beyond lipid profile abnormalities and the risk calculation using SCORE tables&#46;</p></span>"
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            "titulo" => "Objectives"
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          2 => array:2 [
            "identificador" => "abst0015"
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        "resumen" => "<span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Introducci&#243;n</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Se desconoce la asociaci&#243;n entre ateromatosis subcl&#237;nica e infecci&#243;n cr&#243;nica por el virus de la hepatitis C &#40;VHC&#41;&#44; relevante ahora que los antivirales mejoran la supervivencia en los pacientes infectados&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Objetivos</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Conocer si el VHC es factor de riesgo independiente de ateromatosis subcl&#237;nica y analizar las modificaciones del perfil lip&#237;dico seg&#250;n niveles de ARN viral y fibrosis hep&#225;tica&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Pacientes y m&#233;todos</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Estudio observacional y transversal&#59; incluye 102 pacientes VHC positivos y 102 sujetos VHC negativos con paridad de sexo y edad&#44; sin antecedentes de enfermedad cardiovascular&#44; renal ni diabetes&#46; La ateromatosis &#40;presencia de placas de ateroma&#41; y el grosor &#237;ntima-media carot&#237;deo &#40;GIMc&#41; se evalu&#243; mediante ecograf&#237;a de arterias car&#243;tidas y femorales&#46;</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Resultados</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">La presencia de ateromatosis en cualquier territorio vascular fue mayor en pacientes VHC que en sujetos no infectados &#40;58&#44;8&#37; frente a 28&#44;4&#37;&#44; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46; En el an&#225;lisis multivariante&#44; los factores significativamente asociados con ateromatosis incluyeron infecci&#243;n por VHC &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>14&#44;37 &#91;5&#44;5-37&#44;3&#93;&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#44; edad &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#44;12 &#91;1&#44;1-1&#44;2&#93;&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#44; sexo masculino &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4&#44;32 &#91;1&#44;9-9&#44;5&#93;&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; y el coeficiente triglic&#233;ridos&#47;colesterol HDL &#40;TG&#47;HDL-indicador indirecto de insulinorresistencia&#41; &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#44;34 &#91;1&#44;1-1&#44;6&#93;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;007&#41;&#46; Los pacientes VHC con placas de ateroma presentaban mayor coeficiente TG&#47;HDL&#44; sin diferencias significativas en cuanto a la carga viral ni grado de fibrosis hep&#225;tica con un perfil lip&#237;dico de &#171;bajo riesgo&#187;&#46;</p></span> <span id="abst0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conclusiones</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">La infecci&#243;n VHC es factor de riesgo independiente de ateromatosis subcl&#237;nica&#46; La ecograf&#237;a arterial sist&#233;mica en esta poblaci&#243;n mejora la evaluaci&#243;n del riesgo cardiovascular m&#225;s all&#225; de las alteraciones del perfil lip&#237;dico y del c&#225;lculo de riesgo por tablas SCORE&#46;</p></span>"
        "secciones" => array:5 [
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            "titulo" => "Introducci&#243;n"
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        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0020">Please cite this article as&#58; Revuelto Artigas T&#44; Zaragoza Velasco N&#44; G&#243;mez Arbones X&#44; Vidal Ballester T&#44; Pi&#241;ol Felis C&#44; Re&#241;e Espinet JM&#44; et al&#46; Infecci&#243;n cr&#243;nica por el virus de la hepatitis C&#58; un factor de riesgo independiente para la ateromatosis subcl&#237;nica&#46; Rev Clin Esp&#46; 2019&#59;219&#58;293&#8211;302&#46;</p>"
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          "leyenda" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviations</span>&#58; CIMT&#44; carotid intima-media thickness&#59; CRP&#44; C-reactive protein&#59; DBP&#44; diastolic blood pressure&#59; HCV&#44; hepatitis C virus&#59; HDL&#44; high-density lipoprotein&#59; IMT&#44; intima-media thickness&#59; LDL&#44; low-density lipoprotein&#59; NS&#44; not significant&#59; SBP&#44; systolic blood pressure&#59; TC&#44; total cholesterol&#59; TG&#44; triglycerides&#46;</p><p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Quantitative variable&#58; mean &#40;SD&#44; range&#41;&#46;</p><p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Qualitative variable&#58; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&#46;</p><p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">Significance threshold&#58; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;05&#46;</p>"
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                  \t\t\t\t">135 &#40;20&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">&#60;&#46;001&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">73&#46;7 &#40;10&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">79&#46;1 &#40;11&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">&#60;&#46;001&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">94&#46;2 &#40;13&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">96&#46;5 &#40;13&#46;1&#41;&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">NS&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;8 &#40;0&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#60;&#46;001&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">167&#46;7 &#40;34&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">206&#46;2 &#40;36&#46;1&#41;&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">114&#46;1 &#40;35&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">145&#46;8 &#40;35&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#60;&#46;001&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
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                  \t\t\t\t"><span class="elsevierStyleItalic">LDL cholesterol&#44; mg&#47;dL</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">93&#46;7 &#40;31&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">121&#46;6 &#40;35&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t\tvoid\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Without plaques &#40;<span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>42&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">With plaques &#40;<span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>60&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span><a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Without plaques &#40;<span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>73&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">With plaques &#40;<span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>29&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span><a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \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="elsevierStyleItalic">Male sex</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">10 &#40;23&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">40 &#40;66&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">33 &#40;45&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20 &#40;68&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;03&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="elsevierStyleItalic">Age&#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">51&#46;6 &#40;31&#8211;74&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">54&#46;2 &#40;34&#8211;75&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">51&#46;8 &#40;32&#8211;75&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">67&#46;3 &#40;37&#8211;75&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;&#46;001&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="elsevierStyleItalic">Smoke&#47;ex-smoker</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">23 &#40;54&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">49 &#40;81&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;003&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">48 &#40;65&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17 &#40;58&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NS&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="elsevierStyleItalic">BMI&#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 &#40;3&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">26&#46;6 &#40;4&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27&#46;8 &#40;5&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27&#46;9 &#40;3&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NS&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="elsevierStyleItalic">SBP&#44; mmHg</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">119&#46;2 &#40;18&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">127&#46;4 &#40;13&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;011&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">130&#46;1 &#40;20&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">147&#46;2 &#40;16&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;&#46;001&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="elsevierStyleItalic">DBP&#44; mmHg</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">72&#46;9 &#40;11&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">74&#46;2 &#40;10&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">77&#46;3 &#40;11&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">83&#46;7 &#40;8&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;003&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Blood glucose&#44; g&#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">90&#46;6 &#40;9&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">96&#46;7 &#40;16&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;029&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">95&#46;7 &#40;13&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">98&#46;6 &#40;11&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NS&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="elsevierStyleItalic">Creatinine&#44; g&#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">0&#46;7 &#40;0&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;8 &#40;0&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;8 &#40;0&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;9 &#40;0&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NS&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="elsevierStyleItalic">Total cholesterol&#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">167 &#40;32&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">168&#46;1 &#40;36&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">206&#46;2 &#40;38&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">206 &#40;29&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col">Patients without atheromatous plaques &#40;<span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>115&#41;&nbsp;\t\t\t\t\t\t\n
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Original article
Chronic hepatitis C infection: An independent risk factor for subclinical atheromatosis
Infección crónica por el virus de la hepatitis C: un factor de riesgo independiente para la ateromatosis subclínica
T. Revuelto Artigasa,b,c,d,
Corresponding author
tamararevuelto@gmail.com

Corresponding author.
, N. Zaragoza Velascob,c,d, X. Gómez Arbonesd,e, T. Vidal Ballesterc, C. Piñol Felisd,e, J.M. Reñe Espinetb,d,e, A. Betriu Barsc,d
a Servicio de Aparato Digestivo, Hospital Universitario Santa María, Lleida, Spain
b Servicio de Aparato Digestivo, Hospital Universitario Arnau de Vilanova, Lleida, Spain
c Unidad de Detección y Tratamiento de Enfermedades Aterotrombóticas (UDETMA), Hospital Universitario Arnau de Vilanova (Grupo de Investigación Translacional Vascular y Renal, IRBLleida), Lleida, Spain
d Instituto de Investigación Biomédica, Lleida, Spain
e Universidad de Lleida (UdL), Lleida, Spain
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          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Distribution of atheromatous plaques depending on the affected territory and vascular load &#40;number of atheromatous plaques&#41; for each population&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Background</span><p id="par0005" class="elsevierStylePara elsevierViewall">Chronic hepatitis C virus &#40;HCV&#41; infection is a global health problem&#44; with a worldwide prevalence of approximately 71 million individuals with the infection and 399&#44;000 deaths every year&#46; In Spain&#44; HCV affects almost 500&#44;000 individuals&#44; although this rate has changed in recent years since the use of new interferon-free therapies&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">1&#44;2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">HCV infection is one of the main causes of chronic liver disease and hepatocellular carcinoma and is associated with extrahepatic manifestations and significant metabolic disorders&#46;<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">3&#44;4</span></a> Recent reports have indicated an increase in subclinical atheromatosis and a higher rate of cardiovascular events in patients with HCV&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">5&#44;6</span></a> A number of studies have shown that chronic HCV infection is an independent risk factor for carotid atheromatosis&#44; coronary artery disease and stroke&#59; however&#44; the results of the various studies are inconclusive&#46;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">7&#8211;11</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">HCV infection increases the secretion of proinflammatory cytokine and alters the activity of the immune system&#46; This sustained inflammatory condition can promote atherogenesis in patients with the infection&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">12</span></a> Additionally&#44; HCV and liver disease are known to cause lipid and lipoprotein modification&#44; especially of apolipoprotein B&#44; using them as hosts for the replication and dissemination of HCV&#46; The virus circulates bound to low-density lipoproteins &#40;LDL&#41; and very low-density lipoproteins &#40;VLDL&#41; and interacts with LDL cell receptors&#44; penetrating the artery wall&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">13</span></a> In vivo studies have demonstrated HCV RNA colonizing and reproducing in cholesterol-rich atheromatous plaques&#46;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">14&#44;15</span></a> This cardiovascular risk can be increased by other HCV-associated disorders such as hyperhomocysteinemia&#44; hypoadiponectinemia and&#44; especially&#44; insulin resistance&#46; Despite the lack of consensus on particular aspects of the relationship between HCV infection and the formation of atheromatous plaques&#44; cardiovascular disease is an emerging problem in patients infected by this virus&#46;<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">16&#8211;20</span></a> Therefore&#44; although there are currently effective antiviral treatments for curing the viral infection&#44; a better understanding is needed of how HCV infection affects cardiovascular risk&#46; In this study&#44; we investigated whether HCV is an independent risk factor for subclinical atheromatosis&#44; whether there are differences in the lipid profile of patients with HCV infection&#44; with or without atheromatous plaques&#44; and its association with viral load and progression of liver disease as measured by the degree of fibrosis&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Patients and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Study design and patients</span><p id="par0020" class="elsevierStylePara elsevierViewall">This observational and cross-sectional study included outpatients with chronic HCV infection &#40;HCV<span class="elsevierStyleSup">&#43;</span>&#41; and a control group of patients without infection &#40;HCV<span class="elsevierStyleSup">&#8722;</span>&#41; followed-up in 2 university hospitals between March 2015 and June 2016&#46; The HCV<span class="elsevierStyleSup">&#43;</span> group consisted of patients with serologically confirmed &#40;i&#46;e&#46;&#44; positive for HCV antibodies and detectable viral load&#41; chronic HCV infection of any genotype and degree of hepatic fibrosis&#46; The patients were recruited from the hepatology units of the university hospitals Arnau de Vilanova and Santa Mar&#237;a &#40;Lleida&#44; Spain&#41; and entered the study before starting treatment with direct-acting antivirals&#46; The control group included HCV<span class="elsevierStyleSup">&#8722;</span> patients with moderate-low cardiovascular risk &#40;Systematic Coronary Risk Evaluation &#91;SCORE&#93; index &#60;5&#37;&#44; SCORE charts for Low-Risk European populations&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">21</span></a> The control patients were recruited from a cardiovascular risk unit where they underwent arterial ultrasonography to diagnose subclinical atheromatosis &#40;Detection and Treatment of Atherothrombotic Diseases Unit &#91;UDETMA&#93; of University Hospital Arnau de Vilanova of Lleida&#41;&#46; The exclusion criteria for both groups were as follows&#58; &#40;1&#41; age &#60;30 or &#62;75 years&#59; &#40;2&#41; decompensated cirrhosis&#59; &#40;3&#41; presence of hepatocellular carcinoma or other tumors&#59; &#40;4&#41; chronic non-HCV liver disease &#40;due to alcohol&#44; hepatitis B virus&#44; autoimmune disease or iron deposit&#41;&#59; &#40;5&#41; HIV infection&#59; &#40;6&#41; inflammatory disease or acute or chronic infection&#59; &#40;7&#41; previous history of cardiovascular events according to the International Classification of Diseases-10th edition-Clinical Modification&#44; &#40;ICD10-CM&#41; &#91;&#40;a&#41; cerebrovascular disease&#58; transient ischemic attack and&#47;or stable stroke&#59; &#40;b&#41; ischemic heart disease&#58; acute myocardial infarction&#44; unstable angina pectoris&#44; arrhythmias and&#47;or congestive heart failure&#59; &#40;c&#41; peripheral arterial disease of the legs or aortic aneurysm&#93;&#59; &#40;8&#41; chronic renal failure &#40;Chronic Kidney Disease Epidemiology Collaboration equation &#60;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;&#59; &#40;9&#41; diagnosis of diabetes mellitus&#59; &#40;10&#41; dyslipidemia treated with hypolipidemic agents&#59; and &#40;11&#41; history of arterial hypertension undergoing treatment&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">All patients signed an informed consent form before entering the study&#44; which was approved by the ethics committee of the 2 hospitals involved&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Clinical and laboratory data</span><p id="par0030" class="elsevierStylePara elsevierViewall">Clinical data were collected in a standardized interview in the follow-up consultation visit&#46; We used blood samples under fasting conditions to measure the following serum parameters&#58; glucose&#44; total cholesterol &#40;TC&#41;&#44; LDL and HDL cholesterol&#44; triglycerides&#44; creatinine and C-reactive protein &#40;CRP&#41;&#46; We calculated the following lipid coefficients&#58; non-HDL cholesterol &#40;total cholesterol<span class="elsevierStyleHsp" style=""></span>&#8722;<span class="elsevierStyleHsp" style=""></span>HDL cholesterol&#41;&#44; TG&#47;HDL cholesterol &#40;indicator of insulin resistance&#41; and TC&#47;HDL cholesterol &#40;atherogenic index&#41;&#44; performing all measurements in the same laboratory&#46; The anthropometric measurements &#40;weight and height&#41; for calculating the body mass index &#40;BMI&#41; and blood pressure were recorded in the UDETMA before performing the arterial ultrasonography&#46; Systolic and diastolic blood pressure was measured on 3 occasions in the seated position and after 10<span class="elsevierStyleHsp" style=""></span>min of rest&#44; using an automatic pressure monitor &#40;OMRON HEM-705 CP<span class="elsevierStyleSup">&#174;</span>&#41;&#46; We recorded the mean of the last 2 measurements&#46; The patients were also classified according to their history of tobacco use as smokers&#44; former smokers or nonsmokers&#46; The cardiovascular risk was calculated using SCORE risk charts&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">21</span></a> In the patient group with chronic hepatitis&#44; we analyzed the HCV RNA viral load using reverse transcription-polymerase chain reaction &#40;RT-PCR&#41;&#44; with a detection limit of 12<span class="elsevierStyleHsp" style=""></span>IU&#47;mL&#46; We performed transient elastography &#40;Fibroscan<span class="elsevierStyleSup">&#174;</span> &#91;FS&#93;&#44; Echosens&#44; Paris&#44; France&#41; to assess the degree of hepatic fibrosis and classify it as follows&#58; &#60;7&#46;5<span class="elsevierStyleHsp" style=""></span>kPa<span class="elsevierStyleHsp" style=""></span>s &#8211; no fibrosis &#40;F0&#8211;1&#41;&#59; 7&#46;6&#8211;9&#46;5<span class="elsevierStyleHsp" style=""></span>kPa<span class="elsevierStyleHsp" style=""></span>s &#8211; moderate fibrosis &#40;F2&#41;&#59; 9&#46;6&#8211;12&#46;5<span class="elsevierStyleHsp" style=""></span>kPa<span class="elsevierStyleHsp" style=""></span>s &#8211; significant fibrosis &#40;F3&#41;&#59; and &#62;12&#46;5<span class="elsevierStyleHsp" style=""></span>kPa<span class="elsevierStyleHsp" style=""></span>s &#8211; hepatic cirrhosis &#40;F4&#41;&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Assessment of subclinical arterial atheromatosis</span><p id="par0035" class="elsevierStylePara elsevierViewall">We determined the presence of atheromatous plaques in carotid and femoral territories using a General Electronic ultrasound &#40;model Vivid-I<span class="elsevierStyleSup">&#174;</span>&#41; with a 12L-SR vascular probe following a previously described standardized method&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">22</span></a> All images were captured and read by a single team&#44; consisting of previously certified practitioners&#46; The Kappa coefficient for intraobserver reliability was set at 1&#46; Atheromatous plaque is defined as a focal structure that protrudes into the vascular lumen or an intima-media thickness &#40;IMT&#41; &#62;1&#46;5<span class="elsevierStyleHsp" style=""></span>mm&#44; according to the Mannheim consensus&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">23</span></a> We analyzed 12 vascular territories to diagnose the presence of atheromatous plaques&#46; We examined carotid arteries &#40;common&#44; bifurcation&#44; internal and external&#41; and femoral arteries &#40;common and superficial&#41; bilaterally&#44; using a single axial and longitudinal plane&#44; with mode-B and color Doppler ultrasound&#46; We defined subclinical atheromatosis as the presence of 1 or more plaques in any of the studied territories&#46; In the patients without atheromatous plaques&#44; we measured the carotid IMT &#40;CIMT&#41; in the distal segment of the artery&#44; with the final value equal to the mean of the carotid territory&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Statistical analysis</span><p id="par0040" class="elsevierStylePara elsevierViewall">The categorical variables are listed as frequencies and percentages and were compared using Pearson&#39;s chi-squared test&#46; The quantitative variables are listed as median and interquartile range &#40;IQR&#41; or mean and standard deviation &#40;SD&#41;&#44; depending on their distribution&#46; We compared the normally distributed variables with Student&#39;s <span class="elsevierStyleItalic">t</span>-test and compared the non-normally distributed variables with the nonparametric Mann&#8211;Whitney <span class="elsevierStyleItalic">U</span> test&#46; The variables that showed significant differences between the patients with and without atheromatous plaques were included in a backward stepwise conditional multiple logistic regression to predict the presence of atheromatous plaques&#46; We employed a receiver operating characteristic &#40;ROC&#41; analysis to establish an age limit and determine the presence of plaques according to the study population&#39;s age&#44; transforming the quantitative variable into a dichotomous variable according to the obtained cutoff values&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">We studied the association of the changes in lipid profile according to the degree of hepatic fibrosis using an analysis of variance &#40;ANOVA&#41; and the presence of a correlation between the viral load and lipid levels using Spearman&#39;s <span class="elsevierStyleItalic">R</span>&#46; Statistical significance was established by a bilateral <span class="elsevierStyleItalic">&#945;</span> value &#60;0&#46;05&#44; and all analyses were performed using SPSS software &#40;IBM Statistics for Windows&#44; version 20&#46;0&#59; IBM Corp&#46;&#44; Armonk&#44; NY&#41;&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Results</span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Study population characteristics</span><p id="par0050" class="elsevierStylePara elsevierViewall">The study sample included 204 patients&#58; 102 in the HCV<span class="elsevierStyleSup">&#43;</span> group and 102 in the control group&#46; <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> lists the clinical and laboratory data for both populations&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">The study groups presented no statistically significant differences in terms of sex&#44; age or history of tobacco use&#46; The control group presented significantly higher values in most of the classical cardiovascular risk factors&#44; including BMI&#44; systolic and diastolic blood pressure and serum lipid profile&#46; There were no significant differences in terms of glucose and triglyceride levels&#44; TG&#47;HDL coefficient or the indicator of insulin resistance&#44; although the levels were&#44; in all cases&#44; higher for the control patients &#40;96&#46;5 vs&#46; 94&#46;2<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;888&#59; 121&#46;5 vs&#46; 102&#46;9<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;070&#59; and 2&#46;3 vs&#46; 2&#46;1&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;449&#41;&#46; Additionally&#44; the control patients presented significantly higher levels of serum creatinine and CRP and a higher cardiovascular risk index &#40;SCORE&#41;&#44; although the risk was low to moderate for both groups&#46; Almost 55&#37; of the patients with chronic HCV infection presented advanced liver disease &#40;29&#46;4&#37; of whom had grade 4 cirrhosis or fibrosis measured by hepatic elastography&#41;&#46; Some 67&#46;2&#37;&#44; 6&#46;7&#37;&#44; 9&#46;7&#37; and 16&#46;4&#37; were genotypes 1&#44; 2&#44; 3 and 4&#44; respectively&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">The percentage of patients with atheromatosis was significantly greater in the HCV<span class="elsevierStyleSup">&#43;</span> group than in the control group &#40;58&#46;8 vs&#46; 28&#46;4&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#44; with no significant differences in the CIMT measured in the patients without atheromatosis &#40;0&#46;76 vs&#46; 0&#46;89<span class="elsevierStyleHsp" style=""></span>mm&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;18&#41;&#44; although the CIMT was greater in the patients with infection&#46; In the control group&#44; the plaques were distributed 35&#37; in the carotid territory&#44; 23&#46;9&#37; in the femoral territory and 41&#46;1&#37; in both territories&#44; while the patients with HCV infection had a distribution of 45&#46;3&#37; in the carotid territory&#44; 19&#46;8&#37; in the femoral territory and 34&#46;9&#37; in both vascular areas&#46; The mean number of atheromatous plaques was 2&#46;95 &#40;1&#8211;10&#41; in the patients with infection compared with 2&#46;44 &#40;1&#8211;8&#41; in the patients without infection&#46; There were no significant differences between the populations in terms of affected vascular territory &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;710&#41; or in the mean number of detected plaques &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;420&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> analyzes the factors associated with the presence of atheromatous plaques in each of the study populations&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">The presence of atheromatous plaques in both groups &#40;with and without HCV infection&#41; was associated in a statistically significant manner with the male sex&#44; higher blood pressure readings&#44; high triglyceride levels and a greater cardiovascular risk according to the SCORE charts&#46; In terms of age&#44; there was no association with the presence of atheromatous plaques in the patients with infection&#46; In the control group&#44; however&#44; there was an association&#44; such that the presence of plaques was associated with an older age &#40;51&#46;8 years in the control patients without atheromatosis vs&#46; 67&#46;3 years in the control patients with atheromatosis&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#46; In terms of smoking&#44; an association was detected in the patients with HCV &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;003&#41;&#44; with plaques more frequent in the smokers and ex-smokers &#40;81&#46;6&#37;&#41; but not in the control group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;499&#41;&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">In terms of the lipid profile&#44; the patients with HCV and plaques presented lower HDL cholesterol readings &#40;57&#46;6 vs&#46; 50&#46;9<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;023&#41; and higher triglyceride levels &#40;89&#46;3 vs&#46; 112&#46;6<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;029&#41;&#44; TG&#47;HDL coefficient &#40;1&#46;7 vs&#46; 2&#46;3&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;026&#41; and TC&#47;HDL coefficient &#40;3 vs&#46; 3&#46;4&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;035&#41; than the patients with infection but no plaques&#46; There was no significance for these lipid factors between the control patients with or without atheromatous plaques&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">In terms of the viral factors in the patients with HCV infection&#44; we found no association between the presence of plaques and the viral load quantified by RNA &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;936&#41;&#44; but there were significant differences with the degree of hepatic fibrosis&#44; with the presence of plaques occurring more frequently in the patients with advanced fibrosis &#40;F4 without atheromatosis &#91;23&#46;8&#37;&#93; vs&#46; F4 with atheromatosis &#91;33&#46;3&#37;&#93;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;016&#41;&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">We analyzed the age&#44; according to the ROC analysis&#44; and an age older than 54 years was the best cut-off for predicting the presence of atheromatous plaques &#40;AUC&#44; 0&#46;682&#59; standard error&#44; 0&#46;039&#59; 95&#37; CI 0&#46;6&#8211;0&#46;7&#59; 67&#37; sensitivity&#59; 60&#37; specificity&#41;&#46; Below this cutoff &#40;&#60;54 years&#41;&#44; the percentage of patients with atheromatous plaques was 57&#37; in the HCV<span class="elsevierStyleSup">&#43;</span> group and 4&#37; in the control group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#46; In the patients 54 years of age or older&#44; the rate of atheromatosis increased to 61&#37; in the HCV<span class="elsevierStyleSup">&#43;</span> group and to 50&#37; in the control group&#44; without significant differences in this age group between the populations &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;252&#41;&#46; In the age group younger than 54 years&#44; the HCV<span class="elsevierStyleSup">&#43;</span> patients had a much higher probability of atheromatosis than the control group &#40;OR&#44; 30&#59; 95&#37; CI 6&#46;58&#8211;136&#46;67&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Factors associated with subclinical atheromatosis</span><p id="par0090" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> lists the clinical characteristics of the patients with and without subclinical atheromatosis&#46; Chronic HCV infection was significantly associated with the presence of subclinical atheromatosis&#44; as were the classical cardiovascular risk factors such as male sex&#44; advanced age&#44; systolic blood pressure&#44; high scores on SCORE&#44; low serum HDL cholesterol levels and higher triglyceride levels&#46; Chronic HCV infection was also associated with increased TG&#47;HDL quotients&#46; The presence of atheromatous plaques was not associated with BMI&#44; glucose levels or CRP values&#46; There was also no association with the lipid profile consisting of total cholesterol&#44; LDL and non-HDL cholesterol nor with the atherogenic index &#40;TC&#47;HDL&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0095" class="elsevierStylePara elsevierViewall">The multivariate analysis revealed a much higher probability of atheromatosis in the HCV<span class="elsevierStyleSup">&#43;</span> patients than in the control group &#40;OR&#44; 14&#46;37&#59; 95&#37; CI 5&#46;5&#8211;37&#46;5&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46; Other independent risk factors for subclinical atheromatosis included male sex&#44; advanced age and an increased TG&#47;HDL coefficient or indirect indicator of insulin resistance&#46; Neither systolic blood pressure nor the lipid profile contributed to the predictive model for the presence of atheromatous plaques&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Description of the lipid profile according to the degree of hepatic fibrosis in the patients with HCV in terms of the presence of atheromatous plaques</span><p id="par0100" class="elsevierStylePara elsevierViewall">We analyzed the lipid profile of the patients with HCV and with and without atheromatosis&#44; taking into account the degree of hepatic fibrosis measured by elastography&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">In the patients with HCV without atheromatosis&#44; there were no significant differences in any of the classical lipid profile values&#44; the coefficients indicative of insulin resistance &#40;TG&#47;HDL&#41; or the atherogenic factor &#40;TC&#47;HDL&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>a and b&#41;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0110" class="elsevierStylePara elsevierViewall">In the patients with HCV and atheromatosis &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>c and d&#41;&#44; there were significant differences in total cholesterol &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;018&#41;&#44; non-HDL cholesterol &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;002&#41; and LDL cholesterol levels &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;002&#41;&#44; as well as in the atherogenic index &#40;TC&#47;HDL&#41; &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#44; with an increasing trend as the hepatic fibrosis progressed and decreasing significantly in the presence of cirrhosis&#46; There were no changes in HDL cholesterol or triglyceride levels&#44; TG&#47;HDL coefficient or the degree of fibrosis in the presence of atheromatous plaques&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">When analyzing the correlation between the viral load and lipid profile&#44; we detected only a slight association between HCV RNA and non-HDL cholesterol levels &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;219&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;04&#41; and no association with any other analytical parameter&#46;</p></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Discussion</span><p id="par0120" class="elsevierStylePara elsevierViewall">This observational study analyzed the presence of atheromatosis in patients with and without chronic HCV infection and found that the patients with infection had a greater presence of subclinical atheromatosis and at a younger age than the controls&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Our results agree with those recently published in 2 meta-analyses that reported a greater presence of atheromatosis in populations with HCV infection &#40;between 38&#37; and 65&#37;&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">5&#44;6</span></a> In these studies&#44; the atheromatous plaques were identified by vascular Doppler ultrasonography&#44; and the diagnosis was established with a CIMT value &#62;1&#46;3<span class="elsevierStyleHsp" style=""></span>mm&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">20</span></a> In our study&#44; we followed the Mannheim criteria for diagnosing atheromatosis&#44; defining the plaque as an CIMT &#62;1&#46;5<span class="elsevierStyleHsp" style=""></span>mm&#46; One of the possible reasons for our higher rates was the expansion of the femoral study&#44; which increased the probability of detecting atheromatosis&#46; The presence of atheromatosis in the femoral territory in the absence of carotid plaques has been reported in the general population&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">24</span></a> We also analyzed various viral genotypes that have not been evaluated in previously published studies&#44;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">20</span></a> although genotype 3 is known to produce more metabolic disorders than the other genotypes&#46;<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">25&#44;26</span></a> Although the presence of plaques was greater in the patients with infection&#44; these patients had a low cardiovascular risk index according to the SCORE European Risk Charts&#46; Several populational studies have shown an association between the presence of plaques in peripheral arteries and the incidence of cardiovascular events&#44; even in patients without previous events &#40;1&#46;8-fold increased risk of coronary events and 4&#46;1-fold increased risk of cardiovascular events&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">27&#44;28</span></a> In line with these publications&#44; the presence of atheromatous plaques in our population was not associated with classical cardiovascular risk factors such as BMI&#44; blood glucose and dyslipidemia&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Our study involved the first Spanish patient cohort monoinfected with chronic HCV&#44; although it has a number of limitations intrinsic to a cross-sectional design and a selection bias in the control patients&#44; given that they belonged to a patient group from a cardiovascular risk office&#46; To minimize this bias&#44; we limited the selection criteria to patients with a low to moderate risk &#40;&#60;5&#37; probability of experiencing cardiovascular events at 10 years&#41;&#44; with no previous cardiovascular disease and who were not taking drugs for hypertension or dyslipidemia&#46; We excluded patients with diabetes and chronic kidney disease to avoid confounding factors&#46; A number of publications have indicated that HCV promotes the development of diabetes and chronic renal failure&#44; which predisposes patients to the presence of atheromatous lesions&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">16</span></a> Another confounding factor could be the larger presence of ex-smokers and active smokers among those patients with HCV<span class="elsevierStyleSup">&#43;</span> plaques&#44; as could the differences between the degree of hepatic fibrosis in the patients with and without plaques&#46; As shown by the multivariate analysis&#44; however&#44; neither tobacco nor fibrosis affected the development of atheromatous plaques&#46; There was&#44; however&#44; a high association &#40;OR&#44; 14&#46;37&#41; of HCV per se&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Based on these results&#44; we identified chronic HCV infection as an independent risk factor for atheromatosis&#44; with no influence from other classical cardiovascular factors&#44; which suggests a direct role of HCV in the development of atheromatous lesions&#46; Recent studies have shown the presence of HCV RNA in carotid plaques<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">14&#44;15</span></a> and due to the proinflammatory environment that the virus induces&#46;<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">4&#8211;12</span></a> In our study&#44; CRP levels &#40;a widely accepted marker of cardiovascular risk and systemic inflammation for the population<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">22</span></a>&#41; showed no significant differences between the two groups&#44; although hepatic synthesis proteins such as CRP can be altered in patients with chronic liver disease&#46; We also detected the presence of atheromatosis in the population with HCV&#44; which develops at an earlier age than in the group without HCV infection&#46; Below 54 years of age&#44; there were significant differences in the presence of plaques in the patients with infection compared with the controls &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; This finding suggests that the patients with HCV infection have accelerated atheromatosis or premature vascular aging&#44; similar to that observed in other chronic inflammatory and autoimmune diseases&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">29</span></a> In addition to age and HCV infection&#44; the male sex and TG&#47;HDL coefficient &#40;indirect marker of insulin-resistance&#41; were the only factors significantly associated with the presence of atheromatosis&#46; This coefficient is a predictive indicator of cardiovascular disease&#44; used as a marker of atherogenesis in the general population&#46; Although there are few data&#44; its predictive value in heart disease is high&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">30</span></a> The coefficient is also a good marker of atherogenesis in the population with infection&#44; because it does not change significantly with the progression of the liver disease or with the viral load&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">In this study&#44; we analyzed the changes in lipid profile in the various stages of liver disease progression measured by elastography &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41; and detected that&#44; in the patients with infection but without atheromatous plaques&#44; there were no differences in terms of serum lipid levels and hepatic fibrosis&#46; In the patients with HCV and atheromatosis&#44; the most atherogenic particles &#40;composed of LDL and VLDL&#41;&#44; which are the main transporters of HCV in plasma&#44; increased as the fibrosis progressed and decreased significantly once hepatic cirrhosis was established&#46; These more atherogenic particles are weakly correlated with the viral load&#44; without no association with the development of atheromatous plaques&#44; which could be due to the fluctuation in the viremia time or to the fact that these values depend on the progression of the hepatic fibrosis&#44; decreasing in stages of cirrhosis&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">In summary&#44; our results show that the patients with chronic HCV infection had a greater prevalence of subclinical atheromatosis than the population without infection&#44; with an early age at onset &#40;accelerated atheromatosis&#41;&#46; The metabolic profile and cardiovascular risk assessment using classical charts are not good predictors&#44; because most of these patients had low risk SCORES and a &#8220;low-risk&#8221; lipid profile &#40;lower non-HDL cholesterol and LDL cholesterol readings&#41;&#46; These results support the need for additional noninvasive cardiovascular tests for routine use&#44; such as arterial ultrasonography&#44; which could improve the risk stratification for this population&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Conflicts of interest</span><p id="par0150" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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              "titulo" => "Assessment of subclinical arterial atheromatosis"
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              "titulo" => "Description of the lipid profile according to the degree of hepatic fibrosis in the patients with HCV in terms of the presence of atheromatous plaques"
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            1 => "Atheromatous plaque"
            2 => "Subclinical atherosclerosis"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The association between subclinical atheromatosis and chronic hepatitis C virus &#40;HCV&#41; infection is unknown but is relevant now that antivirals are improving the survival of patients with the infection&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objectives</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">To determine whether HCV is an independent risk factor for subclinical atheromatosis and to analyze the changes in lipid profiles according to viral RNA levels and hepatic fibrosis&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Patients and methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">We conducted an observational&#44; cross-sectional study that included 102 HCV-positive patients and 102 HCV-negative patients with parity in terms of sex and age&#44; with no history of cardiovascular or kidney disease or diabetes&#46; Atheromatosis &#40;the presence of atheromatous plaques&#41; and the carotid intima-media thickness &#40;CIMT&#41; were assessed using ultrasonography of the carotid and femoral arteries&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">There was a greater presence of atheromatosis in any vascular territory in HCV-positive patients than in the patients without infection &#40;58&#46;8&#37; vs&#46; 28&#46;4&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;0001&#41;&#46; In the multivariate analysis&#44; the factors significantly associated with atheromatosis included HCV infection &#40;OR&#44; 14&#46;37 &#91;5&#46;5&#8211;37&#46;3&#93;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#44; age &#40;OR&#44; 1&#46;12 &#91;1&#46;1&#8211;1&#46;2&#93;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#44; male sex &#40;OR&#44; 4&#46;32 &#91;1&#46;9&#8211;9&#46;5&#93;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41; and the triglyceride&#47;HDL cholesterol coefficient &#40;TG&#47;HDL-indirect indicator of insulin resistance&#41; &#40;OR&#44; 1&#46;34 &#91;1&#46;1&#8211;1&#46;6&#93;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;007&#41;&#46; The HCV-positive patients with atheromatous plaques had a higher TG&#47;HDL coefficient but no significant differences in terms of the viral load or degree of hepatic fibrosis and with a &#8216;low risk&#8217; lipid profile&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusions</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">HCV infection is an independent risk factor for subclinical atheromatosis&#46; Systemic arterial ultrasonography for this population improves the cardiovascular risk assessment beyond lipid profile abnormalities and the risk calculation using SCORE tables&#46;</p></span>"
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        "resumen" => "<span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Introducci&#243;n</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Se desconoce la asociaci&#243;n entre ateromatosis subcl&#237;nica e infecci&#243;n cr&#243;nica por el virus de la hepatitis C &#40;VHC&#41;&#44; relevante ahora que los antivirales mejoran la supervivencia en los pacientes infectados&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Objetivos</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Conocer si el VHC es factor de riesgo independiente de ateromatosis subcl&#237;nica y analizar las modificaciones del perfil lip&#237;dico seg&#250;n niveles de ARN viral y fibrosis hep&#225;tica&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Pacientes y m&#233;todos</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Estudio observacional y transversal&#59; incluye 102 pacientes VHC positivos y 102 sujetos VHC negativos con paridad de sexo y edad&#44; sin antecedentes de enfermedad cardiovascular&#44; renal ni diabetes&#46; La ateromatosis &#40;presencia de placas de ateroma&#41; y el grosor &#237;ntima-media carot&#237;deo &#40;GIMc&#41; se evalu&#243; mediante ecograf&#237;a de arterias car&#243;tidas y femorales&#46;</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Resultados</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">La presencia de ateromatosis en cualquier territorio vascular fue mayor en pacientes VHC que en sujetos no infectados &#40;58&#44;8&#37; frente a 28&#44;4&#37;&#44; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46; En el an&#225;lisis multivariante&#44; los factores significativamente asociados con ateromatosis incluyeron infecci&#243;n por VHC &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>14&#44;37 &#91;5&#44;5-37&#44;3&#93;&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#44; edad &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#44;12 &#91;1&#44;1-1&#44;2&#93;&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#44; sexo masculino &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4&#44;32 &#91;1&#44;9-9&#44;5&#93;&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; y el coeficiente triglic&#233;ridos&#47;colesterol HDL &#40;TG&#47;HDL-indicador indirecto de insulinorresistencia&#41; &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#44;34 &#91;1&#44;1-1&#44;6&#93;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;007&#41;&#46; Los pacientes VHC con placas de ateroma presentaban mayor coeficiente TG&#47;HDL&#44; sin diferencias significativas en cuanto a la carga viral ni grado de fibrosis hep&#225;tica con un perfil lip&#237;dico de &#171;bajo riesgo&#187;&#46;</p></span> <span id="abst0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conclusiones</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">La infecci&#243;n VHC es factor de riesgo independiente de ateromatosis subcl&#237;nica&#46; La ecograf&#237;a arterial sist&#233;mica en esta poblaci&#243;n mejora la evaluaci&#243;n del riesgo cardiovascular m&#225;s all&#225; de las alteraciones del perfil lip&#237;dico y del c&#225;lculo de riesgo por tablas SCORE&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0020">Please cite this article as&#58; Revuelto Artigas T&#44; Zaragoza Velasco N&#44; G&#243;mez Arbones X&#44; Vidal Ballester T&#44; Pi&#241;ol Felis C&#44; Re&#241;e Espinet JM&#44; et al&#46; Infecci&#243;n cr&#243;nica por el virus de la hepatitis C&#58; un factor de riesgo independiente para la ateromatosis subcl&#237;nica&#46; Rev Clin Esp&#46; 2019&#59;219&#58;293&#8211;302&#46;</p>"
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          "leyenda" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviations</span>&#58; CIMT&#44; carotid intima-media thickness&#59; CRP&#44; C-reactive protein&#59; DBP&#44; diastolic blood pressure&#59; HCV&#44; hepatitis C virus&#59; HDL&#44; high-density lipoprotein&#59; IMT&#44; intima-media thickness&#59; LDL&#44; low-density lipoprotein&#59; NS&#44; not significant&#59; SBP&#44; systolic blood pressure&#59; TC&#44; total cholesterol&#59; TG&#44; triglycerides&#46;</p><p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Quantitative variable&#58; mean &#40;SD&#44; range&#41;&#46;</p><p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Qualitative variable&#58; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&#46;</p><p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">Significance threshold&#58; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;05&#46;</p>"
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                  \t\t\t\t">135 &#40;20&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">&#60;&#46;001&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">79&#46;1 &#40;11&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Blood glucose&#44; g&#47;dL</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">94&#46;2 &#40;13&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">96&#46;5 &#40;13&#46;1&#41;&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">NS&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">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "leyenda" => "<p id="spar0100" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviations</span>&#58; BMI&#44; body mass index&#59; CRP&#44; C-reactive protein&#59; CT&#44; total cholesterol&#59; DBP&#44; diastolic blood pressure&#59; HCV&#44; hepatitis C virus&#59; HDL&#44; high-density lipoprotein&#59; LDL&#44; low-density lipoprotein&#59; NS&#44; not significant&#59; SBP&#44; systolic blood pressure&#59; TG&#44; triglycerides&#46;</p><p id="spar0105" class="elsevierStyleSimplePara elsevierViewall">Quantitative variable&#58; mean &#40;SD&#44; range&#41;&#46;</p><p id="spar0110" class="elsevierStyleSimplePara elsevierViewall">Qualitative variable&#58; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&#46;</p><p id="spar0115" class="elsevierStyleSimplePara elsevierViewall">Significance threshold&#58; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;05&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Without plaques &#40;<span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>42&#41;&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">With plaques &#40;<span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>60&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span><a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Without plaques &#40;<span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>73&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">With plaques &#40;<span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>29&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span><a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a>&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\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \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">&#60;&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t  " align="char" valign="\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\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\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">51&#46;6 &#40;31&#8211;74&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">54&#46;2 &#40;34&#8211;75&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">51&#46;8 &#40;32&#8211;75&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">67&#46;3 &#40;37&#8211;75&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;&#46;001&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
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                  \t\t\t\t"><span class="elsevierStyleItalic">Smoke&#47;ex-smoker</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">23 &#40;54&#46;7&#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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">49 &#40;81&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;003&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">48 &#40;65&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17 &#40;58&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NS&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="elsevierStyleItalic">BMI&#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 &#40;3&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">26&#46;6 &#40;4&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27&#46;8 &#40;5&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27&#46;9 &#40;3&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NS&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="elsevierStyleItalic">SBP&#44; mmHg</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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">119&#46;2 &#40;18&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">127&#46;4 &#40;13&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;011&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">130&#46;1 &#40;20&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">147&#46;2 &#40;16&#46;6&#41;&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">&#60;&#46;001&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="elsevierStyleItalic">DBP&#44; mmHg</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">72&#46;9 &#40;11&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \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">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">77&#46;3 &#40;11&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">83&#46;7 &#40;8&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;003&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Blood glucose&#44; g&#47;dL</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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">90&#46;6 &#40;9&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">96&#46;7 &#40;16&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;029&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" scope="col">Patients without atheromatous plaques &#40;<span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>115&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Chronic HCV infection</span>&nbsp;\t\t\t\t\t\t\n
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                  "referenciaCompleta" => "World Health Organization&#46; Hepatitis C&#46; n&#46;d&#46; Available from&#58; <a target="_blank" href="http://www.euro.who.int/en/what-we-do/health-topics/communicable-diseases/hepatitis">http&#58;&#47;&#47;www&#46;euro&#46;who&#46;int&#47;en&#47;what-we-do&#47;health-topics&#47;communicable-diseases&#47;hepatitis</a> &#91;accessed 2018&#93;&#46;"
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        "texto" => "<p id="par0155" class="elsevierStylePara elsevierViewall">The authors would like to thank the entire UDETMA team for performing the arterial ultrasounds for detecting subclinical atheromatosis&#46;</p>"
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Original language: English
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