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Vascular target organ damage in patients with Philadelphia negative myeloproliferative syndrome: A propensity score analysis
Lesión de órgano diana vascular en pacientes con síndrome mieloproliferativo cromosoma Filadelfia negativo: comparación con población sana mediante Propensity Score
Carmen Patino-Alonsoa,b,
Corresponding author
carpatino@usal.es

Corresponding author.
, Marta Gómez-Sáncheza, Jesús M. Hernández-Rivasd,f,g, José R. González-Porrasf,g, José M. Bastida-Bermejof,g, Ana-Africa Martínf,g, Emiliano Rodríguez-Sáncheza,d, José I. Recio-Rodrígueza,e, Jesús González-Sáncheza,e, José A. Maderuelo-Fernándeza, Luis García-Ortiza,c, Manuel A. Gómez-Marcosa,d
a Primary Care Research Unit of Salamanca (APISAL), Biomedical Research Institute of Salamanca (IBSAL), 37005 Salamanca, Spain
b Department of Statistics, University of Salamanca, Salamanca, Spain
c Department of Biomedical and Diagnostic Sciences, University of Salamanca, Salamanca, Spain
d Department of Medicine, University of Salamanca, Salamanca, Spain
e Department of Nurse and Physiotherapy, University of Salamanca, Salamanca, Spain
f Department of Hematology, Hospital Clínico Universitario, Salamanca, Spain
g Center of Cancer Research, Biomedical Research Institute of Salamanca (IBSAL), Salamanca, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Philadelphia chromosome negative myeloproliferative neoplasms &#40;Ph-MPNs&#41; are a heterogeneous group of chronic clonal blood diseases of the myeloid line whose abnormality occurs in bone marrow haematopoietic stem cells&#44; leading to an excessive proliferation&#44; expansion and accumulation of cells&#46;<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">1&#44;2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Ph-MPNs are associated with venous thrombosis and up to 60&#37; of subjects experience a thrombotic event during their lifetime&#44; leading to stroke or myocardial infarction&#44; which are the causes of death in 30&#8211;50&#37; of subjects&#46;<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">2&#8211;4</span></a> The occurrence of thrombotic complications has been related to hematocrit levels greater than 45&#37; in patients with polycythemia vera &#40;PV&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">1&#44;5</span></a> Patients with polycythemia vera &#40;PV&#41;&#44; a myeloproliferative neoplasm characterized by an elevated red blood cell mass&#44; are at high risk of vascular and thrombotic complications and have reduced quality of life&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">6</span></a> At present&#44; both PV and essential thrombocythaemia &#40;ET&#41; lead to a significant increase in cardiovascular risk&#44;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">5</span></a> associated with impaired coronary artery reserve flow due to impaired coronary microcirculation&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">4</span></a> Some authors claim that therapeutic erythrocytapheresis safely reduces haematocritvalues in patients with PV&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">7</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The incidence of morbidity and mortality from cardiovascular disease is usually associated with the presence of cardiac&#44; renal or vascular target organ damage &#40;TOD&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">8&#8211;12</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Since the main cause of death in subjects with Ph-MPNs is cardiovascular disease&#44; we think that the presence of TOD will be greater in this group of subjects&#46; However&#44; we have found no studies analyzing whether subjects with Ph-MPNs have a higher percentage of TOD or increased arterial stiffness&#46; Therefore&#44; the objective of this study is to assess whether subjects with Ph-MPNs show differences in the presence of vascular&#44; cardiac or renal target organ damage &#40;TOD&#41; and other vascular function parameters as compared to individuals without this condition&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Study design</span><p id="par0025" class="elsevierStylePara elsevierViewall">An observational study of subjects with Ph-MPNs&#44; with a control group without this disease has been performed&#46; Subjects were recruited at the Salamanca Health Area&#44; subjects with Ph-MPNs at the Haematology Department of Clinical Hospital and subjects without Ph-MPNs at Primary care Research Unit The Alamedilla&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Study population</span><p id="par0030" class="elsevierStylePara elsevierViewall">By consecutive sampling in the hematology clinic&#44; 57 subjects diagnosed with Ph-MPNs &#40;27 with polycythemia vera&#44; 29 with essential thrombocythemia and 1 with primary myelofibrosis&#41; were included&#46; Two cases were selected without Ph-MPNs for each case among the subjects referred to the La Alamedilla Research Unit to assess cardiovascular risk and the presence of TOD&#46; A total of 114 subjects between the ages of 39 and 85 years were included&#44; withouth diagnosis of cerebrovascular or ischemic heart disease&#46; Data were collected since 1 January 2015&#8211;31 December 2015&#46; The median time from diagnosis of Ph-MPN to inclusion in the study was five years&#44; inter-quartile range &#40;IQR&#41;&#58; &#40;3&#8211;9&#41;&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">The size sample was estimated to detect a difference in the mean intima-media thickness &#40;IMT&#41; of 0&#46;05<span class="elsevierStyleHsp" style=""></span>mm between the subjects with Ph-MPNs and controls&#44; accepting an alpha risk of 0&#46;05 and a beta risk of 0&#46;20 in a two-sided test with a 1&#58;2 ratio and assuming a SD of 0&#46;10<span class="elsevierStyleHsp" style=""></span>mm&#44; 48 subjects were required in the first group and 96 in the second&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Variables and measurement instruments</span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Anthropometric measurements</span><p id="par0040" class="elsevierStylePara elsevierViewall">Body weight was determined using a scale &#40;Seca 770&#44; Medical scale and measurement systems&#44; Birmingham&#44; United Kingdom&#41; following due calibration &#40;precision<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;1<span class="elsevierStyleHsp" style=""></span>kg&#41;&#46; These readings were rounded to 100<span class="elsevierStyleHsp" style=""></span>g&#46; Height was measured with a height rod &#40;Seca 222&#41;&#46; The values used in the study were the average of two weights and two measurements of height&#46; Body mass index &#40;BMI&#41; was calculated using the formula&#58; &#40;BMI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>weight &#40;kg&#41;&#47;height &#40;m<span class="elsevierStyleSup">2</span>&#41;&#46; A BMI<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>30<span class="elsevierStyleHsp" style=""></span>kg&#47;m<span class="elsevierStyleSup">2</span>was defined as obesity&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">13</span></a> Waist Society for the Study of Obesity in 2007&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">14</span></a> A WC<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>88<span class="elsevierStyleHsp" style=""></span>cm in women and WC<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>102 in men was considered abdominal obesity&#46; All measurements were taken with the subjects standing&#44; wearing light clothing and shoeless&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Office clinical blood pressure</span><p id="par0045" class="elsevierStylePara elsevierViewall">Three readings of systolic blood pressure &#40;SBP&#41; and diastolic pressure &#40;DBP&#41; were performed&#46; An OMRON model M10&#174; sphygmomanometer was used &#40;Omron Healthcare&#44; Kyoto&#44; Japan&#41;&#44; validated by the European Society of Hypertension&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">15</span></a> Measurements were made in the participant&#39;s dominant arm&#44; in a seated position after at least 5<span class="elsevierStyleHsp" style=""></span>min of rest&#44; with a cuff of appropriate size at the circumference of the upper arm and following the recommendations of the European Society of Hypertension&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">13</span></a> We used the mean of the last two measurements as clinical blood pressure reference values&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Laboratory determinations</span><p id="par0050" class="elsevierStylePara elsevierViewall">A venous blood sample was taken between 08&#58;00 and 09&#58;00<span class="elsevierStyleHsp" style=""></span>a&#46;m&#46; after fasting for at least 12<span class="elsevierStyleHsp" style=""></span>h&#46; Blood and urine samples were collected at the health centre and analysed at the laboratory of the reference hospital&#46; Samples were taken to measure blood count&#44; kidney function&#44; albumin-to-creatinine ratio&#44; blood glucose&#44; lipid profile&#44; HbA1c&#44; and serum electrolytes&#46; Cholesterol and triglyceride levels were measured by enzymatic methods and HDL cholesterol after precipitation of apo B-containing lipoproteins&#46; LDL cholesterol was measured using the Friedewald formula&#46;</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Measurements</span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Heart damage</span><p id="par0055" class="elsevierStylePara elsevierViewall">Left ventricular hypertrophy &#40;LVH&#41;&#58; It was assessed with a digital electrocardiograph that automatically measures voltage and wave duration&#46; It was calibrated at an amplitude of 10<span class="elsevierStyleHsp" style=""></span>mm&#47;mV and at a speed of 25<span class="elsevierStyleHsp" style=""></span>mm&#47;s&#46; The Sokolow and Cornell VDP criteria were used to assess the presence of LVH&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">16</span></a></p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Kidney damage</span><p id="par0060" class="elsevierStylePara elsevierViewall">Renal impairment was measured by plasma creatinine&#44; glomerular filtration rate&#44; estimated using the Chronic Kidney Disease Epidemiology Collaboration &#40;CKD-EPI&#41; equation &#40;30&#41;&#44; and the presence of microalbuminuria&#44; which was measured using the albumin-to-creatinine ratio&#46; Renal TOD was defined with the criteria of the European Society of Hypertension and Cardiology guidelines&#46;</p></span></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Vascular damage</span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Assessment of carotid intima-media thickness&#40;C-IMT&#41;</span><p id="par0065" class="elsevierStylePara elsevierViewall">Using the SonoSite MicroMaxx digital ultrasound machine &#40;Sonosite Inc&#46;&#44; Bothell&#44; Washington&#44; USA&#41;&#44; with a high-resolution linear transducer of 5&#8211;10<span class="elsevierStyleHsp" style=""></span>MHz&#44; carotid intima-media thickness &#40;IMT&#41; was assessed following the recommendations of the Mannheim consensus&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">16</span></a> The Sonocal software was used&#44; which performs automated IMT measurements to optimize reproducibility&#46; Longitudinal B-mode ultrasound was performed with the subject in a supine position&#44; with extension and slight cephalic rotation contralateral to the carotid artery to be measured&#46; Measurements were made on a longitudinal section of 10<span class="elsevierStyleHsp" style=""></span>mm in the common carotid artery at a distance of 1<span class="elsevierStyleHsp" style=""></span>cm proximal to the bifurcation&#44; performing measurements in the proximal and distal walls&#44; in lateral &#40;90&#41;&#44; anterior &#40;45&#41; and posterior &#40;135&#176;&#41; views&#44; following an axis perpendicular to the artery&#46; A total of 60 measurements were made in the right carotid and 60 measurements in the left carotid&#44; ten for each segment analysed&#46; The average and maximum values calculated by the software were used&#46; This protocol has a better association with the presence of other target organ damage and estimated CVR using the Framingham scale&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">17</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">Intima-media thickness was defined as the distance between the lumen-intima interface and the mid-adventitia interface of the distal carotid wall expressed in millimetres&#46; Target organ damage was considered to exist when plaque was present&#44; defined as a diffuse thickening greater than 1&#46;5<span class="elsevierStyleHsp" style=""></span>mm&#44; an increase in focal IMT of at least 0&#46;5<span class="elsevierStyleHsp" style=""></span>mm&#44; or a 50&#37; increase in the thickness of the adjacent wall of the carotid artery&#44; or IMT is greater than 0&#46;90<span class="elsevierStyleHsp" style=""></span>mm&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">13</span></a></p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Carotid femoral PWV</span><p id="par0075" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Carotid femoral PWV</span> &#40;cf-PWV&#41; was estimated using the SphygmoCor System &#40;AtCor Medical Pty Ltd&#46;&#44; Head Office&#44; West Ryde&#44; Australia&#41;&#46; Cf-PWV was estimated with patients in the supine position&#46; The pulse wave of the carotid and femoral arteries were analyzed to estimate the delay with respect to the ECG wave and calculate the cf-PWV&#46; Distance measurements were collected with a measuring tape from the sternal notch to the carotid and femoral arteries at the sensor location&#46; We considered TOD if the PWV was higher than 10<span class="elsevierStyleHsp" style=""></span>m&#47;s&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">13</span></a></p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Cardio ankle vascular index &#40;CAVI&#41;&#44; and brachial ankle pulse wave velocity &#40;ba-PWV&#41;</span><p id="par0080" class="elsevierStylePara elsevierViewall">CAVI was measured using a VaSera VS-1500&#174; device &#40;Fukuda Denshi&#41;&#46; It is a device that assesses arterial stiffness ensuring good repetitiveness&#44; ease of use&#44; and less discomfort for subjects&#46; CAVI is a more precise calculation of the degree of arterial stiffness&#44; since it integrates the cardiovascular elasticity derived from PWV from the aortic valve to the ankle using an oscillometric method and is used as a good parameter of vascular stiffness&#46; It does not depend on the blood pressure at the time of measurement&#46;<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">18&#44;19</span></a> CAVI values were calculated automatically by substituting the stiffness parameter in the following equation for detecting vascular elasticity and PWV&#44; stiffness parameter<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#946;</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2<span class="elsevierStyleItalic">&#961;</span><span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>1&#47;&#40;Ps<span class="elsevierStyleHsp" style=""></span>&#8722;<span class="elsevierStyleHsp" style=""></span>Pd&#41;<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>ln &#40;Ps&#47;Pd&#41;<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>PWV&#44;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">2</span></a> where <span class="elsevierStyleItalic">&#961;</span> is the density of blood&#44; Ps and Pd are SBP and DBP in mmHg&#44; and PWV is measured between the aortic valve and the ankle&#46;<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">18&#44;19</span></a> The mean coefficient of variation of the measurement of CAVI is less than 5&#37;&#44; which is small enough to be used in the clinic and confirms that CAVI has favourable reproducibility&#46;<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">18&#44;19</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">CAVI was classified as normal &#40;CAVI<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>9&#41; and abnormal &#40;CAVI<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>9&#41;&#46; Brachial-ankle PWV<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>15&#46;5<span class="elsevierStyleHsp" style=""></span>m&#47;s is considered abnormal&#46; The mean values for the CAVI and ba-PWV were considered for the study&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">The researchers who performed the different tests were blinded to the clinical data of the subjects&#46;</p></span></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Statistical analysis</span><p id="par0095" class="elsevierStylePara elsevierViewall">Continuous variables were expressed as the mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>standard deviation for normally distributed continuous data&#46; The median &#40;interquartile range&#58; IQR&#41; was used for asymmetrically-distributed continuous data&#44; and the frequency distribution was used for categorical data&#46; Statistical normality was tested using the Kolmogorov&#8211;Smirnov test&#46; Qualitative variables were compared using the Chi-square test and Fisher&#39;s exact test&#46; The Student&#39;s <span class="elsevierStyleItalic">t</span>-test and Mann&#8211;Whitney <span class="elsevierStyleItalic">U</span> test were used to compare the difference in means of quantitative variables between two categories&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">A logistic regression analysis was performed&#44; using the presence of TOD as the dependent variable&#44; Ph-MPNs &#40;0<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>No&#44; 1<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>Yes&#41; as the independent variable&#44; and DBP&#44; WC&#44; LDL-Cholesterol&#44; HbA1c&#44; fibrinogen&#44; and antihypertensive drugs were used as adjustment variables&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Groups were balanced using the propensity scores to match subjects with and without Ph-MPNs in a 1&#58;2 ratio from an initial sample of 264 subjects&#46; To calculate propensity&#44; demographic variables and clinical characteristics &#40;gender&#44; type 2 diabetes mellitus&#44; arterial hypertension&#44; hyperlipidemia and smoking&#41; were used&#46; The data were analyzed using the IBM SPSS Statistics for Windows&#44; Version 25&#46;0 &#40;IBM Corp&#44; Armonk&#44; NY&#41;&#46; A value of <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05 was considered statistically significant&#46;</p></span></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Results</span><p id="par0110" class="elsevierStylePara elsevierViewall">The study included 171 patients&#44; aged 39-85 years&#44; of whom 55&#37; were women&#46; Differences in demographic and clinical characteristics between subjects with and without Ph-MPNs are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; Subjects with Ph-MPNs had lower WC values &#40;92&#46;1 vs 96&#46;3&#41;&#44; total cholesterol &#40;176 vs 196<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#41;&#44; LDL-cholesterol &#40;101 vs 117<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#41;&#44; fibrinogen &#40;315 vs 342<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#41; and higher pulse pressure &#40;57 vs 51<span class="elsevierStyleHsp" style=""></span>mmHg&#41; &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05 in all cases&#41;&#46; They also have a lower number of red blood cells and a higher leukocyte and platelet count&#44; with greater consumption of antiplatelet drugs&#46; Before the study&#44; 8&#46;8&#37; of the patients had had thrombosis in vascular territories other than the coronary and cerebral arteries &#40;men 8&#37;&#44; women 9&#46;4&#37;&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0115" class="elsevierStylePara elsevierViewall">The percentage of JAK2&#44; CALR and MPL mutations performed can be found in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>S of the supplementary material&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Regarding the presence of renal&#44; cardiac&#44; or vascular TOD&#44; subjects with Ph-MPNs had a higher albumin&#47;creatinine ratio and a higher frequency of carotid artery damage than controls &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0125" class="elsevierStylePara elsevierViewall">In the logistic regression analysis&#44; we considered having or not having Ph-MPNs as the independent variables and the presence or absence of renal&#44; cardiac&#44; or vascular TOD &#40;carotid injury&#44; cf-PWV<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>10&#44; and CAVI<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>9&#41; and as dependent variables&#46; We adjusted for DBP&#44; WC&#44; LDL-C&#44; HbA1c&#44; fibrinogen&#44; and antihypertensive drugs&#46; Subjects with Ph-MPNs had an OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#46;382 &#40;1&#46;066&#8211;5&#46;323&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;034&#41; for carotid injury compared to those without hematological disease &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#44; with no association with the other dependent variables&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Discussion</span><p id="par0130" class="elsevierStylePara elsevierViewall">The results of this study show that subjects with Ph-MPNs have a two times greater risk of vascular TOD &#40;carotid artery injury&#41; than controls&#44; with no association with the presence of cardiac and renal TOD after adjusting for possible confounding factors&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Although no previous studies have found the presence of renal&#44; cardiac&#44; or vascular TOD in subjects with Ph-MPNs&#44; the results of this study suggest a higher risk of carotid TOD and increased albumin -to-creatinine ratio&#46; These results agree with previous studies suggesting that this condition is associated to an increase in thrombotic events&#44; resulting in stroke and&#47;or myocardial infarction and thus leading to increased cardiovascular risk&#46;<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">2&#8211;4</span></a> On the other hand&#44; high IMT&#44; and particularly the presence of plaques<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">20</span></a> is associated with atherosclerosis in other vascular systems and an increased risk of future cardiovascular events in both the general population and in subjects with coronary heart disease&#46;<a class="elsevierStyleCrossRefs" href="#bib0260"><span class="elsevierStyleSup">21&#44;22</span></a> This target organ damage is an independent predictor of the incidence of cardiac&#44; coronary&#44; and cerebrovascular disease&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">23</span></a> Similarly&#44; alteration in arterial stiffness parameters is associated with an increased number of cardiovascular events&#46;<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">24&#8211;28</span></a> Thus&#44; for every 1<span class="elsevierStyleHsp" style=""></span>m&#47;s increase in cf-PWV&#44; there is an associated increase in the risk of cardiovascular events of 10&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">26</span></a> Also&#44; CAVI is a predictor of cardiovascular events in obese subjects<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">28</span></a> and has been associated with atherosclerosis in coronary and carotid arteries&#46;<a class="elsevierStyleCrossRefs" href="#bib0300"><span class="elsevierStyleSup">29&#8211;31</span></a> Another finding in this study was the lack of difference in the presence of cardiac and renal TOD between cases and controls&#46; This could suggest that the greater increase in the number of cardiovascular events found in the group of subjects with Ph-MPNs is associated with the increased risk of arterial thrombosis and changes in the vascular wall&#44; but not with an increased risk of having left ventricular hypertrophy or impaired renal function&#46; Nevertheless&#44; the number of subjects with cardiac or renal TOD is very small&#44; and this may influence the statistical power to detect an association among these variables&#46; However&#44; the albumin-to-creatinine ratio is higher in subjects with Ph-MPNs&#46; This could be explained&#44; as has been shown in the coronary microcirculation&#44;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">4</span></a> by the fact that these subjects have altered renal microcirculation&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">In summary&#44; the results found in this study are novel&#44; since no previous studies have analysed whether there are differences in the presence of cardiac&#44; renal or vascular TOD and other vascular function parameters in subjects with Ph-MPNs compared to controls without this disease&#44; The results found suggest that impaired vascular structure and function parameters are greater in subjects with Ph-MPNs&#44; which would increase the cardiovascular risk of these patients due to increased thrombosis risk caused by the disease they suffer&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">This study has certain limitations&#46; First&#44; it is a cross-sectional design&#44; which does not allow us to establish causal relationships or the direction of the influence of vascular structure and function parameters in haematological subjects&#44; only associations&#46; Second&#44; the samples were obtained at the clinical hospital and primary care centres&#44; which could lead to a selection bias&#46; Third&#44; the small number of haematological subjects included and the fact that patients were not at the time of diagnosis&#44; may prevent us from reaching significance in existing associations&#46; Finally&#44; subjects with Ph-MPNs were not included at the time of diagnosis and were medically treated on antiaggregant&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">In conclusion&#44; subjects with Ph-MPNs have twice the risk of carotid injury&#44; as compared to subjects without haematological disease&#46;</p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Ethics statement</span><p id="par0155" class="elsevierStylePara elsevierViewall">All participants were informed about the objectives and procedures of the study and signed the informed consent form before inclusion&#46; The study was approved by the Clinical Research Ethics Committee of the Health Care Area of Salamanca&#46; The study was conducted according to the recommendations of the Declaration of Helsinki&#46; The confidentiality of the information provided by the participants was ensured&#44; complying with the rules established by Spanish Law 15&#47;1999 on the Protection of Personal Data&#46;</p></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Sources of funding</span><p id="par0160" class="elsevierStylePara elsevierViewall">This work was supported by grants from the <span class="elsevierStyleGrantSponsor" id="gs1">Spanish Ministry of Science and Innovation &#40;MICINN&#41;</span>&#44; by RedIAPP&#58; &#40;<span class="elsevierStyleGrantNumber" refid="gs1">RD16&#47;0007&#47;0003</span>&#41;&#44; cofinanced with <span class="elsevierStyleGrantSponsor" id="gs2">European Union ERDF and the Regional Health Management of Castilla y Le&#243;n</span> &#40;<span class="elsevierStyleGrantNumber" refid="gs2">BIO&#47;SA53&#47;15</span>&#59; <span class="elsevierStyleGrantNumber" refid="gs2">GRS 1275&#47;B&#47;16</span>&#41;&#46;</p></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0165">Conflicts of interest</span><p id="par0165" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflict of interest&#46;</p></span></span>"
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                  "titulo" => "Anthropometric measurements"
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                  "titulo" => "Office clinical blood pressure"
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              "titulo" => "Vascular damage"
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                  "identificador" => "sec0065"
                  "titulo" => "Assessment of carotid intima-media thickness&#40;C-IMT&#41;"
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                  "identificador" => "sec0070"
                  "titulo" => "Carotid femoral PWV"
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                  "identificador" => "sec0075"
                  "titulo" => "Cardio ankle vascular index &#40;CAVI&#41;&#44; and brachial ankle pulse wave velocity &#40;ba-PWV&#41;"
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    "fechaRecibido" => "2021-03-31"
    "fechaAceptado" => "2021-05-27"
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          "clase" => "keyword"
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          "palabras" => array:4 [
            0 => "Polycythemia vera"
            1 => "Essential thrombocythemia"
            2 => "Target organ damage"
            3 => "Arterial stiffness"
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          "clase" => "keyword"
          "titulo" => "Palabras clave"
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          "palabras" => array:4 [
            0 => "Policitemia vera"
            1 => "Trombocitemia esencial"
            2 => "Lesi&#243;n de &#243;rgano diana"
            3 => "Rigidez arterial"
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    "resumen" => array:2 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Purpose</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To assess whether subjects with Philadelphia negative myeloproliferative neoplasms &#40;Ph-MPNs&#41; show differences in the presence of vascular&#44; cardiac or renal target organ damage &#40;TOD&#41; and other vascular function parameters as compared to individuals without this condition&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">An observational study was conducted&#46; Fifty-seven subjects diagnosed with Ph-MPNs used as cases and 114 subjects without Ph-MPNs as controls&#46; We matched the subjects with and without Ph-MPNs using the propensity scores in a 1&#58;2 ratio using the variables gender&#44; type 2 diabetes mellitus&#44; high blood pressure&#44; hyperlipidaemia and smoking&#46; Vascular&#44; cardiac and renal TOD were established according to the criteria of the European Society of Hypertension and Cardiology guidelines&#46; Arterial stiffness was also assessed using the cardio-ankle vascular index &#40;CAVI&#41;&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Mean age was 63&#46;50<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11&#46;70 and 62&#46;90<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#46;32 years in subjects with and without Ph-MPNs&#44; 32 females &#40;56&#37;&#41; in the first group and 62 &#40;54&#37;&#41; in the second&#46; Subjects with Ph-MPNs have a higher percentage of carotid injury than subjects without Ph-MPNs &#40;35&#46;1&#37; vs&#46; 21&#46;1&#37;&#41; and higher albumin&#47;creatinine ratio&#46; In the logistic regression analysis&#44; subjects with Ph-MPNs had an OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#46;382 &#40;IC95&#37; 1&#46;066&#8211;5&#46;323&#41; for carotid injury versus those without haematological disease&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Subjects with Ph-MPNs have twice the risk of by carotid injury than those without haematological disease&#46;</p></span>"
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            "identificador" => "abst0005"
            "titulo" => "Purpose"
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            "identificador" => "abst0010"
            "titulo" => "Methods"
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          2 => array:2 [
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Evaluar si los sujetos con neoplasias mieloproliferativas Filadelfia negativos &#40;NMPs-FN&#41; muestran diferencias en cuanto a presencia de lesi&#243;n de &#243;rgano diana &#40;LOD&#41; vascular&#44; cardiaca o renal y en otros par&#225;metros de funci&#243;n vascular con respecto a los individuos sin esta patolog&#237;a&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Se realiz&#243; un estudio observacional&#46; Se incluyeron 57 sujetos con diagn&#243;stico de NMPs-FN utilizados como casos y 114 sujetos sin NMPs-FN como controles&#46; Emparejamos a los sujetos con y sin NMPs-FN con la t&#233;cnica de <span class="elsevierStyleItalic">Propensity Score</span> en la proporci&#243;n 1&#58;2&#44; utilizando las variables sexo&#44; diabetes mellitus tipo<span class="elsevierStyleHsp" style=""></span>2&#44; hipertensi&#243;n arterial&#44; hiperlipemia y consumo de tabaco&#46; La LOD vascular&#44; cardiaca y renal se estableci&#243; siguiendo los criterios de las gu&#237;as de las sociedades europeas de hipertensi&#243;n y cardiolog&#237;a&#46; La rigidez arterial tambi&#233;n se evalu&#243; con el &#237;ndice vascular coraz&#243;n-tobillo &#40;CAVI&#41;&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">La edad media fue de 63&#44;50<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11&#44;70 y 62&#44;90<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#44;32 a&#241;os en los sujetos con y sin NMPs&#44; 32 mujeres &#40;56&#37;&#41; en el primer grupo y 62 &#40;54&#37;&#41; en el segundo&#46; Los sujetos con NMPs-FN tienen un mayor porcentaje de lesi&#243;n carot&#237;dea que los sujetos sin NMPs-FN &#40;35&#44;1&#37; frente al 21&#44;1&#37;&#41; y un mayor ratio alb&#250;mina&#47;creatinina&#46; En el an&#225;lisis de regresi&#243;n log&#237;stica&#44; los sujetos con NMPs-FN ten&#237;an un OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#44;382 &#40;IC<span class="elsevierStyleHsp" style=""></span>95&#37;&#58; 1&#44;066 a 5&#44;323&#41; para la lesi&#243;n carot&#237;dea frente a los que no presentaban enfermedad hematol&#243;gica&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Los sujetos con NMPs-FN presentan el doble de riesgo de lesi&#243;n de &#243;rgano diana vascular que los sujetos que no presentaban enfermedad hematol&#243;gica&#46;</p></span>"
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            "titulo" => "Resultados"
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            "apendice" => "<p id="par0190" class="elsevierStylePara elsevierViewall">The following are the supplementary data to this article&#58;<elsevierMultimedia ident="upi0005"></elsevierMultimedia></p>"
            "etiqueta" => "Appendix A"
            "titulo" => "Supplementary data"
            "identificador" => "sec0115"
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      0 => array:8 [
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          "leyenda" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Values are means &#40;standard deviations&#41; for normally distributed continuous data and medians &#40;interquartile range&#41; for asymmetrically distributed continuous data and number and proportions for categorical data&#46;</p><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Ph-MPNs&#58; Philadelphia negative myeloprofiferative neoplasm&#46; BMI&#58; body mass index&#46; SBP&#58; systolic blood pressure&#46; DBP&#58; diastolic blood pressure&#46; HDL&#58; high density lipoprotein&#46; LDL&#58; low density lipoprotein&#46; HbA1c&#58; glycosylated hemoglobin&#46; hs-CRP&#58; high-sensitivity C-reactive protein&#46; RCV&#58; cardiovascular risk&#46;</p>"
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;550&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">Waist circumference &#40;cm&#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">92&#46;07<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12&#46;39&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;26<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&#46;15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;019&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">Abdominal obesity <span class="elsevierStyleItalic">n</span> &#40;&#37;&#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">25 &#40;43&#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">60 &#40;52&#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">0&#46;279&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">Cigarettes&#47;day &#40;<span class="elsevierStyleItalic">n</span>&#176;&#47;day&#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">10 &#40;4&#46;25&#8211;19&#46;50&#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">20 &#40;5&#46;50&#8211;28&#46;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">0&#46;078&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">Alcohol &#40;g&#47;week&#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">10 &#40;0&#46;00&#8211;72&#46;50&#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">30 &#40;30&#8211;76&#46;25&#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;133&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">Hear rate &#40;beats&#47;minute&#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">70&#46;48<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11&#46;06&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">69&#46;33<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#46;11&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;469&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">SBP &#40;mmHg&#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">133&#46;57<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>25&#46;69&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">129&#46;25<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>15&#46;73&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;177&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">DBP &#40;mmHg&#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">75&#46;66<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11&#46;40&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">78&#46;11<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#46;56&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;118&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">Pulse pressure &#40;mmHg&#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">57&#46;91<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>19&#46;58&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;14<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>13&#46;16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;008&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">Total cholesterol &#40;mg&#47;dl&#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">176&#46;23<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>31&#46;25&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">196&#46;83<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>32&#46;69&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">&#60;0&#46;01&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tryglicerides &#40;mg&#47;dl&#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">88 &#40;67&#8211;118&#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">97 &#40;76&#8211;137&#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;103&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">HDL cholesterol &#40;mg&#47;dl&#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;98<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>14&#46;31&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">57&#46;05<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>15&#46;88&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;408&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">LDL cholesterol &#40;mg&#47;dl&#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">101&#46;30<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>23&#46;42&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">117&#46;84<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>27&#46;71&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">&#60;0&#46;01&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HbA1c &#40;&#37;&#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">5&#46;40 &#40;5&#46;10&#8211;5&#46;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">5&#46;50 &#40;5&#46;20&#8211;5&#46;73&#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;055&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">Red cells &#40;&#42;10<span class="elsevierStyleSup">3</span>&#47;&#956;L&#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">4&#46;53<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;93&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46;80<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;39&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;008&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">Hematocrit &#40;&#37;&#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">42&#46;72<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;38&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">42&#46;84<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;97&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;866&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">Hemoglobin &#40;gr&#47;dL&#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">14&#46;30<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;73&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">14&#46;65<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;24&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;134&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">Total leukocyte count &#40;&#42;10<span class="elsevierStyleSup">3</span>&#47;&#956;L&#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">6&#46;90 &#40;5&#46;10&#8211;10&#46;35&#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">6&#46;20 &#40;5&#46;40&#8211;7&#46;30&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;029&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Platelets &#40;&#42;10<span class="elsevierStyleSup">3</span>&#47;&#956;L&#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">396 &#40;312&#8211;593&#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">216 &#40;189&#8211;261&#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">&#60;0&#46;01&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hs-CRP &#40;mg&#47;dl&#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;14 &#40;0&#46;06&#8211;0&#46;43&#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;15 &#40;0&#46;07&#8211;0&#46;34&#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;829&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">Fibrinogen &#40;mg&#47;dl&#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">315&#46;93<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>73&#46;87&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">342&#46;84<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>64&#46;26&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;017&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">Lipid Lowering drugs <span class="elsevierStyleItalic">n</span> &#40;&#37;&#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">16 &#40;28&#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">39 &#40;34&#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;418&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">Antidiabetic drugs <span class="elsevierStyleItalic">n</span> &#40;&#37;&#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">4 &#40;7&#46;0&#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">8 &#40;7&#46;0&#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;634&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">Antihypertensive drugs <span class="elsevierStyleItalic">n</span> &#40;&#37;&#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">25 &#40;43&#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">56 &#40;49&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;516&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">Antiaggregants drugs <span class="elsevierStyleItalic">n</span> &#40;&#37;&#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;86&#46;0&#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">14 &#40;12&#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">&#60;0&#46;01&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">RCV SCORE&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;58 &#40;1&#46;07&#8211;4&#46;82&#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">2&#46;58 &#40;0&#46;63&#8211;6&#46;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">0&#46;738&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "leyenda" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Values are means &#40;standard deviations&#41; for normally distributed continuous data and medians &#40;interquartile range&#41; for asymmetrically distributed continuous data and number and proportions for categorical data&#46;</p><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">NMPs-FN&#58; Philadelphia negative myeloprofiferative neoplasm&#46; IMT&#58; Intima media thickness&#46; GFR&#58; Glomerular filtration rate&#46; TOD&#58; Target organ damagge&#46; CAVI&#58; Cardio-Ankle Vascular Index&#46; PWV-cf&#58; Carotid-femoral pulse wave velocity&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><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">Variable&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 Ph-MPNs&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>57&#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">Without Ph-MPNs&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>114&#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>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Creatinine &#40;mg&#47;dl&#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;81<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;19&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;85<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;21&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;188&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">GFR &#40;mg&#47;dl&#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">86&#46;12<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>16&#46;91&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">84&#46;10<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>16&#46;33&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;451&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">Albumin creatinine ratio &#40;ml&#47;g&#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">6&#46;12 &#40;3&#46;66&#8211;13&#46;13&#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">3&#46;99 &#40;2&#46;83&#8211;6&#46;97&#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;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">Renal TOD <span class="elsevierStyleItalic">n</span> &#40;&#37;&#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">3 &#40;5&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4 &#40;3&#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">0&#46;684&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">20&#46;33<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;42&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;459&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">Cardiac TOD <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">C-IMT &#40;mm&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">CAVI&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">PWV-cf &#40;m&#47;seg&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">PWV-cf<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleHsp" style=""></span>m&#47;s <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">TOD&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">39 &#40;34&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " colspan="2" align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&#40;95&#37; CI&#41;</th><th class="td" title="\n
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                  \t\t\t\t">Renal TOD&nbsp;\t\t\t\t\t\t\n
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        "texto" => "<p id="par0170" class="elsevierStylePara elsevierViewall">We are grateful to all professionals and participants of the TRIPLE A study&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">Members of the TRIPLE A group Salamanca&#58;</p><p id="par0180" class="elsevierStylePara elsevierViewall">Participating center &#40;Primary Care Research Unit&#44; La Alamedilla Health Center&#44; Salamanca&#44; Spain&#41;&#58; L&#46; Garc&#237;a Ortiz&#44; MA G&#243;mez-Marcos&#46; JI Recio Rodr&#237;guez&#44; MC Patino Alonso&#44; C&#46; Agudo Conde&#44; M&#46; Gomez-Sanchez&#44; Jose A Maderuelo- Fernandez&#44; Jes&#250;s M&#46; Hern&#225;ndez-Rivas&#44; Jose R&#46; Gonz&#225;lez-Porras&#44; MD&#59; Jose M&#46; Bastida-Bermejo&#44; Ana Africa-Mart&#237;n&#44; Emiliano Rodr&#237;guez-S&#225;nchez&#44; Rafael H&#237;pola-Mu&#241;oz and Jes&#250;s Gonz&#225;lez-S&#225;nchez&#46;</p>"
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ISSN: 00257753
Original language: English
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