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Original article
Phenotype of haptoglobin and presence of subclinical vascular disease: Population study
Fenotipo de la haptoglobina y presencia de enfermedad vascular subclínica: estudio poblacional
Jose M. Mostazaa,
Corresponding author
, Olaya de Diosb, Carlos Lahoza, Marta Arribasa, Alicia Pérez Arroyob, Miguel A Salinero-Fortc, Fernando Lagunaa, Eva Estiradoa, Francisca García-Iglesiasa, Teresa González Alegrea, Concesa Sabínd, Silvia Lópezd, Vanesa Sánchezd, Víctor Cornejod, Carmen Garcésb, on behalf of the investigators of the ESPREDIA study
a Unidad de Lípidos y Riesgo Cardiovascular, Servicio de Medicina Interna, Hospital Carlos III, Madrid, Spain
b Laboratorio de Lípidos, IIS-Fundación Jiménez Díaz, UAM, Madrid, Spain
c Gerencia Adjunta de Planificación y Calidad, Atención Primaria, Servicio Madrileño de Salud, Madrid, Spain
d Unidad de día, Hospital Carlos III, Madrid, 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">Haptoglobin is a glycoprotein the main biological function of which lies in its non-covalent binding to free haemoglobin to form a complex that will be subsequently cleared by the reticuloendothelial system through CD163-mediated endocytosis&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Haptoglobin&#44; in this way&#44; prevents the potential oxidative damage of iron contained in the haemoglobin molecule&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> In the absence of this clearing mechanism&#44; haemoglobin favours the production of free radicals and&#44; subsequently&#44; the oxidation of LDL cholesterol&#44; an early mechanism in the development of arteriosclerosis&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Similarly&#44; it promotes the oxidation of HDL cholesterol&#44; which leads to the creation of dysfunctional HDL&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Haptoglobin can also bind to apolipoprotein A1 at the same binding site of the LCAT enzyme&#44;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> which reduces the activity of the enzyme&#44; altering reverse cholesterol transport and preventing the normal maturation of HDL particles&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">The haptoglobin gene is located on the long arm of chromosome 16 and is polymorphic&#44; with two codominant alleles&#44; Hp1 and Hp2&#44; whose products give rise to three isoforms&#44; Hp1-1&#44; Hp1-2 and Hp2-2&#44; with frequencies of 16&#44; 48 and 36&#37;&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Hp2-2 subjects have a lower antioxidant capacity than Hp1 carriers&#46; This is because they have a lower plasma concentration of haptoglobin&#44; because their haptoglobin has a lower affinity for haemoglobin&#44; since the plasma clearance of the Hp-haemoglobin complex is slowed&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> This fact is more evident in patients with diabetes&#44; who are subject to greater oxidative stress&#46; In addition&#44; in this population&#44; Hp2-2 homozygotes have reduced CD163 expression and have difficulties in transferring from the haem to the haptoglobin as a result of haemoglobin glycation&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">These alterations have a translation in the symptoms&#46; Several studies have shown that Hp2-2 subjects have an increased risk of cardiovascular complications&#44; especially the diabetic population&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> However&#44; there are few studies that have evaluated whether such a genotype is associated with an increased risk of subclinical vascular disease&#44; and have been preferably performed in the diabetic population&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#8211;9</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Our study evaluates the presence of subclinical carotid disease in relation to the haptoglobin phenotype in subjects free of cardiovascular disease&#44; with and without diabetes&#44; randomly selected from a Spanish population&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Patients and methods</span><p id="par0030" class="elsevierStylePara elsevierViewall">The Screening PRE-diabetes and type 2 DIAbetes &#40;SPREDIA-2&#41; study is a prospective population cohort study conducted in the Autonomous Community of Madrid&#46; The characteristics of this study and the selected population have been previously published&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> In summary&#44; 1592 subjects between 45 and 74 years of age randomly selected from the population of the northwest area of Madrid were included&#46; Participants were called on an empty stomach for the performance of lab work&#44; an oral overload with 75&#8239;g of glucose&#44; anthropometric measurements and the performance of a carotid ultrasound&#46; Of the total participants&#44; 1256 had no cardiovascular disease at the time of inclusion&#44; had a carotid ultrasound&#44; and had a reading of the haptoglobin phenotype&#44; being included in the present analysis&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">The diagnosis of prediabetes and diabetes was made according to the criteria of the ADA&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> Prediabetes was defined as not having diabetes but having a baseline glucose between 100 and 125&#8239;mg&#47;dl &#40;altered baseline glucose&#41; or an A1C concentration of between 5&#46;7 and 6&#46;4&#37;&#44; or a blood glucose at 2&#8239;h from the OGTT between 140 to 199&#8239;mg&#47;dl &#40;glucose intolerance&#41;&#46; Diabetes was defined as a previous diagnosis of diabetes&#44; being treated with antidiabetic drugs or having a baseline blood glucose &#8805;126&#8239;mg&#47;dl or a concentration of A1C&#8239;&#8805;&#8239;6&#46;5&#37; or a blood glucose level at 2&#8239;h after the OGTT&#8239;&#8805;&#8239;200&#8239;mg&#47;dl&#46; Subjects without altered baseline glucose&#44; without glucose intolerance and with an A1C&#8239;&#60;&#8239;5&#46;7&#37; were considered normoglycaemic&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">The haptoglobin phenotype &#40;Hp1-1&#44; Hp2-1 and Hp2-2&#41; was determined qualitatively by an immunoenzymatic assay &#40;VIT-A710-01&#8239;M Haptotype&#44; Vitro S&#46;A&#46;&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> according to the protocol established by the trading house&#46; The trial presented an intra-and intertrial accuracy of 1&#46;8 and 10&#46;6&#37;&#44; respectively&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">A Doppler ultrasound was performed of both carotids with a 7&#46;5&#8239;mHz probe &#40;SonoSite MicroMaxx Ultrasound&#44; SonoSite Inc&#46;&#44; Bothell&#44; Wash&#44; USA&#41;&#46; The presence of plaques throughout the extension of the common carotid artery&#44; carotid bulb and internal and external carotid arteries was explored bilaterally&#46; The existence of carotid plaques was defined as a focal thickening &#62;1&#46;5&#8239;mm or a thickening &#62;50&#37; of the value of the surrounding intima-media thickness &#40;IMT&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> Images of the distal wall of the common carotid artery&#44; 1&#8239;cm prior to the bifurcation&#44; were obtained at three different viewing angles&#46; The IMT was obtained by automated software &#40;SonoSite&#44; SonoCalc IMT Software&#44; SonoSite Inc&#46;&#44; Bothell&#44; Wash&#44; USA&#41; as the average of the mean and maximum thickness measured in each of the six segments &#40;three different angles on the right and left side&#41;&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Statistical analysis</span><p id="par0050" class="elsevierStylePara elsevierViewall">Quantitative variables are presented as mean and standard deviation&#46; Qualitative variables&#44; as percentages&#46; Comparisons between the quantitative variables were made using the t-test&#44; and those of the qualitative variables&#44; using the chi-square test&#46; A logistic regression analysis was performed using the &#34;enter&#34; method to assess the independent relationship of the haptoglobin phenotype with the presence of carotid plaques&#46; Variables with p&#8239;&#60;&#8239;0&#46;10 in the bivariate analysis and the clinically relevant ones were included in the model&#44; trying to avoid overfitting&#46; The magnitude of the associations was expressed as OR and 95&#37; CI&#46; The data were analysed using SPSS for Windows&#44; version 9&#46;0&#59; IBM Corp&#44; Armonk&#44; New York&#44; USA&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Ethical considerations</span><p id="par0055" class="elsevierStylePara elsevierViewall">The study was approved by the Clinical Research Ethics Committee of the Hospital Carlos III in Madrid&#44; complying with the Declaration of Helsinki and international guidelines for epidemiological studies &#40;Geneva&#44; 1991&#41;&#46; All participants signed an informed consent form&#46;</p></span></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Results</span><p id="par0060" class="elsevierStylePara elsevierViewall">A total of 1256 subjects were included in the analysis&#46; The prevalence of Hp1-1&#44; Hp1-2 and Hp2-2 phenotypes was 13&#46;3&#37; &#40;n&#8239;&#61;&#8239;167&#41;&#44; 48&#46;5&#37; &#40;n&#8239;&#61;&#8239;609&#41; and 38&#46;2&#37; &#40;n&#8239;&#61;&#8239;480&#41;&#46; Since the risk of cardiovascular complications has been associated with the Hp2-2 phenotype&#44; subjects with Hp1-1 and Hp1-2 phenotypes were grouped for statistical calculations&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">The characteristics of the population according to the haptoglobin phenotype can be seen in <a class="elsevierStyleCrossRefs" href="#tbl0005">Tables 1 and 2</a>&#46; Subjects with the Hp2-2 phenotype had a higher prevalence of self-referred dyslipidaemia and hypertension&#46; They also received antihypertensive and lipid-lowering therapy more frequently&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">Subjects with the Hp2-2 phenotype had a higher prevalence of carotid plaques &#40;OR&#58; 1&#46;35&#59; 95&#37; CI&#58; 1&#46;07&#8211;1&#46;69&#59; p&#8239;&#61;&#8239;0&#46;011&#41;&#46; No differences were observed in the common carotid IMT between the groups&#46; The proportion of patients with plaques based on their glycaemic status can be seen in <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#46; The OR for the presence of plaques was similar in patients with and without diabetes &#40;OR&#58; 1&#46;60&#59; 95&#37; CI&#58; 0&#46;84&#8211;3&#46;06&#59; p&#8239;&#61;&#8239;0&#46;151 in diabetics&#44; and OR&#58; 1&#46;30&#59; 95&#37; CI&#58; 1&#46;01&#8211;1&#46;67&#59; p&#8239;&#61;&#8239;0&#46;044 in non-diabetics&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">To establish whether the association between the haptoglobin phenotype and the presence of carotid plaques was independent of cardiovascular risk factors&#44; we performed a logistic regression analysis adjusting for clinically relevant factors &#40;age&#44; sex&#44; presence of diabetes&#41; and factors associated with the haptoglobin phenotype &#40;history of dyslipidaemia&#44; history of hypertension&#44; statin therapy&#44; antihypertensive therapy&#44; systolic blood pressure and uric acid concentration&#44; CRP and LDL cholesterol&#41;&#44; maintaining the relationship &#40;OR&#58; 1&#46;31&#59; 95&#37; CI&#58; 1&#46;01&#8211;1&#46;70&#44; p&#8239;&#61;&#8239;0&#46;044&#41;&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Discussion</span><p id="par0080" class="elsevierStylePara elsevierViewall">Our results show that the subjects with the Hp2-2&#8239;haptoglobin phenotype have a higher prevalence of carotid arteriosclerosis than Hp1-1 and Hp1-2 subjects&#46; These subjects also have a higher self-referred prevalence of dyslipidaemia and hypertension and&#44; in parallel&#44; greater use of statins and antihypertensives&#46; However&#44; the association between Hp2-2 phenotype and the presence of carotid plaques was independent of dyslipidaemia and hypertension&#44; as demonstrated in the multivariate analysis&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Several studies have shown that the rate of cardiovascular complications is higher in Hp2-2 subjects&#46; Although this fact has been mostly associated with populations with diabetes&#44; it has also been observed in the general population&#46;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14&#44;15</span></a> Despite this&#44; not all studies are in agreement&#44; since in some of them this relationship has not been found&#44;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> and in others the results differ between patients with and without diabetes&#44; suggesting that diabetic subjects carrying the Hp2-2 genotype could have less cardiovascular disease compared to a higher prevalence in H2-2 subjects without diabetes&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">The association between the haptoglobin phenotype and the presence of subclinical carotid disease has been evaluated in a very small number of studies and mostly in populations with diabetes&#44; usually with a limited sample size&#46; In a study conducted on 64-year-old women&#44; the carriers of the Hp2-2 genotype had a higher prevalence of carotid plaques and a higher IMT in the carotid bulb&#44; with no differences observed in the IMT of the common carotid artery&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> These associations&#44; however&#44; were only observed in women with long-standing diabetes&#46; Haptoglobin phenotype did not influence carotid arteriosclerosis in participants without diabetes or in those with newly-diagnosed diabetes&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> Other studies have shown that subjects with diabetes and a Hp2-2 phenotype also have a greater IMT than subjects with an Hp1 allele&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;9</span></a> Our data extend the association between the Hp2-2 phenotype and subclinical carotid disease by demonstrating that it is present in both patients with and without diabetes and that it is independent of glycaemic status&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Our data also indicate an association between the presence of dyslipidaemia referred by the patient him&#47;herself&#44; statin therapy and the Hp2-2 phenotype&#46; The relationship between Hp2-2 and cholesterol levels has barely been explored&#44; although some large epidemiological studies have also observed that the Hp2 allele is associated with higher levels of total cholesterol and LDL cholesterol&#46;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">18&#44;19</span></a> Not all studies&#44; however&#44; have found these findings&#44; perhaps because most of them are performed in people with diabetes&#44; many of them already being treated with statins regardless of their cholesterol levels&#46; Haptoglobin can interfere with lipoprotein metabolism by binding to apolipoprotein E<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> and prevent its oxidation&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> The oxidation of apoE hinders lipid clearance&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> The higher affinity of Hp1 to bind to apoE and prevent oxidation would favour these subjects having a lower concentration of plasma cholesterol&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Similarly&#44; our data indicate that subjects with a Hp2-2 phenotype have a higher self-referred prevalence of hypertension and receive antihypertensive therapy more frequently&#46; Again&#44; there are no data in this regard in the literature&#44; although some studies have shown that these patients have more complications derived from hypertension and forms of hypertension more resistant to treatment&#46;<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">23&#44;24</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">In any case&#44; the higher prevalence of carotid plaques has been demonstrated independent of the presence of dyslipidaemia or hypertension and of the treatments for these risk factors&#46; It has been postulated that the arteriosclerosis of these patients derives from the increased oxidation of LDL particles and alterations in the metabolism of HDL&#46; In fact&#44; several intervention studies have shown that antioxidant therapy with vitamin E in patients with diabetes is associated with a lower risk of cardiovascular complications&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> However&#44; studies with a larger sample size that demonstrate that the Hp2-2 phenotype is associated with an increased risk of future cardiovascular complications&#44; and that its determination improves the prediction of the risk obtained from classical risk factors are needed&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Our study has limitations from its cross-sectional design&#44; which prevents drawing inferences about causation&#46; However&#44; it has a large sample size&#44; participants have been randomly selected from the population and the haptoglobin phenotype was determined without knowing the situation of carotid arteriosclerosis&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">In summary&#44; the population with a haptoglobin Hp2-2 phenotype has a higher prevalence of dyslipidaemia and hypertension&#44; and they are more frequently treated with statins and antihypertensives&#46; These subjects also have a higher prevalence of carotid plaques&#44; independent of the aforementioned risk factors&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Funding</span><p id="par0120" class="elsevierStylePara elsevierViewall">The study has been partially funded by an unconditional grant from <span class="elsevierStyleGrantSponsor" id="gs0005">Novo Nordisk</span> and the <span class="elsevierStyleGrantSponsor" id="gs0010">Fundaci&#243;n para el Fomento y Desarrollo de la Investigaci&#243;n Cl&#237;nica</span> &#91;Foundation for the Promotion and Development of Clinical Research&#93; &#40;FYDIC&#41;&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Conflicts of interest</span><p id="par0125" class="elsevierStylePara elsevierViewall">The authors state that this manuscript does not imply any conflict of interest with any of the authors&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction and objectives</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Haptoglobin is a protein involved in the protection against oxidative damage caused by iron in haemoglobin&#46; This protein is polymorphic&#44; with 3 isomorphs prevalent in the population&#46; The carriers of the Hp2-2 isoform have a lower antioxidant capacity and&#44; in the population with diabetes&#44; an increased risk of subclinical vascular disease and cardiovascular complications&#46; The objective of this study was to evaluate whether this isomorphy is associated with an increased risk of carotid arteriosclerosis in subjects with and without diabetes&#44; and free of cardiovascular disease&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Patients and methods</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">A study was conducted in a population between 45 and 74 years of age&#44; randomly selected from the northwest area of Madrid&#46; The participants were characterised in terms of their glycaemic status by oral glucose overload and the determination of the concentration of Hb1Ac&#46; The haptoglobin phenotypes in all of them were determined by means of an immunoenzymatic assay&#44; and the presence of carotid arteriosclerosis by ultrasound&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Of the 1256 participants included in the present analysis &#40;mean age 61&#46;6&#8239;&#177;&#8239;6 years&#44; 41&#46;8&#37; males&#41;&#44; the distribution of the isoforms of haptoglobin was as follows&#58; Hp1-1&#58; 13&#46;3&#37;&#44; Hp1-2&#58; 48&#46;5&#37;&#44; and Hp2-2&#58; 38&#46;2&#37;&#46; In comparison with subjects Hp1-1 and Hp1-2&#44; those with the Hp2-2 phenotype had a higher prevalence of dyslipidaemia &#40;53&#46;3&#37; vs 43&#37;&#59; <span class="elsevierStyleItalic">p</span>&#8239;&#60;&#8239;&#46;0001&#41; and arterial hypertension &#40;39&#46;2&#37; vs&#46; 32&#46;2&#37;&#44; <span class="elsevierStyleItalic">p&#8239;&#61;</span>&#8239;&#46;012&#41;&#44; and they more frequently received treatment with statins &#40;31&#46;5&#37; vs 21&#46;6&#37;&#44; <span class="elsevierStyleItalic">p</span>&#8239;&#60;&#8239;&#46;0001&#41;&#44; and with antihypertensive agents &#40;38&#46;4&#37; vs 30&#46;8&#37;&#44; <span class="elsevierStyleItalic">p&#8239;&#61;</span>&#8239;&#46;006&#41;&#46; The carriers of the Hp2-2 isoform had a higher prevalence of carotid plaques &#40;OR&#58; 1&#46;35&#44; 95&#37; CI&#58; 1&#46;07&#8211;1&#46;69&#44; <span class="elsevierStyleItalic">p&#8239;&#61;</span>&#8239;&#46;011&#41;&#44; with no differences in that prevalence as regards the glycaemic status&#46; There were no differences in the intima-media thickness between the different phenotypes&#46; The relationship of the Hp2-2 phenotype with the presence of plaques in the carotid was independent of age&#44; gender&#44; presence of risk factors &#40;dyslipidaemia&#44; hypertension and diabetes&#41;&#44; the concentration of LDL-cholesterol&#44; C-reactive protein and uric acid&#44; blood pressure&#44; and treatment with statins&#44; and hypertensive drugs &#40;OR&#58; 1&#46;31&#44; 95&#37; CI 1&#46;01&#8211;1&#46;70&#44; <span class="elsevierStyleItalic">p&#8239;&#61;</span>&#8239;&#46;044&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Subjects with the Hp2-2 phenotype of haptoglobin have a higher prevalence of carotid arteriosclerosis&#44; which is independent of the presence of other cardiovascular risk factors and their glycaemic status&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducci&#243;n y objetivos</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">La haptoglobina es una prote&#237;na implicada en la protecci&#243;n frente al da&#241;o oxidativo producido por el hierro de la hemoglobina&#46; Esta prote&#237;na es polim&#243;rfica&#44; con 3 isomorfas prevalentes en la poblaci&#243;n&#46; Los portadores de la isoforma Hp2-2 tienen una menor capacidad antioxidante y&#44; en la poblaci&#243;n con diabetes&#44; un mayor riesgo de enfermedad vascular subcl&#237;nica y de complicaciones cardiovasculares&#46; Nuestro objetivo fue evaluar si dicha isomorfa se asocia con un mayor riesgo de arteriosclerosis carotidea en sujetos con y sin diabetes&#44; libres de enfermedad cardiovascular&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Pacientes y M&#233;todos</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Estudio realizado en una poblaci&#243;n de entre 45 y 74 a&#241;os de edad&#44; seleccionada aleatoriamente del &#225;rea noroeste de Madrid&#46; Los participantes fueron caracterizados en cuanto a su estatus gluc&#233;mico mediante una sobrecarga oral de glucosa y la determinaci&#243;n de la concentraci&#243;n de HBA1c&#46; A todos ellos se les determin&#243; el fenotipo de la haptoglobina mediante un ensayo inmunoenzim&#225;tico y la presencia de arteriosclerosis carot&#237;dea mediante ecograf&#237;a&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">De los 1256 participantes incluidos en el presente an&#225;lisis &#40;edad media 61&#44;6&#8239;&#177;&#8239;6 a&#241;os&#44; 41&#44;8&#37; varones&#41;&#44; la distribuci&#243;n de las isoformas de la haptoglobina fue la siguiente&#58; Hp 1-1&#58; 13&#44;3&#37;&#44; Hp1-2&#58; 48&#44;5&#37; y Hp2-2&#58; 38&#44;2&#37;&#46; En comparaci&#243;n con los sujetos Hp1-1 y Hp1-2&#44; aquellos con el fenotipo Hp2-2 tuvieron una mayor prevalencia de dislipemia &#40;53&#44;3&#37; vs 43&#37;&#44; p&#8239;&#60;&#8239;0&#44;0001&#41; e hipertensi&#243;n arterial &#40;39&#44;2&#37; vs 32&#44;2&#37;&#44; p&#8239;&#61;&#8239;0&#44;012&#41;&#44; y recibieron con m&#225;s frecuencia tratamiento con estatinas &#40;31&#44;5&#37; vs 21&#44;6&#37;&#44; p&#8239;&#60;&#8239;0&#44;0001&#41; y con antihipertensivos &#40;38&#44;4&#37; vs 30&#44;8&#37;&#44; p&#8239;&#61;&#8239;0&#44;006&#41;&#46; Los portadores de la isoforma Hp2-2 tuvieron una mayor prevalencia de placas carotideas &#40;OR 1&#44;35&#59; IC95&#37; 1&#44;07&#8211;1&#44;69&#44; p&#8239;&#61;&#8239;0&#44;011&#41;&#44; sin diferencias en dicha prevalencia en funci&#243;n del estatus gluc&#233;mico&#46; No existieron diferencias en el grosor &#237;ntima-medio entre los diferentes fenotipos&#46; La relaci&#243;n del fenotipo Hp2-2 con la presencia de placas en car&#243;tida fue independiente de la edad&#44; sexo&#44; presencia de factores de riesgo &#40;dislipemia&#44; hipertensi&#243;n y diabetes&#41;&#44; de la concentraci&#243;n de colesterol-LDL&#44; prote&#237;na C reactiva y &#225;cido &#250;rico&#44; de la presi&#243;n arterial&#44; y del tratamiento con estatinas y antihipertensivos &#40;OR 1&#44;31&#59; IC95&#37; 1&#44;01&#8211;1&#44;70&#44; p&#8239;&#61;&#8239;0&#44;044&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusi&#243;n</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Los sujetos con el fenotipo Hp2-2 de la haptoglobina tienen una mayor prevalencia de arteriosclerosis carotidea&#44; que es independiente de la presencia de otros factores de riesgo cardiovascular y de su estatus gluc&#233;mico&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Introducci&#243;n y objetivos"
          ]
          1 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "Pacientes y M&#233;todos"
          ]
          2 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Resultados"
          ]
          3 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Conclusi&#243;n"
          ]
        ]
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Mostaza JM&#44; de Dios O&#44; Lahoz C&#44; Arribas M&#44; P&#233;rez Arroyo A&#44; Salinero-Fort MA&#44; et al&#46;&#59; en representaci&#243;n de los investigadores del estudio ESPREDIA&#46; Fenotipo de la haptoglobina y presencia de enfermedad vascular subcl&#237;nica&#58; estudio poblacional&#46; Cl&#237;n Investig Arterioscler&#46; 2020&#46; <span class="elsevierStyleInterRef" id="intr0005" href="https://doi.org/10.1016/j.arteri.2019.03.007">https&#58;&#47;&#47;doi&#46;org&#47;10&#46;1016&#47;j&#46;arteri&#46;2019&#46;03&#46;007</span></p>"
      ]
    ]
    "apendice" => array:1 [
      0 => array:1 [
        "seccion" => array:1 [
          0 => array:4 [
            "apendice" => "<p id="par0130" class="elsevierStylePara elsevierViewall">The following authors have collaborated in the collection and analysis of data&#58; Carmen de Burgos-Lunar&#44; Paloma G&#243;mez-Campelo&#44; Bel&#233;n Fern&#225;ndez Puntero&#44; Luis Montesano S&#225;nchez&#44; David Vicent L&#243;pez&#44; Pedro J&#46; Fern&#225;ndez Garc&#237;a&#44; Jes&#250;s Castro Toro and Pedro Patr&#243;n Barand&#237;o&#46;</p> <p id="par0135" class="elsevierStylePara elsevierViewall">We appreciate the collaboration of all the doctors of the ESPREDIA group&#58; Concepci&#243;n Aguilera Linde &#40;C&#46;S&#46; Ciudad de los Periodistas&#41;&#44; &#193;lvaro R&#46; Aguirre de Carcer Escolano &#40;C&#46;S&#46; La Ventilla&#41;&#44; Patricio Alonso Sacrist&#225;n &#40;C&#46;S&#46; Ciudad de los Periodistas&#41;&#44; M&#46; Jes&#250;s &#193;lvarez Otero &#40;C&#46;S&#46; Dr&#46; Castroviejo&#41;&#44; Paloma Arribas P&#233;rez &#40;C&#46;S&#46; Santa Hortensia&#41;&#44; Mar&#237;a Luisa Asensio Ruiz &#40;C&#46;S&#46; Fuentelarreina&#41;&#44; Pablo Astorga D&#237;az &#40;C&#46;S&#46; Barrio Pilar&#41;&#44; Bego&#241;a Berriatua Ena &#40;C&#46;S&#46; Dr&#46; Castroviejo&#41;&#44; Ana Isabel Bezos Varela &#40;C&#46;S&#46; Jos&#233; Marv&#225;&#41;&#44; Mar&#237;a Jos&#233; Calatrava Triguero &#40;C&#46;S&#46; Ciudad Jard&#237;n&#41;&#44; Carlos Casanova Garc&#237;a &#40;C&#46;S&#46; Barrio Pilar&#41;&#44; &#193;ngeles Conde Llorente &#40;C&#46;S&#46; Barrio Pilar&#41;&#44; Concepci&#243;n D&#237;az Laso &#40;C&#46;S&#46; Fuentelarreina&#41;&#44; Emilia Elviro Garc&#237;a &#40;C&#46;S&#46; Ciudad de los Periodistas&#41;&#44; Orlando Enr&#237;quez Due&#241;as &#40;C&#46;S&#46; Fuentelarreina&#41;&#44; Mar&#237;a Isabel Ferrer Zapata &#40;C&#46;S&#46; El Greco&#41;&#44; Froil&#225;n Antu&#241;a &#40;C&#46;S&#46; Ciudad de los Periodistas&#41;&#44; Mar&#237;a Isabel Garc&#237;a Lazaro &#40;C&#46;S&#46; Ciudad de los Periodistas&#41;&#44; M&#46; Teresa G&#243;mez Rodr&#237;guez &#40;C&#46;S&#46; Barrio Pilar&#41;&#44; &#193;frica G&#243;mez Lucena &#40;C&#46;S&#46; La Ventilla&#41;&#44; Francisco Herrero Hern&#225;ndez &#40;C&#46;S&#46; La Ventilla&#41;&#44; Rosa Juli&#225;n Vi&#241;als &#40;C&#46;S&#46; Dr&#46; Castroviejo&#41;&#44; Gerardo L&#243;pez Ruiz Ogarrio &#40;C&#46;S&#46; Barrio Pilar&#41;&#44; M&#46; Carmen Lumbreras Manzano &#40;C&#46;S&#46; Jos&#233; Marv&#225;&#41;&#44; Sonsoles Paloma Luquero L&#243;pez &#40;C&#46;S&#46; Ciudad de los Periodistas&#41;&#44; Ana Mart&#237;nez Cabrera Pel&#225;ez &#40;C&#46;S&#46; Barrio Pilar&#41;&#44; Montserrat Nieto Candenas &#40;C&#46;S&#46; La Ventilla&#41;&#44; Mar&#237;a Alejandra Rabanal Carrera &#40;C&#46;S&#46; Barrio Pilar&#41;&#44; &#193;ngel Castellanos Rodr&#237;guez &#40;C&#46;S&#46; Ciudad de los Periodistas&#41;&#44; Ana L&#243;pez Castellanos &#40;C&#46;S&#46; La Ventilla&#41;&#44; Milagros Vel&#225;zquez Garc&#237;a &#40;C&#46;S&#46; Barrio Pilar&#41; and Margarita Ruiz Pacheco &#40;C&#46;S&#46; Dr&#46; Castroviejo&#41;&#46;</p>"
            "etiqueta" => "Appendix A"
            "titulo" => "Collaborators"
            "identificador" => "sec0045"
          ]
        ]
      ]
    ]
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                  \t\t\t\t" scope="col">&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">Total&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">Hp1-1 and Hp1-2&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col">p&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">n&#8239;&#61;&#8239;1256&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">n&#8239;&#61;&#8239;776 &#40;61&#46;8&#37;&#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">n&#8239;&#61;&#8239;480 &#40;38&#46;2&#37;&#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
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Sex &#40;&#37; males&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">41&#46;8&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">41&#46;6&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">42&#46;1&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;873&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">Age &#40;years&#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">61&#46;6&#8239;&#177;&#8239;5&#46;8&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">61&#46;5&#8239;&#177;&#8239;5&#46;9&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">61&#46;7&#8239;&#177;&#8239;5&#46;9&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;558&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">Active smoker &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">16&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">15&#46;6&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">17&#46;7&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;330&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">Diabetes &#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">15&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&#46;7&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">16&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#46;346&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">HTN &#40;&#37;&#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">34&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">32&#46;2&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&#46;2&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;012&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">Dyslipidaemia &#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">46&#46;9&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">43&#46;0&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">53&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;0001&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 therapy &#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">33&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30&#46;8&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">38&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;006&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">Statin therapy &#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&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">21&#46;6&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">31&#46;5&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;0&#46;0001&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">CKF &#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">1&#46;0&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;6&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">1&#46;5&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;150&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">Mean IMT &#40;mm&#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;720&#8239;&#177;&#8239;0&#46;123&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;720&#8239;&#177;&#8239;0&#46;122&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;719&#8239;&#177;&#8239;0&#46;123&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;863&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">Maximum IMT &#40;mm&#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;861&#8239;&#177;&#8239;0&#46;155&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;861&#8239;&#177;&#8239;0&#46;150&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;861&#8239;&#177;&#8239;0&#46;160&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;889&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">Patients with plaques &#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">45&#46;2&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;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">49&#46;8&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;011&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2243040.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Characteristics of the population without known cardiovascular disease depending on the haptoglobin phenotype&#46;</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0015"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <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">&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">Total&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">Hp1-1 and Hp1-2&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">Hp2-2&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">p&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr><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">&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">n&#8239;&#61;&#8239;1256&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">n&#8239;&#61;&#8239;776 &#40;61&#46;8&#37;&#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">n&#8239;&#61;&#8239;480 &#40;38&#46;2&#37;&#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">&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">Glucose &#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">105&#8239;&#177;&#8239;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">104&#8239;&#177;&#8239;17&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">106&#8239;&#177;&#8239;20&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;068&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">Hb1Ac &#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;8&#8239;&#177;&#8239;0&#46;6&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;7&#8239;&#177;&#8239;0&#46;5&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;8&#8239;&#177;&#8239;0&#46;6&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;201&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">209&#8239;&#177;&#8239;37&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">209&#8239;&#177;&#8239;35&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">208&#8239;&#177;&#8239;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">0&#46;697&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">134&#8239;&#177;&#8239;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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">134&#8239;&#177;&#8239;32&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&#8239;&#177;&#8239;34&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;543&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">55&#8239;&#177;&#8239;15&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">54&#8239;&#177;&#8239;15&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">55&#8239;&#177;&#8239;15&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">0&#46;751&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">Triglycerides &#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
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                  \t\t\t\t">103&#8239;&#177;&#8239;66&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">102&#8239;&#177;&#8239;70&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">103&#8239;&#177;&#8239;58&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">0&#46;826&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">Uric acid &#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">5&#46;3&#8239;&#177;&#8239;1&#46;2&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">0&#46;099&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">C-reactive protein&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">5&#46;4&#8239;&#177;&#8239;6&#46;8&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">4&#46;8&#8239;&#177;&#8239;5&#46;6&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">0&#46;081&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">Body mass index &#40;kg&#47;m<span class="elsevierStyleSup">2</span>&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">28&#46;3&#8239;&#177;&#8239;4&#46;7&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">28&#46;3&#8239;&#177;&#8239;4&#46;7&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">28&#46;4&#8239;&#177;&#8239;4&#46;7&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">95&#8239;&#177;&#8239;12&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">95&#8239;&#177;&#8239;12&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;390&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">Systolic blood pressure &#40;mmHg&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">125&#8239;&#177;&#8239;17&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">124&#8239;&#177;&#8239;17&nbsp;\t\t\t\t\t\t\n
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Biochemical and anthropometric values in 1256 participants without known cardiovascular disease on the basis of the haptoglobin phenotype&#46;</p>"
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es en pt

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?

Você é um profissional de saúde habilitado a prescrever ou dispensar medicamentos