{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:41:24Z","timestamp":1787244084686,"version":"build-2736575974"},"reference-count":29,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2018,3]]},"abstract":"<jats:sec>\n                    <jats:title>Objective\u2014<\/jats:title>\n                    <jats:p>The objectives of this study were to decipher whether age-independent cardiovascular risk is associated with DNA methylation at 5\u2032-cytosine-phosphate-guanine-3\u2032 (CpG) level and to determine whether these differential methylation signatures are associated with the incidence of cardiovascular events.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Approach and Results\u2014<\/jats:title>\n                    <jats:p>\n                      We designed a 2-stage, cross-sectional, epigenome-wide association study. Age-independent cardiovascular risk calculation was based on vascular age and on the residuals of the relationship between age and cardiovascular risk. Blood DNA methylomes from 2 independent populations were profiled using the Infinium HumanMethylation450 BeadChip. The discovery stage of these studies was performed in the REGICOR cohort (REgistre GIron\u00ed del COR; n=645). Next, we validated the initial findings in the Framingham Offspring Study (n=2542). Eight CpGs located in 4 genes (\n                      <jats:italic>AHRR<\/jats:italic>\n                      ,\n                      <jats:italic>CPT1A<\/jats:italic>\n                      ,\n                      <jats:italic>PPIF<\/jats:italic>\n                      , and\n                      <jats:italic>SBNO2<\/jats:italic>\n                      ) and 3 intergenic regions showed differential methylation in association with age-independent cardiovascular risk (\n                      <jats:italic>P<\/jats:italic>\n                      \u22641.17\u00d710\n                      <jats:sup>\u22127<\/jats:sup>\n                      ). These CpGs explained 12.01% to 15.16% of the variability of age-independent cardiovascular risk in REGICOR and 7.51% to 8.53% in Framingham Offspring Study. Four of them were only related to smoking, 3 were related to smoking and body mass index, and 1 to diabetes mellitus, triglycerides levels, and body mass index (\n                      <jats:italic>P<\/jats:italic>\n                      \u22647.81\u00d710\n                      <jats:sup>\u22124<\/jats:sup>\n                      ). In addition, we developed methylation risk scores based on these CpGs and observed an association between these scores and cardiovascular disease incidence (hazard ratio=1.32; 95% confidence interval: 1.16\u20131.51).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions\u2014<\/jats:title>\n                    <jats:p>Age-independent cardiovascular risk was related to different DNA methylation profiles, with 8 CpGs showing differential methylation patterns. Most of these CpGs were associated with smoking, and 3 of them were also related to body mass index. Risk scores based on these differential methylation patterns were associated with cardiovascular events and could be useful predictive indices.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/atvbaha.117.310340","type":"journal-article","created":{"date-parts":[[2018,1,11]],"date-time":"2018-01-11T05:01:50Z","timestamp":1515646910000},"page":"645-652","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":44,"title":["DNA Methylation and Age-Independent Cardiovascular Risk, an Epigenome-Wide Approach"],"prefix":"10.1161","volume":"38","author":[{"given":"Alba","family":"Fern\u00e1ndez-Sanl\u00e9s","sequence":"first","affiliation":[{"name":"From the Cardiovascular Epidemiology and Genetics Research Group, REGICOR Study Group, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain (A.F.-S., S.S.-B., I.S., J.M., R.E.); Universitat Pompeu Fabra, Barcelona, Spain (A.F.-S., S.S.-B.); CIBER Cardiovascular Diseases, Barcelona, Spain (S.S.-B., J.M., R.E.); CIBER Epidemiology and Public Health (CIBERESP), Barcelona, Spain (I.S.); Centro Universitario de Investigaci\u00f3n, Innovaci\u00f3n y Diagn\u00f3stico Arterial (CUiiDARTE), Physiology..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergi","family":"Sayols-Baixeras","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Epidemiology and Genetics Research Group, REGICOR Study Group, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain (A.F.-S., S.S.-B., I.S., J.M., R.E.); Universitat Pompeu Fabra, Barcelona, Spain (A.F.-S., S.S.-B.); CIBER Cardiovascular Diseases, Barcelona, Spain (S.S.-B., J.M., R.E.); CIBER Epidemiology and Public Health (CIBERESP), Barcelona, Spain (I.S.); Centro Universitario de Investigaci\u00f3n, Innovaci\u00f3n y Diagn\u00f3stico Arterial (CUiiDARTE), Physiology..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santiago","family":"Curcio","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Epidemiology and Genetics Research Group, REGICOR Study Group, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain (A.F.-S., S.S.-B., I.S., J.M., R.E.); Universitat Pompeu Fabra, Barcelona, Spain (A.F.-S., S.S.-B.); CIBER Cardiovascular Diseases, Barcelona, Spain (S.S.-B., J.M., R.E.); CIBER Epidemiology and Public Health (CIBERESP), Barcelona, Spain (I.S.); Centro Universitario de Investigaci\u00f3n, Innovaci\u00f3n y Diagn\u00f3stico Arterial (CUiiDARTE), Physiology..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isaac","family":"Subirana","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Epidemiology and Genetics Research Group, REGICOR Study Group, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain (A.F.-S., S.S.-B., I.S., J.M., R.E.); Universitat Pompeu Fabra, Barcelona, Spain (A.F.-S., S.S.-B.); CIBER Cardiovascular Diseases, Barcelona, Spain (S.S.-B., J.M., R.E.); CIBER Epidemiology and Public Health (CIBERESP), Barcelona, Spain (I.S.); Centro Universitario de Investigaci\u00f3n, Innovaci\u00f3n y Diagn\u00f3stico Arterial (CUiiDARTE), Physiology..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaume","family":"Marrugat","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Epidemiology and Genetics Research Group, REGICOR Study Group, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain (A.F.-S., S.S.-B., I.S., J.M., R.E.); Universitat Pompeu Fabra, Barcelona, Spain (A.F.-S., S.S.-B.); CIBER Cardiovascular Diseases, Barcelona, Spain (S.S.-B., J.M., R.E.); CIBER Epidemiology and Public Health (CIBERESP), Barcelona, Spain (I.S.); Centro Universitario de Investigaci\u00f3n, Innovaci\u00f3n y Diagn\u00f3stico Arterial (CUiiDARTE), Physiology..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Elosua","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Epidemiology and Genetics Research Group, REGICOR Study Group, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain (A.F.-S., S.S.-B., I.S., J.M., R.E.); Universitat Pompeu Fabra, Barcelona, Spain (A.F.-S., S.S.-B.); CIBER Cardiovascular Diseases, Barcelona, Spain (S.S.-B., J.M., R.E.); CIBER Epidemiology and Public Health (CIBERESP), Barcelona, Spain (I.S.); Centro Universitario de Investigaci\u00f3n, Innovaci\u00f3n y Diagn\u00f3stico Arterial (CUiiDARTE), Physiology..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)32130-X"},{"key":"e_1_3_5_3_2","unstructured":"WHO. 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