{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T00:06:48Z","timestamp":1787962008616,"version":"build-2784847793"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"24","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2019,12,17]]},"abstract":"\n Background<\/jats:title>\n \n Genetic variation in catechol\u2010O\u2010methyltransferase (\n \n COMT<\/jats:styled-content>\n <\/jats:italic>\n ), a key enzyme in estrogen and catecholamine metabolism, has plausible physiological links to cardiovascular disease (\n CVD<\/jats:styled-content>\n ) and its risk factors. In\n WHS<\/jats:styled-content>\n (Women's Health Study),\n \n COMT<\/jats:styled-content>\n <\/jats:italic>\n variants rs4818 and rs4680 were associated with a lower risk of\n CVD<\/jats:styled-content>\n among women receiving placebo but not aspirin, suggesting a possible role of\n \n COMT<\/jats:styled-content>\n <\/jats:italic>\n in thrombosis.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n To evaluate potential pathways linking\n \n COMT<\/jats:styled-content>\n <\/jats:italic>\n with\n CVD<\/jats:styled-content>\n , and\n \n COMT<\/jats:styled-content>\n <\/jats:italic>\n effect modification of aspirin in prevention, we examined\n \n COMT<\/jats:styled-content>\n <\/jats:italic>\n association with\n CVD<\/jats:styled-content>\n risk and subclinical measures, coronary artery calcium, and carotid intima\u2010media thickness in MESA (Multi\u2010Ethnic Study of Atherosclerosis). In 65\u00a0957\u00a0person\u2010years of follow\u2010up, during which 498 events occurred,\n \n COMT<\/jats:styled-content>\n <\/jats:italic>\n rs4818 was associated with lower\n CVD<\/jats:styled-content>\n risk (hazard ratio, 0.85; 95% CI, 0.74\u20130.97 [\n P<\/jats:italic>\n =0.02]). This association remained virtually unchanged after adjusting for common\n CVD<\/jats:styled-content>\n risk factors. Fibrinogen was the only risk factor associated with rs4818 (\u03b2, \u22123.65;\n SE<\/jats:styled-content>\n , 1.35 mg\/\n dL<\/jats:styled-content>\n [\n P<\/jats:italic>\n =0.007]). Results were directionally similar but not significant for rs4680. Adjusted hazard ratios for\n \n COMT<\/jats:styled-content>\n <\/jats:italic>\n rs4818\n CVD<\/jats:styled-content>\n association were 0.79 (95% CI, 0.65\u20130.95;\n P<\/jats:italic>\n =0.02) among individuals who used aspirin <3\u00a0days per week and 0.89 (95% CI, 0.71\u20131.13;\n P<\/jats:italic>\n =0.34) among more frequent users (\n P<\/jats:italic>\n interaction<\/jats:sub>\n =0.39). Neither intima\u2010media thickness nor coronary artery calcium was associated with\n \n COMT<\/jats:styled-content>\n <\/jats:italic>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n In a multiethnic prospective cohort of men and women, the\n \n COMT<\/jats:styled-content>\n <\/jats:italic>\n rs4818G allele was associated with lower\n CVD<\/jats:styled-content>\n risk and lower fibrinogen levels but not with radiographic measures of subclinical atherosclerosis. These results suggest a plausible role of\n \n COMT<\/jats:styled-content>\n <\/jats:italic>\n in the latter stages of\n CVD<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.119.014986","type":"journal-article","created":{"date-parts":[[2019,12,16]],"date-time":"2019-12-16T10:07:15Z","timestamp":1576490835000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":16,"title":["Catechol\u2010O\u2010Methyltransferase and Cardiovascular Disease: MESA"],"prefix":"10.1161","volume":"8","author":[{"given":"Kathryn T.","family":"Hall","sequence":"first","affiliation":[{"name":"Division of Preventive Medicine Department of Medicine Brigham and Women's Hospital Harvard Medical School Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Battinelli","sequence":"additional","affiliation":[{"name":"Division of Hematology Department of Medicine Brigham and Women's Hospital Harvard Medical School Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel I.","family":"Chasman","sequence":"additional","affiliation":[{"name":"Division of Preventive Medicine Department of Medicine Brigham and Women's Hospital Harvard Medical School Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul M","family":"Ridker","sequence":"additional","affiliation":[{"name":"Division of Preventive Medicine Department of Medicine Brigham and Women's Hospital Harvard Medical School Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce M.","family":"Psaty","sequence":"additional","affiliation":[{"name":"Cardiovascular Health Research Unit Department of Medicine University of Washington Seattle WA"},{"name":"Kaiser Permanente Washington Health Research Institute Seattle WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerome I.","family":"Rotter","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Medicine The Institute for Translational Genomics and Population Sciences Los Angeles Biomedical Research Institute at Harbor\u2010UCLA Medical Center Torrance CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ted J.","family":"Kaptchuk","sequence":"additional","affiliation":[{"name":"Division of General Medicine and Primary Care Beth Israel Deaconess Medical Center Harvard Medical School Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell P.","family":"Tracy","sequence":"additional","affiliation":[{"name":"Laboratory for Clinical Biochemistry Research University of Vermont, College of Medicine Colchester VT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina L.","family":"Wassel","sequence":"additional","affiliation":[{"name":"Applied Sciences Premier, Inc Charlotte NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth J.","family":"Mukamal","sequence":"additional","affiliation":[{"name":"Division of General Medicine and Primary Care Beth Israel Deaconess Medical Center Harvard Medical School Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.114.303845"},{"key":"e_1_3_1_3_2","first-page":"593","article-title":"Catechol\u2010O\u2010methyltransferase (COMT): biochemistry, molecular biology, pharmacology, and clinical efficacy of the new selective COMT inhibitors","volume":"51","author":"Mannisto PT","year":"1999","unstructured":"Mannisto PT, Kaakkola S. 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