{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T07:22:13Z","timestamp":1792653733940,"version":"4.5.0"},"reference-count":41,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2022,6,21]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Epidemiological studies show that women are generally at lower risk for cardiovascular disease than men. Here, we investigated the sex\u2010specific differential effect of genetically increased low\u2010density lipoprotein cholesterol (LDL\u2010C) on cardiovascular disease (CVD) and other lipid\u2010associated diseases.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              This is a 2\u2010sample Mendelian randomization study that uses individual participant data from 425\u00a0043 participants from the UK Biobank, including 229\u00a0279 female participants. An 80\u2010variant LDL\u2010C weighted genetic score was generated. Linear and logistic regression models with interactions were used to identify differences between sex\u2010specific LDL\u2010C effects on lipids, carotid\u2010intima media thickness, and multiple cardiovascular outcomes such as CVD, ischemic heart disease, peripheral artery disease, heart failure, aortic valve disease, type 2 diabetes, atrial fibrillation, and aortic aneurysm and dissection. After correction for multiple testing, we observed that the genetically increased LDL\u2010C effect on CVD events was sex specific: per SD genetically increased LDL\u2010C, female participants had a higher LDL\u2010C increase but an attenuated CVD risk increase compared with male participants (LDL\u2010C: female participants 0.71\u00a0mmol\/L, 95% CI, 0.70\u20130.72 and male participants 0.57\u00a0mmol\/L, 95% CI, 0.56\u20130.59.\n              <jats:italic>P<\/jats:italic>\n              for interaction: 5.03\u00d710\n              <jats:sup>\u221260<\/jats:sup>\n              ; CVD: female participants: odds ratio [OR], 1.32; 95% CI 1.24\u20131.40 and male participants: OR, 1.52; 95% CI, 1.46\u20131.58.\n              <jats:italic>P<\/jats:italic>\n              for interaction: 9.88\u00d710\n              <jats:sup>\u22125<\/jats:sup>\n              ). We also observed attenuated risks for ischemic heart disease and (nominally for) heart failure in female participants, and genetically increased LDL\u2010C results in higher risk for aortic valve disease in female participants compared with male participants. Genetically increased LDL\u2010C was also associated with an attenuated carotid\u2010intima media thickness increase in female participants. We did not observe other significant attenuations. Sensitivity analyses with an unweighted genetic score and sex\u2010specific weighted genetic scores showed similar results.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">We found that genetically increased LDL\u2010C has a sex\u2010specific differential effect on the risk for cardiovascular disease, ischemic heart disease, heart failure, and aortic valve stenosis. Our observations provide evidence that LDL\u2010C might be a less important determinant of CVD in women compared with men, suggesting that male patients might benefit more from LDL\u2010C targeted therapies for CVD management than female patients and warranting investigations into the sex\u2010specific relative contribution of risk factors for CVD.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.121.024248","type":"journal-article","created":{"date-parts":[[2022,6,14]],"date-time":"2022-06-14T10:34:37Z","timestamp":1655202877000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":35,"title":["Low\u2010Density Lipoprotein Cholesterol Attributable Cardiovascular Disease Risk Is Sex Specific"],"prefix":"10.1161","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3300-8124","authenticated-orcid":false,"given":"Arjen J.","family":"Cupido","sequence":"first","affiliation":[{"name":"Department of Vascular Medicine Amsterdam University Medical Centerslocation AMCUniversity of Amsterdam Netherlands"},{"name":"Department of Cardiology Division of Heart &amp; Lungs University Medical Center UtrechtUtrecht University Utrecht the Netherlands"},{"name":"Division of Cardiology Department of Medicine University of California, Los Angeles Los Angeles CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1692-8669","authenticated-orcid":false,"given":"Folkert W.","family":"Asselbergs","sequence":"additional","affiliation":[{"name":"Department of Cardiology Division of Heart &amp; Lungs University Medical Center UtrechtUtrecht University Utrecht the Netherlands"},{"name":"Faculty of Population Health Sciences Institute of Cardiovascular ScienceUniversity College London London United Kingdom"},{"name":"Health Data Research UK and Institute of Health Informatics University College London London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1327-0424","authenticated-orcid":false,"given":"A. Floriaan","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Department of Cardiology Division of Heart &amp; Lungs University Medical Center UtrechtUtrecht University Utrecht the Netherlands"},{"name":"Faculty of Population Health Sciences Institute of Cardiovascular ScienceUniversity College London London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8145-1676","authenticated-orcid":false,"given":"G. 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