{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T09:13:42Z","timestamp":1784625222469,"version":"3.55.0"},"reference-count":52,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"21","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2023,11,7]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">The risk of atherosclerotic cardiovascular disease (ASCVD) increases sharply with age. Some older individuals, however, remain unaffected despite high predicted risk. These individuals may carry cardioprotective genetic variants that contribute to resilience. Our aim was to assess whether asymptomatic older individuals without prevalent ASCVD carry cardioprotective genetic variants that contribute to ASCVD resilience.<\/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              We performed a genome\u2010wide association study using a 10\u2010year predicted ASCVD risk score as a quantitative trait, calculated only in asymptomatic older individuals aged \u226570\u2009years without prevalent ASCVD. Our discovery genome\u2010wide association study of N=12\u2009031 ASCVD event\u2010free individuals from the ASPREE (Aspirin in Reducing Events in the Elderly) trial identified 2 independent variants, rs9939224 (\n              <jats:italic>P<\/jats:italic>\n              &lt;5\u00d710\n              <jats:sup>\u22128<\/jats:sup>\n              ) and rs56156922 (\n              <jats:italic>P<\/jats:italic>\n              &lt;10\n              <jats:sup>\u22126<\/jats:sup>\n              ), in the\n              <jats:italic>CETP<\/jats:italic>\n              (cholesteryl ester transfer protein) gene. The\n              <jats:italic>CETP<\/jats:italic>\n              gene is a regulator of plasma high\u2010density lipoprotein cholesterol, low\u2010density lipoprotein cholesterol, and lipoprotein(a) levels, and it is a therapeutic drug target. The associations were replicated in the UK Biobank (subpopulation of N=13\u2009888 individuals aged \u226569\u2009years without prevalent ASCVD). Carriers of the identified\n              <jats:italic>CETP<\/jats:italic>\n              variants (versus noncarriers) had higher plasma high\u2010density lipoprotein cholesterol levels, lower plasma low\u2010density lipoprotein cholesterol levels, and reduced risk of incident ASCVD events during follow\u2010up. Expression quantitative trait loci analysis predicted the identified\n              <jats:italic>CETP<\/jats:italic>\n              variants reduce\n              <jats:italic>CETP<\/jats:italic>\n              gene expression across various tissues. Previously reported associations between genetic\n              <jats:italic>CETP<\/jats:italic>\n              inhibition and increased risk of age\u2010related macular degeneration were not observed among the 3917 ASPREE trial participants with retinal imaging and genetic data available.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Common genetic variants in the\n              <jats:italic>CETP<\/jats:italic>\n              gene region are associated with cardiovascular resilience during aging.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Registration<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              URL:\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n              ; Unique identifier: NCT01038583.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.123.031459","type":"journal-article","created":{"date-parts":[[2023,11,6]],"date-time":"2023-11-06T11:29:06Z","timestamp":1699270146000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":20,"title":["Genome\u2010Wide Association Study of Cardiovascular Resilience Identifies Protective Variation in the\n            <i>CETP<\/i>\n            Gene"],"prefix":"10.1161","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0546-2779","authenticated-orcid":false,"given":"Chenglong","family":"Yu","sequence":"first","affiliation":[{"name":"School of Public Health and Preventive Medicine Monash University Melbourne VIC 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