Monogenic familial hypercholesterolemia (FH) and polygenic hypercholesterolemia are associated with greater risk of CVD than hypercholesterolemia without a known genetic cause. In this genetic-association, case-control, cohort study, individuals aged 40 to 69 years were recruited by the UK Biobank from across the United Kingdom. A monogenic FH variant for hypercholesterolemia was found in 277 individuals (0.57%, 1 in 176 individuals), polygenic hypercholesterolemia in 2379 individuals (4,9%).
Participants with monogenic FH were significantly more likely than those without monogenic FH to experience an atherosclerotic CVD event at 55 years or younger (17 of 277 [6.1%] vs 988 of 48 464 [2.0%]; P < .001). Moreover, among individuals with comparable levels of LDL-C, both monogenic (hazard ratio, 1.93; 95% CI, 1.34-2.77; P < 0.001) and polygenic hypercholesterolemia (hazard ratio, 1.26; 95% CI, 1.03-1.55; P = 0.03) were significantly associated with an increased risk of CVD events compared with the risk of such events in individuals with hypercholesterolemia without an identified genetic cause.
Thus, the authors emphasize what understanding the possible genetic cause of hypercholesterolemia may provide important prognostic information to treat patients.
Source: 1. Mark Trinder; Gordon A. Francis; Liam R. Brunham. Association of Monogenic vs Polygenic Hypercholesterolemia With Risk of Atherosclerotic Cardiovascular Disease. JAMA Cardiol. 2020 Feb 12. doi: 10.1001/jamacardio.2019.5954.
