{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T12:30:56Z","timestamp":1782563456454,"version":"3.54.5"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2019,2,12]],"date-time":"2019-02-12T00:00:00Z","timestamp":1549929600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Eur J Prev Cardiolog"],"published-print":{"date-parts":[[2019,8]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p> Familial hypercholesterolemia (FH) is the most common genetic disorder in medicine, with a prevalence of 1\/250. Affected individuals have elevated low-density lipoprotein cholesterol (LDL-C) and an increased lifetime risk of atherosclerotic cardiovascular disease (ASCVD). The diagnosis of FH is based on algorithms that include LDL-C levels, physical manifestations, family history of high LDL-C and premature ASCVD, and, more recently, genetic testing. We sought to determine the impact of genetic testing on the: 1) diagnosis of \u2018definite familial hypercholesterolemia\u2019, 2) initiation and adherence of lipid-lowering therapy and 3) risk of ASCVD. <\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p> We performed a systematic review and meta-analysis, pooling odds ratios and 95% confidence intervals for ASCVD from studies comparing risk estimates in individuals harboring FH-causing variants and unaffected individuals. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p> After screening 3304 unique publications, 56 studies were included in the analysis. 1) Genetic testing provided confirmation of FH in 28\u201380%, over clinical criteria alone, depending on the diagnostic algorithm and the method of analysis. In two large population-based studies comprising 76,751 individuals, an FH-causing variant was identified in only 1.7\u20132.5% of subjects with an LDL-C\u2009&gt;\u20094.9 mmol\/L (190\u2009mg\/dL). 2) A confirmed molecular diagnosis increased lipid-lowering therapy adherence (five studies, n\u2009=\u20094181 definite FH). 3) Loss-of-function variant of the LDLR were at a markedly increased risk of myocardial infarction (odds ratio 6.77, 95% confidence interval 4.75\u20139.66), and patients with a milder (hypomorphic) pathogenic LDLR change had a 4.4-fold increase in risk (odds ratio 4.4, 95% confidence interval 2.34\u20138.26), compared with controls. <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p> DNA sequencing confirms the diagnosis of FH but has a poor yield in unselected patients whose sole criterion is an elevated LDL-C. Initiation and adherence to treatment is improved. The risk of ASCVD is 4.4- to 6.8-fold increased in patients with an FH-causing variant compared with controls, depending on the severity of the DNA change. <\/jats:p><\/jats:sec>","DOI":"10.1177\/2047487319829746","type":"journal-article","created":{"date-parts":[[2019,2,13]],"date-time":"2019-02-13T12:57:33Z","timestamp":1550062653000},"page":"1262-1270","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":41,"title":["Genetic testing for familial hypercholesterolemia: Impact on diagnosis, treatment and cardiovascular risk"],"prefix":"10.1093","volume":"26","author":[{"given":"Seohyuk","family":"Lee","sequence":"first","affiliation":[{"name":"Research Institute of the McGill University Health Centre, Royal Victoria Hospital, Montreal, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo E","family":"Akioyamen","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of 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