Enough Evidence, Time to Act!
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- cardiovascular diseases
- cholesterol, LDL
- coronary diseases
- myocardial infarction
Article, see p 9
Familial hypercholesterolemia (FH) is an autosomal dominant disorder caused by mutations in 3 genes — LDLR, APOB, PCSK9 — that impact plasma low-density lipoprotein cholesterol (LDL-C) clearance, thereby resulting in a lifelong elevation in LDL-C and a markedly increased risk of atherosclerotic cardiovascular disease (ASCVD), particularly premature coronary heart disease (CHD).1 Recent large-scale genetic surveys indicate that causal FH mutations occur in 1 in 200 to 250 people of European ancestry.2,3 Natural history studies of FH patients have demonstrated the importance of LDL-C in the pathogenesis of CHD,4 with notable improvements in life expectancy with aggressive LDL-C lowering.5
A recent scientific statement from the American Heart Association highlighted the difficulties in early diagnosis and tracking of FH patients, in part, because of the lack of a specific International Classification of Diseases code for FH and the lack of consensus on how to identify FH in broad populations.1 Existing diagnostic criteria based on features such as LDL-C level, personal and family history of ASCVD, and certain pathognomonic physical findings (xanthomas) were designed to select individuals that were likely to have a positive genetic test for FH. Although these algorithms are quite reasonable for this purpose, they are too complex to be used as screening tools for large populations. Genetic testing holds promise and, when used, can help confirm a monogenic FH diagnosis and may improve cascade (family-based) screening efforts.6 However, genetic testing has been expensive and used infrequently in many countries, including the United States. Furthermore, a substantial fraction of patients with a phenotype largely indistinguishable from monogenic FH may actually have a polygenic cause for their elevated LDL-C levels.7
In 2015, the authors of the American Heart Association scientific statement on FH therefore recommended criteria with a …