Genetic identification of familial hypercholesterolemia within a single U.S. health care system

TLDR

Familial hypercholesterolemia remains underdiagnosed despite widespread cholesterol screening. The study used exome sequencing and electronic health record data from 50,726 Geisinger patients to estimate FH prevalence and clinical impact. The analysis found an overall FH prevalence of 1:256 (1:118 in cardiac‑lab patients), carriers had higher coronary artery disease risk, yet only 24 % met presequencing diagnostic criteria, 58 % were on statins, and 46 % of those had LDL < 100 mg/dl, indicating that genomic screening can identify FH patients who are largely undertreated.

Abstract

Familial hypercholesterolemia (FH) remains underdiagnosed despite widespread cholesterol screening. Exome sequencing and electronic health record (EHR) data of 50,726 individuals were used to assess the prevalence and clinical impact of FH-associated genomic variants in the Geisinger Health System. The estimated FH prevalence was 1:256 in unselected participants and 1:118 in participants ascertained via the cardiac catheterization laboratory. FH variant carriers had significantly increased risk of coronary artery disease. Only 24% of carriers met EHR-based presequencing criteria for probable or definite FH diagnosis. Active statin use was identified in 58% of carriers; 46% of statin-treated carriers had a low-density lipoprotein cholesterol level below 100 mg/dl. Thus, we find that genomic screening can prompt the diagnosis of FH patients, most of whom are receiving inadequate lipid-lowering therapy.