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Objective There is no coordinated cascade testing program for familial hypercholesterolemia (FH) in the U.S. We evaluated the contemporary cost-effectiveness of cascade genetic testing relatives of FH probands with a pathogenic variant. Methods A simulation model was created to simulate multiple family trees starting with progenitor individuals carrying a pathogenic variant for FH who were followed through several generations. This approach allowed us to examine a family tree that had grown sufficiently to have large numbers of relatives across multiple degrees of relatedness. The model estimated costs and life years gained (LYG) when cascade genetic testing was implemented for relatives of FH probands identified through standard care who were at or older than designated age thresholds (5, 10, 15, 20, 25, 30, 35, 40). Costs were valued in 2018 U.S. dollars. Future costs and LYG projected by the model were discounted at an annual rate of 3%. Results For 1st degree relatives, cascade testing at every age threshold resulted in a positive number of average LYG per person, though this number decreased as testing was started at higher age thresholds. Testing was not cost-effective if initiated at an age threshold of 40 and older but was cost-effective at younger age thresholds, with a discounted cost per LYG per person of less than $50,000. For 2nd degree relatives, testing was cost-effective with a screening age threshold of 10 but no longer cost-effective at a threshold of 15 or higher. In more distant relatives, cascade genetic testing was not beneficial or cost-effective. Conclusions Based on our simulation model, cascade genetic testing for FH in the U.S. is cost-effective if started before age 40 in 1st degree relatives and before age 15 in 2nd degree relatives.

Key PointsQuestionWhat is the prevalence of familial hypercholesterolemia in a population of blood donors?FindingsIn this cohort study of 1 178 102 individual blood donors, 3473 individuals (or 1 of every 339) met criteria for familial hypercholesterolemia.MeaningBlood donation may serve as a novel method of identifying individuals with familial hypercholesterolemia.

Objectives Patients with severe hyperlipidemia (low-density lipoprotein-cholesterol (LDL-C) ≥190 ​mg/dL) have a significantly increased risk of cardiovascular disease (CVD) and are more likely to have familial hypercholesterolemia (FH). We sought to determine how often health care providers recognize the implications of and adjust therapy for an LDL-C ≥190 ​mg/dL. Methods We conducted a retrospective review of patients with an LDL-C measurement in the medical record of a large health care system between November 2015 and June 2016. Patients were restricted to those with LDL-C ≥190 ​mg/dL and without secondary causes of dyslipidemia, with sensitivity analyses for those with LDL-C ≥220 ​mg/dL. Results Of 27,963 patients, 227 had LDL-C ≥190 ​mg/dL. Only 21% were on a statin at the time of LDL-C measurement. More than 90% had a follow-up clinic visit, but 41% had no change in treatment. FH was only included in the differential for 14%. The presence/absence of a family history of dyslipidemia, myocardial infarction, and premature CVD were documented in 26%, 29%, and 31%. Only 20.7% and 22.1% had documentation of the presence or absence of tendinous xanthomas or corneal arcus, respectively. Among those without prior specialist care (cardiologist or endocrinologist), only 13% were referred. These measures were only slightly better for those with LDL-C ≥220 ​mg/dL. Conclusion In a large health care system, the possibility of FH was rarely acknowledged in those with residual LDL-C ≥190 ​mg/dL, few were referred to specialists, and therapeutic adjustments were suboptimal. Additional efforts are required to understand barriers to improving the evaluation and management of patients with LDL-C ≥190 ​mg/dL.