The Silent Genetic Threat: Why Most Patients with Familial Hypercholesterolemia Are Still Falling Through the Clinical Cracks

Introduction: The Persistent Challenge of Familial Hypercholesterolemia

Familial hypercholesterolemia (FH) represents one of the most common and clinically significant genetic conditions globally. Characterized by lifelong elevation of low-density lipoprotein cholesterol (LDL-C), FH serves as a primary driver for premature atherosclerotic cardiovascular disease (ASCVD). Despite our deep understanding of the genetic basis of this condition—primarily involving mutations in the LDLR, APOB, and PCSK9 genes—clinical identification and effective management remain disappointingly low. A recent landmark study published in JAMA Cardiology by Spinks et al. utilizes the ‘All of Us’ (AoU) Research Program to shed light on the prevalence, management, and real-world consequences of genotype-positive FH in a diverse US population.

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