Elevated low-density lipoprotein cholesterol is a risk factor for atherosclerotic disease irrespective of familial hypercholesterolemia status

1. In a large registry-based cohort study, patients who underwent genetic testing for familial hypercholesterolemia between 1991 and 2023 were examined for cardiovascular outcomes and compared to those with negative genetic mutation status.

Evidence Rating Level: 2 (Good)

Familial Hypercholesterolemia (FH) is an inherited condition caused by pathogenic mutations of the LDL-receptor, apolipoprotein B, or PCSK9 genes, associated with elevated low-density lipoprotein cholesterol (LDL-C) and increased rates of cardiovascular disease. However, many patients experience high LDL-C levels and increased cardiovascular disease risk with negative FH mutations. This study aimed to compare the long-term cardiovascular health outcomes in patients with varying elevated LDL-C levels in both confirmed FH status and negative FH status. In this observational cohort study, all patients genetically tested for FH from January 1991 to December 2022 were analyzed for atherosclerotic cardiovascular disease, cardiovascular death, angina pectoris, or stroke. Patients with elevated LDL-C were significantly associated with the risk for future atherosclerotic cardiovascular disease, with a Hazard Ratio (HR) of 1.17 (95% CI, 1.13-1.22, P<0.001). No significant differences were found between patients with a genetic FH mutation compared to those without a genetic FH mutation. Overall, this study concluded that elevated LDL-C was a main causal risk factor for developing atherosclerotic disease and related comorbidities, irrespective of FH genetic mutation. 

Click here to read this study in Journal of Clinical Lipidology

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