Long-Term Risk of Atherosclerotic CVD in Adults With Familial Hypercholesterolemia

Study Questions:

What is the long-term risk for coronary heart disease (CHD) and total atherosclerotic cardiovascular disease (ASCVD) among US adults with a heterozygous familial hypercholesterolemia (FH) phenotype?

Methods:

Pooled data from six large epidemiologic cohorts within the Cardiovascular Lifetime Risk Pooling Projection were used for the present analysis. Adults residing in the United States, aged 20-79 years, were stratified by low-density lipoprotein (LDL) cholesterol levels. The FH phenotype was defined by an LDL cholesterol level of ≥190 mg/dl. The referent group was defined by an LDL cholesterol level of <130 mg/dl. The primary outcomes of interest were 30-year hazards for CHD (CHD death or nonfatal myocardial infarction) and total ASCVD (CHD or stroke).

Results:

A total of 68,565 adults who completed baseline exams were included, of which 3,850 (5.6%) had the FH phenotype. After adjustment for potential confounders, the FH phenotype was associated with an elevated 30-year risk for CHD (hazard ratio [HR], 5.0; 95% confidence interval [CI], 1.1–21.7). Across index ages, CHD risk was accelerated in those with the FH phenotype by 10-20 years in men and 20-30 years in women. Similar associations were observed for total ASCVD risk (HR, 4.1; 95% CI, 1.2–13.4). Alternative FH phenotype definitions incorporating family history, more stringent age based on LDL cholesterol thresholds, or alternative lipid fractions decreased the FH phenotype prevalence to as low as 0.2-0.4% without materially affecting CHD risk estimates.

Conclusions:

The investigators concluded that in the general US population, the long-term ASCVD burden related to phenotypic FH, defined by LDL cholesterol ≥190 mg/dl, is likely substantial. The finding of CHD risk acceleration may aid efforts in risk communication.

Perspective:

These data suggest that screening for FH will improve management of elevated LDL and result in reduction of CHD and ASCVD.

Clinical Topics: Diabetes and Cardiometabolic Disease, Clinical Topic Collection: Dyslipidemia, Prevention, Homozygous Familial Hypercholesterolemia, Lipid Metabolism, Nonstatins, Primary Hyperlipidemia

Keywords: Atherosclerosis, Cholesterol, LDL, Coronary Artery Disease, Dyslipidemias, Hypercholesterolemia, Hyperlipoproteinemia Type II, Myocardial Infarction, Phenotype, Primary Prevention, Risk Factors, Stroke


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