Abstract 19544: The Familial Hypercholesterolemia Phenotype in the United States is Associated With an Age-dependent Increase in Long-term Coronary Heart Disease Risk

Abstract

Introduction: Heterozygous familial hypercholesterolemia (FH) has an estimated prevalence of 1:200-500, affecting up to 1,500,000 individuals in the US. Available CHD risk prediction equations do not account for lifetime exposure to elevated LDL-C in FH patients, and while relative risks of 7-100 have been reported for CHD in FH, US outcomes of FH are unknown. We aimed to evaluate long-term CHD risk in US adults with an FH phenotype. Methods: Using pooled data from 6 US epidemiologic cohorts, participants were stratified by LDL-C level at index ages 25, 35, 45, 55, 65 and 75 years. LDL-C≥190 and <130 mg/dL defined the FH phenotype and referent groups, respectively. We used Cox regression models to assess covariate-adjusted associations of the FH phenotype with the hazard for fatal/nonfatal MI and CHD death and to generate 30-year event-free survival curves. Results: A total of 42,390 baseline person-exams were available across the index ages. The table shows the 30-year event rates for patients with the FH phenotype (LDL-C≥190 mg/dL) compared with the referent from each index age, as well as covariate-adjusted HRs for CHD death or fatal/nonfatal MI. As expected, the relative increase in 30-year events is highest for the youngest individuals, with rates up to 12 times higher for CHD death, and attenuates at older index ages. After adjustment, HRs for both CHD death and fatal/nonfatal MI are more modest but show a similar age-dependent pattern. The figure shows the adjusted 30-year survival free of fatal/nonfatal MI for the youngest two index ages, by LDL-C stratum. Conclusions: In the US, the FH phenotype is associated with substantial long-term CHD risk in younger adults, with more modest elevations in risk at older ages. The absolute HRs are lower than previously described, possibly due to unique features in the US population, improved management compared to other historical cohorts, or misclassification of some participants who did not have longstanding high LDL-C.