Identifying Markers of Cardiovascular Event-Free Survival in Familial Hypercholesterolemia

Familial hypercholesterolemia (FH) is an autosomal dominant trait characterized by elevated low-density lipoprotein-cholesterol (LDL-C) concentrations appearing at birth and is associated with increased risk of premature atherosclerotic cardiovascular disease (CVD). However, in some cases, FH subjects over 70 years of age have surprisingly never experienced any CVD symptoms throughout their entire lives. The objective of this study consists of identifying biological and environmental markers acting as cardioprotective factors and associated with unexpected survival in FH. Upon age and reported cardiovascular events (CVE) stratification, we identified a total of 458 French-Canadian FH subjects with premature reported CVE, and 1297 young adults as well as 24 elderly subjects (>= 70 years) who have never reported CVE requiring hospitalization. Logistic regression models were used to depict cardioprotective markers among FH survivors (>= 70 years). Regression analyses of the FH cohort showed that female sex (odds ratio (OR) = 12.92 (4.23-39.46); p < 0.0001), high levels of high-density lipoprotein (HDL)-C (OR = 6.76 (2.43-18.79); p = 0.0002) and elevated concentrations of adiponectin (OR = 71.40 (5.20-980.47); p = 0.001) were significant contributory factors in reducing FH-related CVD risk. Notably, female (OR = 11.45 (1.25-105.98); p = 0.031) and high HDL-C (OR = 9.78 (1.75-54.67); p = 0.009) were shown to be significant covariates associated with survival in FH. Non-smoking (OR = 11.73 (4.36-31.56); p < 0.0001) was also identified as an environmental factor associated with CVE-free survival. Based on this configured model of premature CVE occurrence, these results demonstrated that, beyond LDL-C levels, female sex, high HDL-C, elevated adiponectin and non-smoking are important markers that contribute to a reduced risk of CVD and CVE-free survival in FH.

Automated summary

This study identified female sex, high levels of high-density lipoprotein (HDL)-C, elevated concentrations of adiponectin, and non-smoking as important markers contributing to a reduced risk of cardiovascular disease (CVD) and cardiovascular event (CVE)-free survival in individuals with familial hypercholesterolemia (FH), beyond LDL-C levels.