Prevalence and prognosis of genetically proven familial hypercholesterolemia in subjects with angiographically documented premature coronary artery disease.

Few studies have genetically screened variants related to familial hypercholesterolemia (FH) in patients with angiographically documented premature coronary artery disease (CAD) and evaluated its impact on survival. Patients with coronary angiography confirmed CAD diagnosed at age<45 in men or age <55 in women (N=266) were retrospectively investigated. Their genomic DNAs were sequenced for FH-related genetic variants. All-cause and cardiovascular mortality data served as the major outcome. A total of 266 subjects were analyzed and 18 subjects (6.8%) had pathogenic or likely pathogenic variants related to FH. The median follow-up duration was 67 months and 35 died in the follow-up with 20 of them due to cardiovascular causes. Those who carried the FH-related genetic variant had significantly higher peak and baseline low-density lipoprotein cholesterol but lower HbA1c than those of non-carriers. Carrying the FH-related genetic variant did not have a significant impact on the survival of premature CAD. In Cox regression analyses, a higher estimated glomerular filtration rate and a better left ventricular ejection fraction were protective of a lower all-cause mortality, while a higher HbA1c was associated with a worse all-cause mortality. Further larger studies are needed to evaluate the impact of carrying the FH-related genetic variants on the survival of premature CAD.