Patients With and Gene Variants Experienced Higher Incidence of Cardiovascular Outcomes in Heterozygous Familial Hypercholesterolemia.

Background Patients with familial hypercholesterolemia who harbored both low-density lipoprotein receptor () and (proprotein convertase subtilisin/kexin type 9) gene variants exhibit severe phenotype associated with substantially high levels of low-density lipoprotein cholesterol. In this study, we investigated the cardiovascular outcomes in patients with both and gene variants. Methods and Results A total of 232 unrelated patients with and/or gene variants were stratified as follows: patients with and () gene variants, patients with gene variant, and patients with gene variant. Clinical demographics and the occurrence of primary outcome (nonfatal myocardial infarction) were compared. The observation period of primary outcome started at the time of birth and ended at the time of the first cardiac event or the last visit. Patients with gene variants were identified in 6% of study patients. They had higher levels of low-density lipoprotein cholesterol (=0.04) than those with gene variants. On multivariate Cox regression model, they experienced a higher incidence of nonfatal myocardial infarction (hazard ratio, 4.62; 95% CI, 1.66-11.0; =0.003 versus patients with gene variant). Of note, risk for nonfatal myocardial infarction was greatest in male patients with gene variants compared with those with gene variant (86% versus 24%; <0.001). Conclusions Patients with gene variants were high-risk genotype associated with atherogenic lipid profiles and worse cardiovascular outcomes. These findings underscore the importance of genetic testing to identify patients with gene variants, who require more stringent antiatherosclerotic management.