FCHL and FH Associated With Increased and Similar Coronary Artery Disease Risk

vitamin d supplementation does not reduce cvd risk.
vitamin d supplementation does not reduce cvd risk.
Researchers investigated the relationship between cardiovascular risk and the genetic architecture of familial combined hyperlipidemia.

Individuals with familial combined hyperlipidemia (FCHL) and familial hypercholesterolemia (FH) have a significantly greater risk of incident coronary artery disease (CAD) compared with control patients, according to research presented at the National Lipid Association Scientific Sessions, from June 2nd through 5th, in Scottsdale, AZ.

These findings are based on an analysis of participants in the UK Biobank cohort. Using modified versions of 5 different diagnostic criteria, the researchers identified individuals with an FCHL phenotype from 349,222 unrelated participants of European ancestry. Discovery, case-control, genome-wide association studies were conducted for the different criteria.

The investigators then evaluated the association of clinical and genetic risk factors with FCHL and examined the risk for incident CAD compared with participants with monogenic FH.

The FCHL phenotype prevalence was 11.44%, 5.01%, 1.48%, 1.10%, and 0.48% per modified versions of the Consensus, Dutch, Mexico, Brunzell, and Goldstein criteria, respectively.

According to the Mexico criteria, the researchers identified 64 lead single-nucleotide variants (SNVs) associated with FCHL at P <10-8. All lead SNVs were previously associated with triglyceride levels, low-density lipoprotein-cholesterol, or total cholesterol.

The participants with FCHL (odds ratio [OR], 2.72 [2.33-3.18]) and FH (OR, 2.38 [1.75-3.24]) had a significantly greater risk of incident CAD compared with the control cohort.

“FCHL phenotype represents a polygenic susceptibility to dyslipidemia in combination with metabolic abnormalities,” the study authors wrote. “The cardiovascular risk associated with an FCHL phenotype is similar to that of monogenic FH, despite being [approximately] 5x more common.”


Trinder M, Vikulova D, Mancini GBJ, Brunham LR. Genetic architecture and cardiovascular risk of familial combined hyperlipidemia. Presented at: National Lipid Association Scientific Sessions; June 2-5, 2022; Scottsdale, AZ. Abstract #6.