Impact of High-Density Lipoprotein Function, Rather Than High-Density Lipoprotein Cholesterol Level, on Cardiovascular Disease Among Patients With Familial Hypercholesterolemia

Background: Recently, the function of high-density lipoprotein (HDL), rather than the HDL cholesterol (HDL-C) level, has been attracting more attention in risk prediction for coronary artery disease (CAD). Methods and Results: Patients with clinically diagnosed familial hypercholesterolemia (FH; n=108; male/female, 51/57) were assessed cross-sectionally. Serum cholesterol uptake capacity (CUC) levels were determined using our original cell-free assay. Linear regression was used to determine associations between CUC and clinical variables, including low-density lipoprotein cholesterol and the carotid plaque score. Multivariable logistic regression analysis was used to test factors associated with the presence of CAD. Among the 108 FH patients, 30 had CAD. CUC levels were significantly lower among patients with than without CAD (median [interquartile range] 119 [92-139] vs. 142 [121-165] arbitrary units [AU]; P=0.0004). In addition, CUC was significantly lower in patients with Achilles tendon thickness >= 9.0 mm than in those without Achilles tendon thickening (133 [110-157] vs. 142 [123-174] AU; P=0.047). Serum CUC levels were negatively correlated with the carotid plaque score (Spearman's r=0.37; P=0.00018). Serum CUC levels were significantly associated with CAD, after adjusting for other clinical variables (odds ratio=0.86, 95% CI=0.76-0.96, P=0.033), whereas HDL-C was not. Conclusions: HDL function, assessed by serum CUC level, rather than HDL-C level, adds risk stratification information among FH patients.

Automated summary

The function of high-density lipoprotein (HDL) is more important than the HDL cholesterol (HDL-C) level in predicting the risk of coronary artery disease (CAD). A study on patients with familial hypercholesterolemia (FH) found that serum cholesterol uptake capacity (CUC) levels were significantly lower in patients with CAD compared to those without CAD. The study also showed that CUC levels were negatively correlated with the carotid plaque score and were independently associated with CAD, while HDL-C was not.