Anti-oxidative and cholesterol efflux capacities of high-density lipoprotein are reduced in ischaemic cardiomyopathy

Abstract

Aims: Various pathological changes lead to the development of heart failure (HF). HDL is dysfunctional in both acute coronary syndrome, as measured by the HDL inflammatory index (HII) assay, and stable coronary disease, as measured by cholesterol efflux capacity. We therefore hypothesized that these functions of HDL are also impaired in subjects with ischaemic cardiomyopathy.

Methods and results: A case-control study was performed on subjects in the University of Pennsylvania Catheterization Study (PennCath) cohort of patients with angina. Cases had EF <50% and angiographic CAD (≥70% stenosis of any vessel; n = 23); controls included those with EF ≥55% and no CAD (n = 46). Serum from subjects was apolipoprotein-B depleted to isolate an HDL fraction. To measure HDL anti-oxidative capacity, the HDL fraction was incubated with LDL and a reporter lipid that fluoresces when oxidized. To measure cholesterol efflux capacity, the HDL fraction was also incubated with macrophages and tritium-labelled cholesterol. Mean HII was higher and efflux capacity lower in subjects with ischaemic cardiomyopathy (HII 0.26 vs. -0.028; efflux 0.80 vs. 0.92; P < 0.05). In a multivariable logistic regression model, both high HII and low efflux capacity were significant risk factors for HF [HII odds ratio (OR) 2.8, 95% confidence interval (CI) 2.0-3.9, P = 0.002; efflux OR 2.1, 95% CI 1.5-3.0, P = 0.03]. These effects persisted after adjustment for covariates and traditional risk factors for HF.

Conclusion: Subjects with reduced EF from ischaemia have lower HDL concentration and also impaired HDL function. HDL is a versatile lipoprotein particle with various anti-inflammatory and vasoprotective functions, whose impairment may contribute to ischaemic heart failure.

Keywords: Coronary artery disease; HDL cholesterol; Heart failure.

Figure 1

Associations of the high-density lipoprotein inflammatory index (HII) and efflux capacity with heart failure (HF). HII values were skewed and were therefore log-transformed. Comparison of the mean HII in cases (ischaemic HF) and controls (no ischaemia, no HF) by the Student's t-test revealed a significant difference (0.26 vs. –0.028, P = 0.02). Efflux values were normally distributed, and comparison of means by the Student's t-test also showed a significant difference (0.80 vs. 0.92, P = 0.02). HF correlates with a high HII (impaired anti-oxidant capacity) and low efflux capacity ratio (reduced cholesterol efflux capacity). Error bars represent the standard error of the mean.