Abstract 9542: HDL is Dysfunctional in Patients with Ischemic Cardiomyopathy

Abstract

Objectives: Various pathologic changes lead to the development of systolic heart failure. We previously showed that HDL is dysfunctional in both acute coronary syndrome (ACS), as measured by the HDL inflammatory index (HII) assay, and stable CAD, as measured by cholesterol efflux capacity. We therefore hypothesized that these functions of HDL are also impaired in subjects with ischemic heart failure. Methods: A nested case-control study was performed on subjects in the PennCath cohort of patients with angina undergoing cardiac catheterization. Cases had ejection fraction (EF) less than 55% (measured by ventriculography) and angiographic CAD (≥20% stenosis of any vessel; n=23); controls included those with EF≥55% and no CAD (n=46). The HII and cholesterol efflux assays were performed as previously described. Briefly, apo-B depleted serum from subjects was incubated with either oxidized LDL and a lipid substrate that fluoresces when oxidized, or macrophages and tritium-labeled cholesterol. Impaired anti-oxidative capacity corresponds with a higher HII value, and reduced cholesterol efflux capacity corresponds with lower percent efflux. Results: Mean HII was higher in subjects with ischemic heart failure (0.26 v. -0.028; p = 0.012); mean cholesterol efflux was lower in the same population (0.80 v. 0.92; p = 0.021). Subjects with ischemic heart failure also had more incident diabetes and hypertension, worse renal function, and lower HDL mass. In a multivariable linear regression model for risk factors of heart failure, both high HII and low efflux capacity were significant risk factors (Table). Conclusion: Subjects with ischemic cardiomyopathy have lower HDL mass and also impaired HDL function. This research supports prior findings of dysfunctional HDL in nonischemic cardiomyopathy, ACS, and chronic CAD. HDL is a versatile molecule with various anti-inflammatory and vasoprotective functions, whose impairment may contribute to heart failure.