HDL anti-oxidative and cholesterol efflux function is impaired in ischaemic HF

Patel PJ, Khera AV, Wilensky RL, Rader DJ
Eur J Heart Fail. 2013 May 24. [Epub ahead of print]

Background

HDL-C levels correlate to incident congestive heart failure (HF) in patients with ischaemia and predicts HF exacerbations and adverse CV events [1-6]. It is, however, unclear if HDL function plays a role in this correlation. HF patients show reduced capacity to counter inflammation and oxidative stress and increased inflammatory mediators [7-10]. HDL appears to attenuate inflammatory mediators, but it is unclear how. Furthermore, HDL may prevent oxidation of LDL in lipid core plaque, which can be measured in the in vitro HDL inflammatory index (HII) assay. HII has been shown to be impaired in patients with acute coronary syndrome (ACS)[11]. HDL is thought to transfer cholesterol from VLDL and LDL to the liver for excretion. This HDL-C efflux capacity is reduced in patients with stable CAD [12].
This study studied the hypothesis that patients with reduced ejection fraction and chronic ischaemia  have impaired HDL anti-oxidative capacity and reduced cholesterol efflux capacity. Serum samples of 23 cases (EF<50% and angiographic CAD or prior CABG or PCI) and 46 controls (no angiographic CAD and EF>55%) were subjected to the HII assay and the cholesterol efflux capacity test.

Main results

• Patients with ischaemic cardiomyopathy showed a higher average HII (0.26 vs. -0.028, P=0,02) and lower cholesterol efflux capacity (0.80 vs. 0.92, P=0.02) as compared to controls. Correction for HDL concentration strengthened these associations, in line with their dependence on HDL-C levels.
• Higher HDL-concentration was associated with a reduced HII (better anti-oxidative capacity, r²=0.09, P=0.01) but increased efflux capacity (r²=0.23, P=0.0005). HII and efflux capacity did not correlate with each other.
• High HII (OR: 2.8, 95%CI: 2.0-3.9, P=0.002) and low efflux capacity OR: 2.1, 95%CI: 1.5-3.0, P=0.03) are risk factors for HF, even after correction for clinical variables that were associated with HF, as well as after correction for traditional risk factors for HF.

Conclusion

By means of two separate assays, this study shows that HDL function is impaired in HF patients with chronic ischaemia. Reduced anti-oxidative capacity and cholesterol efflux capacity appear to contribute to HF, possibly through inflammation

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