HDL anti-oxidative and cholesterol efflux function is impaired in ischaemic HF
Anti-oxidative and cholesterol efflux capacities of high-density lipoprotein are reduced in ischaemic cardiomyopathy.
Literature - Patel PJ, Khera AV, Wilensky RL, Rader DJ - Eur J Heart Fail. 2013 May 24Patel 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 inflammationReferences
1. Holme I, Strandberg TE, Faergeman O, et al. Incremental Decrease in End Points Through Aggressive Lipid Lowering Study Group. Congestive heart failure is associated with lipoprotein components in statin-treated patients with coronary heart disease Insights from the Incremental Decrease in End points Through Aggressive
Lipid Lowering Trial (IDEAL). Atherosclerosis 2009;205:522–527.
2. Aronow WS, Ahn C. Frequency of congestive heart failure in older persons with prior myocardial infarction and serum low-density lipoprotein cholesterol >or=125 mg/dl treated with statins versus no lipid-lowering drug. Am J Cardiol 2002;90:147–149.
3. Freitas HF, Barbosa EA, Rosa FH, et al. Association of HDL cholesterol and triglycerides with mortality in patients with heart failure. Braz J Med Biol Res 2009;42:420–425.
4. Mehra MR, Uber PA, Lavie CJ, et al. High-density lipoprotein cholesterol levels and prognosis in advanced heart failure. J Heart Lung Transplant 2009;28:876–880.
5. Christ M, Klima T, GrimmW, et al. Prognostic significance of serum cholesterol levels in patients with idiopathic dilated cardiomyopathy. Eur Heart J 2006;27:691–699.
6. Rauchhaus M, Koloczek V, Volk H, et al. Inflammatory cytokines and the possible immunological role for lipoproteins in chronic heart failure. Int J Cardiol 2000;76:125–133.
7. Levine B, Kalman J, Mayer L et al. Elevated circulating levels of tumor necrosis factor in severe chronic heart failure. N Engl J Med 1990;323:236–241.
8. McMurray J, Abdullah I, Dargie HJ, Shapiro D. Increased concentrations of tumour necrosis factor in ‘cachectic’ patients with severe chronic heart failure. Br Heart J 1991;66:356–358.
9. Anker SD, Egerer KR, Volk HD, et al. Elevated soluble CD14 receptors and altered cytokines in chronic heart failure. Am J Cardiol 1997;79:1426–1430.
10. Niebauer J, Volk HD, Kemp M, et al. Endotoxin and immune activation in chronic heart failure: a prospective cohort study. Lancet 1999;353:1838–1842.
11. Patel PJ, KheraAV, Jafri K, et al. The anti-oxidative capacity of high density lipoprotein is reduced in acute coronary syndrome but not in stable coronary artery disease. J Am Coll Cardiol 2011;58:2068–2075.
12. Khera AV, Cuchel M, de la Llera-Moya M, et al. Cholesterol efflux capacity, high-density lipoprotein function, and atherosclerosis.N Engl J Med 2011;364:127–135.