Physicians' Academy for Cardiovascular Education

HDL dysfunction in STEMI patients is independent of plasma HDL-C levels

Literature - Annema W et al., J Clin Lipidol. 2016

 
HDL function is impaired in acute myocardial infarction independent of plasma HDL cholesterol levels

 
Annema W, Willemsen HM, de Boer JF, et al.
J Clin Lipidol 2016; published online ahead of print
 

Background

Although increased HDL-C levels have been independently associated with significant protection against CV morbidity and mortality, pharmacological studies with the objective to increase HDL-C levels showed no reduction of CV events [1-3].  Moreover, high HDL-C levels can be found in some patients who experience CVD events [4,5]. Therefore, it has hypothesised that the HDL particle might be dysfunctional in patients with CVD.
In this study, three key functional properties of HDL were assessed in STEMI patients, independent of HDL-C plasma levels, and compared with non-STEMI and non-MI patients (groups matched for HDL-c level and age):
  • mediation of cholesterol efflux from macrophage foam cells
  • anti-oxidative properties by means of prevention of LDL oxidation
  • anti-inflammatory properties by means of inhibition of TNF-α-induced vascular adhesion molecule-1 expression in endothelial cells.
The extent of MI was assessed based on plasma levels of creatine kinase (CK) and CK-MB (myocardial band).
 

Main results

  • The efflux capacity of HDL was significantly lower in STEMI patients (0.89±0.16) compared to non-MI (1.00+0.09) and non-STEMI patients (1.0+0.07, P<0.001 for each).
  • No differences were seen in anti-oxidative capacity of HDL; HDL from all three groups similarly reduced oxidation of native LDL (P=0.48).
  • Anti-inflammatory activity of HDL from STEMI patients was higher than of HDL from non-MI patients; TNF-α-induced VCAM-1 expression was 3.2-fold higher (3.16±2.04; P<0.001) and more than doubled compared with non-STEMI patients (P=0.001).
  • In univariate analysis, efflux potential of HDL significantly correlated with anti-inflammatory capacity of HDL (r=-0.355; P<0.001). There was no relation between the anti-oxidative capacity of HDL and the efflux potential of HDL (r=-0.041; P=0.674), or the anti-oxidative capacity of HDL and the anti-inflammatory capacity of HDL (r=0.062; P=0.554).
  • A decreased efflux potential of HDL was significantly associated with higher maximum plasma levels of CK (r=-0.250; P=0.020) and CK-MB (r=-0.255; P=0.017). Univariate correlations were observed between the anti-inflammatory functionality of HDL and plasma levels of CK (r=0.292; P=0.011) and CK-MB (r=0.326; P=0.004).
  • Increased plasma myeloperoxidase levels were associated with decreased efflux (r=-0.330; P=0.002) and with lower anti-inflammatory function of HDL (r=0.452; P<0.001).
  • The lower efflux potential and the decreased anti-inflammatory capacity of HDL were associated with MI (OR for efflux: 5.66; 95% CI: 1.26-25.50; P=0.024 and OR for anti-inflammatory capacity: 5.53; 95% CI: 1.83-16.73; P=0.002).

Conclusion

HDL from STEMI patients was found to be dysfunctional in terms of cholesterol efflux and anti-inflammatory properties, when compared with HDL from non-STEMI or non-MI patients. Plasma myeloperoxidase levels were independently associated with impaired HDL function and MI was significantly associated with the efflux as well as the anti-inflammatory functionality of HDL. These data provide proof-of-concept for important differences in HDL function in different clinical situations, independently of HDL-C plasma levels.
 
Find this article online at J Clin Lipidol
 

References

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2. Barter, P, Gotto, AM, LaRosa, JC, et al., HDL cholesterol, very low levels of LDL cholesterol, and cardiovascular events, N Engl J Med, 2007;357:1301-1310.
3. Rader, DJ, New Therapeutic Approaches to the Treatment of Dyslipidemia, Cell Metab, 2016;23:405-412.
4. Triolo, M, Annema, W, Dullaart, RP, et al., Assessing the functional properties of highdensity lipoproteins: an emerging concept in cardiovascular research, Biomark Med,2013;7:457-472.
5. Corsetti, JP, Gansevoort, RT, Sparks, CE, et al., Inflammation reduces HDL protection against primary cardiac risk, Eur J Clin Invest, 2010;40:483-489.