Physicians' Academy for Cardiovascular Education

HDL particle concentration may better predict CVD event risk than HDL-c

Literature - Mora S, Glynn RJ, Ridker PM - Circulation. 2013 Sep 10;128(11):1189-97


High-density lipoprotein cholesterol, size, particle number, and residual vascular risk after potent statin therapy.

 

Mora S, Glynn RJ, Ridker PM
Circulation. 2013 Sep 10;128(11):1189-97. doi: 10.1161/CIRCULATIONAHA.113.002671
 

Background

The residual CVD risk in statin-treated individuals has driven interest in therapeutic interventions targeted at modulating HDL-c levels. Both experimental studies and large-scale trials have explored this option. To date raising HDL-c have not yielded a reduction of CV events [1-3] or atherosclerosis [4].
It is possible that HDL-c is not the best clinical measure of HDL. An analysis of Justification for the Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) challenged the long-standing idea that low HDL-c is an important risk factor for residual risk among statin-treated patients [5,6]. In JUPITER, on-treatment HDL-c was not predictive of residual risk among statin-treated individuals, while HDL-c did have predictive value among those taking placebo. On-treatment apolipoprotein A-I (apoA-I) and triglycerides were also found to be of no use for prediction of residual risk [7].
Chemically measured HDL-c evaluates the cholesterol carried by HDL particles. This may not fully reflect HDL-related cardioprotection. HDL function, size or the concentration (number) of HDL particles (HDL-P) have therefore been proposed as better clinical markers of HDL. Very little is known about the impact of statin therapy on measures of HDL other than HDL-c.
This paper reports the evaluation of whether residual CVD risk is better explained by HDL-P in comparison with HDL-c, making use of JUPITER data. In JUPITER, potent statin therapy or placebo was randomly assigned in a primary prevention population that achieved very low LDL-c levels.
 

Main results

  • HDL-P correlated only moderately with HDL-c at baseline (r=0.55, P<0.0001) and after 1 year of statin therapy (r=0.63, P<0.0001). HDL-P correlated more strongly with apoA-I at baseline (r=0.69, P<0.0001) and after 1 year of statin treatment (r=0.72, P<0.0001).
  • Rosuvastatin 20 mg/d decreased LDL-c by 51 mg/dL (49%) and increased HDL-c by 3 mg/dL and apoA-I by 3 mg/dL. HDL size was increased by 0.1 nm, and HDL-P by 1.3 µmol/L (P<0.0001 for all).
  • Among rosuvastatin-allocated individuals, baseline HDL-P was statistically significantly associated with CVD events (0.78, 95%CI: 0.61-0.99 per 6.32 µmol/L), while no significant associations were seen for baseline HDL-c, apoA-I or HDL size.
    On-treatment HDL-P in rosuvastatin-treated individuals was significantly and somewhat stronger associated with CVD (0.73, 95%CI: 0.57-0.93, P=0.01) than HDL-c (0.82, 95%CI:0.63-1.08, P=0.16) or apoA-I (0.86, 95%CI: 0.67-1.10, P=0.22).
  • Overall, similar patterns of associations were seen for women and men.
  • Further adjustment for hsCRP and LDL particle concentration did not alter the association of HDL-P with CVD.
 

Conclusion

This study suggests that HDL-P may be a better marker of residual risk than HDL-c or apoA-I among individuals who receive potent statin therapy to achieve very low LDL-c levels. HDL-P appears to be less correlated with factors that affect the association of HDL-c with CVD. Also, HDL-P may better reflect greater reverse cholesterol transport capacity and other functional properties than does HDL-c.
Since this study was observational and thus only hypothesis-generating, future studies will need to examine the various functional properties of HDL in relation to HDL-P, HDL size and other measures of HDL and how these are impacted by therapies targeting HDL.  
 

References

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2. Boden WE, Probstfield JL, Anderson T, et al. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med. 2011;365:2255–2267.
3. Schwartz GG, Olsson AG, Abt M, et al. dal-OUTCOMES Investigators. Effects of dalcetrapib in patients with a recent acute coronary syndrome. N Engl J Med. 2012;367:2089–2099.
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7. Mora S, Glynn RJ, Boekholdt SM, et al. On-treatment non-high-density lipoprotein cholesterol, apolipoprotein B, triglycerides, and lipid ratios in relation to residual vascular risk after treatment with potent statin therapy: JUPITER (Justification for the use of statins in prevention: an intervention trial evaluating rosuvastatin). J Am Coll Cardiol. 2012;59:1521–1528.
 

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