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Differential Effects of Lipid-lowering Drugs in Modulating Morphology of Cholesterol Particles
Published on: November 10, 2017
High-density lipoprotein cholesterol, size, particle number, and residual vascular risk after potent statin therapy
Samia Mora1, Robert J Glynn, Paul M Ridker
1Center for Cardiovascular Disease Prevention, Division of Preventive Medicine (S.M., R.J.G., P.MR.) and Division of Cardiovascular Medicine (S.M., P.MR.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and Department of Biostatistics, Harvard School of Public Health, Boston, MA (R.J.G.).
Insights
High-density lipoprotein particle number (HDL-P) may better predict cardiovascular disease risk than HDL cholesterol (HDL-C) in patients on statin therapy. This finding suggests HDL-P could be a more effective target for future therapies.
Area of Science:
- Cardiovascular Medicine
- Lipid Metabolism
- Pharmacology
Background:
- Chemically measured high-density lipoprotein cholesterol (HDL-C) may not accurately reflect HDL's clinical efficacy.
- The role of alternative HDL measures like HDL particle number (HDL-P) in residual cardiovascular risk during statin therapy is largely unknown.
Purpose of the Study:
- To investigate whether HDL particle number (HDL-P) or HDL size are better predictors of residual cardiovascular disease (CVD) risk compared to HDL cholesterol (HDL-C) and apolipoprotein A-I (apoA-I) in patients receiving rosuvastatin.
- To assess the impact of rosuvastatin on various HDL parameters.
Main Methods:
- Analysis of data from the Justification for the Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) study.
- Measurement of HDL size and HDL-P using nuclear magnetic resonance spectroscopy.
- Chemical assays for HDL-C and apolipoprotein A-I (apoA-I) in 10,886 participants before and after rosuvastatin treatment.
Main Results:
- HDL-P showed a stronger correlation with apoA-I than HDL-C.
- Rosuvastatin significantly reduced LDL-C and increased HDL-C, apoA-I, HDL-P, and HDL size.
- On-treatment HDL-P demonstrated a significant inverse association with CVD risk in patients treated with rosuvastatin, which remained significant even after adjusting for HDL-C.
Conclusions:
- HDL particle number (HDL-P) may serve as a superior marker for residual cardiovascular risk compared to HDL-C and apoA-I in patients undergoing potent statin therapy.
- These findings have implications for the development of novel therapies targeting HDL metabolism and function.
Background:
Chemically measured high-density lipoprotein cholesterol (HDL-C) may not be the best clinical measure of HDL. Little is known about alternative HDL measures such as HDL size or particle number (HDL-P) as determinants of residual risk after potent statin therapy.
Methods And Results:
In Justification for the Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER), HDL size and HDL-P were measured by nuclear magnetic resonance spectroscopy, and HDL-C and apolipoprotein A-I (apoA-I) were chemically assayed in 10 886 participants without cardiovascular disease (CVD) before and after random allocation to rosuvastatin 20 mg/d or placebo. Levels were examined with first CVD (n=234). HDL-P correlated better with apoA-I (Spearman r=0.69, P<0.0001) than with HDL-C (r=0.55, P<0.0001). Rosuvastatin lowered low-density lipoprotein cholesterol (49%) and raised HDL-C (6.1%), apoA-I (2.1%), HDL-P (3.8%), and HDL size (1.2%); all P<0.0001. Among placebo-allocated individuals, on-treatment HDL-C, apoA-I, and HDL-P had similar inverse associations with CVD (risk factor-adjusted hazard ratio and 95% confidence interval per 1 standard deviation: 0.79 [0.63-0.98], 0.75 [0.62-0.92], and 0.81 [0.67-0.97], respectively). Among rosuvastatin-allocated individuals, on-treatment HDL-P had a statistically significant and somewhat stronger association with CVD (0.73, 0.57-0.93, P=0.01) than HDL-C (0.82, 0.63-1.08, P=0.16) or apoA-I (0.86, 0.67-1.10, P=0.22). Among rosuvastatin-allocated individuals, on-treatment HDL-P remained significant (0.72, 0.53-0.97, P=0.03) after additionally adjusting for HDL-C. In risk factor-adjusted models, HDL size showed no significant association with CVD.
Conclusions:
In the setting of potent statin therapy, HDL particle number may be a better marker of residual risk than chemically measured HDL-C or apoA-I. This has potential implications for evaluating novel therapies targeting HDL.
Clinical Trial Registration Url:
http://www.clinicaltrials.gov. Unique identifier: NCT00239681.
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