title: High-density lipoprotein cholesterol, size, particle number, and residual vascular risk after potent statin therapy.
abstract: 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.
  
  
  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.
  
  
  BACKGROUND
  http://www.clinicaltrials.gov. Unique identifier: NCT00239681.
authors.affiliation: Center 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.).
authors.forename: Samia
authors.initials: S
authors.lastname: Mora
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Glynn
authors.forename: Paul M
authors.initials: PM
authors.lastname: Ridker
mesh_terms: D000368:Aged; D000789:Angina, Unstable / Q000453:epidemiology; D016632:Apolipoprotein A-I / Q000097:blood; D058070:Asymptomatic Diseases; D015415:Biomarkers; D002318:Cardiovascular Diseases / Q000401:mortality / Q000517:prevention & control; D008076:Cholesterol, HDL / Q000097:blood* / Q000737:chemistry; D008078:Cholesterol, LDL / Q000097:blood; D023381:Endpoint Determination; D005260:Female; D005464:Fluorobenzenes / Q000008:administration & dosage / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology; D009204:Myocardial Revascularization; D019906:Nuclear Magnetic Resonance, Biomolecular; D010316:Particle Size; D016016:Proportional Hazards Models; D011743:Pyrimidines / Q000008:administration & dosage / Q000627:therapeutic use*; D012306:Risk; D000068718:Rosuvastatin Calcium; D016037:Single-Blind Method; D020521:Stroke / Q000453:epidemiology; D013449:Sulfonamides / Q000008:administration & dosage / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood
chemical_list: D016632:Apolipoprotein A-I; D015415:Biomarkers; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; D014280:Triglycerides; D000068718:Rosuvastatin Calcium
keywords: HMG-CoA; inflammation; lipids; lipoproteins; prevention & control; statins