title: Atherogenic Lipoprotein Subfractions Determined by Ion Mobility and First Cardiovascular Events After Random Allocation to High-Intensity Statin or Placebo: The Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) Trial.
abstract: BACKGROUND
  Cardiovascular disease (CVD) can occur in individuals with low low-density lipoprotein (LDL) cholesterol (LDL-C). We investigated whether detailed measures of LDL subfractions and other lipoproteins can be used to assess CVD risk in a population with both low LDL-C and high C-reactive protein who were randomized to high-intensity statin or placebo.
  
  
  RESULTS
  In 11 186 Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) participants, we tested whether lipids, apolipoproteins, and ion mobility-measured particle concentrations at baseline and after random allocation to rosuvastatin 20 mg/d or placebo were associated with first CVD events (n=307) or CVD/all-cause death (n=522). In placebo-allocated participants, baseline LDL-C was not associated with CVD (adjusted hazard ratio [HR] per SD, 1.03; 95% confidence interval [CI], 0.88-1.21). In contrast, associations with CVD events were observed for baseline non-high-density lipoprotein (HDL) cholesterol (HR, 1.18; 95% CI, 1.01-1.38), apolipoprotein B (HR, 1.28; 95% CI, 1.11-1.48), and ion mobility-measured non-HDL particles (HR, 1.19; 95% CI, 1.05-1.35) and LDL particles (HR, 1.21; 95% CI, 1.07-1.37). Association with CVD events was also observed for several LDL and very-low-density lipoprotein subfractions but not for ion mobility-measured HDL subfractions. In statin-allocated participants, CVD events were associated with on-treatment LDL-C, non-HDL cholesterol, and apolipoprotein B; these were also associated with CVD/all-cause death, as were several LDL and very-low-density lipoprotein subfractions, albeit with a pattern of association that differed from the baseline risk.
  
  
  CONCLUSIONS
  In JUPITER, baseline LDL-C was not associated with CVD events, in contrast with significant associations for non-HDL cholesterol and atherogenic particles: apolipoprotein B and ion mobility-measured non-HDL particles, LDL particles, and select subfractions of very-low-density lipoprotein particles and LDL particles. During high-intensity statin therapy, on-treatment levels of LDL-C and atherogenic particles were associated with residual risk of CVD/all-cause death.
  
  
  BACKGROUND
  URL: http://www.clinicaltrials.gov. Unique identifier: NCT00239681.
authors.affiliation: From the Divisions of Preventive (S.M., R.J.G., P.MR.) and Cardiovascular Medicine (S.M., P.MR.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Quest Diagnostics, Alameda, CA (M.P.C., J.W., Z.C., C.M.R.); Cholesterol, Genetics, and Heart Disease Institute, Carmel, CA (H.R.S.); and Children's Hospital Oakland Research Institute, Oakland, CA (R.M.K.). smora@partners.org.
authors.forename: Samia
authors.initials: S
authors.lastname: Mora
authors.affiliation: From the Divisions of Preventive (S.M., R.J.G., P.MR.) and Cardiovascular Medicine (S.M., P.MR.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Quest Diagnostics, Alameda, CA (M.P.C., J.W., Z.C., C.M.R.); Cholesterol, Genetics, and Heart Disease Institute, Carmel, CA (H.R.S.); and Children's Hospital Oakland Research Institute, Oakland, CA (R.M.K.).
authors.forename: Michael P
authors.initials: MP
authors.lastname: Caulfield
authors.affiliation: From the Divisions of Preventive (S.M., R.J.G., P.MR.) and Cardiovascular Medicine (S.M., P.MR.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Quest Diagnostics, Alameda, CA (M.P.C., J.W., Z.C., C.M.R.); Cholesterol, Genetics, and Heart Disease Institute, Carmel, CA (H.R.S.); and Children's Hospital Oakland Research Institute, Oakland, CA (R.M.K.).
authors.forename: Jay
authors.initials: J
authors.lastname: Wohlgemuth
authors.affiliation: From the Divisions of Preventive (S.M., R.J.G., P.MR.) and Cardiovascular Medicine (S.M., P.MR.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Quest Diagnostics, Alameda, CA (M.P.C., J.W., Z.C., C.M.R.); Cholesterol, Genetics, and Heart Disease Institute, Carmel, CA (H.R.S.); and Children's Hospital Oakland Research Institute, Oakland, CA (R.M.K.).
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Chen
authors.affiliation: From the Divisions of Preventive (S.M., R.J.G., P.MR.) and Cardiovascular Medicine (S.M., P.MR.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Quest Diagnostics, Alameda, CA (M.P.C., J.W., Z.C., C.M.R.); Cholesterol, Genetics, and Heart Disease Institute, Carmel, CA (H.R.S.); and Children's Hospital Oakland Research Institute, Oakland, CA (R.M.K.).
authors.forename: H Robert
authors.initials: HR
authors.lastname: Superko
authors.affiliation: From the Divisions of Preventive (S.M., R.J.G., P.MR.) and Cardiovascular Medicine (S.M., P.MR.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Quest Diagnostics, Alameda, CA (M.P.C., J.W., Z.C., C.M.R.); Cholesterol, Genetics, and Heart Disease Institute, Carmel, CA (H.R.S.); and Children's Hospital Oakland Research Institute, Oakland, CA (R.M.K.).
authors.forename: Charles M
authors.initials: CM
authors.lastname: Rowland
authors.affiliation: From the Divisions of Preventive (S.M., R.J.G., P.MR.) and Cardiovascular Medicine (S.M., P.MR.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Quest Diagnostics, Alameda, CA (M.P.C., J.W., Z.C., C.M.R.); Cholesterol, Genetics, and Heart Disease Institute, Carmel, CA (H.R.S.); and Children's Hospital Oakland Research Institute, Oakland, CA (R.M.K.).
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Glynn
authors.affiliation: From the Divisions of Preventive (S.M., R.J.G., P.MR.) and Cardiovascular Medicine (S.M., P.MR.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Quest Diagnostics, Alameda, CA (M.P.C., J.W., Z.C., C.M.R.); Cholesterol, Genetics, and Heart Disease Institute, Carmel, CA (H.R.S.); and Children's Hospital Oakland Research Institute, Oakland, CA (R.M.K.).
authors.forename: Paul M
authors.initials: PM
authors.lastname: Ridker
authors.affiliation: From the Divisions of Preventive (S.M., R.J.G., P.MR.) and Cardiovascular Medicine (S.M., P.MR.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Quest Diagnostics, Alameda, CA (M.P.C., J.W., Z.C., C.M.R.); Cholesterol, Genetics, and Heart Disease Institute, Carmel, CA (H.R.S.); and Children's Hospital Oakland Research Institute, Oakland, CA (R.M.K.).
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Krauss
mesh_terms: D000368:Aged; D050197:Atherosclerosis / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D002318:Cardiovascular Diseases / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D061345:Early Medical Intervention / Q000379:methods*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D017136:Ion Transport / Q000187:drug effects / Q000502:physiology; D008077:Lipoproteins, LDL / Q000037:antagonists & inhibitors* / Q000097:blood; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D000068718:Rosuvastatin Calcium / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008077:Lipoproteins, LDL; D000068718:Rosuvastatin Calcium
keywords: hydroxymethylglutaryl-CoA reductase inhibitors; inflammation; lipids; lipoproteins; prevention and control