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Circulation. 2015 Dec 8;132(23):2220-9. doi: 10.1161/CIRCULATIONAHA.115.016857. Epub 2015 Sep 25.

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.

Author information

1
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.
2
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.).

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.

METHODS AND 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.

CLINICAL TRIAL REGISTRATION:

URL: http://www.clinicaltrials.gov. Unique identifier: NCT00239681.

KEYWORDS:

hydroxymethylglutaryl-CoA reductase inhibitors; inflammation; lipids; lipoproteins; prevention and control

PMID:
26408274
PMCID:
PMC4674425
DOI:
10.1161/CIRCULATIONAHA.115.016857
[Indexed for MEDLINE]
Free PMC Article

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