Atherogenic Lipoprotein Subfractions Determined by Ion Mobility and First Cardiovascular Events After Random Allocation to High-Intensity Statin or Placebo: The JUPITER Trial
Background—Cardiovascular disease (CVD) can occur in individuals with low 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 that was randomized to high-intensity statin or placebo.
Methods and Results—In 11,186 JUPITER participants, we tested whether lipids, apolipoproteins, and ion mobility (IM)-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 HR per SD, 1.03, 95% CI 0.88-1.21). In contrast, associations with CVD events were observed for baseline non-HDL-cholesterol (non-HDL-c: 1.18, 1.01-1.38), apolipoprotein B (apoB: 1.28, 1.11-1.48), and IM-measured non-HDL particles (non-HDL-p: 1.19, 1.05-1.35) and LDL particles (LDL-p: 1.21, 1.07-1.37). Association with CVD events was also observed for several LDL and VLDL subfractions, but not for IM-measured HDL subfractions. In statin-allocated participants, CVD events were associated with on-treatment LDL-c, non-HDL-c, and apoB; these were also associated with CVD/all-cause death, as were several LDL and VLDL 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-c and atherogenic particles: apoB and IM-measured non-HDL-p, LDL-p, and select subfractions of VLDL-p and LDL-p. 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 Information—ClinicalTrials.gov. Identifier: NCT00239681.
- Received April 3, 2015.
- Revision received July 30, 2015.
- Accepted September 16, 2015.