Abstract 630: Lipoprotein Subclasses by Ion Mobility and First Cardiovascular Events: An Analysis of 11,227 Participants From the JUPITER Trial
Background: Ion mobility (IM) measures lipoprotein subclasses based on physically separating particles by their size. It is uncertain how IM lipoproteins compare with standard lipids and apolipoproteins in predicting CVD, and whether they relate to residual risk after statin therapy.
Methods: JUPITER recruited participants based on LDL-C <130 mg/dL and hsCRP ≥2 mg/L. In 11,227 participants, baseline and on-treatment lipoproteins were measured by IM, and lipids and apolipoproteins were chemically assayed before and after randomization to rosuvastatin or placebo. Levels were examined with the primary trial endpoint of first CVD (n=309) and an expanded endpoint of CVD/all-cause death (n=524).
Results: In placebo-allocated participants, baseline LDL-C was not associated with CVD (risk-factor adjusted hazard ratio [HR] per 1-SD, 1.04, 95% CI 0.90-1.20), in contrast to significant associations for baseline non-HDL-C, apoB, and IM-measured non-HDL particles (non-HDL-P), LDL particles (LDL-P) and most LDL subclasses. Significant associations were also noted for baseline triglycerides, medium and large VLDL, and HDL-C, but not IM IDL or HDL subclasses. In addition, IM measures a region (size range between very small LDL and large HDL) with two fractions that were significantly associated with CVD: Mid-Zone 1 (190-180 Angstrom) and Mid-Zone 2 (180-145 Angstrom). In separate models that adjusted for risk factors plus standard lipids, significant associations were noted for apoB (adjusted HR per 1-SD 1.26, 1.02-1.56), non-HDL-P (1.19, 1.03-1.39), LDL-P (1.18, 1.03-1.36), Mid-Zones 1 (1.20, 1.04-1.38) and 2 (1.15, 1.04-1.28), several LDL subclasses, and small IDL. In statin-allocated participants, risk of CVD was associated with on-treatment LDL-C, non-HDL-C, and apoB but not on-treatment IM lipoproteins although some, such as Mid-Zone 2, were related to risk of CVD/all-cause death.
Conclusion: In placebo-allocated JUPITER participants, LDL particle-based measures were more strongly related to CVD than LDL-C, while in statin-allocated participants, residual risk was related to on-treatment LDL-C, non-HDL-C and apoB. Furthermore, this is the first study to identify two novel fractions that signified increased risk and warrant future investigation.
Author Disclosures: S. Mora: Research Grant; Significant; Institutional research grant from Atherotech Diagnostics, Institutional research grant from AstraZeneca. Other Research Support; Significant; Quest Diagnostics performed the ion mobility assays at no additional cost, The JUPITER trial was funded by AstraZeneca. Consultant/Advisory Board; Modest; Cerenis Therapeutics, Genzyme, Quest Diagnostics. M.P. Caulfield: Employment; Significant; Quest Diagnostics. Other; Significant; Quest Diagnostics hold a patent for the lipoprotein analysis performed by ion mobility. J. Wohlgemuth: Employment; Significant; Quest Diagnostics. Ownership Interest; Significant; Equity in Quest Diagnostics. Z. Chen: Employment; Significant; Quest Diagnostics. H.R. Superko: Employment; Significant; Quest Diagnostics. R.J. Glynn: Research Grant; Significant; Institutional research grant from Novartis. P.M. Ridker: Research Grant; Significant; AstraZeneca, Pfizer, Novartis. Other Research Support; Significant; Amgen. Consultant/Advisory Board; Modest; ISIS, Vascular Biogenics, Genzyme, Boston HeartLab, Aegerion, Johnson & Johnson, Merck, Jannsen. Other; Significant; Dr Ridker is listed as a co-inventor on patents held by the Brigham and Women's Hospital that relate to the use of inflammatory biomarkers in CVD that are licensed to Siemens and AstraZeneca. R.M. Krauss: Research Grant; Modest; Sanofi-Regeneron. Research Grant; Significant; Quest Diagnostics. Honoraria; Modest; Merck, Jannsen, Amarin, Celera, National Lipid Association. Consultant/Advisory Board; Modest; Merck, Jannsen, Amarin, Celera, National Lipid Association. Other; Significant; Royalties from patents for ion mobility analysis of lipoproteins.
- © 2014 by American Heart Association, Inc.