Author + information
- Received October 18, 2011
- Revision received December 15, 2011
- Accepted December 20, 2011
- Published online April 24, 2012.
- Samia Mora, MD⁎,⁎ (, )
- Robert J. Glynn, ScD⁎,†,
- S. Matthijs Boekholdt, MD‡,
- Børge G. Nordestgaard, MD§,
- John J.P. Kastelein, MD‡ and
- Paul M. Ridker, MD⁎
- ↵⁎Reprint requests and correspondence:
Dr. Samia Mora, Brigham and Women's Hospital, 900 Commonwealth Avenue East, Boston, Massachusetts 02215
Objectives The goal of this study was to determine whether residual risk after high-dose statin therapy for primary prevention individuals with reduced levels of low-density lipoprotein cholesterol (LDL-C) is related to on-treatment apolipoprotein B, non–high-density lipoprotein cholesterol (non–HDL-C), trigylcerides, or lipid ratios, and how they compare with on-treatment LDL-C.
Background Guidelines focus on LDL-C as the primary target of therapy, yet residual risk for cardiovascular disease (CVD) among statin-treated individuals remains high and not fully explained.
Methods Participants in the randomized placebo-controlled JUPITER (Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin) trial were adults without diabetes or CVD, with baseline LDL-C levels <130 mg/dl, high-sensitivity C-reactive protein levels ≥2 mg/l, and triglyceride concentrations <500 mg/dl. Individuals allocated to receive rosuvastatin 20 mg daily with baseline and on-treatment lipids and lipoproteins were examined in relation to the primary endpoint of incident CVD (nonfatal myocardial infarction or stroke, hospitalization for unstable angina, arterial revascularization, or cardiovascular death).
Results Using separate multivariate Cox models, statistically significant associations of a similar magnitude with residual risk of CVD were found for on-treatment LDL-C, non–HDL-C, apolipoprotein B, total cholesterol/HDL-C, LDL-C/HDL-C, and apolipoprotein B/A-I. The respective adjusted standardized hazard ratios (95% confidence intervals) for each of these measures were 1.31 (1.09 to 1.56), 1.25 (1.04 to 1.50), 1.27 (1.06 to 1.53), 1.22 (1.03 to 1.44), 1.29 (1.09 to 1.52), and 1.27 (1.09 to 1.49). The overall residual risk and the risk associated with these measures decreased among participants achieving on-treatment LDL-C ≤70 mg/dl, on-treatment non–HDL-C ≤100 mg/dl, or on-treatment apolipoprotein B ≤80 mg/dl. In contrast, on-treatment triglycerides showed no association with CVD.
Conclusions In this primary prevention trial of nondiabetic individuals with low LDL-C and elevated high-sensitivity C-reactive protein, on-treatment LDL-C was as valuable as non–HDL-C, apolipoprotein B, or ratios in predicting residual risk. (JUPITER—Crestor 20mg Versus Placebo in Prevention of Cardiovascular [CV] Events; NCT00239681)
The JUPITER trial was financially supported by AstraZeneca, who collected the trial data and monitored the study sites but had no role in the conduct of the analyses, in drafting this report, or in the decision to submit these analyses for publication. Dr. Mora received research grant support from the National Heart, Lung, and Blood Institute (K08 HL094375), AstraZeneca, and Merck & Co.; served as a consultant for Pfizer and Quest Diagnostics; and received nonpromotional speaker honorarium from Abbott. Dr. Glynn received grant support from AstraZeneca, Novartis, and Bristol-Myers Squibb; and has a consulting agreement with Merck. Dr. Boekholdt has served as a consultant to Pfizer. Dr. Nordestgaard has served as a consultant for AstraZeneca, Abbott, Merck & Co., and Pfizer. Dr. Kastelein is a recipient of the Lifetime Achievement Award (2010T082) of the Dutch Heart Foundation; and is a consultant for and has received research grants from AstraZeneca. Dr. Ridker received research support from AstraZeneca, Novartis, Roche, and Sanofi-Aventis, and nonfinancial research support from Amgen. Dr. Ridker is coinventor on patents held by Brigham and Women's Hospital related to the use of inflammatory biomarkers in cardiovascular disease that have been licensed to Siemens and AstraZeneca; has served as a research consultant to Schering-Plough, Sanofi/Aventis, Isis, Siemens, Abbott, Merck, and Vascular Biogenics; and has received research grants from AstraZeneca.
- Received October 18, 2011.
- Revision received December 15, 2011.
- Accepted December 20, 2011.
- American College of Cardiology Foundation