Affiliation:
1. From the Brigham and Women's Hospital and Harvard Medical School, Boston, MA (S.M.); Emory University School of Medicine, Atlanta, GA (N.K.W.); Pfizer, New York, NY (D.A.D., A.B.); University of Amsterdam, Amsterdam, the Netherlands (S.M.B., B.J.A., J.J.P.K.); University of California San Francisco, Fresno (P.D.); and University of California San Francisco, San Francisco (D.D.W.).
Abstract
Background—
Cardiovascular events occur among statin-treated patients, albeit at lower rates. Risk factors for this “residual risk” have not been studied comprehensively. We aimed to identify determinants of this risk above and beyond lipid-related risk factors.
Methods and Results—
A total of 9251 coronary patients with low-density lipoprotein cholesterol <130 mg/dL randomized to double-blind atorvastatin 10 or 80 mg/d in the Treating to New Targets (TNT) study had complete on-treatment 1-year lipid data. Median follow-up was 4.9 years. The primary end point was major cardiovascular events (n=729): coronary death, nonfatal myocardial infarction, resuscitation after cardiac arrest, or fatal or nonfatal stroke. Multivariable determinants of increased risk were older age (adjusted hazard ratio [aHR], 1.13 per 1 SD [8.8 years]; 95% confidence interval [CI], 1.04–1.23), increased body mass index (aHR, 1.09; 95% CI, 1.02–1.17 per 4.5 kg/m
2
), male sex (aHR, 1.33; 95% CI, 1.07–1.65), hypertension (aHR, 1.38; 95% CI, 1.17–1.63), diabetes mellitus (aHR, 1.33; 95% CI, 1.11–1.60), baseline apolipoprotein B (aHR, 1.19; 95% CI, 1.11–1.28 per 19 mg/dL), and blood urea nitrogen (aHR, 1.10; 95% CI, 1.03–1.17 per 4.9 mg/dL), in addition to current smoking, prior cardiovascular disease, and calcium channel blocker use. Determinants of decreased risk were high-dose statin (aHR, 0.82; 95% CI, 0.70–0.94), aspirin use (aHR, 0.67; 95% CI, 0.56–0.81), and baseline apolipoprotein A-I (aHR, 0.91; 95% CI, 0.84–0.99 per 25 mg/dL). On-treatment 1-year lipids or apolipoproteins were not additionally associated with risk in multivariable models. Known baseline variables performed moderately well in discriminating future cases from noncases (Harrell c index=0.679).
Conclusions—
Determinants of residual risk in statin-treated secondary prevention patients included lipid-related and nonlipid factors such as baseline apolipoproteins, increased body mass index, smoking, hypertension, and diabetes mellitus. A multifaceted prevention approach should be underscored to address this risk.
Clinical Trial Registration—
URL:
http://clinicaltrials.gov
. Unique identifier: NCT00327691.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Physiology (medical),Cardiology and Cardiovascular Medicine