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March 28, 2012

Association of LDL Cholesterol, Non–HDL Cholesterol, and Apolipoprotein B Levels With Risk of Cardiovascular Events Among Patients Treated With Statins: A Meta-analysis

Author Affiliations

Author Affiliations: Departments of Cardiology (Dr Boekholdt), Vascular Medicine (Drs Arsenault and Kastelein), and Clinical Epidemiology and Biostatistics (Dr Zwinderman), Academic Medical Center, Amsterdam, the Netherlands; Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Boston, Massachusetts (Drs Mora and Ridker); Center of Preventive Medicine, Oslo University Hospital, Ulleval, and University of Oslo, Norway (Dr Pedersen); State University of New York Health Science Center, Brooklyn (Dr LaRosa); Baker Heart and Diabetes Research Institute, Melbourne, Australia (Dr Nestel); NHMRC Clinical Trials Centre, University of Sydney, Sydney, Australia (Dr Simes); School of Biomedicine, University of Manchester, Manchester, United Kingdom (Dr Durrington); Centre for Diabetes and Metabolic Medicine, Barts, and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom (Dr Hitman); Rosalind Franklin University of Medicine and Science, North Chicago, Illinois (Dr Welch); Global Pharmaceuticals Pfizer, New York, New York (Dr DeMicco); Touro University, Mare Island, California (Dr Clearfield); Department of Medicine, University of Texas Health Science Center, and VERDICT, South Texas Veterans Health Care System, San Antonio (Dr Downs); Medical Research Institute, University of Dundee, Dundee, United Kingdom (Dr Colhoun); Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia (Dr Tonkin); and Weill Cornell Medical College, New York, New York (Dr Gotto).

JAMA. 2012;307(12):1302-1309. doi:10.1001/jama.2012.366

Context The associations of low-density lipoprotein cholesterol (LDL-C), non–high-density lipoprotein cholesterol (non–HDL-C), and apolipoprotein B (apoB) levels with the risk of cardiovascular events among patients treated with statin therapy have not been reliably documented.

Objective To evaluate the relative strength of the associations of LDL-C, non–HDL-C, and apoB with cardiovascular risk among patients treated with statin therapy.

Design Meta-analysis of individual patient data from randomized controlled statin trials in which conventional lipids and apolipoproteins were determined in all study participants at baseline and at 1-year follow-up.

Data Sources Relevant trials were identified by a literature search updated through December 31, 2011. Investigators were contacted and individual patient data were requested and obtained for 62 154 patients enrolled in 8 trials published between 1994 and 2008.

Data Extraction Hazard ratios (HRs) and corresponding 95% CIs for risk of major cardiovascular events adjusted for established risk factors by 1-SD increase in LDL-C, non–HDL-C, and apoB.

Results Among 38 153 patients allocated to statin therapy, 158 fatal myocardial infarctions, 1678 nonfatal myocardial infarctions, 615 fatal events from other coronary artery disease, 2806 hospitalizations for unstable angina, and 1029 fatal or nonfatal strokes occurred during follow-up. The adjusted HRs for major cardiovascular events per 1-SD increase were 1.13 (95% CI, 1.10-1.17) for LDL-C, 1.16 (95% CI, 1.12-1.19) for non–HDL-C, and 1.14 (95% CI, 1.11-1.18) for apoB. These HRs were significantly higher for non–HDL-C than LDL-C (P = .002) and apoB (P = .02). There was no significant difference between apoB and LDL-C (P = .21).

Conclusion Among statin-treated patients, on-treatment levels of LDL-C, non–HDL-C, and apoB were each associated with risk of future major cardiovascular events, but the strength of this association was greater for non–HDL-C than for LDL-C and apoB.

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