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

S. Matthijs Boekholdt, MD, PhD; Benoit J. Arsenault, PhD; Samia Mora, MD, MHS; Terje R. Pedersen, MD, PhD; John C. LaRosa, MD; Paul J. Nestel, MD; R. John Simes, MD; Paul Durrington, MD; Graham A. Hitman, MD; K. M. A. Welch, MB, ChB; David A. DeMicco, DPharm; Aeilko H. Zwinderman, PhD; Michael B. Clearfield, DO; John R. Downs, MD; Andrew M. Tonkin, MD; Helen M. Colhoun, MD; Antonio M. Gotto, MD, DPhil; Paul M Ridker, MD, MPH; John J. P. Kastelein, MD, PhD
JAMA. 2012;307(12):1302-1309. doi:10.1001/jama.2012.366.
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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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Figure 1. Association Between on-Statin Lipid or Apolipoprotein Levels and Risk of Major Cardiovascular Events Stratified by Baseline Characteristics
Graphic Jump Location

Data markers indicate hazard ratios for risk of major cardiovascular events per 1-SD increase of the lipid or apolipoprotein and 95% CIs. Dashed line indicates point estimate for all participants combined. All interaction terms were by presence or absence of the listed characteristics and were nonsignificant. BMI indicates body mass index; CHD, coronary heart disease; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; and TG, triglyceride.

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Figure 2. Association Between on-Statin Lipid or Apolipoprotein Levels and Risk of Major Cardiovascular Events Stratified by Study
Graphic Jump Location

Data markers indicate hazard ratios (HRs) for risk of major cardiovascular events per 1-SD increase of on-statin low-density lipoprotein cholesterol (LDL-C), non–high-density lipoprotein cholesterol (non–HDL-C), or apolipoprotein B (apoB) and 95% CIs. For placebo-controlled trials, data from the placebo group were not used in this analysis. Dashed line indicates point estimate for all participants combined. All interaction terms by study were nonsignificant.

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Figure 3. Risk of Major Cardiovascular Events by LDL and non-HDL Cholesterol Categories
Graphic Jump Location

Data markers indicate hazard ratios (HRs) and 95% CIs for risk of major cardiovascular events. Results are shown for 4 categories of statin-treated patients based on whether or not they reached the low-density lipoprotein cholesterol (LDL-C) target of 100 mg/dL and the non–high-density lipoprotein cholesterol (non–HDL-C) target of 130 mg/dL. HRs were adjusted for sex, age, smoking, diabetes, systolic blood pressure, and trial.

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References

July 11, 2012
Seth S. Martin, MD; Steven R. Jones, MD
JAMA. 2012;308(2):131-133. doi:10.1001/jama.2012.6614.
July 11, 2012
Robert D. Brook, MD; Melvyn Rubenfire, MD
JAMA. 2012;308(2):131-133. doi:10.1001/jama.2012.6616.
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