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 Boekholdt, Benoit Arsenault, Samia Mora, Terje Pedersen, John LaRosa, Paul Nestel, John Simes, Paul Durrington, Graham Hitman, K Welch, David DeMicco, Aeilko Zwinderman, Michael Clearfield, John Downs, Andrew Tonkin, Helen Colhoun, Antonio Gotto, Paul Ridker, John Kastelein

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    Abstract

    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 62154 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.

    Original languageEnglish
    Pages (from-to)1302-1309
    Number of pages8
    JournalJAMA-Journal of The American Medical Association
    Volume307
    Issue number12
    DOIs
    Publication statusPublished - 2012

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    Boekholdt, S., Arsenault, B., Mora, S., Pedersen, T., LaRosa, J., Nestel, P., Simes, J., Durrington, P., Hitman, G., Welch, K., DeMicco, D., Zwinderman, A., Clearfield, M., Downs, J., Tonkin, A., Colhoun, H., Gotto, A., Ridker, P., & Kastelein, J. (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. JAMA-Journal of The American Medical Association, 307(12), 1302-1309. https://doi.org/10.1001/jama.2012.366