Major lipids, apolipoproteins, and risk of vascular disease.
Level 1 - systematic review of randomized trials
Individual participant data meta-analysis of prospective cohort studies
PubMed 19903920 · doi:10.1001/jama.2009.1619
What was done
Individual-participant data meta-analysis from 68 long-term prospective cohort studies (mostly in Europe and North America) including 302,430 individuals without baseline vascular disease followed for 2.79 million person-years. Investigators assessed associations between baseline lipid and apolipoprotein levels and vascular outcomes (8,857 nonfatal myocardial infarctions, 3,928 coronary heart disease [CHD] deaths, 2,534 ischemic strokes, 513 hemorrhagic strokes, and 2,536 unclassified strokes), adjusting for conventional cardiovascular risk factors and within-person variation.
What was found
Adjusted hazard ratios (HRs) per 1-standard deviation higher baseline level for CHD were: - Triglyceride (0.52 log(e)): 0.99 (95% CI, 0.94-1.05) - High-density lipoprotein cholesterol (HDL-C, 15 mg/dL): 0.78 (95% CI, 0.74-0.82) - Non-HDL-C (43 mg/dL): 1.50 (95% CI, 1.39-1.61) A combination of 80 mg/dL lower non-HDL-C and 15 mg/dL higher HDL-C was associated with an HR of 0.35 (95% CI, 0.30-0.42) for CHD. For ischemic stroke, adjusted HRs were 1.02 (95% CI, 0.94-1.11) with triglyceride, 0.93 (95% CI, 0.84-1.02) with HDL-C, and 1.12 (95% CI, 1.04-1.20) with non-HDL-C. In subsets with available measurements, the non-HDL-C/HDL-C ratio (HR 1.50, 95% CI 1.38-1.62) performed similarly to the apo B/apo AI ratio (HR 1.49, 95% CI 1.39-1.60), and non-HDL-C (HR 1.42, 95% CI 1.06-1.91) performed similarly to directly measured LDL-C (HR 1.38, 95% CI 1.09-1.73). Associations were at least as strong in non-fasting participants as in fasting participants.
Why it matters
Vascular disease risk assessment can be simplified by measuring non-HDL-C and HDL-C without requiring fasting or measuring apolipoproteins.
Limits
Participants were drawn mostly from Europe and North America, potentially limiting generalizability to other populations. Observational design cannot entirely rule out residual confounding or determine causality on its own.
Cited by
- contradicts When corrected for triglyceride and HDL levels, LDL cholesterol loses statistical significance as a predictor of heart disease.
- supports Multiple major cardiology studies show that ApoB is a superior predictor of cardiovascular events compared to LDL cholesterol alone.