Major lipids, apolipoproteins, and risk of vascular disease

Abstract

Context: Associations of major lipids and apolipoproteins with the risk of vascular disease have not been reliably quantified.

Objective: To assess major lipids and apolipoproteins in vascular risk.

Design, setting, and participants: Individual records were supplied on 302,430 people without initial vascular disease from 68 long-term prospective studies, mostly in Europe and North America. During 2.79 million person-years of follow-up, there were 8857 nonfatal myocardial infarctions, 3928 coronary heart disease [CHD] deaths, 2534 ischemic strokes, 513 hemorrhagic strokes, and 2536 unclassified strokes.

Main outcome measures: Hazard ratios (HRs), adjusted for several conventional factors, were calculated for 1-SD higher values: 0.52 log(e) triglyceride, 15 mg/dL high-density lipoprotein cholesterol (HDL-C), 43 mg/dL non-HDL-C, 29 mg/dL apolipoprotein AI, 29 mg/dL apolipoprotein B, and 33 mg/dL directly measured low-density lipoprotein cholesterol (LDL-C). Within-study regression analyses were adjusted for within-person variation and combined using meta-analysis.

Results: The rates of CHD per 1000 person-years in the bottom and top thirds of baseline lipid distributions, respectively, were 2.6 and 6.2 with triglyceride, 6.4 and 2.4 with HDL-C, and 2.3 and 6.7 with non-HDL-C. Adjusted HRs for CHD were 0.99 (95% CI, 0.94-1.05) with triglyceride, 0.78 (95% CI, 0.74-0.82) with HDL-C, and 1.50 (95% CI, 1.39-1.61) with non-HDL-C. Hazard ratios were at least as strong in participants who did not fast as in those who did. The HR for CHD was 0.35 (95% CI, 0.30-0.42) with a combination of 80 mg/dL lower non-HDL-C and 15 mg/dL higher HDL-C. For the subset with apolipoproteins or directly measured LDL-C, HRs were 1.50 (95% CI, 1.38-1.62) with the ratio non-HDL-C/HDL-C, 1.49 (95% CI, 1.39-1.60) with the ratio apo B/apo AI, 1.42 (95% CI, 1.06-1.91) with non-HDL-C, and 1.38 (95% CI, 1.09-1.73) with directly measured LDL-C. Hazard ratios for ischemic stroke 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.

Conclusion: Lipid assessment in vascular disease can be simplified by measurement of either total and HDL cholesterol levels or apolipoproteins without the need to fast and without regard to triglyceride.

Figure 1

Hazard Ratios for Coronary Heart Disease or Ischemic Stroke Across Quantiles of Usual Triglyceride, HDL-C, and Non-HDL-C Levels. Analyses for coronary heart disease were based on 302 430 participants (involving 12 785 cases) from 68 studies. Analyses for ischemic stroke were based on 173 312 participants (involving 2534 cases) from 32 studies. Regression analyses were stratified, where appropriate, by sex and trial group. Values with further adjustments were adjusted for age, systolic blood pressure, smoking status, history of diabetes mellitus, and body mass index; furthermore, analyses of loge triglyceride were ad-justed for high-density lipoprotein cholesterol (HDL-C) and non-HDL-C levels, analyses of HDL-C were adjusted for non-HDL-C and loge triglyceride levels, and analyses of non-HDL-C were adjusted for HDL-C and loge triglyceride levels. Studies with fewer than 10 cases were excluded from analysis. Sizes of data markers are proportional to the inverse of the variance of the hazard ratios. The y-axes are shown on a log scale. The x-axes for triglyceride are shown on a log scale. Referent groups are lowest quantiles for triglyceride and non-HDL-C and highest quantiles for HDL-C. Error bars indicate 95% confidence intervals.

Figure 2

Hazard Ratios for Coronary Heart Disease Across Fifths of Non-HDL-C by Levels of HDL-C and Fifths of HDL-C by Levels of Non-HDL-C Analyses were based on 302 430 participants (involving 12 785 cases) from 68 studies. Median values in the Emerging Risk Factors Collaboration were 50 mg/dL for high-density lipoprotein cholesterol (HDL-C) and 169 mg/dL for non-HDL-C. Regression analyses were stratified, where appropriate, by sex and trial group and adjusted for age, systolic blood pressure, smoking status, history of diabetes mellitus, body mass index, and loge triglyceride levels. Studies with fewer than 10 cases were excluded from analysis. Sizes of data markers are proportional to the inverse of the variance of the hazard ratios. The y-axes are shown on a log scale. Referent groups are lowest fifth of non-HDL-C in the higher level of HDL-C and highest fifth of HDL-C in the lower level of non-HDL-C. Lines are fitted by log-linear regression of log hazard ratios on mean levels. Error bars indicate 95% confidence intervals.

Figure 3

Hazard Ratios for Coronary Heart Disease Across Fifths of Usual Lipids or Apolipoproteins Analyses were based on 91 307 participants (involving 4499 cases) from 22 studies. Regression analyses were stratified, where appropriate, by sex and trial group and adjusted for age, systolic blood pressure, smoking status, history of diabetes mellitus, and body mass index; furthermore, analyses of non-HDL-C were adjusted for HDL-C and loge triglyceride, analyses of apolipoprotein B (apo B) were adjusted for apolipoprotein AI (apo AI) and loge triglyceride, analyses of HDL-C were adjusted for non-HDL-C and loge triglyceride, and analyses of apo AI were adjusted for apo B and loge triglyceride. Studies with fewer than 10 cases were excluded from analysis. Sizes of data markers are proportional to the inverse of the variance of the hazard ratios. Referent groups are lowest fifths. Lines are fitted by first-degree fractional polynomial regression of log hazard ratios on mean SD score. Error bars indicate 95% confidence intervals. The y-axis is shown on a log scale. The x-axis is shown on a Z-transformed scale.