brand logo

Am Fam Physician. 2014;89(8):662A-662B

Author disclosure: No relevant financial affiliations.

Clinical Question

Is measurement of apolipoproteins better than traditional lipid measurements for predicting cardiovascular risk?

Evidence-Based Answer

Measurement of apolipoprotein B and apolipoprotein A-I is no better than traditional lipid measurements and should not be used to predict cardiovascular risk. (Strength of Recommendation: B, based on meta-analyses with conflicting results.) Apolipoprotein B and non–high-density lipoprotein cholesterol (HDL-C) predict cardiovascular risk slightly better than low-density lipoprotein cholesterol. Elevated levels of apolipoprotein A-I predict a lower risk of cardiovascular events except stroke, but not as well as elevated HDL-C levels.

Evidence Summary

Apolipoproteins are structural components of lipoproteins and have a role in receptor binding and enzyme activation. Apolipoprotein B is carried on all proatherogenic lipoproteins in a 1:1 ratio, and apolipoprotein A-I is found on nearly all HDL particles.1

High levels of apolipoprotein B predict cardiovascular risk about as well as non–HDL-C. A 2012 meta-analysis pooled data from prospective cohort studies of patients without baseline cardiovascular disease and found that non–HDL-C and apolipoprotein B levels were similarly predictive of fatal and nonfatal cardiovascular events2 (Table 124 ). Using a clinical model, the authors calculated that substituting total cholesterol and HDL-C measurements with apolipoprotein A-I and B measurements diminished risk prediction by 1% (95% confidence interval [CI], 0.2% to 1.9%), whereas adding them did not significantly improve risk classification. A 2011 meta-analysis of prospective cohort and case-control studies found that apolipoprotein B was a slightly better predictor of cardiovascular risk than non–HDL-C, and both were superior to low-density lipoprotein cholesterol.3

Number and type of studiesOutcomes measuredAdverse eventsBiomarker measuredRisk of elevated biomarker (95% CI)
26 prospective cohort trials (N = 139,581)2 Fatal and nonfatal coronary artery disease and stroke12,234Non–HDL-CHR = 1.27 (1.22 to 1.33)*
Apolipoprotein BHR = 1.24 (1.19 to 1.29)*
Apolipoprotein A-IHR = 0.87 (0.84 to 0.90)*
HDL-CHR = 0.83 (0.78 to 0.87)*
12 (8 prospective cohort and case-control studies; N = 233,455)3 Fatal and nonfatal ischemic cardiovascular events22,950Apolipoprotein BRR = 1.43 (1.35 to 1.51)
Non–HDL-CRR = 1.34 (1.24 to 1.44)
Low-density lipoprotein cholesterolRR = 1.25 (1.18 to 1.33)
8 randomized controlled trials (N = 38,153)4 Fatal or nonfatal myocardial infarction, fatal coronary artery disease, hospitalization for unstable angina, and fatal or nonfatal stroke at 1 year6,286Non–HDL-CHR = 1.16 (1.12 to 1.19)*
Apolipoprotein BHR = 1.14 (1.11 to 1.18)*
Low-density lipoprotein cholesterolHR = 1.13 (1.10 to 1.17)*

Among patients receiving statins, measurement of apolipoprotein B is comparable to that of non–HDL-C. A 2012 meta-analysis of randomized controlled trials of patients on statin therapy found that time to the first major cardiovascular event was most strongly associated with non–HDL-C levels, followed by apolipoprotein B and low-density lipoprotein cholesterol levels.4 The differences between hazard ratios were small but statistically significant (P = .002 for non–HDL-C vs. low-density lipoprotein cholesterol, and P = .02 for non–HDL-C vs. apolipoprotein B).

The benefits of measuring apolipoprotein B include the ability to use serum from non-fasting patients, standardization, and direct measurement compared with the calculated measurement of low-density lipoprotein cholesterol, which may be inaccurate in patients with hypertriglyceridemia.5,6

Elevated apolipoprotein A-I levels predict coronary events except stroke, but not as well as elevated HDL-C levels. Apolipoprotein A-I levels are inversely associated with cardiovascular disease. In the 2012 meta-analysis discussed previously, comparable inverse associations for cardiovascular risk were seen with HDL-C and apolipoprotein A-I measurements.2 A 2011 prospective cohort study of healthy women found an inverse relationship between apolipoprotein A-I levels and the incidence of stroke and coronary events (myocardial infarction, coronary revascularization, or coronary death).7 Participants included health care professionals 45 years and older who were not receiving lipid-lowering therapy and had a low risk of cardiovascular disease. They were grouped into quintiles based on apolipoprotein A-I or HDL-C levels. The average follow-up was 11.1 years. There were 319 strokes and 602 coronary events among the 26,881 women. Lower apolipoprotein A-I and HDL-C levels were associated with a higher risk of coronary events except stroke. However, in all quintiles the coronary event association with apolipoprotein A-I was weaker than that of HDL-C (hazard ratio for apolipoprotein A-I [lowest vs. highest quintiles] = 1.58 [95% CI, 1.14 to 2.20]; hazard ratio for HDL-C [lowest vs. highest quintiles] = 2.19 [95% CI, 1.51 to 3.19]).7

Recommendations from Others

The American College of Cardiology Foundation/American Heart Association and the National Academy of Clinical Biochemistry recommend against measurement of apolipoproteins or any additional lipid parameters beyond a standard fasting lipid panel for global cardiovascular risk assessment.8,9

Clinical Inquiries provides answers to questions submitted by practicing family physicians to the Family Physicians Inquiries Network (FPIN). Members of the network select questions based on their relevance to family medicine. Answers are drawn from an approved set of evidence-based resources and undergo peer review. The strength of recommendations and the level of evidence for individual studies are rated using criteria developed by the Evidence-Based Medicine Working Group (

The complete database of evidence-based questions and answers is copyrighted by FPIN. If interested in submitting questions or writing answers for this series, go to or email:

This series is coordinated by John E. Delzell Jr., MD, MSPH, associate medical editor.

A collection of FPIN’s Clinical Inquiries published in AFP is available at

Continue Reading

More in AFP

More in PubMed

Copyright © 2014 by the American Academy of Family Physicians.

This content is owned by the AAFP. A person viewing it online may make one printout of the material and may use that printout only for his or her personal, non-commercial reference. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP.  See permissions for copyright questions and/or permission requests.