A meta-analysis of low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B as markers of cardiovascular risk

Sniderman, Allan D.; Williams, Ken; Contois, John H.; Monroe, Howard M.; McQueen, Matthew J.; de Graaf, Jacqueline; Furberg, Curt D.

doi:10.1161/circoutcomes.110.959247

Cited by 659Lipoproteins and Cardiovascular HealthDiabetes, Cardiovascular Risks, and LipoproteinsCholesterol and Lipid Metabolism

A meta-analysis of low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B as markers of cardiovascular risk

Sniderman, Allan D., Williams, Ken, Contois, John H., Monroe, Howard M., McQueen, Matthew J., de Graaf, Jacqueline, Furberg, Curt D.·2011·Circulation: Cardiovascular Quality and Outcomes

DOI 10.1161/circoutcomes.110.959247

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Abstract

Background—: Whether apolipoprotein B (apoB) or non-high-density lipoprotein cholesterol (HDL-C) adds to the predictive power of low-density lipoprotein cholesterol (LDL-C) for cardiovascular risk remains controversial. Methods and Results—: This meta-analysis is based on all the published epidemiological studies that contained estimates of the relative risks of non-HDL-C and apoB of fatal or nonfatal ischemic cardiovascular events. Twelve independent reports, including 233 455 subjects and 22 950 events, were analyzed. All published risk estimates were converted to standardized relative risk ratios (RRRs) and analyzed by quantitative meta-analysis using a random-effects model. Whether analyzed individually or in head-to-head comparisons, apoB was the most potent marker of cardiovascular risk (RRR, 1.43; 95% CI, 1.35 to 1.51), LDL-C was the least (RRR, 1.25; 95% CI, 1.18 to 1.33), and non-HDL-C was intermediate (RRR, 1.34; 95% CI, 1.24 to 1.44). The overall comparisons of the within-study differences showed that apoB RRR was 5.7%>non-HDL-C ( P <0.001) and 12.0%>LDL-C ( P <0.0001) and that non-HDL-C RRR was 5.0%>LDL-C ( P =0.017). Only HDL-C accounted for any substantial portion of the variance of the results among the studies. We calculated the number of clinical events prevented by a high-risk treatment regimen of all those >70th percentile of the US adult population using each of the 3 markers. Over a 10-year period, a non-HDL-C strategy would prevent 300 000 more events than an LDL-C strategy, whereas an apoB strategy would prevent 500 000 more events than a non-HDL-C strategy. Conclusions—: These results further validate the value of apoB in clinical care.

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Assessing apo B-containing lipoproteins is favored to account for remnant and small dense lipoproteins that contribute to residual ASCVD risk not captured by a standard lipid panel.
“Accumulating evidence favors the need to assess apo Becontaining lipoproteins to account for remnant lipoproteins and small dense lipoproteins responsible for residual ASCVD risk not seen with a standard lipid panel of total cholesterol, LDL-C, and HDL-C.”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [316]
The Summary (page unavailable) favors routine apoB measurement and says it can reveal elevated LDL particle numbers when LDL-C is normal, improving cardiovascular-risk assessment. The paper also discusses VLDL and cholesterol-depleted LDL particles, but the cited passages do not establish the claim’s more specific account of remnant and small dense lipoproteins as causes of residual ASCVD risk. (LLM, conf=0.85)
Experimental — accuracy not yet measured
Systematic reviews found that Apo B100 and the Apo B100/Apo A1 ratio improved prediction of cardiovascular risk.
“Systematic reviews have examined the risk prediction power of Apo A1, A2 and B100 for cardiovascular risk and found Apo B100 and the Apo B100/Apo A1 ratio improved prediction [12–14].”
From Estimating the Effect of Aerobic Exercise Training on Novel Lipid Biomarkers: A Systematic Review and Multivariate Meta-Analysis of Randomized Controlled Trials (2023) · cites this paper as [13]
The Summary (page not provided) concludes that apoB is a better predictor of cardiovascular risk than non-HDL-C or LDL-C. The paper does not report a finding that the apoB/apoA-I ratio improves prediction, and its analysis does not examine apoA-I or apoA-II as predictors. (LLM, conf=0.88)
Experimental — accuracy not yet measured
These cardiovascular disease risk biomarkers appear to be superior predictors of cardiovascular disease risk compared to the standard lipid profile.
“which appear to be superior predictors of CVD risk compared to the SLP [4, 5, 9–14].”
From Estimating the Effect of Aerobic Exercise Training on Novel Lipid Biomarkers: A Systematic Review and Multivariate Meta-Analysis of Randomized Controlled Trials (2023) · cites this paper as [13]
The Discussion reports that apoB predicts cardiovascular risk more accurately than non-HDL-C, which in turn outperforms LDL-C. The paper compares these individual markers, principally against LDL-C; it does not establish that the biomarkers outperform the standard lipid profile as a whole. (LLM, conf=0.82)
Experimental — accuracy not yet measured
These results explain why treatment of subjects for primary or secondary prevention based on apoB should be more effective than treatment based on LDL-C or non-HDL-C.
“These results also explain why treatment of subjects for primary or secondary prevention based on apoB should be more effective than treatment based on LDL-C or non-HDL-C.28”
From Discordance among apoB, non-high-density lipoprotein cholesterol, and triglycerides: implications for cardiovascular prevention (2024) · cites this paper as [28]
The Summary (page not provided) says apoB-based diagnosis and therapy would prevent more events than approaches based on LDL-C or non-HDL-C. Population Implications (page not provided) models that advantage under a preventive treatment strategy, but does not establish it separately for both primary and secondary prevention; the authors also caution that the calculations illustrate clinical implications rather than advocate the modeled strategy. (LLM, conf=0.82)
Experimental — accuracy not yet measured
In another meta-analysis, apolipoprotein B was superior to LDL-C and non-HDL-C as a marker of cardiovascular risk.
“In contrast, in another meta-analysis of LDL-C, non-HDL-C and apoB, the latter was superior as a marker of CV risk. 103”
From 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias (2016) · cites this paper as [103]

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[4]4. Sniderman AD, McQueen MJ, Contois JH, Williams K, Couture P, Furberg CD. Why is non-HDL-cholesterol a better marker of cardiovas- cular risk than LDL-cholesterol? J Clin Lipidol. 2010;4:152-155.

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Authors: Sniderman, A. D., Williams, K., Contois, J. H., Monroe, H. M., McQueen, M. J., de Graaf, J., & Furberg, C. D.
Affiliations: Our Lady of the Lake University (US)
From the Mike Rosenbloom Laboratory for Cardiovascular Research, Royal Victoria Hospital, McGill University Health Centre, Montreal, Quebec, Canada (A.D.S.); KenAnCo Biostatistics and University of Texas Health Science Center at San Antonio, San Antonio, TX (K.W.); Maine Standards Company, Windham, ME (J.H.C.); KenAnCo Biostatistics and Department of Mathematics, Our Lady of the Lake University, San Antonio, TX (H.M.M.); Population Health Research Institute and McMaster University, Hamilton, Ontario...
ORCID: Sniderman, Allan D.
Contois, John H.
Venue: Circulation: Cardiovascular Quality and Outcomes
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2011-05
Volume: 4
Issue: 3
Pages: 337-345
ISSN: 1941-7705 (ISSN-L)
1941-7713
DOI: 10.1161/circoutcomes.110.959247
OpenAlex: W2158901329
Cited by: 659
References: 41
Citations by year: 2026: 40 · 2025: 35 · 2024: 44 · 2023: 70 · 2022: 45 · 2021: 37 · 2020: 44 · 2019: 36 · 2018: 39 · 2017: 37 · 2016: 38 · 2015: 39 · 2014: 40 · 2013: 56 · 2012: 40
FWCI: 8.89
Type: journal article
Language: en
Open access: closed
Locations: Circulation Cardiovascular Quality and Outcomes (publishedVersion)
PubMed (publishedVersion)
Radboud Repository (Radboud University) (submittedVersion)
Funders: McGill University
McGill University Health Centre
Topics: Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
Keywords: apolipoprotein B, non-HDL cholesterol, LDL cholesterol, cardiovascular risk prediction, ischemic cardiovascular events, relative risk, HDL cholesterol, cardiovascular disease prevention
MeSH terms: Apolipoproteins B, Cardiovascular Diseases, Humans, Cholesterol, HDL, Cholesterol, LDL, Predictive Value of Tests, Risk Factors, Reproducibility of Results, Biomarkers

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A meta-analysis of low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B as markers of cardiovascular risk

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