Cited by 368Lipoproteins and Cardiovascular HealthCholesterol and Lipid MetabolismDiabetes, Cardiovascular Risks, and Lipoproteins

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Meta-Analysis of the Relationship Between Non–High-Density Lipoprotein Cholesterol Reduction and Coronary Heart Disease Risk

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Robinson, Jennifer G., Wang, Songfeng, Smith, Brian J., Jacobson, Terry A.·2009·Journal of the American College of Cardiology

DOI 10.1016/j.jacc.2008.10.024

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Abstract

Objectives To determine the relationship between non-high-density lipoprotein cholesterol (HDL-C) lowering and coronary heart disease (CHD) risk reduction for various lipid-modifying therapies.Background Non-HDL-C is the second lipid target of therapy after low-density lipoprotein cholesterol (LDL-C).Methods Randomized placebo or active-controlled trials were evaluated. The effect of mean non-HDL-C reduction on the relative risk of nonfatal myocardial infarction and CHD death was estimated using Bayesian random-effects meta-analysis models adjusted for study duration. Cochrane's Q was used to test for heterogeneity.Results Inclusion criteria were met by 14 statin (n = 100,827), 7 fibrate (n = 21,647), and 6 niacin (n = 4,445) trials, and 1 trial each of a bile acid sequestrant (n = 3,806), diet (n = 458), and ileal bypass surgery (n = 838). For statins, each 1% decrease in non-HDL-C resulted in an estimated 4.5-year CHD relative risk of 0.99 (95% Bayesian confidence interval: 0.98 to 1.00). The fibrate model did not differ from the statin model (Bayes factor K = 0.49) with no evidence of heterogeneity. The niacin model was moderately different from the statin model (K = 7.43), with heterogeneity among the trials (Q = 11.8, 5 df; p = 0.038). The only niacin monotherapy trial (n = 3,908) had a 1:1 relationship between non-HDL-C and risk reduction. No consistent relationships were apparent for the 5 small trials of niacin in combination. The 95% confidence intervals for the single trials of diet, bile acid sequestrants, and surgery also included the 1:1 relationship.Conclusions Non-HDL-C is an important target of therapy for CHD prevention. Most lipid-modifying drugs used as monotherapy have an approximately 1:1 relationship between percent non-HDL-C lowering and CHD reduction.

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Authors: Robinson, J. G., Wang, S., Smith, B. J., & Jacobson, T. A.
Affiliations: University of Iowa (US)
Emory University (US)
Corresponding author: Robinson, Jennifer G.
ORCID: Robinson, Jennifer G.
Jacobson, Terry A.
Venue: Journal of the American College of Cardiology
Publisher: Elsevier BV
Published: 2009-01
Volume: 53
Issue: 4
Pages: 316-322
ISSN: 0735-1097 (ISSN-L)
DOI: 10.1016/j.jacc.2008.10.024
OpenAlex: W1996592745
Cited by: 368
References: 61
Citations by year: 2026: 6 · 2025: 5 · 2024: 9 · 2023: 13 · 2022: 16 · 2021: 16 · 2020: 15 · 2019: 24 · 2018: 21 · 2017: 21 · 2016: 30 · 2015: 24 · 2014: 27 · 2013: 31 · 2012: 33
FWCI: 5.80
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 1657 d)
Locations: Journal of the American College of Cardiology (publishedVersion)
PubMed (publishedVersion)
Funders: Bristol-Myers Squibb
Pfizer
AstraZeneca
GlaxoSmithKline
Sanofi
Daiichi-Sankyo
Topics: Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Keywords: non-HDL cholesterol, coronary artery disease, lipid-lowering therapy, statins, fibrates, nicotinic acid, bile acid sequestrants, myocardial infarction, coronary heart disease mortality, relative risk
MeSH terms: Clofibric Acid, Coronary Disease, Female, Humans, Cholesterol, HDL, Cholesterol, LDL, Male, Niacin, Risk Factors, Hydroxymethylglutaryl-CoA Reductase Inhibitors

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Meta-Analysis of the Relationship Between Non–High-Density Lipoprotein Cholesterol Reduction and Coronary Heart Disease Risk

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