Meta-Analysis of the Relationship Between Non–High-Density Lipoprotein Cholesterol Reduction and Coronary Heart Disease Risk
Open accessAbstract
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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There is a direct, consistent relationship between the magnitude of non-HDLC lowering and cardiovascular risk reduction observed in meta-analyses and trials with statins and other lipid-lowering agents.
“Like LDLC, non-HDLC is treatable with existing lipid-lowering agents and there is a direct, consistent relationship between the magnitude of non-HDLC lowering and cardiovascular risk reduction observed in meta-analyses and trials with statins and other lipid-lowering agents [56,57].”
From Quantifying atherogenic lipoproteins for lipid-lowering strategies: Consensus-based recommendations from EAS and EFLM (2020) · cites this paper as [56]
Non-HDL-C may estimate risk better than LDL-C, especially in hypertriglyceridaemia with diabetes, metabolic syndrome, or CKD.
“Non-HDL-C can provide a better risk estimation compared with LDL-C, in particular in HTG combined with diabetes, the MetS, or CKD.This is supported by a recent meta-analysis including 14 statin trials, seven fibrate trials, and six nicotinic acid trials.44”
From ESC/EAS Guidelines for the management of dyslipidaemias (2011) · cites this paper as [44]
Non-HDL cholesterol predicts cardiovascular disease risk similarly to or even better than LDL cholesterol.
“Non-HDL cholesterol predicts CVD risk similarly to or even better than LDL cholesterol.483”
From European Guidelines on cardiovascular disease prevention in clinical practice (version 2012) (2012) · cites this paper as [483]
A meta-analysis demonstrated that non-HDL-C lowering translates into a reduction in cardiovascular risk independent of the mechanisms (statins, resins, diet, ileal bypass).
“In this respect, it is relevant that a meta-analysis of the relationship between improvement of the plasma lipoprotein profile and the rate of CV events has demonstrated that non-HDL-C lowering translates into a reduction in risk independent of the mechanisms (statins, resins, diet and ileal bypass) involved. 131”
From 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias (2016) · cites this paper as [131]
The meta-analysis of Robinson et al. indicates that LDL cholesterol reduction translates into cardiovascular benefits, independent of the mechanism involved.
“However, the meta-analysis of Robinson et al . 131 indicates that LDL-C reduction translates into CV benefits, independent of the mechanism involved.”
From 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias (2016) · cites this paper as [131]
A meta-analysis demonstrated that non-HDL-C lowering translates into risk reduction independent of the mechanisms (statins, resins, diet, ileal bypass).
“In this respect, it is relevant that a meta-analysis of the relationship between improvement of the plasma lipoprotein profile and the rate of CV events has demonstrated that non-HDL-C lowering translates into a reduction in risk independent of the mechanisms (statins, resins, diet and ileal bypass) involved.131”
From 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias (2016) · cites this paper as [131]
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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.
- 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)
- 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
- 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 › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Surgery › 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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