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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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“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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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European Guidelines on cardiovascular disease prevention in clinical practice (version 2012)
Authors/Task Force Members:, Perk, J., De Backer, G., Gohlke, H., Graham, I., Reiner, Ž., Verschuren, M., Albus, C., Benlian, P., Boysen, G., et al. (2012) · European Heart Journal · doi:10.1093/eurheartj/ehs092 · Cited by 8,490
2016 European Guidelines on cardiovascular disease prevention in clinical practice
Piepoli, M. F., Hoes, A. W., Agewall, S., Albus, C., Brotons, C., Catapano, A. L., Cooney, M.-T., Corrà, U., Cosyns, B., Deaton, C., et al. (2016) · European Heart Journal · doi:10.1093/eurheartj/ehw106 · Cited by 6,457
Mach, F., Baigent, C., Catapano, A. L., Koskinas, K. C., Casula, M., Badimon, L., Chapman, M. J., De Backer, G. G., Delgado, V., Ference, B. A., et al. (2019) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2019.08.014 · Cited by 4,854
European guidelines on cardiovascular disease prevention in clinical practice: executive summary
Graham, I., Atar, D., Borch‐Johnsen, K., Boysen, G., Burell, G. K., Cífková, R., Dallongeville, J., Backer, G. D., Ebrahim, S. B. J., Gjelsvik, B., et al. (2007) · European Heart Journal · doi:10.1093/eurheartj/ehm316 · Cited by 3,865
ESC/EAS Guidelines for the management of dyslipidaemias
Reiner, Ž., Catapano, A. L., De Backer, G., Graham, I., Taskinen, M.-R., Wiklund, O., Agewall, S., Alegria, E., Chapman, M. J., Durrington, P., et al. (2011) · European Heart Journal · doi:10.1093/eurheartj/ehr158 · Cited by 3,549
Metadata
- 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 › 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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