Lipids, apolipoproteins, and their ratios in relation to cardiovascular events with statin treatment

Kastelein, John J.P.; van der Steeg, Wim A.; Holme, Ingar; Gaffney, Michael; Cater, Nilo B.; Barter, Philip; Deedwania, Prakash; Olsson, Anders G.; Boekholdt, S. Matthijs; Demicco, David A.; Szarek, Michael; LaRosa, John C.; Pedersen, Terje R.; Grundy, Scott M.

doi:10.1161/circulationaha.107.713438

Cited by 478Lipoproteins and Cardiovascular HealthCholesterol and Lipid MetabolismDiabetes, Cardiovascular Risks, and Lipoproteins

Lipids, apolipoproteins, and their ratios in relation to cardiovascular events with statin treatment

Kastelein, John J.P., van der Steeg, Wim A., Holme, Ingar, Gaffney, Michael, Cater, Nilo B., Barter, Philip, Deedwania, Prakash, Olsson, Anders G. +6 more·2008·Circulation

DOI 10.1161/circulationaha.107.713438

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Abstract

BACKGROUND: Low-density lipoprotein (LDL) cholesterol is the principal target of lipid-lowering therapy, but recent evidence has suggested more appropriate targets. We compared the relationships of on-treatment levels of LDL cholesterol, non-high-density lipoprotein (HDL) cholesterol, and apolipoprotein B, as well as ratios of total/HDL cholesterol, LDL/HDL cholesterol, and apolipoprotein B/A-I, with the occurrence of cardiovascular events in patients receiving statin therapy. METHODS AND RESULTS: A post hoc analysis was performed that combined data from 2 prospective, randomized clinical trials in which 10,001 ("Treating to New Targets") and 8888 ("Incremental Decrease in End Points through Aggressive Lipid Lowering") patients with established coronary heart disease were assigned to usual-dose or high-dose statin treatment. In models with LDL cholesterol, non-HDL cholesterol and apolipoprotein B were positively associated with cardiovascular outcome, whereas a positive relationship with LDL cholesterol was lost. In a model that contained non-HDL cholesterol and apolipoprotein B, neither was significant owing to collinearity. Total/HDL cholesterol ratio and the apolipoprotein B/A-I ratio in particular were each more closely associated with outcome than any of the individual proatherogenic lipoprotein parameters. CONCLUSIONS: In patients receiving statin therapy, on-treatment levels of non-HDL cholesterol and apolipoprotein B were more closely associated with cardiovascular outcome than levels of LDL cholesterol. Inclusion of measurements of the antiatherogenic lipoprotein fraction further strengthened the relationships. These data support the use of non-HDL cholesterol or apolipoprotein B as novel treatment targets for statin therapy. Given the absence of interventions that have been proven to consistently reduce cardiovascular disease risk through raising plasma levels of HDL cholesterol or apolipoprotein A-I, it seems premature to consider the ratio variables as clinically useful.

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Levels and Changes of HDL Cholesterol and Apolipoprotein A-I in Relation to Risk of Cardiovascular Events Among Statin-Treated Patients: A Meta-Analysis
Boekholdt, S. M., Arsenault, B. J., Hovingh, G. K., Mora, S., Pedersen, T. R., LaRosa, J. C., Welch, K. M. A., Amarenco, P., DeMicco, D. A., Tonkin, A. M., et al. (2013) · Circulation · doi:10.1161/circulationaha.113.002670 · Cited by 196 · see citing works
Incorrect Figure Labels in: Association of LDL Cholesterol, Non–HDL Cholesterol, and Apolipoprotein B Levels With Risk of Cardiovascular Events Among Patients Treated With Statins: A Meta-analysis
(2012) · JAMA · doi:10.1001/jama.2012.3888 · Cited by 6 · see citing works
Treating dyslipidemia in the high-risk patient.
Jones, P. H. (2010) · PubMed · Cited by 2 · see citing works

Authors: Kastelein, J. J. P., van der Steeg, W. A., Holme, I., Gaffney, M., Cater, N. B., Barter, P., Deedwania, P., Olsson, A. G., Boekholdt, S. M., Demicco, D. A., Szarek, M., LaRosa, J. C., Pedersen, T. R., & Grundy, S. M.
Affiliations: State University of New York (US)
From the Academic Medical Center, University of Amsterdam (J.J.P.K., W.A.v.d.S., S.M.B.), Amsterdam, the Netherlands; Center for Preventive Medicine, Ullevål University Hospital (I.H., T.R.P.), Oslo, Norway; Pfizer Inc (M.G., N.B.C., D.A.D., M.S.), New York, NY; the Heart Research Institute (P.B.), Sydney, Australia; Veterans Affairs Central California Healthcare System and University of California San Francisco School of Medicine (P.D.), San Francisco, Calif; University Hospital (A.G.O.),...
ORCID: Kastelein, John J.P.
Gaffney, Michael
Cater, Nilo B.
Deedwania, Prakash
Olsson, Anders G.
Boekholdt, S. Matthijs
Demicco, David A.
Szarek, Michael
Pedersen, Terje R.
Grundy, Scott M.
Venue: Circulation
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2008-06-10
Volume: 117
Issue: 23
Pages: 3002-3009
ISSN: 0009-7322 (ISSN-L)
1524-4539
DOI: 10.1161/circulationaha.107.713438
OpenAlex: W1982036768
Cited by: 478
References: 45
Citations by year: 2026: 10 · 2025: 14 · 2024: 16 · 2023: 17 · 2022: 16 · 2021: 24 · 2020: 23 · 2019: 24 · 2018: 23 · 2017: 25 · 2016: 14 · 2015: 32 · 2014: 23 · 2013: 36 · 2012: 31
FWCI: 52.34
Type: journal article
Language: en
Open access: closed
Locations: Circulation (publishedVersion)
PubMed (publishedVersion)
Data Archiving and Networked Services (DANS) (submittedVersion)
Pure Amsterdam UMC (submittedVersion)
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: statin therapy, non-HDL cholesterol, apolipoprotein B, apolipoprotein B/A-I ratio, TC/HDL-C ratio, LDL cholesterol, apolipoprotein A-I, cardiovascular events, coronary artery disease, lipid-lowering targets, lipoprotein ratios
MeSH terms: Aged, Apolipoproteins B, Coronary Disease, Female, Humans, Lipids, Cholesterol, HDL, Cholesterol, LDL, Male, Middle Aged, Risk, Triglycerides, Proportional Hazards Models, Randomized Controlled Trials as Topic, Databases, Factual, Apolipoprotein A-I, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Dyslipidemias

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Lipids, apolipoproteins, and their ratios in relation to cardiovascular events with statin treatment

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