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Cited by 196Lipoproteins and Cardiovascular HealthCholesterol and Lipid MetabolismCancer, Lipids, and Metabolism

Levels and Changes of HDL Cholesterol and Apolipoprotein A-I in Relation to Risk of Cardiovascular Events Among Statin-Treated Patients: A Meta-Analysis

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Boekholdt, S. Matthijs, Arsenault, Benoit J., Hovingh, G. Kees, Mora, Samia, Pedersen, Terje R., LaRosa, John C., Welch, K.M.A., Amarenco, Pierre +13 more·2013·Circulation
DOI 10.1161/circulationaha.113.002670PMC PMC3807966
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Abstract

Background—: It is unclear whether levels of high-density lipoprotein cholesterol (HDL-C) or apolipoprotein A-I (apoA-I) remain inversely associated with cardiovascular risk among patients who achieve very low levels of low-density lipoprotein cholesterol on statin therapy. It is also unknown whether a rise in HDL-C or apoA-I after initiation of statin therapy is associated with a reduced cardiovascular risk. Methods and Results—: We performed a meta-analysis of 8 statin trials in which lipids and apolipoproteins were determined in all study participants at baseline and at 1-year follow-up. Individual patient data were obtained for 38 153 trial participants allocated to statin therapy, of whom 5387 suffered a major cardiovascular event. HDL-C levels were associated with a reduced risk of major cardiovascular events (adjusted hazard ratio [HR], 0.83; 95% confidence interval [CI], 0.81–0.86 per 1 standard deviation increment), as were apoA-I levels (HR, 0.79; 95% CI, 0.72–0.82). This association was also observed among patients achieving on-statin low-density lipoprotein cholesterol levels <50 mg/dL. An increase of HDL-C was not associated with reduced cardiovascular risk (HR, 0.98; 95% CI, 0.94–1.01 per 1 standard deviation increment), whereas a rise in apoA-I was (HR, 0.93; 95% CI, 0.90–0.97). Conclusions—: Among patients treated with statin therapy, HDL-C and apoA-I levels were strongly associated with a reduced cardiovascular risk, even among those achieving very low low-density lipoprotein cholesterol. An apoA-I increase was associated with a reduced risk of major cardiovascular events, whereas for HDL-C this was not the case. These findings suggest that therapies that increase apoA-I concentration require further exploration with regard to cardiovascular risk reduction.

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Authors
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., Sullivan, D. R., Kirby, A., Colhoun, H. M., Hitman, G. A., Betteridge, D. J., Durrington, P. N., Clearfield, M. B., Downs, J. R., Gotto, A. M., Ridker, P. M., & Kastelein, J. J. P.
Affiliations
  • Oslo University Hospital (NO)
  • From the Departments of Cardiology (S.M.B.) and Vascular Medicine (B.J.A., G.K.H., J.J.P.K.), Academic Medical Center, Amsterdam, The Netherlands; Center for Cardiovascular Disease Prevention, Brigham and Women’s Hospital, Boston, MA (S.M., P.M.R.); Center of Preventive Medicine, Oslo University Hospital, Ulleval and University of Oslo, Norway (T.R.P.); State University of New York Health Science Center, Brooklyn, NY (J.C.L.); Rosalind Franklin University of Medicine and Science, North Chicago, IL ...
ORCID
Venue
Circulation
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2013-10
Volume
128
Issue
14
Pages
1504-1512
ISSN
  • 0009-7322 (ISSN-L)
  • 1524-4539
DOI
10.1161/circulationaha.113.002670
PMC
PMC3807966
OpenAlex
W2015450538
Cited by
196
References
8
Citations by year
2026: 4 · 2025: 11 · 2024: 14 · 2023: 10 · 2022: 12 · 2021: 15 · 2020: 16 · 2019: 8 · 2018: 21 · 2017: 16 · 2016: 14 · 2015: 32 · 2014: 21 · 2013: 1
FWCI
22.36
Type
journal article
Language
en
Open access
Locations
  • Circulation (publishedVersion)
  • PubMed (publishedVersion)
  • Discovery Research Portal (University of Dundee) (publishedVersion)
  • Pure Amsterdam UMC (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
Funders
National Heart, Lung, and Blood Institute (R01HL117861)
Topics
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
Keywords
HDL cholesterol, apolipoprotein A-I, statin therapy, cardiovascular risk, major cardiovascular events, low LDL cholesterol, lipid-lowering therapy
MeSH terms
Angina, Unstable, Cardiovascular Diseases, Clinical Trials as Topic, Follow-Up Studies, Heart Failure, Humans, Cholesterol, HDL, Cholesterol, LDL, Myocardial Infarction, Risk Factors, Triglycerides, Proportional Hazards Models, Apolipoprotein A-I, Treatment Outcome, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Stroke, Risk Reduction Behavior, Peripheral Arterial Disease

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