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European Heart Journal Advance Access published online on February 20, 2009

European Heart Journal, doi:10.1093/eurheartj/ehp037
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2009. For permissions please email: journals.permissions@oxfordjournals.org

The influence of body mass index on mortality and bleeding among patients with or at high-risk of atherothrombotic disease

Koon-Hou Mak1,*, Deepak L. Bhatt2, Mingyuan Shao3, Steven M. Haffner4, Christian W. Hamm5, Graeme J. Hankey6, S. Claiborne Johnston7, Gilles Montalescot8, Philippe Gabriel Steg9, Steven R. Steinhubl10, Keith A.A. Fox11 and Eric J. Topol12

1 Gleneagles Medical Centre, 6 Napier Road, No. 08-13, Singapore 258499, Singapore
2 VA Boston Healthcare System and Brigham and Women's Hospital, Boston, MA, USA
3 Cleveland Clinic, Cleveland, OH, USA
4 University of Texas Health Science Center, San Antonio, TX, USA
5 Kerckhoff Heart Center, Bad Nauheim, Germany
6 Royal Perth Hospital and School of Medicine and Pharmacology, The University of Western Australia, Perth, Australia
7 University of California San Francisco, San Francisco, CA, USA
8 Institut de Cardiologie, Centre Hospitalier Universitaire Pitié-Salpêtrière, Paris, France
9 Hôpital Bichat-Claude Bernard, Paris, France
10 The Geisinger Clinic, Danville, PA, USA and The Medicines Company, Zurich, Switerland
11 University and Royal Infirmary of Edinburgh, Edinburgh, UK
12 Scripps Translational Research Institute, La Jolla, CA, USA

* Corresponding author. Tel: +65 6476 0880, Fax: +65 6475 0880, Email: makheart{at}gmail.com

Aims: We aimed to determine the relationship between body mass index (BMI) and cardiovascular events among individuals with or at-risk of atherothrombotic disease.

Methods and results: This was a prospective observational study of 15 532 patients enrolled in the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) trial who were randomly assigned to clopidogrel or placebo, and followed-up for a median of 28 months for the occurrence of the primary endpoint (cardiovascular death, myocardial infarction, or stroke), all-cause mortality, and bleeding complications. Compared with the highest BMI quartile, the primary endpoint, cardiovascular, and all-cause mortality all occurred more frequently among patients in the lowest BMI quartile (about a third lower). The relationship between continuous BMI and adverse cardiovascular outcomes were presented as two linear spline terms with 29 kg/m2 as the cut-point for all-cause mortality. Lower BMI was associated with an increase in moderate and severe bleeding complications, largely accounted for by those receiving dual-antiplatelet agents with the highest tertile aspirin dose.

Conclusion: Adverse cardiovascular events and bleeding complications occurred more frequently among individuals with or at-risk for atherothrombotic disease and low BMI. Further studies should be directed to these patients to improve outcomes.

The CHARISMA trial is registered with ClinicalTrials.gov, NCT00050817 [ClinicalTrials.gov] .

Key Words: Aspirin • Cardiovascular • Clopidogrel • Myocardial infarction • Obesity • Stroke


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