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CLINICAL RESEARCH: CORONARY ARTERY DISEASE

Leptin and Coronary Heart Disease

Prospective Study and Systematic Review

Naveed Sattar, FRCPath^_*,_*, Goya Wannamethee, PhD, Nadeem Sarwar, MRPharmS, MPhil, Julia Chernova, MSc, Debbie A. Lawlor, MB, ChB, PhD^||, Anne Kelly, PhD^_*, A. Michael Wallace, PhD^_*, John Danesh, DPhil, FRCP and Peter H. Whincup, FRCP^¶

^_* BHF Glasgow Cardiovascular Research Centre, Faculty of Medicine, University of Glasgow, Glasgow, Scotland
Department of Primary Care and Population Sciences, Royal Free University College London Medical School, London, England
Department of Public Health and Primary Care, University of Cambridge, Cambridge, England
Trent Research and Development Support Unit, Department of Health Sciences, University of Leicester, Leicester, England
^|| Medical Research Council Centre of Causal Analyses in Translational Epidemiology, Department of Social Medicine, University of Bristol, Bristol, England
^¶ Division of Community Health Sciences, St. George's, University of London, London, England

Manuscript received May 20, 2008; revised manuscript received September 16, 2008, accepted September 23, 2008.

^_* Reprint requests and correspondence: Dr. Naveed Sattar, Professor of Metabolic Medicine, BHF Glasgow Cardiovascular Research Centre, Faculty of Medicine, University of Glasgow, Glasgow G12 8TA, Scotland (Email: nsattar{at}clinmed.gla.ac.uk).

Objectives: This study sought to better determine the link between leptin and coronary heart disease (CHD).

Background: Circulating leptin is considered a risk factor for CHD but larger studies are needed.

Methods: Leptin levels were measured in 550 men with fatal CHD or nonfatal myocardial infarction and in 1,184 controls nested within a prospective study of 5,661 British men and set in context with a meta-analysis.

Results: Baseline leptin correlated with body mass index (BMI), blood pressure, total cholesterol, triglyceride, and inflammatory markers; correlations persisted after BMI adjustment. The within-person consistency of leptin values over 4 years (correlation coefficient: 0.79; 95% confidence interval [CI]: 0.73 to 0.83) was higher than those of some established cardiovascular risk factors. In a comparison of individuals in the top third with those in the bottom third of baseline leptin, the age- and town-adjusted odds ratio for CHD was 1.25 (95% CI: 0.96 to 1.62), decreasing to 0.98 (95% CI: 0.72 to 1.34) after adjustment for BMI. A systematic review identified 7 prospective reports with heterogeneous findings (I² = 60%, 13% to 82%). The combined adjusted risk ratio across all studies was 1.44 (95% CI: 0.95 to 2.16) in a comparison of extreme thirds of leptin levels. The inconsistency between studies was partially explained by sample size, with combined estimates from studies involving >100 CHD cases (1.28, 95% CI: 0.80 to 2.04) being somewhat weaker than those from smaller studies (1.81, 95% CI: 0.76 to 4.31).

Conclusions: Previous studies appear to have overestimated associations of leptin and CHD risk. Our results suggest a moderate association that is largely dependent on BMI.

Key Words: obesity • leptin • metabolism • coronary heart disease

Abbreviations and Acronyms   BMI = body mass index   CHD = coronary heart disease

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J. Am. Coll. Cardiol. 2009 53: A24. [Full Text] [PDF]