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(Circulation. 2002;106:1919.)
© 2002 American Heart Association, Inc.

Clinical Investigation and Reports

Influence of Leptin on Arterial Distensibility

A Novel Link Between Obesity and Cardiovascular Disease?

Atul Singhal, MD, MRCP; I. Sadaf Farooqi, PhD, MRCP; Tim J. Cole, ScD; Stephen O’Rahilly, MD, FRCP; Mary Fewtrell, MD, MRCP; Mia Kattenhorn, BSc; Alan Lucas, MD, FRCP, FMed Sci; John Deanfield, FRCP

From the MRC Childhood Nutrition Research Center (A.S., M.F., M.K., A.L.), Department of Pediatric Epidemiology and Biostatistics (T.J.C.), and Department of Vascular Physiology (M.K., J.D.), Institute of Child Health, London; and the University Department of Medicine (I.S.F., S.O.R.), Addenbrooke’s Hospital, Cambridge, UK.

Correspondence Dr A. Singhal, MRC Childhood Nutrition Research Center, 30 Guilford St, London WC1N 1EH, UK. E-mail a.singhal{at}ich.ucl.ac.uk

Background— The mechanisms by which obesity increases the risk of atherosclerotic cardiovascular disease (CVD) are poorly understood. In experimental models, leptin, a hormone produced by adipose tissue, has been shown adversely to affect vascular health. Therefore, we tested the hypothesis that high leptin concentrations are associated with lower arterial distensibility, an index of circulatory function relevant to the atherosclerotic process.

Methods and Results— Noninvasive, high-resolution, vascular ultrasound was used to measure brachial artery distensibility in 294 healthy adolescents (aged 13 to 16 years) who had a broad range of body mass indexes. Fat mass was measured by bioelectric impedance analysis; fasting serum leptin concentration by radioimmunoassay; and lipid profile, fasting insulin, glucose, and C-reactive protein concentrations by standard laboratory techniques. Higher leptin concentrations were associated with impaired arterial distensibility (regression coefficient, -1.3% change in arterial distension per 10% increase in leptin; 95% CI, -1.9% to -0.8%; P<0.001). This association was independent of fat mass, blood pressure, and C-reactive protein, fasting insulin, or LDL cholesterol concentrations.

Conclusions— Elevation in leptin was associated with impaired vascular function, independent of the metabolic and inflammatory disturbances associated with obesity. Our observations are consistent with data from experimental models and suggest that high leptin concentration is an important mechanism for the adverse influence of body fatness on CVD.

Key Words: atherosclerosis • obesity • cardiovascular diseases

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Does Leptin Cause Vascular Disease?

John P. Cooke and Roberta K. Oka
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