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(Circulation. 2001;104:3052.)
© 2001 American Heart Association, Inc.

Clinical Investigation and Reports

Plasma Leptin and the Risk of Cardiovascular Disease in the West of Scotland Coronary Prevention Study (WOSCOPS)

A. Michael Wallace, PhD; Alex D. McMahon, PhD; Chris J. Packard, DSc; Anne Kelly, MIBiol; James Shepherd, PhD; Allan Gaw, MD; Naveed Sattar, MD PhD, on behalf of the WOSCOPS Executive Committee

From the Department of Pathological Biochemistry (A.M.W., C.J.P., A.K., J.S., N.S.), Clinical Trials Unit (A.G.), Glasgow Royal Infirmary, and Robertson Centre for Biostatistics (A.D.M.), University of Glasgow, Glasgow, Scotland.

Correspondence to Dr Naveed Sattar, Department of Pathological Biochemistry, 4th Floor QEB, Glasgow Royal Infirmary, Glasgow G31 2ER, UK. E-mail nsattar{at}clinmed.gla.ac.uk

Background— Leptin plays a role in fat metabolism and correlates with insulin resistance and other markers of the metabolic syndrome, independent of total adiposity. Therefore, we hypothesized that raised leptin levels may identify men at increased risk of a coronary event in the West of Scotland Coronary Prevention Study (WOSCOPS).

Methods and Results— Plasma leptin levels were measured at baseline in 377 men (cases) who subsequently experienced a coronary event and in 783 men (controls) who remained free of an event during the 5-year follow-up period of the study. Controls were matched to cases on the basis of age and smoking history and were representative of the entire WOSCOPS cohort. Leptin levels were significantly higher in cases than controls (5.87±2.04 ng/mL versus 5.04±2.09 ng/mL, P<0.001). In univariate analysis, for each 1 SD increase in leptin, the relative risk (RR) of an event increased by 1.25 (95% confidence interval [CI], 1.10 to 1.43; P<0.001). There was minimal change in this RR with correction for body mass index (RR, 1.24; 95% CI, 1.06 to 1.45; P=0.006) or with further correction for classic risk factors, including age, lipids, and systolic blood pressure (RR, 1.20; 95% CI, 1.02 to 1.42; P=0.03). Leptin correlated with C-reactive protein (r=0.24, P<0.001) and, even with this variable added to the model, leptin retained significance as a predictor of coronary events (RR, 1.18; 95% CI, 1.00 to 1.39; P=0.05) at the expense of C-reactive protein.

Conclusions— We show, for the first time, in a large prospective study that leptin is a novel, independent risk factor for coronary heart disease.

Key Words: adipocytes • insulin resistance • inflammation • cardiovascular diseases

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