DiabetologiaPlasma leptin and the risk of cardiovascular disease in the West of Scotland Study

Sattar N, McMahon AD, Packard CJ, Kelly A, Shepherd J, Gaw A, Wallace AM on behalf of the WOSCOPS Executive
Departments of pathological Biochemistry, (AMW, CJP, AK, JS, NS), Clinical Trials Unit (AG) Royal Glasgow Infirmary, Glasgow, G31 2ER and Robertson Centre for Biostatistics (ADM) University of Glasgow, Glasgow G12 8QQ

Background and Aims: Leptin plays a role in fat metabolism and obesity, and correlates with insulin resistance and other markers of the dysmetabolic syndrome independent of total adiposity. Raised leptin levels also appear to predict those at risk for diabetes. In light of these observations, we hypothesized that raised plasma leptin levels may identify men at increased risk of a coronary event in the West of Scotland Coronary Prevention Study (WOSCOPS).
Materials and Methods: Plasma leptin was measured at baseline in 377 men (cases) who subsequently suffered a myocardial infarction, sudden coronary death or underwent coronary revascularisation, and 783 men (controls) who remained free of any coronary events 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.
Results: Leptin was significantly higher in cases than controls (mean SD of 5.87 2.04 mg/l versus 5.04 2.09 mg/L, 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% CI 1.10-1.3, p<0.0006]. There was minimal change in this RR with correction for BMI -RR 1.24 [95% CI 1.06 to 1.45, p<0.0062] or with further correction for traditional risk factors including age, BMI, lipids, BP - RR 1.21 [95%CI 1.02 to 1.42, p<0.02]. Leptin was correlated with CRP (r=0.24, p<0.001) but even with this variable in the model, leptin retained borderline significance as a predictor of coronary events - RR 1.18 [95% CI 1.00 to 1.39, p=0.05].
Conclusions: In conclusion, we have shown for the first time in a large prospective study that plasma leptin concentration is a novel and independent risk factor for CHD.

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