Relationship between increasing body weight, insulin resistance, inflammation, adipocytokine leptin, and coronary circulatory function

Thomas H. Schindler, Jerson Cardenas, John O. Prior, Alvaro D. Facta, Michael C. Kreissl, Xiao Li Zhang, James Sayre, Magnus Dahlbom, Julio Licinio, Heinrich R. Schelbert

Research output: Contribution to journalArticlepeer-review

186 Scopus citations


OBJECTIVES: We sought to evaluate effects of obesity, insulin resistance, and inflammation on coronary circulatory function and its relationship to leptin plasma levels. BACKGROUND: It is not known whether obesity, commonly paralleled by insulin resistance, inflammation, and leptin, is independently associated with coronary circulatory dysfunction. METHODS: Myocardial blood flow (MBF) responses to cold pressor test (CPT) and pharmacologic vasodilation was measured with positron emission tomography and 13N-ammonia. Study participants were divided into three groups based on their body mass index (BMI, kg/m2): control, 20 ≤ BMI <25 (n = 19); overweight, 25 ≤ BMI <30 (n = 21); and obese, BMI >30 (n = 32). RESULTS: Body mass index was significantly correlated to the Homeostasis Model Assessment Index of insulin resistance and C-reactive protein levels (r = 0.60 and r = 0.47, p < 0.0001). Compared with control subjects, endothelium-related change in MBF (ΔMBF) to CPT progressively declined in overweight and obese groups (0.32 ± 0.09 vs. 0.21 ± 0.19 and 0.07 ± 0.16 ml/g/min; p < 0.03 and p < 0.0001). The dipyridamole-induced total vasodilator capacity was significantly lower in obese than in control subjects (1.77 ± 0.51 vs. 2.04 ± 0.37 ml/g/min, p < 0.02). On multivariate analysis, BMI (p < 0.012) and age (p < 0.035) were significant independent predictors of ΔMBF. Finally, only in the obese group leptin plasma levels significantly correlated with ΔMBF (r = 0.37, p < 0.036). CONCLUSIONS: Increased body weight is independently associated with abnormal coronary circulatory function that progresses from an impairment in endothelium-related coronary vasomotion in overweight individuals to an impairment of the total vasodilator capacity in obese individuals. The findings that elevated leptin plasma levels in patients that are obese might exert beneficial effects on the coronary endothelium to counterbalance the adverse effects of increases in body weight on coronary circulatory function should be tested.

Original languageEnglish
Pages (from-to)1188-1195
Number of pages8
JournalJournal of the American College of Cardiology
Issue number6
StatePublished - Mar 21 2006


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