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, com...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(Δ MBF) 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-in- duced 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 Δ MBF. Finally, only in the obese group leptin plasma levels significantly correlated with Δ MBF(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.展开更多
Abnormal coronary endothelial reactivity has been demonstrated in diabetes and is associated with an increased rate of cardiovascular events. Our objectives were to investigate the presence of functional coronary circ...Abnormal coronary endothelial reactivity has been demonstrated in diabetes and is associated with an increased rate of cardiovascular events. Our objectives were to investigate the presence of functional coronary circulatory abnormalities over the full spectrum of insulin resistance and to determine whether these would differ in severity with more advanced states of insulin resistance. Methods and Results-Myocardial blood flow(MBF) was measured with positron emission tomography and 13N-ammonia to characterize coronary circulatory function in states of insulin resistance without carbohydrate intolerance(IR), impaired glucose tolerance(IGT), and normotensive and hypertensive type 2 diabetes mellitus(DM) compared with insulin-sensitive(IS) individuals. Indices of coronary function were total vasodilator capacity(mostly vascular smooth muscle-mediated) during pharmacological vasodilation and the nitric oxide-mediated, endothelium-dependent vasomotion in response to cold pressor testing. Total vasodilator capacity was similar in normoglycemic individuals(IS, IR, and IGT), whereas it was significantly decreased in normotensive(- 17% ) and hypertensive(- 34% )DM patients. Compared with IS, endothelium- dependent coronary vasomotion was significantly diminished in IR(- 56% ), as well as in IGT and normotensive and hypertensive diabetic patients(- 85% ,- 91% , and- 120% , respectively). Conclusions-Progressively worsening functional coronary circulatory abnormalities of nitric oxide-mediated, endothelium-dependent vasomotion occur with increasing severity of insulin-resistance and carbohydrate intolerance. Attenuated total vasodilator capacity accompanies the more clinically evident metabolic abnormalities in diabetes.展开更多
文摘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(Δ MBF) 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-in- duced 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 Δ MBF. Finally, only in the obese group leptin plasma levels significantly correlated with Δ MBF(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.
文摘Abnormal coronary endothelial reactivity has been demonstrated in diabetes and is associated with an increased rate of cardiovascular events. Our objectives were to investigate the presence of functional coronary circulatory abnormalities over the full spectrum of insulin resistance and to determine whether these would differ in severity with more advanced states of insulin resistance. Methods and Results-Myocardial blood flow(MBF) was measured with positron emission tomography and 13N-ammonia to characterize coronary circulatory function in states of insulin resistance without carbohydrate intolerance(IR), impaired glucose tolerance(IGT), and normotensive and hypertensive type 2 diabetes mellitus(DM) compared with insulin-sensitive(IS) individuals. Indices of coronary function were total vasodilator capacity(mostly vascular smooth muscle-mediated) during pharmacological vasodilation and the nitric oxide-mediated, endothelium-dependent vasomotion in response to cold pressor testing. Total vasodilator capacity was similar in normoglycemic individuals(IS, IR, and IGT), whereas it was significantly decreased in normotensive(- 17% ) and hypertensive(- 34% )DM patients. Compared with IS, endothelium- dependent coronary vasomotion was significantly diminished in IR(- 56% ), as well as in IGT and normotensive and hypertensive diabetic patients(- 85% ,- 91% , and- 120% , respectively). Conclusions-Progressively worsening functional coronary circulatory abnormalities of nitric oxide-mediated, endothelium-dependent vasomotion occur with increasing severity of insulin-resistance and carbohydrate intolerance. Attenuated total vasodilator capacity accompanies the more clinically evident metabolic abnormalities in diabetes.
