Relationship between increasing body weight, insulin resistance, inflammation, adipocytokine leptin, and coronary circulatory function.
OBJECTIVE
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 < or = BMI <25 (n = 19); overweight, 25 < or = 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 (DeltaMBF) 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 DeltaMBF. Finally, only in the obese group leptin plasma levels significantly correlated with DeltaMBF (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.
Department of Molecular, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, California 90095-1735, USA.
Thomas H
TH
Schindler
Jerson
J
Cardenas
John O
JO
Prior
Alvaro D
AD
Facta
Michael C
MC
Kreissl
Xiao-Li
XL
Zhang
James
J
Sayre
Magnus
M
Dahlbom
Julio
J
Licinio
Heinrich R
HR
Schelbert
D000328:Adult; D003326:Coronary Circulation / Q000502:physiology*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000503:physiopathology*; D007333:Insulin Resistance; D020738:Leptin / Q000097:blood*; D008297:Male; D009765:Obesity / Q000097:blood* / Q000503:physiopathology*; D050177:Overweight
D020738:Leptin