Coronary vasomotor control in obesity and morbid obesity: contrasting flow responses with endocannabinoids, leptin, and inflammation.
OBJECTIVE
This study sought to investigate abnormalities in coronary circulatory function in 2 different disease entities of obese (OB) and morbidly obese (MOB) individuals and to evaluate whether these would differ in severity with different profiles of endocannabinoids, leptin, and C-reactive protein (CRP) plasma levels.


BACKGROUND
There is increasing evidence that altered plasma levels of endocannabinoids, leptin, and CRP may affect coronary circulatory function in OB and MOB.


METHODS
Myocardial blood flow (MBF) responses to cold pressor test from rest and during pharmacologically induced hyperemia were measured with N-13 ammonia positron emission tomography/computed tomography. Study participants (n = 111) were divided into 4 groups based on their body mass index (BMI) (kg/m(2)): 1) control group (BMI: 20 to 24.9, n = 30); 2) overweight group (BMI: 25 to 29.9, n = 31), 3) OB group (BMI: 30 to 39.9, n = 25); and 4) MOB group (BMI ≥40, n = 25).


RESULTS
The cold pressor test-induced change in endothelium-related MBF response (ΔMBF) progressively declined in overweight and OB groups when compared with the control group [median: 0.19 (interquartile range [IQR] 0.08, 0.27) and 0.11 (0.03, 0.17) vs. 0.27 (0.23, 0.38) ml/g/min; p ≤ 0.01, respectively], whereas it did not differ significantly between OB and MOB groups [median: 0.11 (IQR: 0.03, 0.17) and 0.09 (-0.01, 0.19) ml/g/min; p = 0.93]. Compared with control subjects, hyperemic MBF subjects comparably declined in the overweight, OB, and MOB groups [median: 2.40 (IQR 1.92, 2.63) vs. 1.94 (1.65, 2.30), 2.05 (1.67, 2.38), and 2.14 (1.78, 2.76) ml/g/min; p ≤ 0.05, respectively]. In OB individuals, ΔMBF was inversely correlated with increase in endocannabinoid anandamide (r = -0.45, p = 0.044), but not with leptin (r = -0.02, p = 0.946) or with CRP (r = -0.33, p = 0.168). Conversely, there was a significant and positive correlation among ΔMBF and elevated leptin (r = 0.43, p = 0.031) and CRP (r = 0.55, p = 0.006), respectively, in MOB individuals that was not observed for endocannabinoid anandamide (r = 0.07, p = 0.740).


CONCLUSIONS
Contrasting associations of altered coronary endothelial function with increases in endocannabinoid anandamide, leptin, and CRP plasma levels identify and characterize OB and MOB as different disease entities affecting coronary circulatory function.
Department of Specialties in Medicine, University Hospitals of Geneva, Geneva, Switzerland.
Alessandra
A
Quercioli
Zoltan
Z
Pataky
Fabrizio
F
Montecucco
Sebastian
S
Carballo
Aurélien
A
Thomas
Christian
C
Staub
Vincenzo
V
Di Marzo
Gabriella
G
Vincenti
Giuseppe
G
Ambrosio
Osman
O
Ratib
Alain
A
Golay
François
F
Mach
Elisabetta
E
Harsch
Thomas H
TH
Schindler
D054392:Adipokines / Q000097:blood; D000328:Adult; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000032:analysis; D002319:Cardiovascular System / Q000503:physiopathology; D003326:Coronary Circulation / Q000187:drug effects* / Q000502:physiology*; D063388:Endocannabinoids / Q000097:blood*; D004730:Endothelium, Vascular / Q000502:physiology; D005260:Female; D006801:Humans; D020738:Leptin / Q000097:blood*; D008875:Middle Aged; D064847:Multimodal Imaging; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D009765:Obesity / Q000097:blood* / Q000503:physiopathology*; D009767:Obesity, Morbid / Q000097:blood* / Q000503:physiopathology*; D049268:Positron-Emission Tomography; D012039:Regional Blood Flow / Q000187:drug effects; D014057:Tomography, X-Ray Computed; D014664:Vasodilation / Q000502:physiology
D054392:Adipokines; D063388:Endocannabinoids; D020738:Leptin; D002097:C-Reactive Protein