Coronary vasomotor control in obesity and morbid obesity: Contrasting flow responses with endocannabinoids, leptin, and inflammation

Alessandra Quercioli, Zoltan Pataky, Fabrizio Montecucco, Sebastian Carballo, Aurlien Thomas, Christian Staub, Vincenzo Di Marzo, Gabriella Vincenti, Giuseppe Ambrosio, Osman Ratib, Alain Golay, Franois MacH, Elisabetta Harsch, Thomas H. Schindler

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Abstract

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. There is increasing evidence that altered plasma levels of endocannabinoids, leptin, and CRP may affect coronary circulatory function in OB and MOB. 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). The cold pressor testinduced 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). 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.

Original languageEnglish
Pages (from-to)805-815
Number of pages11
JournalJACC: Cardiovascular Imaging
Volume5
Issue number8
DOIs
StatePublished - Aug 2012
Externally publishedYes

Keywords

  • 2-AG
  • 2-arachidonoylglycerol
  • AEA
  • ANOVA
  • BMI
  • CAC
  • CAD
  • CI
  • CON
  • CPT
  • CT
  • CVR
  • EC
  • HDL
  • MBF
  • MFR
  • MOB
  • OB
  • OW
  • PET
  • RPP
  • SBP
  • analysis of variance
  • anandamide
  • body mass index
  • cold pressor test
  • computed tomography
  • confidence interval
  • control subject(s)
  • coronary artery calcification
  • coronary artery disease
  • coronary vascular resistance
  • endocannabinoid(s)
  • high-density lipoprotein
  • high-sensitivity C-reactive protein
  • hsCRP
  • morbid obesity
  • myocardial blood flow
  • myocardial flow reserve
  • obesity
  • overweight
  • positron emission tomography
  • rate-pressure product
  • systolic blood pressure

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  • Cite this

    Quercioli, A., Pataky, Z., Montecucco, F., Carballo, S., Thomas, A., Staub, C., Di Marzo, V., Vincenti, G., Ambrosio, G., Ratib, O., Golay, A., MacH, F., Harsch, E., & Schindler, T. H. (2012). Coronary vasomotor control in obesity and morbid obesity: Contrasting flow responses with endocannabinoids, leptin, and inflammation. JACC: Cardiovascular Imaging, 5(8), 805-815. https://doi.org/10.1016/j.jcmg.2012.01.020