Systemic inflammation is related to coronary microvascular dysfunction in obese patients without obstructive coronary disease

Nutr Metab Cardiovasc Dis. 2014 Apr;24(4):447-53. doi: 10.1016/j.numecd.2013.09.021. Epub 2013 Nov 6.

Abstract

Background and aims: Obesity, systemic inflammation and changes in the heart functions are associated with increased cardiovascular risk. This study aimed to investigate coronary microvascular dysfunction as an early marker of atherosclerosis in obese patients without any evidence of cardiovascular disease.

Methods and results: 86 obese subjects (aged 44 ± 12 years, body mass index (BMI) 41 ± 8 kg m(-2)), without evidence of heart disease, and 48 lean controls were studied using transthoracic Doppler echocardiography for detecting coronary flow reserve (CFR). A value of CFR ≤ 2.5 was considered abnormal. We measured interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α) and adiponectin in all patients. Patients with abnormal CFR underwent coronary multislice computed tomography (MSCT) in order to exclude an epicardial stenosis. CFR in obese subjects was lower than in lean subjects (3.2 ± 0.8 vs. 3.7 ± 0.7, p = 0.02) and was abnormal in 27 (31%) obese patients and in one (2%) control (p < 0.0001). All subjects with abnormal CFR showed no coronary stenosis at MSCT. At multivariable analysis, IL-6 and TNF-α were the only determinants of CFR (p < 0.02 and p < 0.02, respectively). At multivariable logistic regression analysis, IL-6 and TNF-α were the only determinants of CFR ≤ 2.5 (p < 0.03 and p < 0.03, respectively).

Conclusions: CFR is often reduced in obese subjects without clinical evidence of heart disease, suggesting a coronary microvascular impairment. This microvascular dysfunction seems to be related to a chronic inflammation mediated by adipocytokines. Our findings may explain the increased cardiovascular risk in obesity, independently of BMI.

Keywords: Coronary flow reserve; Inflammation; Microvascular dysfunction; Obesity; Prevention.

MeSH terms

  • Adiponectin / blood
  • Adult
  • Biomarkers / blood
  • Body Mass Index
  • Case-Control Studies
  • Chi-Square Distribution
  • Coronary Angiography / methods
  • Coronary Artery Disease / diagnosis
  • Coronary Artery Disease / etiology*
  • Coronary Artery Disease / physiopathology
  • Coronary Vessels / diagnostic imaging
  • Coronary Vessels / physiopathology*
  • Cross-Sectional Studies
  • Echocardiography, Doppler
  • Female
  • Fractional Flow Reserve, Myocardial
  • Humans
  • Inflammation / blood
  • Inflammation / complications*
  • Inflammation / diagnosis
  • Inflammation Mediators / blood
  • Interleukin-6 / blood
  • Logistic Models
  • Male
  • Microcirculation
  • Microvessels / diagnostic imaging
  • Microvessels / physiopathology*
  • Middle Aged
  • Multidetector Computed Tomography
  • Multivariate Analysis
  • Obesity / blood
  • Obesity / complications*
  • Obesity / diagnosis
  • Predictive Value of Tests
  • Risk Factors
  • Severity of Illness Index
  • Tumor Necrosis Factor-alpha / blood

Substances

  • ADIPOQ protein, human
  • Adiponectin
  • Biomarkers
  • IL6 protein, human
  • Inflammation Mediators
  • Interleukin-6
  • Tumor Necrosis Factor-alpha