T Christen1, S Trompet2, P C N Rensen3, K Willems van Dijk4, H J Lamb5, J W Jukema6, F R Rosendaal7, S le Cessie8, R de Mutsert7. 1. Department of Clinical Epidemiology, Leiden University Medical Center (LUMC), PO Box 9600, 2300, RC, Leiden, the Netherlands. Electronic address: t.christen@lumc.nl. 2. Department of Medicine, Division of Gerontology and Geriatrics, LUMC, PO Box 9600, 2300, RC, Leiden, the Netherlands. 3. Department of Medicine, Division of Endocrinology, LUMC, PO Box 9600, 2300, RC, Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, LUMC, PO Box 9600, 2300, RC, Leiden, the Netherlands. 4. Department of Medicine, Division of Endocrinology, LUMC, PO Box 9600, 2300, RC, Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, LUMC, PO Box 9600, 2300, RC, Leiden, the Netherlands; Department of Human Genetics, LUMC, PO Box 9600, 2300, RC, Leiden, the Netherlands. 5. Department of Radiology, LUMC, PO Box 9600, 2300, RC, Leiden, the Netherlands. 6. Department of Cardiology, LUMC, PO Box 9600, 2300, RC, Leiden, the Netherlands. 7. Department of Clinical Epidemiology, Leiden University Medical Center (LUMC), PO Box 9600, 2300, RC, Leiden, the Netherlands. 8. Department of Clinical Epidemiology, Leiden University Medical Center (LUMC), PO Box 9600, 2300, RC, Leiden, the Netherlands; Department of Biomedical Data Sciences, LUMC, PO Box 9600, 2300, RC, Leiden, the Netherlands.
Abstract
BACKGROUND AND AIMS: Inflammation may underlie the association between obesity, atherosclerosis and cardiovascular disease. We investigated to what extent markers of inflammation mediate associations between overall and visceral body fat and subclinical atherosclerosis. METHODS AND RESULTS: In this cross-sectional analysis of the Netherlands Epidemiology of Obesity study we estimated total body fat (TBF) by bio-impedance analysis, carotid artery intima media thickness (cIMT) by ultrasound, C-reactive protein (hs-CRP) and glycoprotein acetyls (GlycA) concentrations in fasting blood samples (n = 5627), and visceral adipose tissue (VAT) by magnetic resonance imaging (n = 2247). We examined associations between TBF and VAT, and cIMT using linear regression, adjusted for potential confounding factors, and for mediators: cardiometabolic risk factors (blood pressure, glucose and low-density lipoprotein cholesterol), and inflammation using CRP and GlycA as proxies. Mean (SD) cIMT was 615 (90) μm. Per SD of TBF (8%), cIMT was 19 μm larger (95% confidence interval, CI: 10, 28). This association was 17 μm (95% CI: 8, 27) after adjustment for cardiometabolic risk factors, and did not change after adjustment for markers of inflammation. Per SD (56 cm2) VAT, cIMT was 9 μm larger (95% CI: 2, 16) which changed to 5 μm (95% CI: -3, 12) after adjustment for cardiometabolic risk factors, and did not change after adjustment for inflammatory markers. CONCLUSION: Our results suggest that associations between measures of overall and visceral body fat and subclinical atherosclerosis are not mediated by inflammation as measured by CRP and GlycA. Obesity may exert cardiovascular risk via other markers of systemic inflammation.
BACKGROUND AND AIMS: Inflammation may underlie the association between obesity, atherosclerosis and cardiovascular disease. We investigated to what extent markers of inflammation mediate associations between overall and visceral body fat and subclinical atherosclerosis. METHODS AND RESULTS: In this cross-sectional analysis of the Netherlands Epidemiology of Obesity study we estimated total body fat (TBF) by bio-impedance analysis, carotid artery intima media thickness (cIMT) by ultrasound, C-reactive protein (hs-CRP) and glycoprotein acetyls (GlycA) concentrations in fasting blood samples (n = 5627), and visceral adipose tissue (VAT) by magnetic resonance imaging (n = 2247). We examined associations between TBF and VAT, and cIMT using linear regression, adjusted for potential confounding factors, and for mediators: cardiometabolic risk factors (blood pressure, glucose and low-density lipoprotein cholesterol), and inflammation using CRP and GlycA as proxies. Mean (SD) cIMT was 615 (90) μm. Per SD of TBF (8%), cIMT was 19 μm larger (95% confidence interval, CI: 10, 28). This association was 17 μm (95% CI: 8, 27) after adjustment for cardiometabolic risk factors, and did not change after adjustment for markers of inflammation. Per SD (56 cm2) VAT, cIMT was 9 μm larger (95% CI: 2, 16) which changed to 5 μm (95% CI: -3, 12) after adjustment for cardiometabolic risk factors, and did not change after adjustment for inflammatory markers. CONCLUSION: Our results suggest that associations between measures of overall and visceral body fat and subclinical atherosclerosis are not mediated by inflammation as measured by CRP and GlycA. Obesity may exert cardiovascular risk via other markers of systemic inflammation.