Elsevier

Atherosclerosis

Volume 212, Issue 1, September 2010, Pages 274-280
Atherosclerosis

Increased visceral adipose tissue mass is associated with increased C-reactive protein in patients with manifest vascular diseases

https://doi.org/10.1016/j.atherosclerosis.2010.04.029Get rights and content

Abstract

Background

Obesity is related to the development of vascular diseases and metabolic complications. Low grade inflammation is a key feature of central obesity, characterized by elevated plasma levels of C-reactive protein (CRP). We hypothesize that visceral adipose tissue contributes to systemic concentrations of CRP.

Methods

In 2410 patients (1729 men and 681 women) with vascular diseases, subcutaneous and visceral fat masses were analyzed with ultrasonography. Metabolic parameters and CRP were measured in a fasting state. The association between fat measurements and plasma CRP was quantified using linear regression analysis. CRP levels were logarithmically transformed. Adjustments were made for age, smoking, type 2 diabetes mellitus, insulin resistance (HOMA-IR) and medication use.

Results

Visceral fat was categorized into quartiles (Q) ranging from 3.2 to 7.8 cm in Q1 (reference) to 11.0–19.8 cm in Q4 in men and 2.7–6.0 cm in Q1 (reference) to 9.0–17.4 cm in Q4 in women. β-coefficients gradually increased across the quartiles from 0.07 (0.01–0.13) in Q2 to 0.25 (0.19–0.31) in Q4 in men and 0.17 (0.07–0.26) in Q2 to 0.42 (0.32–0.52) in Q4 in women, indicating 0.25 and 0.42 mg/l higher logarithmically transformed (log)CRP levels in Q4 compared to Q1 in respectively men and women. Per standard deviation increase of visceral fat, logCRP levels increased with 0.10 mg/l (0.07–0.12) in men and with 0.11 (0.15–0.19) in women. Likewise, in separate analyses waist circumference and body mass index showed a positive, but weaker association with logCRP levels across quartiles (in men: β 0.21 (0.15–0.27) in Q4 for waist circumference and β 0.23 (0.17–0.30) in Q4 for body mass index; in women: β 0.32 (0.22–0.42) in Q4 for waist circumference and β 0.32 (0.22–0.42) in Q4 for body mass index). In men subcutaneous fat was not associated with logCRP (β-coefficients relative to Q1: −0.01 (−0.07 to −0.05), −0.01 (−0.07 to −0.05) and 0.05 (−0.01 to −0.11) in Q2 to Q4 respectively).

Conclusions

In conclusion, visceral fat thickness is the strongest contributor to the systemic CRP concentrations in patients with vascular diseases.

Introduction

Abdominal obesity is strongly related to the development of vascular diseases and metabolic complications such as dyslipidemia, hypertension, insulin resistance and diabetes mellitus [1]. Low-grade inflammation, as measured by elevated plasma levels of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and C-reactive protein (CRP), is one of the features of central obesity [2], [3]. Adipose tissue produces a wide variety of inflammation modulating proteins, e.g. TNF-α, IL-1β, IL-6, macrophage chemoattractant protein-1 (MCP-1) and transforming growth factor-β (TGF-β) [4]. Immune cells like macrophages and lymphocytes, which may be attracted to adipose tissue by the locally produced pro-inflammatory cytokines, may further aggravate the pro-inflammatory state [5]. Increased fatty acid flux in hypertrophic adipocytes [6] and adipose tissue hypoxia [7] may induce endoplasmic reticulum (ER) stress [8] and activation of toll-like receptor-4 leading to an inflammatory response. Adipokines produced by visceral adipose tissue are directly released into the portal venous system, affecting liver function with respect to lipid- and glucose metabolism and synthesis of acute phase reactants and coagulation factors [9]. Secretion profiles of subcutaneous and visceral adipose tissue depots differ, as IL-6 and PAI-1 are predominantly produced by visceral adipose tissue [10], [11].

Given the close relationship between obesity and inflammation, it is conceivable that inflammation is an important pathophysiologic link between obesity and metabolic and vascular complications [12]. Increased plasma concentrations of inflammatory mediators, especially CRP, have been shown to be associated with elevated risk of vascular diseases [13].

Additional CRP measurement has been recommended to assess the likelihood of recurrent vascular events in patients with manifest vascular disease [14]. The association between subcutaneous and visceral adipose tissue and markers of inflammation, in particular CRP, has been supported by data from previous cross-sectional studies [15], [16], [17], [18], [19]. It is not known however, whether this relation is also present in patients with clinically manifest arterial disease. The objective of this cross-sectional study is to investigate whether ultrasonographically measured abdominal visceral and subcutaneous fat compartments are associated with systemic inflammation, measured by circulating (high sensitive) CRP concentrations, in patients with manifest arterial disease.

Section snippets

Study design and patients

In this study, data from patients enrolled in the SMART study (Second Manifestations of ARTerial disease), an ongoing single centre prospective cohort study carried out at the University Medical Center Utrecht, were used. The SMART study started in September 1996. Patients aged 18–80 years, referred to our institution with clinically manifest atherosclerotic vascular disease (coronary heart disease, cerebrovascular disease, peripheral arterial disease or abdominal aortic aneurysm) or with

Baseline characteristics

The majority of the study population of patients with manifest vascular disease consisted of men (72%) and the mean age of the total population was 59.7 ± 10.4 years. Mean intra-abdominal fat thickness was 9.0 ± 2.6 cm (men: 9.5 ± 2.3 cm, women: 7.6 ± 2.2 cm), mean subcutaneous fat thickness was 2.3 ± 1.2 cm (men: 2.1 ± 1.2 cm women: 2.7 ± 1.3 cm), mean waist circumference was 95 ± 12 cm (men: 98 ± 11 cm, women: 87 ± 13 cm) and mean BMI was 27.0 ± 3.9 kg/m2 (men: 27.2 ± 3.6 kg/m2, women: 27.6 ± 4.7 kg/m2).

The intra-abdominal fat

Discussion

In this cross-sectional study in patients with manifest vascular disease, we observed a positive association between ultrasonographically measured intra-abdominal fat thickness and plasma hsCRP concentrations (in men: in quartiles 3 and 4; in women in quartiles 2–4, Table 3a, Table 3b). This association was, to a lesser degree, also demonstrated with waist circumference and BMI. Subcutaneous fat thickness did not influence CRP concentrations in men. In women however, subcutaneous fat

Conclusions

In conclusion, intra-abdominal fat and waist circumference and to lesser degree BMI, are associated with increased plasma concentrations of CRP in patients with manifest atherosclerotic disease. There is no association between subcutaneous fat and inflammation in men. Although the relation between subcutaneous fat and CRP levels in women is less prominent than the influence of other measures of adiposity on CRP, a significant contribution of subcutaneous fat on CRP levels could be demonstrated

Acknowledgements

This work was supported by a grant from the Leatare Foundation, Monaco and the Catharijne Foundation, the Netherlands.

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