C-Reactive Protein in Healthy Subjects: Associations With Obesity, Insulin Resistance, and Endothelial Dysfunction

Abstract

Abstract-C-reactive protein, a hepatic acute phase protein largely regulated by circulating levels of interleukin-6, predicts coronary heart disease incidence in healthy subjects. We have shown that subcutaneous adipose tissue secretes interleukin-6 in vivo. In this study we have sought associations of levels of C-reactive protein and interleukin-6 with measures of obesity and of chronic infection as their putative determinants. We have also related levels of C-reactive protein and interleukin-6 to markers of the insulin resistance syndrome and of endothelial dysfunction. We performed a cross-sectional study in 107 nondiabetic subjects: (1) Levels of C-reactive protein, and concentrations of the proinflammatory cytokines interleukin-6 and tumor necrosis factor-␣, were related to all measures of obesity, but titers of antibodies to Helicobacter pylori were only weakly and those of Chlamydia pneumoniae and cytomegalovirus were not significantly correlated with levels of these molecules. Levels of C-reactive protein were significantly related to those of interleukin-6 (rϭ0.37, PϽ0.0005) and tumor necrosis factor-␣ (rϭ0.46, PϽ0.0001).(2) Concentrations of C-reactive protein were related to insulin resistance as calculated from the homoeostasis model assessment model, blood pressure, HDL, and triglyceride, and to markers of endothelial dysfunction (plasma levels of von Willebrand factor, tissue plasminogen activator, and cellular fibronectin). A mean standard deviation score of levels of acute phase markers correlated closely with a similar score of insulin resistance syndrome variables (rϭ0.59, PϽ0.00005), this relationship being weakened only marginally by removing measures of obesity from the insulin resistance score (rϭ0.53, PϽ0.00005). These data suggest that adipose tissue is an important determinant of a low level, chronic inflammatory state as reflected by levels of interleukin-6, tumor necrosis factor-␣, and C-reactive protein, and that infection with H pylori, C pneumoniae, and cytomegalovirus is not. Moreover, our data support the concept that such a low-level, chronic inflammatory state may induce insulin resistance and endothelial dysfunction and thus link the latter phenomena with obesity and cardiovascular disease. (Arterioscler Thromb Vasc Biol. 1999;19:972-978.)

Involvement of leptin in the association between percentage of body fat and cardiovascular risk factors

“…Second, several factors such as smoking, hypertension, and treatment with lipid-lowering or antihypertensive drugs may be confounding factors. In addition, our population sample of obese subjects may not be representative of central obesity, in which CRP concentrations are clearly correlated with BF [42]. However, in our study, CRP was significantly correlated with leptin concentrations.…”

Associations of adiponectin with metabolic and vascular risk parameters in the British Regional Heart Study reveal stronger links to insulin resistance-related than to coronory heart disease risk-related parameters

“…21,51 It is hypothesized that increased abdominal adipose tissue is responsible for a mild chronic inflammatory state, which may induce insulin resistance and endothelial dysfunction, markers of which include t-PA antigen levels. 52 Hypoadiponectinemia may directly contribute to the development of endothelial dysfunction by allowing vascular proinflammatory reactions to occur more readily. 5 However, no association was seen with vWF, another potential marker of endothelial dysfunction.…”

The −174 G/C polymorphism of the interleukin-6 gene promoter and essential hypertension in an elderly Italian population

“…16 Third, up to 30% of circulating IL-6 is produced by the adipose tissue 17,18 and the relationship between obesity and hypertension is well known. Finally, IL-6 increases collagen synthesis in the vessel wall 19 and reduces its degradation.…”