Abstract

Background:Atherosclerosis is a multifactorial disease with an inflammatory pathophysiological basis. Cytokines released during the atherosclerotic process induce production of C-reactive protein (CRP) in the liver, which is an important marker of inflammation.Objective:We tested whether inflammatory biomarkers were associated with deterioration of peripheral arterial occlusive disease (PAOD) in a population at high cardiovascular risk.Methods:1,330 subjects ≥30 years of age underwent clinical and laboratory examinations as part of a population-based study of the prevalence of diabetes. PAOD was defined as an ankle-brachial index (ABI) ≤0.90. After application of exclusion criteria, the sample comprised 1,038 subjects. Traditional risk factors, CRP and interleukin 6 (IL-6) were also compared across three ABI categories (≤0.70; 0.71-0.90; ≥0.90). Mean values for these variables were compared by presence/absence of DAOP (Student's t test) and by ABI categories (ANOVA). Poisson regression and logistic regression models were used to test for associations between risk factors and DAOP and between risk factors and the ABI categories. Pearson's linear correlation coefficients were calculated for the relationship between CRP and IL-6 levels.Results:Mean age was 56.8±12.9 years, 54% of the sample were women and the prevalence of DAOP was 21.0% (95%CI 18.4-24.1). Individuals with ABI ≤0.70 had higher concentrations of CRP-us (2.1 vs. 1.8) and of IL-6 (1.25 vs. 1.17). Concentrations of CRP and IL-6 were only correlated in patients with DAOP, (p=0.004).Conclusions:The finding that CRP and IL-6 levels were only elevated among people with advanced DAOP may suggest that these biomarkers have a role to play as indicators of more severe disease. Prospective studies are needed to test this hypothesis.

Highlights

  • Synthesis of C-reactive protein (CRP) in the liver is an innate, nonspecific, immunological defense mechanism[1] that activates the complement system and promotes phagocytosis

  • Synthesis is regulated by interleukin 6 (IL-6), an inflammatory cytokine that is primarily secreted by macrophages and adipocytes.[2]

  • Prevalence rates were higher among men for diabetes, smoking, hypertriglyceridemia, hyperuricemia, hyperhomocysteinemia, low HDLcholesterol and elevated IL-6 concentration, while elevated LDL-cholesterol and CRP-us were more frequent among the women

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Summary

Introduction

Synthesis of C-reactive protein (CRP) in the liver is an innate, nonspecific, immunological defense mechanism[1] that activates the complement system and promotes phagocytosis. Synthesis is regulated by interleukin 6 (IL-6), an inflammatory cytokine that is primarily secreted by macrophages and adipocytes.[2] Experimental studies indicate that smooth muscle and endothelial cells of both normal and aneurysmal arteries can secrete IL-6.3. Objective: We tested whether inflammatory biomarkers were associated with deterioration of peripheral arterial occlusive disease (PAOD) in a population at high cardiovascular risk. Traditional risk factors, CRP and interleukin 6 (IL-6) were compared across three ABI categories (≤0.70; 0.71-0.90; ≥0.90) Mean values for these variables were compared by presence/absence of DAOP (Student’s t test) and by ABI categories (ANOVA). Conclusions: The finding that CRP and IL-6 levels were only elevated among people with advanced DAOP may suggest that these biomarkers have a role to play as indicators of more severe disease.

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