Low-grade inflammation mediates the association between the metabolic syndrome and the ankle-arm index (The CODAM study)

M. Jacobs, M.M.J. van Greevenbroek, C.J.H. van der Kallen, I. Ferreira, E.E. Blaak, E.J.M. Feskens, C.G. Schalkwijk, C.D.A. Stehouwer

Research output: Contribution to journalAbstractAcademic


Background: The Metabolic Syndrome (MetS) is associated with CHD and this association may be related to low-grade inflammation. The metabolic syndrome may also be related to peripheral arterial dysfunction although this relation has not been described extensively. Low-grade inflammation has been implicated in peripheral arterial dysfunction as well. Aims: To determine associations between the metabolic syndrome and ankle-arm index (AAIx; an available and reproducible method for the detection of peripheral arterial dysfunction) and to address the role of low-grade inflammation therein. Materials and methods: The study population consisted of 574 subjects (age: 59.6 + 7.0 years, 61.3% men, 54.7% MetS; NCEP-ATP 2005 criteria) from the Cohort Study Diabetes and Atherosclerosis (CODAM) cohort, who were invited from a large population based cohort on basis of an elevated risk for type 2 diabetes and cardiovascular diseases. The AAIx was calculated by dividing the highest of the ankle pressures (a. dorsalis pedis or a. tibialis) in either leg by the highest pressure at the brachial artery. The following inflammatory markers were measured in fasting plasma: C-reactive protein (CRP), IL6, soluble vascular cell adhesion molecule, soluble intercellular adhesion molecule (sICAM) and serum amyloid A. For each inflammation marker the Z-score was calculated and an inflammation score was then calculated as the average of the Z-scores of the five inflammation markers listed above. Multiple linear regression analyses were used to determine associations between the metabolic syndrome and low-grade inflammation on the one hand, and the AAIx on the other. Results: The metabolic syndrome was associated with the AAIx (Beta [ß] = -0.02, 95%CI: -0.04; -0.002, P = 0.03). Adjustment for age, sex and smoking did not change this association. Inflammation markers that were associated with the AAIx were CRP (ß = -0.04, 95%CI: -0.06; -0.01, P = 0.002), IL6 (ß =-0.05, 95%CI: -0.08; -0.02, P = 0.002), and sICAM (ß = -0.10, 95%CI: -0.17;-0.02, P = 0.017), all adjusted for age, sex and smoking. When both the metabolic syndrome and the inflammation score were included in the linear regression model, the metabolic syndrome was no longer associated with AAIx, but the association between inflammation and the AAIx remained (ßMetS= -0.01, 95%CI: -0.03; 0.01 P = 0.19; ßinflammation= -0.02, 95%CI: -0.04; -0.01 P = 0.002, adjusted for age, sex, smoking). Conclusion: Subjects with the metabolic syndrome show greater levels of peripheral arterial dysfunction (as expressed by AAIx). Importantly, chronic low-grade inflammation mediated, in a great deal, that association, and was independently associated with AAIx
Original languageEnglish
Pages (from-to)S162-S162
Issue number1
Publication statusPublished - 2008

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