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Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19:2355-2363

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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19:2355-2363.)
© 1999 American Heart Association, Inc.


Atherosclerosis and Lipoproteins

Systemic Inflammatory Parameters in Patients With Atherosclerosis of the Coronary and Peripheral Arteries

Michael Erren; Holger Reinecke; Ralf Junker; Manfred Fobker; Helmut Schulte; Josef O. Schurek; Jürgen Kropf; Sebastian Kerber; Günter Breithardt; Gerd Assmann; Paul Cullen

From the Institut für Klinische Chemie und Laboratoriumsmedizin (M.E., R.J., M.F., G.A., P.C.), the Institut für Arterioskleroseforschung (M.E., H.R., R.J., M.F., H.S., G.B., G.A., P.C.), and the Medizinische Klinik und Poliklinik (H.R., S.K., G.B.), Innere Medizin C, Westfälische Wilhelms-Universität, Münster; and the Abteilung für Klinische Chemie und Zentrallaboratorium (J.O.S., J.K.), Philipps-Universität, Marburg, Germany.

Correspondence to Dr Paul Cullen, Institut für Arterioskleroseforschung, Domagkstrasse 3, D-48149 Muenster, Germany. E-mail cullen{at}uni-muenster.de

Abstract—Plasma concentration of markers of inflammation are increased in patients with atherosclerosis. However, it is unclear whether the pattern and magnitude of this increase vary with the site and extent of disease. In 147 patients undergoing semiquantitative coronary angiography, we measured the acute-phase reactants C-reactive protein (CRP) or serum amyloid A (SAA); the proinflammatory cytokine interleukin 6 (IL-6); the active and total fractions of the anti-inflammatory cytokine transforming growth factor-ß (TGF-ß); the macrophage activation marker neopterin; and the infection marker procalcitonin. Compared with 62 patients without either coronary artery disease (CAD) or peripheral artery disease (PAD), 57 patients with CAD but no PAD showed greater median CRP (0.4 versus 0.2 mg/dL, P=0.004) and IL-6 (3.8 versus 1.6 pg/mL, P=0.007) levels and a lower level of active-TGF-ß (57 versus 100 ng/mL, P=0.038). Moreover, CRP, IL-6, and neopterin levels showed a positive and the active TGF-ß level a negative correlation with the extent of coronary atherosclerosis. Compared with these 57 patients with CAD alone, 15 patients with PAD and CAD had higher median levels of SAA (17 versus 7 mg/mL, P=0.008), IL-6 (12 versus 4 pg/mL, P=0.002), neopterin (14 versus 11 mg/dL, P=0.006), and total TGF-ß (11834 versus 6417 ng/L, P=0.001). However, these strong univariate associations of markers of inflammation and atherosclerosis were lost in multivariate analysis once age, sex, and high density lipoprotein cholesterol or fibrinogen were taken into account. Increased plasma levels of CRP, SAA, IL-6, TGF-ß, neopterin, and procalcitonin constitute an inflammatory signature of advanced atherosclerosis and are correlated with the extent of disease but do not provide discriminatory diagnostic power over and above established risk factors.


Key Words: atherosclerosis • coronary artery disease • peripheral artery disease • markers of inflammation • acute-phase response




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