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(Hypertension. 2008;51:1651.)
© 2008 American Heart Association, Inc.

Original Articles

Relations of Inflammatory Biomarkers and Common Genetic Variants With Arterial Stiffness and Wave Reflection

Renate Schnabel; Martin G. Larson; Josée Dupuis; Kathryn L. Lunetta; Izabella Lipinska; James B. Meigs; Xiaoyan Yin; Jian Rong; Joseph A. Vita; Christopher Newton-Cheh; Daniel Levy; John F. Keaney, Jr; Ramachandran S. Vasan; Gary F. Mitchell; Emelia J. Benjamin

From the National Heart Lung and Blood Institute Framingham Study (R.S., M.G.L., J.D., K.L.L., D.L., I.L., C.N.-C., R.S.V., E.J.B.), Framingham, Mass; Departments of Mathematics and Statistics (M.G.L.), Biostatistics (J.D., K.L.L.), and Epidemiology (E.J.B.), Public Health School, Whitaker Cardiovascular Institute (J.A.V., R.S.V., E.J.B.), Evans Memorial Department of Medicine (J.A.V., R.S.V., E.J.B.), and Department of Preventive Medicine (R.S.V., E.J.B.), School of Medicine, Boston University, Boston, Mass; Center for Population Studies (D.L.), National Heart, Lung, and Blood Institute, Bethesda, Md; Department of Medicine (J.B.M.), Division of Cardiology (C.N.-C.), Massachusetts General Hospital, Harvard Medical School, Boston; University of Massachusetts Medical School (J.F.K.), Broad Institute of Harvard and Massachusetts Institute of Technology (C.N.-C.), Cambridge, Mass; and Cardiovascular Engineering, Inc (G.F.M.), Waltham, Mass.

Correspondence to Emelia J. Benjamin, Boston University School of Medicine, Framingham Heart Study, 73 Mount Wayte Ave, Framingham, MA 01702-5827. E-mail emelia{at}bu.edu

Inflammation causes vascular dysfunction and perpetuates proatherosclerotic processes. We hypothesized that a broad panel of inflammatory biomarkers and single nucleotide polymorphisms in inflammatory genes is associated with vascular stiffness. We assessed 12 circulating inflammatory biomarkers (C-reactive protein, fibrinogen, interleukin-6, intercellular adhesion molecule-1, lipoprotein-associated phospholipase-A2 [mass and activity], monocyte chemoattractant protein-1, myeloperoxidase, CD40 ligand, osteoprotegerin, P-selectin, and tumor necrosis factor receptor-II) in relation to tonometry variables (central pulse pressure, mean arterial pressure, forward pressure wave, reflected pressure wave, carotid-femoral pulse wave velocity, and augmentation index) measured in 2409 Framingham Heart Study participants (mean age: 60 years; 55% women; 13% ethnic/racial minorities). Single nucleotide polymorphisms (n=2195) in 240 inflammatory candidate genes were related to tonometry measures in 1036 white individuals. In multivariable analyses, biomarkers explained <1% of any tonometry measure variance. Applying backward elimination, markers related to tonometry (P<0.01) were as follows: tumor necrosis factor receptor-II (inversely) with mean arterial pressure; C-reactive protein (positively) and lipoprotein-associated phospholipase-A2 (inversely) with reflected pressure wave; and interleukin-6 and osteoprotegerin (positively) with carotid-femoral pulse wave velocity. In genetic association analyses, lowest P values (false discovery rate <0.50) were observed for rs10509561 (FAS), P=6.6x10^–5 for central pulse pressure and rs11559271 (ITGB2), P=1.1x10^–4 for mean arterial pressure. These data demonstrate that, in a community-based sample, circulating inflammatory markers tumor necrosis factor receptor-II (mean arterial pressure), C-reactive protein, lipoprotein-associated phospholipase-A2 activity (reflected pressure wave), interleukin-6, and osteoprotegerin (carotid-femoral pulse wave velocity) were significantly but modestly associated with measures of arterial stiffness and wave reflection. Additional studies are needed to determine whether variation in inflammatory marker genes is associated with tonometry measures.

Key Words: tonometry • inflammation • epidemiology • polymorphism • single nucleotide • genetics

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