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(Circulation. 2004;109:3022-3028.)
© 2004 American Heart Association, Inc.

Clinical Investigation and Reports

Obesity Is an Important Determinant of Baseline Serum C-Reactive Protein Concentration in Monozygotic Twins, Independent of Genetic Influences

Jerry R. Greenfield, MBBS, BSc (Med), FRACP; Katherine Samaras, MBBS, PhD, FRACP; Arthur B. Jenkins, BSc, PhD; Paul J. Kelly, MBBS, MD, FRACP; Tim D. Spector, MSc, MD, FRCP; J. Ruth Gallimore, BSc; Mark B. Pepys, MD, PhD, FRCP, FRCPath, FMedSci, FRS; Lesley V. Campbell, MBBS, FRCP, FRACP

From the Department of Endocrinology (J.R.G., K.S., L.V.C.) and Diabetes Centre (L.V.C.), St Vincent’s Hospital, Sydney, Australia; Diabetes and Obesity Research Program (J.R.G., K.S., L.V.C.), Garvan Institute of Medical Research, Sydney, Australia; Department of Biomedical Science (A.B.J.), University of Wollongong, Wollongong, Australia; Orchid BioSciences, Inc (P.J.K.), Princeton, NJ; Twin Research and Genetic Epidemiology Unit (T.D.S.), St Thomas’ Hospital, London, UK; and Centre for Amyloidosis and Acute Phase Proteins (J.R.G., M.B.P.), Department of Medicine, Royal Free and University College Medical School, London, UK.

Correspondence to Lesley Campbell, MBBS, FRCP, FRACP, Diabetes Centre, St Vincent’s Hospital, Victoria St, Darlinghurst, 2010, Sydney, Australia. E-mail l.campbell{at}garvan.org.au

Received October 30, 2003; de novo received December 21, 2003; revision received March 4, 2004; accepted March 15, 2004.

Background— C-reactive protein (CRP) values predict atherothrombotic cardiovascular disease and type 2 diabetes mellitus. Associations between CRP and obesity, predominantly assessed anthropometrically, may partly explain these observations. Previous studies have been unable to control for genetic influences on CRP and obesity. The aim of this study was to examine the relationship between CRP and accurately measured body fat, lipids, apolipoproteins, blood pressure, and environmental and behavioral factors, independent of genetic influences.

Methods and Results— One hundred ninety-four healthy female twins (age 57.2±7 years) were studied after excluding pairs with CRP values >10 mg/L. Total body fat and central abdominal fat (CAF) were measured by dual-energy x-ray absorptiometry. CRP concentration was strongly related to surrogate and direct measures of body fat (r=0.31 to 0.54, P<0.001), diastolic blood pressure (r=0.20, P=0.003), and lipid and apolipoprotein levels (r=0.21 to 0.51, P<0.008). Light-to-moderate alcohol consumers and nonusers of hormone replacement therapy (HRT) had lower CRP levels than abstainers and HRT users, respectively. In stepwise multiple regression analysis, CAF, triglycerides, apolipoprotein B, and HRT use explained 46% of the variance in circulating CRP. In analyses controlling for genetic influences in monozygotic twins, within-pair differences in CRP were associated with within-pair differences in total body fat (r=0.39, P<0.001), CAF (r=0.34, P=0.002), diastolic blood pressure (r=0.24, P=0.03), apolipoprotein AI (r=–0.33, P=0.01), HDL cholesterol (r=–0.42, P=0.001), and triglycerides (r=0.35, P=0.007).

Conclusions— CRP was strongly related to total and central abdominal obesity, blood pressure, and lipid levels, independent of genetic influences. These relationships are likely to contribute significantly to prospective associations between CRP and type 2 diabetes and coronary events.

Key Words: obesity • inflammation • syndrome X • lipids

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