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(Circulation. 2004;109:2181-2185.)
© 2004 American Heart Association, Inc.

Clinical Investigation and Reports

Independent Association Between Plasma Leptin and C-Reactive Protein in Healthy Humans

Abu S.M. Shamsuzzaman, MBBS, PhD; Mikolaj Winnicki, MD, PhD; Robert Wolk, MD, PhD; Anna Svatikova, BA; Bradley G. Phillips, BSc, PharmD; Diane E. Davison, RN, MA; Peter B. Berger, MD; Virend K. Somers, MD, PhD

From the Division of Cardiovascular Disease, Mayo Clinic, Rochester, Minn (A.S.M.S., M.W., R.W., A.S., D.E.D., V.K.S.); Department of Hypertension and Diabetology, Medical University of Gdansk, Gdansk, Poland (M.W.); Division of Clinical and Administrative Pharmacy, University of Iowa, Iowa City (B.G.P.); and Duke University Medical Center and Duke Clinical Research Institute, Durham, NC (P.B.B.).

Correspondence to Virend K. Somers, MD, DPhil, Division of Cardiovascular Diseases, Mayo Clinic Rochester, 200 First St SW, Rochester, MN 55905. E-mail somers.virend{at}mayo.edu

Received October 7, 2003; revision received February 5, 2004; accepted February 6, 2004.

Background— C-reactive protein (CRP) is synthesized from the liver and is regulated by cytokines, especially interleukin-6. Leptin, the adipocyte-derived protein product of the ob gene, is related to amount of body fat. The long form of the leptin receptor resembles cytokine receptors, which include the interleukin-6 receptor. Both leptin and CRP may be increased in women, in obesity, and in inflammation, and both have been linked to cardiovascular pathophysiological processes and increased cardiovascular risk. We tested the hypothesis that leptin is associated with CRP levels independently of the influences of gender, body mass index (BMI), waist-to-hip ratio, and other variables.

Methods and Results— We studied 100 healthy volunteers (48 men, and 52 women). For all subjects, leptin was independently associated with CRP after adjustment for age, gender, BMI, waist-to-hip ratio, smoking, and alcohol consumption (F=12.39, P=0.0007). There was a strong and significant positive relationship between leptin and CRP in both women (R=0.61, P<0.0001) and men (R=0.55, P<0.0001) considered separately. The association between leptin and CRP was significant even after adjustment for age, BMI, waist-to-hip ratio, smoking, and alcohol consumption in women (F=7.13, P=0.01) and men (F=5.69, P=0.02). When only subjects with BMI <25 kg/m² were considered (n=47), CRP was not linked to BMI (R=0.02, P=0.96), but a significant association between leptin and CRP was still evident (R=0.55, P<0.0001).

Conclusions— Leptin and CRP levels are independently associated in normal humans, providing further evidence linking metabolic and inflammatory cardiovascular disease mechanisms.

Key Words: C-reactive protein • cardiovascular diseases • inflammation • leptin • obesity • risk factors

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