Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19:972-978
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© 1999 American Heart Association, Inc.
Original Contributions |
C-Reactive Protein in Healthy Subjects: Associations With Obesity, Insulin Resistance, and Endothelial Dysfunction
A Potential Role for Cytokines Originating From Adipose Tissue?
From the Centre for Diabetes and Cardiovascular Risk, Department of Medicine, University College London Medical School, G Block, Archway Wing, Whittington Hospital, Archway Road, London N19 3UA, UK (J.S.Y., S.W.C.); the Department of Medicine, Academic Hospital Vrije Universiteit and the Institute for Cardiovascular Research Vrije Universiteit, 1081 HV Amsterdam, Netherlands (C.D.A.S.); and the Gaubius Laboratory, TNO-PG, 2301 CE Leiden, Netherlands (J.J.E.).
Correspondence to Professor John S. Yudkin, Centre for Diabetes and Cardiovascular Risk, Department of Medicine, University College London Medical School, G Block, Archway Wing, Whittington Hospital, Archway Road, London N19 3UA, UK. E-mail j.yudkin{at}ucl.ac.uk
Abstract—C-reactive protein, a
hepatic acute phase protein largely regulated by circulating levels of
interleukin-6, predicts coronary heart disease incidence in
healthy subjects. We have shown that subcutaneous adipose tissue
secretes interleukin-6 in vivo. In this study we have sought
associations of levels of C-reactive protein and interleukin-6 with
measures of obesity and of chronic infection as their putative
determinants. We have also related levels of C-reactive protein and
interleukin-6 to markers of the insulin resistance syndrome and of
endothelial dysfunction. We performed a cross-sectional
study in 107 nondiabetic subjects: (1) Levels of C-reactive protein,
and concentrations of the proinflammatory cytokines
interleukin-6 and tumor necrosis factor-
, were related to all
measures of obesity, but titers of antibodies to Helicobacter
pylori were only weakly and those of Chlamydia
pneumoniae and cytomegalovirus were not significantly
correlated with levels of these molecules. Levels of C-reactive protein
were significantly related to those of interleukin-6
(r=0.37, P<0.0005) and tumor necrosis
factor- (r=0.46, P<0.0001). (2)
Concentrations of C-reactive protein were related to insulin resistance
as calculated from the homoeostasis model assessment model, blood
pressure, HDL, and triglyceride, and to markers of
endothelial dysfunction (plasma levels of von
Willebrand factor, tissue plasminogen
activator, and cellular fibronectin). A mean standard
deviation score of levels of acute phase markers correlated closely
with a similar score of insulin resistance syndrome variables
(r=0.59, P<0.00005), this relationship
being weakened only marginally by removing measures of obesity from the
insulin resistance score (r=0.53,
P<0.00005). These data suggest that adipose tissue is
an important determinant of a low level, chronic inflammatory state as
reflected by levels of interleukin-6, tumor necrosis factor-, and
C-reactive protein, and that infection with H
pylori, C pneumoniae, and
cytomegalovirus is not. Moreover, our data support the concept that
such a low-level, chronic inflammatory state may induce insulin
resistance and endothelial dysfunction and thus link
the latter phenomena with obesity and cardiovascular disease.
Key Words: C-reactive protein • insulin resistance • obesity • endothelial dysfunction • interleukin-6
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K. M. Utzschneider and S. E. Kahn The Role of Insulin Resistance in Nonalcoholic Fatty Liver Disease J. Clin. Endocrinol. Metab., December 1, 2006; 91(12): 4753 - 4761. [Abstract] [Full Text] [PDF]
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J. P. Warne, C. D. John, H. C. Christian, J. F. Morris, R. J. Flower, D. Sugden, E. Solito, G. E. Gillies, and J. C. Buckingham Gene deletion reveals roles for annexin A1 in the regulation of lipolysis and IL-6 release in epididymal adipose tissue Am J Physiol Endocrinol Metab, December 1, 2006; 291(6): E1264 - E1273. [Abstract] [Full Text] [PDF]
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S. Kapiotis, G. Holzer, G. Schaller, M. Haumer, H. Widhalm, D. Weghuber, B. Jilma, G. Roggla, M. Wolzt, K. Widhalm, et al. A Proinflammatory State Is Detectable in Obese Children and Is Accompanied by Functional and Morphological Vascular Changes Arterioscler Thromb Vasc Biol, November 1, 2006; 26(11): 2541 - 2546. [Abstract] [Full Text] [PDF]
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Y.-P. Lu, Y.-R. Lou, B. Nolan, Q.-Y. Peng, J.-G. Xie, G. C. Wagner, and A. H. Conney Stimulatory effect of voluntary exercise or fat removal (partial lipectomy) on apoptosis in the skin of UVB light-irradiated mice PNAS, October 31, 2006; 103(44): 16301 - 16306. [Abstract] [Full Text] [PDF]
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I. Aeberli, L. Molinari, G. Spinas, R. Lehmann, D. l'Allemand, and M. B Zimmermann Dietary intakes of fat and antioxidant vitamins are predictors of subclinical inflammation in overweight Swiss children. Am. J. Clinical Nutrition, October 1, 2006; 84(4): 748 - 755. [Abstract] [Full Text] [PDF]
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R. Mehra, A. Storfer-Isser, H. L. Kirchner, N. Johnson, N. Jenny, R. P. Tracy, and S. Redline Soluble interleukin 6 receptor: a novel marker of moderate to severe sleep-related breathing disorder. Arch Intern Med, September 18, 2006; 166(16): 1725 - 1731. [Abstract] [Full Text] [PDF]
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J. Warnberg, E. Nova, L. A Moreno, J. Romeo, M. I Mesana, J. R Ruiz, F. B Ortega, M. Sjostrom, M. Bueno, A. Marcos, et al. Inflammatory proteins are related to total and abdominal adiposity in a healthy adolescent population: the AVENA Study. Am. J. Clinical Nutrition, September 1, 2006; 84(3): 505 - 512. [Abstract] [Full Text] [PDF]
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N. de Rekeneire, R. Peila, J. Ding, L. H. Colbert, M. Visser, R. I. Shorr, S. B. Kritchevsky, L. H. Kuller, E. S. Strotmeyer, A. V. Schwartz, et al. Diabetes, Hyperglycemia, and Inflammation in Older Individuals: The Health, Aging and Body Composition study Diabetes Care, August 1, 2006; 29(8): 1902 - 1908. [Abstract] [Full Text] [PDF]
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S. E. Kahn, B. Zinman, S. M. Haffner, M. C. O'Neill, B. G. Kravitz, D. Yu, M. I. Freed, W. H. Herman, R. R. Holman, N. P. Jones, et al. Obesity is a major determinant of the association of C-reactive protein levels and the metabolic syndrome in type 2 diabetes. Diabetes, August 1, 2006; 55(8): 2357 - 2364. [Abstract] [Full Text] [PDF]
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D M Wunder, M Yared, N A Bersinger, D Widmer, R Kretschmer, and M H Birkhauser Serum leptin and C-reactive protein levels in the physiological spontaneous menstrual cycle in reproductive age women. Eur. J. Endocrinol., July 1, 2006; 155(1): 137 - 142. [Abstract] [Full Text] [PDF]
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P. Trayhurn, C. Bing, and I. S. Wood Adipose Tissue and Adipokines--Energy Regulation from the Human Perspective J. Nutr., July 1, 2006; 136(7): 1935S - 1939S. [Abstract] [Full Text] [PDF]
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M. Briand, I. Lemieux, J. G. Dumesnil, P. Mathieu, A. Cartier, J.-P. Despres, M. Arsenault, J. Couet, and P. Pibarot Metabolic Syndrome Negatively Influences Disease Progression and Prognosis in Aortic Stenosis J. Am. Coll. Cardiol., June 6, 2006; 47(11): 2229 - 2236. [Abstract] [Full Text] [PDF]
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T. Yoshida, T. Kaneshi, T. Shimabukuro, M. Sunagawa, and T. Ohta Serum C-Reactive Protein and Its Relation to Cardiovascular Risk Factors and Adipocytokines in Japanese Children J. Clin. Endocrinol. Metab., June 1, 2006; 91(6): 2133 - 2137. [Abstract] [Full Text] [PDF]
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J. S Yudkin Confounders in chronic stress at work and metabolic syndrome. BMJ, May 13, 2006; 332(7550): 1153 - 1154. [Full Text]
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J.-M. Fernandez-Real, A. Lopez-Bermejo, J. Vendrell, M.-J. Ferri, M. Recasens, and W. Ricart Burden of Infection and Insulin Resistance in Healthy Middle-Aged Men Diabetes Care, May 1, 2006; 29(5): 1058 - 1064. [Abstract] [Full Text] [PDF]
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L. G. K. de Aguiar, L. R. Bahia, N. Villela, C. Laflor, F. Sicuro, N. Wiernsperger, D. Bottino, and E. Bouskela Metformin Improves Endothelial Vascular Reactivity in First-Degree Relatives of Type 2 Diabetic Patients With Metabolic Syndrome and Normal Glucose Tolerance Diabetes Care, May 1, 2006; 29(5): 1083 - 1089. [Abstract] [Full Text] [PDF]
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L. E. Bernstein, J. Berry, S. Kim, B. Canavan, and S. K. Grinspoon Effects of Etanercept in Patients With the Metabolic Syndrome. Arch Intern Med, April 24, 2006; 166(8): 902 - 908. [Abstract] [Full Text] [PDF]
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A. Festa, K. Williams, R. P. Tracy, L. E. Wagenknecht, and S. M. Haffner Progression of Plasminogen Activator Inhibitor-1 and Fibrinogen Levels in Relation to Incident Type 2 Diabetes Circulation, April 11, 2006; 113(14): 1753 - 1759. [Abstract] [Full Text] [PDF]
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J. Bollerslev, T. Ueland, A. P Jorgensen, K. J Fougner, R. Wergeland, T. Schreiner, and P. Burman Positive effects of a physiological dose of GH on markers of atherogenesis: a placebo-controlled study in patients with adult-onset GH deficiency. Eur. J. Endocrinol., April 1, 2006; 154(4): 537 - 543. [Abstract] [Full Text] [PDF]
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M. Hassinen, T. A. Lakka, P. Komulainen, H. Gylling, A. Nissinen, and R. Rauramaa C-Reactive Protein and Metabolic Syndrome in Elderly Women: A 12-year follow-up study Diabetes Care, April 1, 2006; 29(4): 931 - 932. [Full Text] [PDF]
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M. R. Smith, H. Lee, and D. M. Nathan Insulin Sensitivity during Combined Androgen Blockade for Prostate Cancer J. Clin. Endocrinol. Metab., April 1, 2006; 91(4): 1305 - 1308. [Abstract] [Full Text] [PDF]
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D.-J. Kim and E. Barrett-Connor Association of serum proinsulin with hormone replacement therapy in nondiabetic older women: the rancho bernardo study. Diabetes Care, March 1, 2006; 29(3): 618 - 624. [Abstract] [Full Text] [PDF]
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P. Poirier, T. D. Giles, G. A. Bray, Y. Hong, J. S. Stern, F. X. Pi-Sunyer, and R. H. Eckel Obesity and Cardiovascular Disease: Pathophysiology, Evaluation, and Effect of Weight Loss: An Update of the 1997 American Heart Association Scientific Statement on Obesity and Heart Disease From the Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism Circulation, February 14, 2006; 113(6): 898 - 918. [Abstract] [Full Text] [PDF]
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A. A. Quyyumi Women and Ischemic Heart Disease: Pathophysiologic Implications From the Women's Ischemia Syndrome Evaluation (WISE) Study and Future Research Steps J. Am. Coll. Cardiol., February 7, 2006; 47(3_Suppl_S): S66 - S71. [Abstract] [Full Text] [PDF]
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J. B. Meigs, C. J. O'Donnell, G. H. Tofler, E. J. Benjamin, C. S. Fox, I. Lipinska, D. M. Nathan, L. M. Sullivan, R. B. D'Agostino, and P. W.F. Wilson Hemostatic Markers of Endothelial Dysfunction and Risk of Incident Type 2 Diabetes: The Framingham Offspring Study Diabetes, February 1, 2006; 55(2): 530 - 537. [Abstract] [Full Text] [PDF]
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