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The metabolic syndrome is associated with elevated circulating C-reactive protein in healthy reference range, a systemic low-grade inflammatory state

International Journal of Obesity volume 27, pages 443–449 (2003)Cite this article

Abstract

OBJECTIVE: To elucidate the underlying mechanisms between C-reactive protein (CRP) and cardiovascular disease, we exa-mined the association of circulating CRP in healthy reference range (≤1.0 mg/dl) measured by high-sensitive CRP assay with the metabolic syndrome (MS).

DESIGN: Cross-sectional study of circulating CRP in adult men.

SUBJECTS: A total of 3692 Japanese men aged 34–69 y.

MEASUREMENTS: Serum CRP, total cholesterol, triglycerides, LDL-cholesterol, fasting glucose, fasting insulin, uric acid, systolic blood pressure, diastolic blood pressure, and body mass index (BMI).

RESULTS: There was a statistically significant positive correlation between CRP and BMI (r=0.25), total cholesterol (r=0.096), triglycerides (r=0.22), LDL-cholesterol (r=0.12), fasting glucose (r=0.088), fasting insulin (r=0.17), uric acid (r=0.13), systolic blood pressure (r=0.12), and diastolic blood pressure (r=0.11), and a significant negative correlation of CRP with HDL-cholesterol (r=0.24). After adjusting for age, smoking, and all other components of MS, obesity, hypertriglyceridemia, hyper-LDL-cholesterolemia, diabetes, hyperinsulinemia, and hyperuricemia were significantly associated with both mildly (≥0.06 mg/dl) and moderately (≥0.11 mg/dl) elevated CRP. Compared with men who had no such components of the MS, those who had one, two, three, four, and five or more components were, respectively, 1.48, 1.84, 1.92, 3.42, and 4.17 times more likely to have mildly elevated CRP levels (trend P<0.001). As for moderately elevated CRP, the same association was observed.

CONCLUSIONS: These results indicate that a variety of components of the MS are associated with elevated CRP levels in a systemic low-grade inflammatory state.

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References

  1. Pepys MB . C-reactive protein fifty years on. Lancet 1981; 1: 653–657.

    Article  CAS  Google Scholar 

  2. Gauldie J, Richards C, Northemann W, Fey G, Baumann H . IFN beta 2/BSF2/IL-6 is the monocyte-derived HSF that regulates receptor-specific acute phase gene regulation in hepatocytes. Ann NY Acad Sci 1989; 557: 46–58.

    Article  CAS  Google Scholar 

  3. Heinrich PC, Castell JV, Andus T . Interleukin-6 and the acute phase response. Biochem J 1990; 265: 621–636.

    Article  CAS  Google Scholar 

  4. Baumann H, Gauldie J . The acute phase response. Immunol Today 1994; 15: 74–80.

    Article  CAS  Google Scholar 

  5. Chambers JC, Eda S, Bassett P, Karim Y, Thompson SG, Gallimore JR, Pepys MB, Kooner JS . C-reactive protein, insulin resistance, central obesity, and coronary heart disease risk in Indian Asians from the United Kingdom compared with European whites. Circulation 2001; 104: 145–150.

    Article  CAS  Google Scholar 

  6. Danesh J, Whincup P, Walker M, Lennon L, Thomson A, Appleby P, Gallimore JR, Pepys MB . Low grade inflammation and coronary heart disease: prospective study and updated meta-analyses. BMJ 2000; 321: 199–204.

    Article  CAS  Google Scholar 

  7. Rifai N, Ridker PM . High-sensitivity C-reactive protein: a novel and promising marker of coronary heart disease. Clin Chem 2001; 47: 403–411.

    CAS  PubMed  Google Scholar 

  8. Strandberg TE, Tilvis RS . C-reactive protein, cardiovascular risk factors, and mortality in a prospective study in the elderly. Arterioscler Thromb Vasc Biol 2000; 20: 1057–1060.

    Article  CAS  Google Scholar 

  9. Danesh J, Collins R, Appleby P, Peto R . Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with coronary heart disease: meta-analyses of prospective studies. JAMA 1998; 279: 1477–1482.

    Article  CAS  Google Scholar 

  10. Kuller LH, Tracy RP, Shaten J, Meilahn EN . Relation of C-reactive protein and coronary heart disease in the MRFIT nested case-control study, multiple risk factor intervention trial. Am J Epidemiol 1996; 144: 537–547.

    Article  CAS  Google Scholar 

  11. Ridker PM, Cushman M, Stampfer MJ, Tracy RP, Hennekens CH . Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med 1997; 336: 973–979.

    Article  CAS  Google Scholar 

  12. Tracy RP, Lemaitre RN, Psaty BM, Ives DG, Evans RW, Cushman M, Meilahn EN, Kuller LH . Relationship of C-reactive protein to risk of cardiovascular disease in the elderly. Results from the Cardiovascular Health Study and the Rural Health Promotion Project. Arterioscler Thromb Vasc Biol 1997; 17: 1121–1127.

    Article  CAS  Google Scholar 

  13. Koenig W, Sund M, Frohlich M, Fischer HG, Lowel H, Doring A, Hutchinson WL, Pepys MB . C-Reactive protein, a sensitive marker of inflammation, predicts future risk of coronary heart disease in initially healthy middle-aged men: results from the MONICA (monitoring trends and determinants in cardiovascular disease) Augsburg Cohort Study, 1984 to 1992. Circulation 1999; 99: 237–242.

    Article  CAS  Google Scholar 

  14. Lagrand WK, Visser CA, Hermens WT, Niessen HW, Verheugt FW, Wolbink GJ, Hack CE . C-reactive protein as a cardiovascular risk factor: more than an epiphenomenon. Circulation 1999; 100: 96–102.

    Article  CAS  Google Scholar 

  15. Ferrannini E, Haffner SM, Mitchell BD, Stern MP . Hyperinsulinaemia: the key feature of a cardiovascular and metabolic syndrome. Diabetologia 1991; 34: 416–422.

    Article  CAS  Google Scholar 

  16. Gray RS, Fabsitz RR, Cowan LD, Lee ET, Howard BV, Savage PJ . Risk factor clustering in the insulin resistance syndrome. The strong heart study. Am J Epidemiol 1998; 148: 869–878.

    Article  CAS  Google Scholar 

  17. Howard BV, Lee ET, Cowan LD, Fabsitz RR, Howard WJ, Oopik AJ, Robbins DC, Savage PJ, Yeh JL, Welty TK . Coronary heart disease prevalence and its relation to risk factors in American Indians. The strong heart study. Am J Epidemiol 1995; 142: 254–268.

    Article  CAS  Google Scholar 

  18. SPSS Incorporation. SPSS Base 10.0J user's guide. SPSS INC: Chicago, IL, 1999.

  19. Festa A, D'Agostino Jr R, Williams K, Karter AJ, Mayer-Davis EJ, Tracy RP, Haffner SM . The relation of body fat mass and distribution to markers of chronic inflammation. Int J Obes Relat Metab Disord 2001; 25: 1407–1415.

    Article  CAS  Google Scholar 

  20. Yamada S, Gotoh T, Nakashima Y, Kayaba K, Ishikawa S, Nago N, Nakamura Y, Itoh Y, Kajii E . Distribution of serum C-reactive protein and its association with atherosclerotic risk factors in a Japanese population: Jichi Medical School Cohort Study. Am J Epidemiol 2001; 153: 1183–1190.

    Article  CAS  Google Scholar 

  21. Pannacciulli N, Cantatore FP, Minenna A, Bellacicco M, Giorgino R, De Pergola G . C-reactive protein is independently associated with total body fat, central fat, and insulin resistance in adult women. Int J Obes Relat Metab Disord 2001; 25: 1416–1420.

    Article  CAS  Google Scholar 

  22. Mendall MA, Patel P, Ballam L, Strachan D, Northfield TC . C reactive protein and its relation to cardiovascular risk factors: a population based cross sectional study. BMJ 1996; 312: 1061–1065.

    Article  CAS  Google Scholar 

  23. Frohlich M, Imhof A, Berg G, Hutchinson WL, Pepys MB, Boeing H, Muche R, Brenner H, Koenig W . Association between C-reactive protein and features of the metabolic syndrome: a population-based study. Diabetes Care 2000; 23: 1835–1839.

    Article  CAS  Google Scholar 

  24. Hotamisligil GS, Shargill NS, Spiegelman BM . Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 1993; 259: 87–91.

    Article  CAS  Google Scholar 

  25. Mohamed-Ali V, Goodrick S, Rawesh A, Katz DR, Miles JM, Yudkin JS, Klein S, Coppack SW . Subcutaneous adipose tissue releases interleukin-6, but not tumor necrosis factor-alpha, in vivo. J Clin Endocrinol Metab 1997; 82: 4196–4200.

    CAS  PubMed  Google Scholar 

  26. Fernandez-Real JM, Vayreda M, Richart C, Gutierrez C, Broch M, Vendrell J, Ricart W . Circulating interleukin 6 levels, blood pressure, and insulin sensitivity in apparently healthy men and women. J Clin Endocrinol Metab 2001; 86: 1154–1159.

    Article  CAS  Google Scholar 

  27. Hotamisligil GS, Arner P, Caro JF, Atkinson RL, Spiegelman BM . Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. J Clin Invest 1995; 95: 2409–2415.

    Article  CAS  Google Scholar 

  28. Kern PA, Saghizadeh M, Ong JM, Bosch RJ, Deem R, Simsolo RB . The expression of tumor necrosis factor in human adipose tissue, Regulation by obesity, weight loss, and relationship to lipoprotein lipase. J Clin Invest 1995; 95: 2111–2119.

    Article  CAS  Google Scholar 

  29. Baumann H, Gauldie J . Regulation of hepatic acute phase plasma protein genes by hepatocyte stimulating factors and other mediators of inflammation. Mol Biol Med 1990; 7: 147–159.

    CAS  PubMed  Google Scholar 

  30. Vgontzas AN, Papanicolaou DA, Bixler EO, Kales A, Tyson K, Chrousos GP . Elevation of plasma cytokines in disorders of excessive daytime sleepiness: role of sleep disturbance and obesity. J Clin Endocrinol Metab 1997; 82: 1313–1316.

    Article  CAS  Google Scholar 

  31. Heinrich J, Schulte H, Schonfeld R, Kohler E, Assmann G . Association of variables of coagulation, fibrinolysis and acute-phase with atherosclerosis in coronary and peripheral arteries and those arteries supplying the brain. Thromb Haemost 1995; 73: 374–379.

    CAS  PubMed  Google Scholar 

  32. Ridker PM, Buring JE, Shih J, Matias M, Hennekens CH . Plasma concentration of C-reactive protein and risk of developing peripheral vascular disease. Circulation 1998; 97: 425–428.

    Article  CAS  Google Scholar 

  33. Folsom AR, Pankow JS, Tracy RP, Arnett DK, Peacock JM, Hong Y, Djousse L, Eckfeldt JH . Association of C-reactive protein with markers of prevalent atherosclerotic disease. Am J Cardiol 2001; 88: 112–117.

    Article  CAS  Google Scholar 

  34. Hashimoto H, Kitagawa K, Hougaku H, Shimizu Y, Sakaguchi M, Nagai Y, Iyama S, Yamanishi H, Matsumoto M, Hori M . C-reactive protein is an independent predictor of the rate of increase in early carotid atherosclerosis. Circulation 2001; 104: 63–67.

    Article  CAS  Google Scholar 

  35. Hansson GK . Immune and inflammatory mechanisms in the development of atherosclerosis. Br Heart J 1993; 69: 38–41.

    Article  Google Scholar 

  36. Juhan-Vague I, Thompson SG, Jespersen J . Involvement of the hemostatic system in the insulin resistance syndrome, A study of 1500 patients with angina pectoris, The ECAT Angina Pectoris Study Group. Arterioscler Thromb 1993; 13: 1865–1873.

    Article  CAS  Google Scholar 

  37. Fourcade O, Simon MF, Viode C, Rugani N, Leballe F, Ragab A, Fournie B, Sarda L, Chap H . Secretory phospholipase A2 generates the novel lipid mediator lysophosphatidic acid in membrane microvesicles shed from activated cells. Cell 1995; 80: 919–927.

    Article  CAS  Google Scholar 

  38. Hack CE, Wolbink GJ, Schalkwijk C, Speijer H, Hermens WT, van den Bosch H . A role for secretory phospholipase A2 and C-reactive protein in the removal of injured cells. Immunol Today 1997; 18: 111–115.

    Article  CAS  Google Scholar 

  39. Wolbink GJ, Brouwer MC, Buysmann S, ten Berge IJ, Hack CE . CRP-mediated activation of complement in vivo: assessment by measuring circulating complement-C-reactive protein complexes. J Immunol 1996; 157: 473–479.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We are grateful to Dr Noboru Okamoto (Aichi San-no-maru Hospital), Dr Tsutomu Yoshida (Department of Public Health, Fujita Health University School of Medicine), Dr Takashi Kawamura (Kyoto University Center for Student Health), and Dr Junji Toyama (Aichi Prefectural Owari Hospital) for their cooperation in conducting the survey and collecting information for this study.

This work is supported in part by a grant to Hideaki Toyoshima (09470112), Koji Tamakoshi (12670352), and Hiroshi Yatsuya (13770192) from the Ministry of Education, Culture, Sports, and Science and Technology.

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Authors and Affiliations

  1. Department of Public Health/Health Information Dynamics, Field of Social Life Science, Program in Health and Community Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan

    K Tamakoshi, H Yatsuya, T Kondo, Y Hori, M Ishikawa, H Zhang, C Murata, R Otsuka & H Toyoshima

  2. Obesity Research Center, St. Lukes'/Roosevelt Hospital Center, Columbia University College of Physicians & Surgeons, New York, NY, USA

    S Zhu

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  1. K Tamakoshi
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Correspondence to K Tamakoshi.

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Tamakoshi, K., Yatsuya, H., Kondo, T. et al. The metabolic syndrome is associated with elevated circulating C-reactive protein in healthy reference range, a systemic low-grade inflammatory state. Int J Obes 27, 443–449 (2003). https://doi.org/10.1038/sj.ijo.0802260

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