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Obesity, inflammatory markers and cardiovascular disease: distinguishing causality from confounding

Journal of Human Hypertension volume 20, pages 837–840 (2006)Cite this article

Low-grade inflammation may play a specific role in cardiovascular disease1, 2 primarily by decreasing insulin sensitivity3 and increasing arterial lipid deposition causing atherosclerosis and impaired endothelial function.4 The lesions that occur in atherosclerosis emanate from fatty streaks beneath the endothelium formed from macrophages and T cells, and consist of inflammatory and immune cells, connective tissue elements, lipids and debris.5 The inflammatory cells within the lesion secrete inflammatory cytokines, thus perpetuating the process of inflammation. The accumulation of atherosclerotic plaque stemming from the lesion, known as thrombus, can occlude the vessel and restrict blood flow. If blood flow is substantially reduced, myocardial infarction occurs.

Cellular inflammation occurs in response to a variety of stimuli such as cholesterol, infection and injury.6 In the healthy organism, the release of proinflammatory cytokines, such as interleukin (IL)-1, IL-6 and tumour necrosis factor-α and other acute phase reactants, such as C-reactive protein (CRP), which occurs in response to these stimuli, is balanced by the release of anti-inflammatory cytokines, such as IL-4, IL-10 and IL-12.6 The correlation between visceral obesity and chronic activation of the immune system is particularly strong.4 Visceral fat depots release large quantities of free fatty acids into the liver7, 8 and secrete more proinflammatory cytokines than subcutaneous compartments,9, 10 which may explain why central adiposity is a stronger risk factor for cardiovascular morbidity and mortality than total adiposity.11, 12

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References

  1. Ridker PM, Hennekens CH, Buring JE, Rifai N . C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med 2000; 342 (12): 836–843.

    Article  CAS  PubMed  Google Scholar 

  2. Danesh J, Lewington S, Thompson SG, Lowe GD, Collins R, Kostis JB et al. Plasma fibrinogen level and the risk of major cardiovascular diseases and nonvascular mortality: an individual participant meta-analysis. JAMA 2005; 294 (14): 1799–1809.

    CAS  PubMed  Google Scholar 

  3. Vozarova B, Weyer C, Lindsay RS, Pratley RE, Bogardus C, Tataranni PA . High white blood cell count is associated with a worsening of insulin sensitivity and predicts the development of type 2 diabetes. Diabetes 2002; 51 (2): 455–461.

    Article  CAS  PubMed  Google Scholar 

  4. Tataranni PA, Ortega E . A burning question: does an adipokine-induced activation of the immune system mediate the effect of overnutrition on type 2 diabetes? Diabetes 2005; 54 (4): 917–927.

    Article  CAS  PubMed  Google Scholar 

  5. Stary HC, Chandler AB, Dinsmore RE, Fuster V, Glagov S, Insull Jr W et al. A definition of advanced types of atherosclerotic lesions and a histological classification of atherosclerosis: a report from the committee on vascular lesions of the council on arteriosclerosis, American heart association. Circulation 1995; 92 (5): 1355–1374.

    Article  CAS  PubMed  Google Scholar 

  6. Hansson GK . Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 2005; 352 (16): 1685–1695.

    Article  CAS  PubMed  Google Scholar 

  7. Nielsen S, Guo Z, Johnson CM, Hensrud DD, Jensen MD . Splanchnic lipolysis in human obesity. J Clin Invest 2004; 113 (11): 1582–1588.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Bjorntorp P . ‘Portal’ adipose tissue as a generator of risk factors for cardiovascular disease and diabetes. Arteriosclerosis 1990; 10 (4): 493–496.

    Article  CAS  PubMed  Google Scholar 

  9. Fried SK, Bunkin DA, Greenberg AS . Omental and subcutaneous adipose tissues of obese subjects release interleukin-6: depot difference and regulation by glucocorticoid. J Clin Endocrinol Metab 1998; 83 (3): 847–850.

    CAS  PubMed  Google Scholar 

  10. Fain JN, Madan AK, Hiler ML, Cheema P, Bahouth SW . Comparison of the release of adipokines by adipose tissue, adipose tissue matrix, and adipocytes from visceral and subcutaneous abdominal adipose tissues of obese humans. Endocrinology 2004; 145 (5): 2273–2282.

    Article  CAS  PubMed  Google Scholar 

  11. Wang Y, Rimm EB, Stampfer MJ, Willett WC, Hu FB . Comparison of abdominal adiposity and overall obesity in predicting risk of type 2 diabetes among men. Am J Clin Nutr 2005; 81 (3): 555–563.

    Article  CAS  PubMed  Google Scholar 

  12. Kuk JL, Katzmarzyk PT, Nichaman MZ, Church TS, Blair SN, Ross R . Visceral fat is an independent predictor of all-cause mortality in men. Obes Res 2006; 14 (2): 336–341.

    Article  Google Scholar 

  13. Engstrom G, Hedblad B, Janzon L, Lindgarde F . Fatality of acute coronary events in relation to hypertension and low-grade inflammation: a population-based cohort study. J Hum Hypertens [E-pub ahead of print: 4 May 2006; doi:10.1038/sj.jhh.1002037].

    Article  PubMed  Google Scholar 

  14. Orakzai RH, Orakzai SH, Nasir K, Santos RD, Rana JS, Pimentel I et al. Association of white blood cell count with systolic blood pressure within the normotensive range. J Hum Hypertens 2006; 20 (5): 341–347.

    Article  CAS  PubMed  Google Scholar 

  15. Manabe S, Okura T, Watanabe S, Higaki J . Association between carotid haemodynamics and inflammation in patients with essential hypertension. J Hum Hypertens 2005; 19 (10): 787–791.

    Article  CAS  PubMed  Google Scholar 

  16. Duprez DA, Somasundaram PE, Sigurdsson G, Hoke L, Florea N, Cohn JN . Relationship between C-reactive protein and arterial stiffness in an asymptomatic population. J Hum Hypertens 2005; 19 (7): 515–519.

    Article  CAS  PubMed  Google Scholar 

  17. Li X, Zhang H, Huang J, Xie S, Zhu J, Jiang S et al. Gender-specific association between pulse pressure and C-reactive protein in a Chinese population. J Hum Hypertens 2005; 19 (4): 293–299.

    Article  CAS  PubMed  Google Scholar 

  18. Bautista LE . Inflammation, endothelial dysfunction, and the risk of high blood pressure: epidemiologic and biological evidence. J Hum Hypertens 2003; 17 (4): 223–230.

    Article  CAS  PubMed  Google Scholar 

  19. Schutte R, Huisman HW, Schutte AE, Malan NT . Leptin is favourably associated with vascular function in obese Caucasians, but not in obese Africans. J Hum Hypertens 2005; 19 (12): 933–939.

    Article  CAS  PubMed  Google Scholar 

  20. Schutte R, Huisman HW, Schutte AE, Malan NT . Leptin is independently associated with systolic blood pressure, pulse pressure and arterial compliance in hypertensive African women with increased adiposity: the POWIRS study. J Hum Hypertens 2005; 19 (7): 535–541.

    Article  CAS  PubMed  Google Scholar 

  21. Schutte A, Van Vuuren D, Van Rooyen J, Huisman H, Schutte R, Malan L et al. Inflammation, obesity and cardiovascular function in African and Caucasian women from South Africa: The POWIRS study. J Hum Hypertens [E-pub ahead of print: 22 June 2006; doi:10.1038/sj.jhh.1002065].

    Article  CAS  PubMed  Google Scholar 

  22. Franks PW, Brage S, Luan JA, Ekelund U, Rahman M, Farooqi IS et al. Leptin predicts a worsening of the features of the metabolic syndrome independently of obesity. Obes Res 2005; 13 (8): 1476–1484.

    Article  CAS  PubMed  Google Scholar 

  23. Deurenberg P, Yap M, van Staveren WA . Body mass index and percent body fat: a meta analysis among different ethnic groups. Int J Obes Relat Metab Disord 1998; 22 (12): 1164–1171.

    Article  CAS  PubMed  Google Scholar 

  24. Raji A, Seely EW, Arky RA, Simonson DC . Body fat distribution and insulin resistance in healthy Asian Indians and Caucasians. J Clin Endocrinol Metab 2001; 86 (11): 5366–5371.

    Article  CAS  PubMed  Google Scholar 

  25. Whincup PH, Gilg JA, Owen CG, Odoki K, Alberti KGMM, Cook DG . British South Asians aged 13–16 years have higher fasting glucose and insulin levels than Europeans. Diabet Med 2005; 22 (9): 1275–1277.

    Article  CAS  PubMed  Google Scholar 

  26. Thorand B, Baumert J, Doring A, Herder C, Kolb H, Rathmann W et al. Sex differences in the relation of body composition to markers of inflammation. Atherosclerosis 2006; 184 (1): 216–224.

    Article  CAS  PubMed  Google Scholar 

  27. Visser M, Bouter LM, McQuillan GM, Wener MH, Harris TB . Elevated C-reactive protein levels in overweight and obese adults. JAMA 1999; 282 (22): 2131–2135.

    Article  CAS  PubMed  Google Scholar 

  28. Lear SA, Chen MM, Birmingham CL, Frohlich JJ . The relationship between simple anthropometric indices and C-reactive protein: ethnic and gender differences. Metabolism 2003; 52 (12): 1542–1546.

    Article  CAS  PubMed  Google Scholar 

  29. Forouhi NG, Sattar N, McKeigue PM . Relation of C-reactive protein to body fat distribution and features of the metabolic syndrome in Europeans and South Asians. Int J Obes Relat Metab Disord 2001; 25 (9): 1327–1331.

    Article  CAS  PubMed  Google Scholar 

  30. Davey Smith G, Ebrahim S . What can Mendelian randomisation tell us about modifiable behavioural and environmental exposures? BMJ 2005; 330 (7499): 1076–1079.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

I am grateful to Dr Bert Boyer (University of Alaska, Fairbanks, USA) for his helpful comments on this commentary.

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  1. Department of Public Health & Clinical Medicine, Umeå University Hospital, Umeå, Sweden

    P W Franks

  2. MRC Epidemiology Unit, Cambridge, UK

    P W Franks

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Franks, P. Obesity, inflammatory markers and cardiovascular disease: distinguishing causality from confounding. J Hum Hypertens 20, 837–840 (2006). https://doi.org/10.1038/sj.jhh.1002059

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