The Concept of CMR

Inflammation and CHD

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It is now accepted that atherosclerosis has an inflammatory component. Compelling evidence suggests that inflammation plays a central role at every stage of atherogenesis, such as the formation, maturation, and degradation of the atherosclerotic plaque, the initiation of endothelial dysfunction, and the promotion of thrombus formation (37).

The inflammatory component of coronary heart disease (CHD) has been emphasized in recent years, and it has been proposed that it could predict increased risk of acute coronary syndrome by being a marker of atherosclerotic plaque instability (14). For instance, elevated levels of hs-CRP, a marker of a low chronic inflammation state, have been shown to increase risk of myocardial infarction in patients with both stable and unstable CHD (38-40) as well as in healthy individuals (41-44). However, it remains unclear whether hs-CRP is an independent risk factor for CHD. A meta-analysis revealed that hs-CRP concentration was a relatively moderate predictor of CHD risk and that it added only marginally to the predictive value of established CHD risk factors (45). Also, there is no direct evidence to suggest that hs-CRP has a proatherogenic role in vivo (46). Thus, an elevated hs-CRP concentration may therefore only be a marker (albeit a good one) of metabolic disturbances that increase risk of CVD.

Adipose tissue is a complex and highly active metabolic and endocrine organ. The emergence of the concept that obesity is characterized by chronic low-grade inflammation has been an important development in our understanding of obesity. Moreover, the dysregulation of adipokine production and secretion by the adipose tissue in the context of abdominal obesity may be linked to the development of metabolic abnormalities and CVD. In addition, although the clinical relevance of hs-CRP measurements in predicting CHD risk remains unproven, further research into inflammatory response will shed new light on the mechanisms of obesity, insulin resistance, diabetes, and athero-thrombosis.

Reference

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14. Ross R. Atherosclerosis--an inflammatory disease. N Engl J Med 1999; 340: 115-26.

37. Morrow DA and Ridker PM. C-reactive protein, inflammation, and coronary risk. Med Clin North Am 2000; 84: 149-61, ix.

38. Liuzzo G, Biasucci LM, Gallimore JR, et al. The prognostic value of C-reactive protein and serum amyloid a protein in severe unstable angina. N Engl J Med 1994; 331: 417-24.

39. Thompson SG, Kienast J, Pyke SD, et al. Hemostatic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group. N Engl J Med 1995; 332: 635-41.

40. Haverkate F, Thompson SG, Pyke SD, et al. Production of C-reactive protein and risk of coronary events in stable and unstable angina. European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group. Lancet 1997; 349: 462-6.

41. Tracy RP, Lemaitre RN, Psaty BM, et al. 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: 1121-7.

42. Kuller LH, Tracy RP, Shaten J, et al. 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: 537-47.

43. Ridker PM, Cushman M, Stampfer MJ, et al. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med 1997; 336: 973-9.

44. Koenig W, Sund M, Frohlich M, et al. 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: 237-42.

45. Danesh J, Wheeler JG, Hirschfield GM, et al. C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease. N Engl J Med 2004; 350: 1387-97.

46. Trion A, de Maat MP, Jukema JW, et al. No effect of C-reactive protein on early atherosclerosis development in apolipoprotein E*3-leiden/human C-reactive protein transgenic mice. Arterioscler Thromb Vasc Biol 2005; 25: 1635-40.

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