Inflammation, a newly recognized cardiovascular risk factor, occurs in response to vascular injury involving lipid peroxidation and possibly infection (1, 2). There are consistent relationships between markers of inflammation and the risk of future cardiovascular events (3). The effects of hypertension, diabetes, and smoking are amplified by the harmful effects of oxidized LDL cholesterol. The resulting chronic inflammatory response promotes the development of atherosclerotic plaques that are vulnerable to rupture and thrombosis within the vessel. In research settings, regions of inflammation and plaque vulnerability within coronary arteries have been detected using imaging techniques, including computed tomography and magnetic resonance imaging (4).

Circulating concentrations of acute-phase reactants such as cytokines and cell adhesion molecules increase in response to the inflammatory process. Markers of inflammation in patients with stable angina or acute coronary syndromes include C-reactive protein (CRP), interleukin-6, serum amyloid A, tumor necrosis factor-α, soluble intracellular adhesion molecule 1, macrophage inhibitor cytokine 1, sP selectin, and CD40 ligand (Table 2). Of these markers, only the high-sensitivity (hs) CRP assay is well standardized and widely available for clinical use (5, 6).

CRP has emerged as a strong predictor of future myocardial infarction and stroke. In autopsy series that excluded subjects with other inflammatory conditions, hsCRP levels were lowest in both men and women who died from noncardiac causes compared with those with erosive or ruptured plaques. The highest plasma concentrations of CRP were associated with a 1.5- to 7-fold increase in the relative risk of symptomatic atherosclerosis. Patients with elevated plasma CRP levels and coronary artery disease (CAD) risk factors should have increased surveillance for active CAD and undergo early risk stratification for myocardial ischemia, particularly if they are symptomatic.

The presence of mild valvular calcification also is associated with an increased risk of adverse cardiovascular events, independently of conventional risk factors. In the Cardiovascular Health Study, the presence of aortic sclerosis was associated with a 50% increased risk of myocardial infarction and death in subjects with no known CAD at study entry (7). In the Framingham cohort study, mitral annular calcification was associated with a 60% increased risk of cardiovascular death (8). Thus, the identification of valvular calcification on echocardiography should prompt the clinician to increase surveillance for CAD, hypertension, and other comorbid conditions.

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3. Burke AP, Tracy RP, Kolodgie F, Malcom GT, Zieske A, Kutys R, et al. Elevated C-reactive protein values and atherosclerosis in sudden coronary death: association with different pathologies. Circulation. 2002;105:2019-23. [PMID: 11980679]
4. Willerson JT, Ridker PM. Inflammation as a cardiovascular risk factor. Circulation. 2004;109:II2-10. [PMID: 15173056]
5. Ridker PM, Wilson PW, Grundy SM. Should C-reactive protein be added to metabolic syndrome and to assessment of global cardiovascular risk? Circulation. 2004;109:2818-25. [PMID: 15197153]
6. Pearson TA, Mensah GA, Alexander RW, Anderson JL, Cannon RO 3rd, Criqui M, et al. Markers of inflammation and cardiovascular disease: application to clinical and public health practice: A statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation. 2003;107:499-511. [PMID: 12551878]
7. Otto CM, Lind BK, Kitzman DW, Gersh BJ, Siscovick DS. Association of aortic-valve sclerosis with cardiovascular mortality and morbidity in the elderly. N Engl J Med. 1999;341:142-7. [PMID: 10403851]
8. Fox CS, Vasan RS, Parise H, Levy D, O’Donnell CJ, D’Agostino RB, et al. Mitral annular calcification predicts cardiovascular morbidity and mortality: the Framingham Heart Study. Circulation. 2003;107:1492-6. [PMID: 12654605]

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