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C-Reactive Protein Risk Prediction: Low Specificity, High Sensitivity
- Wolfgang Koenig, MD; and
- Mark B. Pepys, MD, PhD
- From the University of Ulm Medical Center, Ulm, Germany; and the Royal Free and University College Medical School, London, United Kingdom
Convincing evidence indicates that both local inflammation in the arterial wall and systemic signs of inflammation are important in atherogenesis and in complications of atherosclerotic disease. Consistent results from more than 15 well-conducted prospective studies in initially healthy persons (1) have shown a strong and independent association between the circulating concentration of C-reactive protein (CRP)—the classic acute-phase reactant, measured by high-sensitivity assays—and cardiovascular end points, including acute myocardial infarction, stroke, and progression of peripheral arterial occlusive disease. This strong association is seen for both primary and secondary prevention (patients with manifest atherosclerotic disease). Increased CRP levels predict recurrent instability in patients admitted with an acute coronary syndrome; in patients undergoing invasive procedures, such as percutaneous transluminal coronary angioplasty, stenting, or bypass grafting; and in other high-risk groups, such as patients with renal insufficiency and those who have had transplantation. Thus, CRP is itself an important general marker of increased risk for cardiovascular events, including death, and has also been shown to add to risk prediction based on conventional risk factors (2). The latter observation is of considerable importance because about half of all new cardiovascular events occur in persons without classic risk factors.
However, it is critically important to recognize that CRP production—and systemic markers of inflammation and the acute-phase response, in general—is an entirely nonspecific reflection of a broad range of diverse pathologic processes (3, 4). This is in the sharpest possible contrast to the exquisite specificity of, for example, measurements of troponins as markers of myocardial damage in acute coronary syndromes. Increased values of CRP and other acute-phase reactants may reflect tissue damage and inflammation not …
