Using Inflammation Markers in Cardiology
From the University of Texas-Houston Health Science Center (E.T.H.Y., J.T.W.), Texas Heart Institute, St Luke’s Episcopal Hospital (E.T.H.Y., J.T.W.), and University of Texas-MD Anderson Cancer Center (E.T.H.Y.), Houston, Tex.
Correspondence to Edward T.H. Yeh, MD, 1515 Holcombe Blvd, Box 449, Houston, TX 77030-4095. E-mail Edward.T.Yeh@uth.tmc.edu
In a recently published prospective study comprising 28 000 women, Ridker et al1 showed that C-reactive protein (CRP) is a better predictor of the risk of cardiovascular events than low-density lipoprotein (LDL) cholesterol. The implication of this and many other supporting studies is profound and will change the way we screen and manage our patients with atherosclerosis and its associated clinical syndromes. CRP is one of the acute phase proteins that increase during systemic inflammation.2,3 Individuals without inflammation usually have CRP levels below 1 µg/mL; however, patients with bacterial infections, autoimmune diseases, and cancer frequently have CRP level as high as 100 µg/mL or even higher. It is clear that a high CRP level has no specificity in differentiating disease entities from one another. Despite its lack of specificity, CRP has now emerged as one of the most powerful predictors of cardiovascular risk. Even more remarkable, CRP’s predictive power resides in the range between 1 to 5 µg/mL, which was previously regarded to be normal in the era preceding the high-sensitivity CRP test. In fact, tests showing serum CRP levels greater than 10 µg/mL in apparently healthy men or women should be repeated to exclude occult infection or other systemic inflammatory process (see Figure). To understand CRP’s transition from an acute phase protein to a most useful inflammatory biomarker for predicting future cardiovascular events, we must know more about the role of the immune system in the pathogenesis of atherosclerosis.
CRP as a Clinical Test in Cardiovascular Practices
High-sensitivity CRP is widely available in most clinical settings throughout the world. When should we order the CRP test? How do we manage patients with high CRP levels? Results from the Women’s Health Study suggest that CRP determinations will be of value in primary prevention.1 We believe that CRP testing should be ordered along with lipid profiles to identify apparently healthy men and women at risk of developing cardiovascular events. The interpretation of CRP levels on the basis current data is summarized in the accompanying figure. Patients with CRP levels between 1 and 3 µg/mL are at intermediate risk and those with levels above 3 µg/mL at high risk. However, tests that show CRP levels above 10 µg/mL should be repeated to exclude other processes. CRP levels should be interpreted in conjunction with the lipid profile. It is particularly useful in patients with LDL cholesterol levels below 160 mg/mL, because 77% of all cardiovascular events occur among women with LDL cholesterol levels below this value.1 A more difficult question to answer is how to manage patients with LDL-cholesterol levels below 160 mg/mL and CRP levels greater than 1 µg/mL. We believe that these patients should receive low-cholesterol and low-fat diets and/or be placed on aggressive statin therapy to lower LDL cholesterol values to well below 100 mg/mL. Statins have been shown to reduce CRP levels by 25% to 50% in previous studies.19–21 Thus, this approach has the potential to lower the LDL cholesterol and CRP level simultaneously. A prospective, long-term study has been planned to test this hypothesis. Furthermore, CRP levels could be used to motivate patients to modify their lifestyles more aggressively. Recent studies have shown that losing weight and controlling diabetes also lower CRP levels.22,23 Thus, patients can use their CRP levels as an inflammation fitness score to monitor improvement in their cardiovascular health.
CRP levels predict clinical outcomes in acute coronary syndromes and may be used in conjunction with troponin I or T levels to identify high-risk patients for more aggressive management with antiplatelet agents and statins.24,25 Similarly, in patients undergoing percutaneous coronary interventions, CRP levels may alert the interventional cardiologist for closer monitoring of the patients or more aggressive management.26 Also, as we stated earlier, "the higher event rates noted in the cohorts with elevated serum CRP values suggest an excellent opportunity to screen and identify patients likely to benefit from novel anti-inflammatory strategies as adjunctive therapies to [percutaneous coronary intervention]."16
Finally, CRP levels can also be used as a guide to start patients on acetylsalicylic acid (ASA) for primary prevention. As shown in the Physician Health Study, ASA usage of 325 mg every other day is most useful in males with CRP levels greater than 0.55 µg/mL.27 One wonders whether other antiplatelet therapies such as Plavix (Bristol-Myers Squibb) might be additive to ASA in reducing platelet-white blood cell interaction and inflammation, further lowering serum CRP values. This needs to be determined by future studies.
CRP as a Biomarker...
CRP as a Clinical...
CRP is not only an excellent biomarker of inflammation, but it is also a direct participant in atherogenesis. It provides a valuable tool for identifying patients at risk of cardiovascular events in primary prevention in conjunction with lowering LDL cholesterol and may also have utility in the treatment of acute coronary syndromes and with percutaneous coronary intervention therapy. Finally, CRP will provide a readily accessible marker for further testing of the inflammatory hypothesis in atherosclerosis.
The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.
CRP as a Biomarker...
CRP as a Clinical...