Value of C-reactive Protein in Managing Cardiovascular Risk
Abstract & Commentary
By Michael H. Crawford, MD, Editor
Source: Sever PS, et al. Evaluation of C-reactive protein prior to and on-treatment as a predictor of benefit from atorvastatin: Observations from the Anglo-Scandinavian Cardiac Outcome Trial. Eur Heart J 2012;33:486-494.
The value of high sensitivity C-reactive protein (CRP) measurements in the management of patients at risk for cardiovascular (CV) events is controversial. Thus, these investigators performed a nested case-control study of participants in the Anglo-Scandinavian Cardiac Outcome Trial (ASCOT) blood pressure lowering study to determine the ability of CRP to predict CV events. They also evaluated the lipid-lowering arm of ASCOT to test whether CRP predicted CV events after 6 months of therapy with atorvastatin 10 mg a day. The participants in ASCOT hypertension had to have three or more risk factors for CV disease, but patients with a history of CV events were excluded. The original trial compared amlodipine to atenolol-based therapy. The lipid arm included those with total cholesterols < 250 mg/dL. Atorvastatin 10 mg/day vs placebo was tested. ASCOT lipid was stopped early due to significant benefits in the atorvastatin arm. The primary endpoint was a combination of CV death, myocardial infarction, coronary revascularization, and stroke. Two or three control patients were selected to be matched with each CV event case. The cases had a somewhat worse clinical profile than the controls.
Baseline LDL cholesterol and CRP predicted CV events (odds ratio [OR] 1.3, 95% confidence interval [CI] 1.1-1.6, P = 0.002 for LDL-C and OR 1.2, CI 1.1-1.3, P = 0.006 for CRP), but baseline CRP did not predict the magnitude of atorvastatin's effect. After 6 months of atorvastatin, LDL was decreased 40% and CRP 27%. The magnitude of LDL reduction on atorvastatin predicted the reduction in CV events (OR 0.41, CI 0.22-0.75, P = 0.004), but this was not the case for CRP (OR 0.86, CI 0.49-1.51, P = 0.6). The authors concluded that among high-risk hypertensive patients, CRP did not appreciably improve CV risk prediction and a reduction in CRP on statin therapy was not predictive of CV outcomes.
Commentary
Since statins reduce LDL cholesterol and CRP, it is difficult to parse out the relative importance of each effect. This study suggests that on-statin CRP is not associated with CV outcomes, which differs from the results of JUPITER and PROVE IT-TIMI 22. There are significant differences in the patients in these trials. PROVE-IT included only patients with known coronary heart disease. JUPITER recruited healthy subjects with LDL cholesterol < 130 mg/dL, but with elevated CRP (mean, 4.3). ASCOT blood pressure subjects were hypertensive and had at least three more risk factors for CV disease. ASCOT lipid subjects had mainly elevated total cholesterol, but < 250 mg/dL. In addition, JUPITER included soft outcomes such as hospitalization, whereas ASCOT only included hard events. Not surprisingly ASCOT had higher CV event rates than JUPITER.
The authors argue that the ASCOT subjects are a more typical population considered at increased risk for CV events than the JUPITER population, and the higher event rates in ASCOT attest to this observation. The modest increment in risk prediction by CRP in the ASCOT patients is not likely to be clinically significant. This conclusion is in line with other prospective studies and adds to our knowledge about the use of CRP measurements.
CRP may be useful in JUPITER-type patients for making a decision on whom to treat with a statin. Healthy individuals with LDL cholesterol between 100-130 mg/dL may not need statin therapy unless they have other risk factors for CV disease or their CRP is elevated. Those with other risk factors or known disease would be treated with LDL-C levels in this range and CRP would add little value. This statement is likely to be controversial. The more contentious finding of this study is that CRP was not predictive of CV outcome in patients on statin treatment. Thus, the use of CRP to establish the utility of statin therapy should also be discouraged.
The value of high sensitivity C-reactive protein (CRP) measurements in the management of patients at risk for cardiovascular (CV) events is controversial.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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