March 26, 2007

March 26, 2007 (Boston, MA) - Levels of CRP are predictive of future risk of cardiovascular events in patients with stable coronary artery disease, and risk starts to increase at lower levels of CRP than previously thought, a new study has shown [ 1].

Lead author Dr Marc Sabatine (Brigham and Women’s Hospital, Boston, MA) explained to heartwire that many studies have shown CRP levels to be a predictor of cardiovascular events in healthy individuals and in patients with ACS, but there was not much information on the population with stable coronary heart disease. “We have data on this from both ends of the spectrum, but until now there has been a large gap in the middle that we have not known much about," he commented. “We have now filled that gap in our knowledge."

In their study, which will be published in the March 27, 2007 issue of Circulation, Sabatine et al measured high-sensitivity (hs) CRP in 3771 patients with stable coronary artery disease enrolled in the PEACE trial, a randomized placebo-controlled trial of the ACE inhibitor trandolapril. Patients were followed up for a median of 4.8 years. Results showed that after adjustment for baseline characteristics and treatments, levels of hs-CRP above 1 mg/L were found to be associated with a significantly greater risk of cardiovascular death, MI, or stroke compared with levels below 1 mg/L.

Risk of CV death/MI or stroke with increased hs-CRP levels

hs-CRP level Hazard ratio of CV death/MI/stroke (95% CI) p
1–3 mg/L 1.39 (1.06–1.81) 0.016
>3 mg/L 1.52 (1.152.02) 0.003



In addition, elevated hs-CRP levels were an independent predictor of new heart failure and new diabetes but did not identify patients who derived particular benefit from the ACE inhibitor.

 

Sabatine pointed out that in most other studies examining CRP levels and future cardiovascular risk, increased risk has not been apparent until CRP levels reached 3 or higher, but in the current study, increased risk was observed at the much lower cutoff value of 1 mg/L. He explained that this study probably gave a more accurate result, as it had greater power than some previous studies, with 400 major events in almost 4000 patients. “The biology of CRP is no different; it’s just that prior studies have been unable to show the increased risk down to this level," he said. Noting that the US Centers for Disease Control and the American Heart Association recommend categorizing patients using predefined CRP cut points of <1, 1 to 3, and >3 mg/L into low-, average-, and high-risk categories, respectively, Sabatine noted that this study suggests people categorized as “average” risk according to this definition are actually at increased risk. ‘These CDC/AHA cutoff points are not unreasonable, but we are saying that it would really be desirable to have a CRP level less than 1," he told heartwire .

Not practice-changing at present

Sabatine noted that treatment of patients will not change because of this information at present, as all such patients should be treated with statins whatever their level of CRP and the effect of ACE inhibition was not different according to CRP levels in this study. “As yet, there is no clinical mandate to measure CRP, but higher levels of CRP do tell us that these patients are at higher absolute risk and therefore will gain a greater relative benefit from interventions. This study also underscores the importance of inflammation in CHD and suggests that if we ever do get an anti-inflammatory therapy, this could be targeted to those patients with increased levels of CRP."

In the paper, the researchers conclude: “Data from studies of statin therapy suggest that patients with CAD who have a persistently elevated hs-CRP level remain at increased risk of adverse cardiovascular events and that lower levels of hs-CRP are achieved with more intensive statin therapy. However, we await the results of prospective trials that target therapy based on CRP levels. Depending on the data that emerge, CRP may then join the other classic risk factors that we routinely measure and treat."

  1. Sabatine MS, Morrow DA, Jablonski KA, et al. Prognostic significance of the Centers for Disease Control/American Heart Association high-sensitivity C-reactive protein cut points for cardiovascular and other outcomes in patients with stable coronary artery disease. Circulation 2007; 115:1528-1536.

The complete contents of Heart wire , a professional news service of WebMD, can be found at www.theheart.org, a Web site for cardiovascular healthcare professionals.

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