CLINICAL STUDY: CORONARY ARTERY DISEASE
C-reactive protein and angiographic coronary artery disease: independent and additive predictors of risk in subjects with angina
James S. Zebrack, MD*,
Joseph B. Muhlestein, MD, FACC*, ,
Benjamin D. Horne, MPH,
Jeffrey L. Anderson, MD, FACC*,* Intermountain Heart Collaboration Study Group
* Division of Cardiology, University of Utah School of Medicine, Salt Lake City, Utah, USA
Cardiovascular Department, LDS Hospital, University of Utah School of Medicine, Salt Lake City, Utah, USA
Manuscript received June 18, 2001;
revised manuscript received October 10, 2001,
accepted November 16, 2001.
* Reprint requests and correspondence: Dr. Jeffrey L. Anderson, Division of Cardiology, University of Utah School of Medicine, 50 North Medical Drive, 4A154, Salt Lake City, Utah 84132, USA.
jeff.anderson{at}hsc.utah.edu
OBJECTIVES: The objective of this study was to determine the prognostic value of C-reactive protein (CRP) independent of coronary angiographic findings.
BACKGROUND: High sensitivity CRP, a marker of inflammation, predicts risk of cardiovascular events. However, it is uncertain whether it remains predictive once angiographic findings are considered.
METHODS: A total of 2,554 patients with angina but without acute myocardial infarction (MI) were studied angiographically; 1,848 patients had coronary artery disease (CAD) and 706 patients did not. Coronary artery disease was quantified in five ways and combined for a CAD score. C-reactive protein was measured and patients were followed for up to five years for death or MI.
RESULTS: C-reactive protein correlated with the extent of CAD, but correlation coefficients were low (0.02 to 0.08). Of angiographic measures, the CAD score best predicted future events (hazard ratio [HR] = 1.8 [1.2 to 2.6], p = 0.004, for CAD score >4). C-reactive protein  1.0 mg/dl was predictive in both patients without CAD (HR = 2.3 [0.9 to 5.5], p = 0.07) and with CAD (HR = 2.1 [1.5 to 3.1], p = 0.0001). Multivariate adjustment resulted in little change in HR. C-reactive protein retained predictive value within each quintile of CAD score. C-reactive protein and CAD independently and additively contributed to the risk prediction: low CRP and lowest CAD score was associated with lowest risk, and high CRP and highest CAD score was associated with the highest risk, with a 10-fold difference between extremes (2.5% vs. 24%).
CONCLUSIONS: C-reactive protein correlates with extent of CAD, but the degree of correlation is low. Severity/extent of CAD and CRP are independent and additive predictors of risk. Therapy should target CRP-associated risk as well as angiographically evident stenosis.
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Abbreviations and Acronyms
| | CAD | | ACE | | angiontensin-converting enzyme | | CAD | | coronary artery disease | | CI | | confidence interval | | CRP | | C-reactive protein | | HR | | hazard ratio | | MI | | myocardial infarction |
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