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CLINICAL RESEARCH: CORONARY ARTERY DISEASE

C-Reactive Protein and Electrocardiographic ST-Segment Depression Additively Predict Mortality

The Strong Heart Study

Peter M. Okin, MD, FACC^_*,_*, Mary J. Roman, MD, FACC^_*, Lyle G. Best, MD, Elisa T. Lee, PhD, James M. Galloway, MD, FACC, Barbara V. Howard, PhD^|| and Richard B. Devereux, MD, FACC^_*

^_* Division of Cardiology, Department of Medicine, Weill Medical College of Cornell University, New York, New York
Missouri Breaks Industries Research Inc., Timber Lake, South Dakota
College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
University of Arizona, Tucson, Arizona
^|| MedStar Research Institute, Washington, DC

Manuscript received December 8, 2004; revised manuscript received February 15, 2005, accepted February 22, 2005.

^_* Reprint requests and correspondence: Dr. Peter M. Okin, Weill Medical College of Cornell University, 525 East 68th Street, New York, New York 10021. (Email: pokin{at}med.cornell.edu).

OBJECTIVES: This study was designed to examine whether high-sensitivity C-reactive protein (CRP) and electrocardiographic (ECG) ST-segment depression (STD) have additive utility for predicting cardiovascular disease (CVD) death and all-cause death (ACD).

BACKGROUND: C-reactive protein, a marker of systemic inflammation, and ECG STD, an index of myocardial ischemia and hypertrophy, independently predict mortality.

METHODS: Electrocardiograms and CRP levels were examined in 2,155 American Indian participants in the second Strong Heart Study examination. ST-segment depression 50 µV (n = 127) and CRP >7.0 mg/l (defining the upper quartile of CRP levels, n = 540) were considered abnormal.

RESULTS: After 5.2 ± 1.2 years follow-up there were 95 CVD deaths and 310 ACD. In univariate Cox analyses, the combination of CRP and ECG STD improved risk stratification compared to either alone, with the presence of both CRP >7.0 and ECG STD associated with a 7.7-fold increased risk of CVD death (95% confidence interval [CI] 3.3 to 18.2) and a 6.5-fold increased risk of ACD (95% CI 4.1 to 10.3). After adjustment for age, gender, and relevant risk factors, the combination of high CRP and STD remained predictive of CVD death and ACD, with the presence of both abnormal CRP and STD associated with the highest risks of CVD death (hazard ratio [HR] 3.2, 95% CI 1.1 to 10.5) and ACD (HR 3.9, 95% CI 2.1 to 7.2) and the presence of either high CRP or abnormal STD associated with intermediate risks of CVD death (HR 2.2, 95% CI 1.4 to 3.4) and ACD (HR 1.5, 95% CI 1.2 to 2.0).

CONCLUSIONS: The combination of ECG STD and CRP increases the risk of mortality, demonstrating the additive impacts of active inflammation and preclinical CVD on prognosis.

Abbreviations and Acronyms   ACD = all-cause death   CI = confidence interval   CRP = C-reactive protein   CVD = cardiovascular disease   ECG = electrocardiogram/electrocardiographic   HDL = high-density lipoprotein   HR = hazard ratio   LDL = low-density lipoprotein   STD = ST-segment depression

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