C-Reactive Protein and Electrocardiographic ST-Segment Depression Additively Predict Mortality: The Strong Heart Study Original Research Article

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.