Predictive value of coronary artery calcification and hs-CRP for myocardial infarction and coronary death – Results from the Heinz Nixdorf Recall Study

Background: High sensitive C-reactive protein (hs-CRP) and coronary artery calcium (CAC) are both associated with impaired outcome in individuals at risk of cardiovascular events. Here we analyzed the predictive value of their combined assessment in a population-based cohort of men and women living in the metropolitan Ruhr area. Methods: CAC, hs-CRP and Framingham risk score (FRS) variables were measured in 3969 persons (aged 59±8 years, 53% women) without known coronary artery disease at baseline. Individuals with acute inflammation (hs-CRP>10.0mg/L) were excluded. All individuals were followed for 5 years for the occurrence of coronary death and non-fatal myocardial 3/≤infarction. Categories of low/high risk were defined as hs-CRP: >3mg/L; CAC: <100, ≥100. Based on this dichotomization, 4 risk categories were defined: hsCRP/CAC: a) low/low, b) high/low, c) low/high and d) high/high. Results: Individuals with events (n=91) versus those without had higher hs-CRP values (median (Q1-Q3): 2.1 (0.9–4.8) versus 1.4 (0.7–2.9), p=0.0007) and higher CAC scores (median (Q1-Q3): 182 (31–982) versus 11 (0–105)). In a multiple logistic model for events including the FRS, hs-CRP, logarithmic transformed CAC, [log(CAC+1)], and cardiovascular medication, hs-CRP, CAC and the FRS remained independent predictors of events (estimates (95% CI): hs-CRP: 1.09 (1.01–1.19), log(CAC+1): 1.39 (1.25–1.55), FRS: 1.03 (1.01–1.05)). Adjusted relative risk in risk categories II, III, and IV compared to risk category I were 2.06 (1.05–4.04), 3.32 (1.92–5.72), and 5.54 (3.01–10.18) respectively. The combined hs-CRP+CAC risk categories (I-IV) further stratified risk within each FRS category (low, intermediate and high risk) allowing for reclassification of risk in up to 56% of intermediate risk individuals. Conclusion: Combined quantification of subclinical atherosclerosis burden and marker of inflammation strongly predicts coronary events, and improves risk assessment in each FRS category.