Abstract 2989: Risk of Stroke After Acute Coronary Syndromes In The MIRACL Study Related to Baseline Inflammatory Markers
Objective: Risk factors for subsequent stroke in patients with acute coronary syndromes (ACS) remain poorly defined. This study tested the hypothesis that inflammation relates to the risk of stroke in patients with ACS, and that statin therapy can mitigate this link. Thus, we assessed the relationship between plasma concentrations of C-reactive protein (CRP), serum amyloid A (SAA), and interleukin-6 (IL6) and the risk of stroke over 16 weeks in patients presenting with ACS.
Methods: Inflammatory markers were measured in 2925 of 3086 (95%) subjects in the MIRACL study - a randomized trial of atorvastatin 80mg/d or placebo in subjects presenting with unstable angina or non-Q-wave myocardial infarction (MI). The risk of fatal and non-fatal stroke over 16 weeks was assessed by survival analysis and hazard ratios (HR) per unit increase in log(marker), and by tertiles of each marker by treatment allocation (using the lowest tertile in the atorvastatin group as the reference category).
Results: Fatal and non-fatal stroke occurred in 30 subjects. The risk of stroke during the 16 weeks after presentation was related to baseline CRP (HR = 1.58, p = 0.03), and to a lesser extent SAA (HR = 1.40, p = 0.06), but not IL6 (HR = 1.29, p = 0.16). These relationships were most evident in the placebo group (HRs: CRP = 1.84, p = 0.15, SAA = 1.77, p = 0.01, IL6 = 1.53, p = 0.06) and absent in the atorvastatin group (HRs: CRP = 1.14, p = 0.7, SAA = 0.83, p = 0.6, IL6 = 0.93, p = 0.8), although the power to find interaction effects was low (p-value for interaction effect: treatment-by-CRP = 0.4, treatment-by-SAA = 0.1, treatment-by-IL6 = 0.3). Analysis by tertiles of markers showed larger HRs for the highest tertile of markers in the placebo versus atorvastatin groups (HRs for CRP = 5.44 vs 1.51, SAA = 3.61 vs 0.58, IL6 = 3.33 vs 0.22).
Conclusions: Baseline inflammatory markers were related to fatal and non-fatal stroke in the 16 weeks after an acute coronary syndrome in the MIRACL study. These results suggest that inflammation contributes to the occurrence of stroke shortly after acute coronary syndromes. Atorvastatin attenuated the risk of stroke associated with high levels of baseline markers, providing evidence that links the anti-inflammatory effects of statins to stroke prevention after ACS.