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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:142.)
© 2008 American Heart Association, Inc.

Clinical and Population Studies

Inflammation, Statin Therapy, and Risk of Stroke After an Acute Coronary Syndrome in the MIRACL Study

Scott Kinlay; Gregory G. Schwartz; Anders G. Olsson; Nader Rifai; Michael Szarek; David D. Waters; Peter Libby; Peter Ganz for the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) Study Investigators

From the Cardiovascular Division (S.K.), Veterans Affairs Boston Healthcare System, West Roxbury, Mass; the Cardiovascular Division (S.K., P.G., P.L.), Brigham and Women’s Hospital and Harvard Medical School, Boston, Mass; the Cardiology Division (G.G.S.), Veterans Affairs Medical Center and University of Colorado Health Sciences Center, Denver, Colo; The Faculty of Health Sciences (A.G.O.), University of Linköping, Sweden; Children’s Hospital Boston and Harvard Medical School (N.R.), Boston Mass; Pfizer Pharmaceuticals Group (M.S.), New York; and the Cardiology Division, San Francisco General Hospital and University of California (D.D.W.), San Francisco, Calif.

Correspondence to Scott Kinlay, MBBS, PhD, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA, 02115. E-mail skinlay{at}partners.org

Abstract

Objective— Patients with acute coronary syndromes have an increased risk of stroke. We measured markers of inflammation in the MIRACL study, a randomized trial of atorvastatin versus placebo in acute coronary syndromes, to assess the relationship of inflammation to stroke.

Methods and Results— Baseline C-reactive protein (CRP), serum amyloid A (SAA), and interleukin-6 (IL-6) were collected in 2926 (95%) subjects. Baseline markers were related to stroke risk over the 16 weeks of the study. Subjects who subsequently experienced a stroke had higher CRP (27.5 versus 10.2 mg/L, P=0.0032), SAA (30.5 versus 16.0 mg/L, P=0.031), IL-6 (11 231 versus 6841 pg/L, P=0.004), and troponin (6.03 versus 3.19 ng/mL P=0.0032). The risk of stroke was related to greater CRP, SAA, and IL-6 in the placebo group only. Similarly, there was a graded increase in risk of stroke across quartiles of inflammatory markers in the placebo patients only.

Conclusions— In acute coronary syndromes, the early risk of stroke relates to both heightened inflammation and size of myocardial necrosis. Treatment with atorvastatin abrogated the risk associated with elevated markers of inflammation in this study, a finding that provides a novel rationale for the use of statins in acute coronary syndromes.

We measured baseline CRP, SAA, and IL-6 in 2926 subjects in the MIRACL study, a randomized trial of atorvastatin versus placebo in acute coronary syndromes. Greater levels of inflammatory markers were related to stroke, and atorvastatin abrogated this risk providing a novel rationale for statins in acute coronary syndromes.

Key Words: stroke • acute coronary syndromes • inflammation • CRP • statin

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