Inflammation, statin therapy, and risk of stroke after an acute coronary syndrome in the MIRACL study.
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.


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.
Kinlay
Scott
S
Cardiovascular Division, Veterans Affairs Boston Healthcare System, West Roxbury, Mass, USA. skinlay@partners.org
Schwartz
Gregory G
GG
Olsson
Anders G
AG
Rifai
Nader
N
Szarek
Michael
M
Waters
David D
DD
Libby
Peter
P
Ganz
Peter
P
D054058:Acute Coronary Syndrome / Q000150:complications* / Q000188:drug therapy / Q000503:physiopathology; D000368:Aged; D000069059:Atorvastatin; D002097:C-Reactive Protein / Q000187:drug effects* / Q000502:physiology; D008078:Cholesterol, LDL / Q000187:drug effects; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007249:Inflammation / Q000188:drug therapy* / Q000503:physiopathology; D015850:Interleukin-6 / Q000097:blood / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000627:therapeutic use*; D012372:ROC Curve; D012307:Risk Factors; D000685:Serum Amyloid A Protein / Q000187:drug effects* / Q000378:metabolism; D020521:Stroke / Q000453:epidemiology / Q000276:immunology / Q000517:prevention & control*
D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D015850:Interleukin-6; D011758:Pyrroles; D000685:Serum Amyloid A Protein; D002097:C-Reactive Protein; D000069059:Atorvastatin