title: The effect of rosuvastatin on thromboinflammation in the setting of acute coronary syndrome.
abstract: In patients with acute coronary syndromes (ACS), early therapy with high-dose statins may reduce short-term adverse clinical outcomes. The mechanisms responsible are not known but could involve anti-inflammatory or anti-thrombotic effects. Compelling evidence from experimental models and clinical studies suggests that the interplay between inflammatory and thrombotic systems, typified by platelet-monocyte and platelet-neutrophil interactions, might be a key regulator of ischemic vascular events. The study sought to determine if early, high-dose administration of the HMG-CoA reductase inhibitor rosuvastatin in the setting of ACS exerts beneficial vascular effects by reducing, and inhibiting biomarkers of thromboinflammation, such as platelet-monocyte and platelet-neutrophil interactions, and biomarkers of myocardial necrosis. A total of 54 patients presenting with ACS within 8 h of symptom onset were randomized to rosuvastatin 40 mg or placebo. Rosuvastatin significantly reduced interactions between platelets and circulating neutrophils (P = 0.015) and monocytes (P = 0.009) within 24 h. No significant effects were observed on platelet aggregation or plasma levels of PF4, sP-selectin, or sCD40L, whereas significant reductions of RANTES occurred over time in both treatment groups. Plasma levels of myeloperoxidase (MPO) declined more rapidly with rosuvastatin therapy than placebo. In a subset of patients with normal cardiac necrosis biomarkers at randomization, rosuvastatin therapy was associated with less myocardial damage as measured by troponin-I or CK-MB. Early administration of high-dose statin therapy in patients with ACS appears to improve biomarkers of inflammation within 8 h, which may translate into fewer ischemic events.
authors.affiliation: The Gill Heart Institute, University of Kentucky, BBSRB B201, Lexington, KY, 40506, USA.
authors.forename: Travis R
authors.initials: TR
authors.lastname: Sexton
authors.forename: Eric L
authors.initials: EL
authors.lastname: Wallace
authors.forename: Tracy E
authors.initials: TE
authors.lastname: Macaulay
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Charnigo
authors.forename: Virgilio
authors.initials: V
authors.lastname: Evangelista
authors.forename: Charles L
authors.initials: CL
authors.lastname: Campbell
authors.forename: Alison L
authors.initials: AL
authors.lastname: Bailey
authors.forename: Susan S
authors.initials: SS
authors.lastname: Smyth
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology; D000328:Adult; D000368:Aged; D015415:Biomarkers; D001792:Blood Platelets; D023201:CD40 Ligand / Q000097:blood; D002450:Cell Communication / Q000187:drug effects*; D052279:Creatine Kinase, MB Form / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D061345:Early Medical Intervention; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage; D007249:Inflammation / Q000097:blood; D008297:Male; D008875:Middle Aged; D009000:Monocytes; D009504:Neutrophils; D019007:P-Selectin / Q000097:blood; D009195:Peroxidase / Q000097:blood*; D010978:Platelet Factor 4 / Q000097:blood; D000068718:Rosuvastatin Calcium / Q000008:administration & dosage*; D013927:Thrombosis / Q000097:blood; D016896:Treatment Outcome; D019210:Troponin I / Q000097:blood*
chemical_list: D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019007:P-Selectin; D019210:Troponin I; D023201:CD40 Ligand; D010978:Platelet Factor 4; D000068718:Rosuvastatin Calcium; D009195:Peroxidase; D052279:Creatine Kinase, MB Form