Myeloid-related protein 8/14 and the risk of cardiovascular death or myocardial infarction after an acute coronary syndrome in the Pravastatin or Atorvastatin Evaluation and Infection Therapy: Thrombolysis in Myocardial Infarction (PROVE IT-TIMI 22) trial.
BACKGROUND
Using a transcriptional profiling approach, we recently identified myeloid-related protein 8/14 (MRP-8/14) to be expressed by platelets during acute myocardial infarction (MI). Elevated concentrations of MRP-8/14 are associated with a higher risk for future cardiovascular events in apparently healthy individuals but have not been assessed with respect to prognosis in patients with acute coronary syndrome.


METHODS
We performed a nested case-control study (n = 237 case-control pairs) among patients enrolled in the Pravastatin or Atorvastatin Evaluation and Infection Therapy: Thrombolysis in Myocardial Infarction 22 (PROVE IT-TIMI 22) trial (mean follow-up 24 months) to investigate the risk of cardiovascular death or MI associated with MRP-8/14 measured at 30 days after an acute coronary syndrome.


RESULTS
Patients with cardiovascular death or MI after 30 days (cases) had higher median [25th, 75th percentile] MRP-8/14 levels than patients who remained free of recurrent events (5.6 [2.8, 13.5] mg/L vs 4.0 [1.9, 10.1] mg/L, P = .020). The risk of a recurrent cardiovascular event increased with each increasing quartile of MRP-8/14 (P-trend = 0.007) such that patients with the highest levels had a 2.0-fold increased odds (95% CI 1.1-3.6, P = .029) of a recurrent event after adjusting for standard risk indicators, randomized treatment, and C-reactive protein. Patients with elevated levels of MRP-8/14 and high-sensitivity C-reactive protein showed significantly increased risk of cardiovascular death or MI compared with patients with the lowest levels of both markers (adjusted odds ratio 2.1, 95% CI 1.2-3.8).


CONCLUSIONS
Myeloid-related protein 8/14 may be a useful biomarker of platelet and inflammatory disease activity in atherothrombosis and may serve as a novel target for therapeutic intervention.
Morrow
David A
DA
Thrombolysis in Myocardial Infarction Study Group, Brigham and Women's Hospital, Boston, MA 02115, USA. dmorrow@rics.bwh.harvard.edu
Wang
Yunmei
Y
Croce
Kevin
K
Sakuma
Masashi
M
Sabatine
Marc S
MS
Gao
Huiyun
H
Pradhan
Aruna D
AD
Healy
Aileen M
AM
Buros
Jacki
J
McCabe
Carolyn H
CH
Libby
Peter
P
Cannon
Christopher P
CP
Braunwald
Eugene
E
Simon
Daniel I
DI
D054058:Acute Coronary Syndrome / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D000368:Aged; D000890:Anti-Infective Agents / Q000008:administration & dosage; D000069059:Atorvastatin; D015415:Biomarkers / Q000097:blood; D040501:Calgranulin A / Q000097:blood*; D040502:Calgranulin B / Q000097:blood*; D016022:Case-Control Studies; D016001:Confidence Intervals; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006538:Heptanoic Acids / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D016017:Odds Ratio; D017035:Pravastatin / Q000008:administration & dosage*; D011336:Probability; D011758:Pyrroles / Q000008:administration & dosage*; D012016:Reference Values; D018570:Risk Assessment; D015996:Survival Rate; D015912:Thrombolytic Therapy / Q000379:methods; D016896:Treatment Outcome
D000890:Anti-Infective Agents; D015415:Biomarkers; D040501:Calgranulin A; D040502:Calgranulin B; D006538:Heptanoic Acids; D011758:Pyrroles; D000069059:Atorvastatin; D017035:Pravastatin