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 Theraphy: Thrombolysis in Myocardial Infarction (PROVE IT-TIMI 22) trial
Received 29 April 2007; accepted 20 August 2007. published online 12 October 2007.
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 Theraphy: 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.
aThrombolysis in Myocardial Infarction (TIMI) Study Group, Brigham and Women's Hospital, Boston, MA
bCardiovascular Division, Brigham and Women's Hospital, Boston, MA
cCenter for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Boston, MA
dDonald W. Reynolds Center for Clinical Cardiovascular Research, Brigham and Women's Hospital, Women's Hospital, Boston, MA
eDepartment of Medicine, Harvard Medical School, Boston, MA
fDivision of Cardiovascular Medicine, University Hospitals Case Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH
Reprint requests: David A. Morrow, MD, MPH, is to be contacted at TIMI Study Group/Cardiovascular Division, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115. Daniel I. Simon, MD, Division of Cardiovascular Medicine, University Hospitals Case Medical Center, 11100 Euclid Avenue Lakeside 3001, Cleveland, OH 44106.
The PROVE IT-TIMI 22 trial was supported by Bristol-Myers Squibb, Princeton, NJ. Drs Morrow and Sabatine are supported in part by National Institutes of Health grant U01 HL083-1341. This work was also supported in part by grants from the National Institutes of Health (HL57506 and HL60942 to Dr Simon). Dr Pradhan is supported by funding from the National Institutes of Health (HL082740). Dr Libby is supported by research funds from the Leducq Foundation (Paris, France), the Doris Duke Foundation (New York, NY), and the Donald W. Reynolds Foundation (Las Vegas, NV).
ABSTRACT