doi: 10.1161/01.ATV.0000252064.97632.2c
© 2007 American Heart Association, Inc.
Letters to the Editor |
Circulating Platelet-Derived Microparticles Are Associated With Atherothrombotic Events
From the Department of Cardiology (M.N., A.T., T.S., Y.N.), Baba Memorial Hospital, Sakai, Japan; the Osaka Ekisaikai Hospital (K.S., J.Y.), Osaka, Japan; Otsuka Phamaceutical Co Ltd (Y.O., S.U.), Japan; and Kishiwada City Hospital (S.N.), Kishiwada, Japan.
Correspondence to Dr Atsushi Tanaka, Department of Cardiology, Baba Memorial Hospital, 4-244, Hamadera-funao-cho Higashi, Sakai, 592-8555 Japan. E-mail m4497147{at}msic.med.osaka-cu.ac.jp
A Marker for Vulnerable Blood
Platelet-derived microparticles (PDMP) are first observed as vesicles released from platelets after adhesion to vessels walls.1–3 Circulating PDMP can therefore be thought of as a marker of in vivo platelet activity.4 In these studies, flow-cytometory was applied to measure PDMP. As a result, the clinical significance of PDMP remains unresolved. In this study, we investigate the usefulness of PDMP that could vary the vulnerability for thrombotic events using newly developed ELISA kit.5
Our population consisted of 66 ACS patients with or without ST segment elevation (the ACS group) and 126 patients with stable angina (the SAP group). A further 26 noncardiac chest-pain syndrome patients were selected as a control group.
Circulating PDMP levels were assayed using the ELISA method5 (supplement I, available online at http://atvb.ahajournals.org). Single vessel diseased patients with first ACS (n=24) were selected for intravascular ultrasound (IVUS) analysis. Clinical follow-up was obtained for 189 (98%) patients. Mean clinical follow-up period was 11.1±2.4 months. The primary end point was major atherothrombotic events defined as sudden death of unknown etiology, recurrent or new onset of ACS, cerebral infarction, and arterial thrombosis. Results were expressed as mean value±SD or numbers (%). Statistical analysis was done with commercially available software (StatView, Abacus Concepts) (supplement II). There were no significant differences in terms of age, gender, or classical coronary risk factors among three groups (supplement III). ACS group patients had higher PDMP levels than their SAP and control counterparts (ACS 33.8±56.9 U/mL, SAP 10.8±8.0 U/mL, control 5.9±3.6 U/mL, P<0.01; supplement IV). The total arc of calcification at the culprit lesion correlated positively with circulating PDMP level (supplement V). After discharge, there were 2 (0.9%) deaths, 8 (3.6%) ACS, 3 (1%) cerebral infarctions, and 3 (1%) arterial thromboses. A multivariate logistic regression model demonstrated that high PDMP levels were an independent predictor for secondary thrombotic events (supplement VI). Kaplan–Meier curves showed that patients with high PDMP levels at discharge were associated with poorer clinical outcomes at one year (P<0.01, Figure).
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ACS is mainly caused by plaque rupture with occlusive thrombosis.6 However, Virmani et al also have reported that nonruptured plaques exist in culprit lesions in ACS, and nodular calcification usually accompanies a luminal thrombus in such cases.7 When endothelial damage occurs at an atherosclerotic plaque as a result of plaque rupture, erosion, or spontaneously occurs in calcified plaques, the exposed vessel-wall tissue factor forms a catalytic complex with circulating Factor VII and Factor VIIa, thereby initiating coagulation. Although platelet deposition is restricted by circulating blood, already-activated platelets with PDMP released by high shear stress crossing though the calcified atherosclerotic plaque8–10 provide a new prothrombotic interface for a growing thrombus, fibrin, and circulating blood.11,12 This results in the growth of the thrombus and a narrowing of the vessel. Increases in shear stress, associated with vessel narrowing, favor this process by further promoting new platelet activation and PDMP release. Ultimately, an occlusive thrombus forms and patients suffer catastrophic events with or without plaque rupture. A recent manuscript proposed the new term "vulnerable blood", high blood coagulability, to prevent clinical events for vulnerable patients as well as plaque disruptions.6 We consider that high PDMP levels reflect "vulnerable blood" status and may be of use for differentiating patients who will develop atherothrombotic events from patients who will develop a stable status.
Study Limitations
This ELISA kit cannot discriminate between particles of different sizes. There is a possibility therefore that this ELISA method may count fragmentary membrane as platelets or that PDMP aggregation may result in an underestimation of the PDMP count.
Acknowledgments
Disclosures
None.
References
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