Author + information
- Paul A. Gurbel, MD∗ (, )
- Rolf P. Kreutz, MD,
- Kevin P. Bliden, MBA and
- Udaya S. Tantry, PhD
- ↵∗Sinai Center for Thrombosis Research, Sinai Hospital of Baltimore, 2401 West Belvedere Avenue, Baltimore, Maryland 21215
We read with interest the paper by Cangemi et al. (1) reporting a significant association between platelet activation and myocardial infarction (MI) that was based on the observation of higher levels of plasma soluble (s)CD-40L and sp-selectin and serum thromboxane (Tx) B2 in patients who were hospitalized for pneumonia and who had development of MI. About 20 years ago, there was tremendous interest in the potential utility of p-selectin as a diagnostic marker of early acute coronary syndromes and as a target for pharmacological inhibition. However, at the present time, the utility of sp-selectin as a reliable marker of platelet activation to identify MI is still a matter of debate. About 17 years ago, we reported the relation of sp-selectin with acute MI (AMI) (2). In our pilot study, sp-selectin levels were determined in identical samples by 2 different enzyme-linked immunosorbent assays at pre-specified time points in 23 patients with AMI enrolled in the GUSTO-III (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries) trial and were compared with healthy control subjects. Plasma concentrations of sp-selectin were consistently at least twice higher in patients with AMI when measured by use of both assays. We also showed that sp-selectin rose early after reperfusion, a factor that may have influenced the detection of elevated sp-selectin in the Cangemi study, because only 2 sp-selectin measurements were made in the latter study. To evaluate the diagnostic utility of sp-selectin and membrane-bound p-selectin, a subsequent single-center study (n = 136) was conducted by our group (3). We showed that the p-selectin profile alone did not reliably differentiate acute coronary syndromes from noncardiac chest pain due to interindividual variability and low overall sensitivity; many patients with noncardiac chest pain had high soluble and membrane-bound p-selectin. Finally, in a multicenter study (n = 338) in patients presenting with chest pain, it was shown that membrane bound p-selectin expression, an established marker of platelet activation, was unrelated to the level of sp-selectin, irrespective of the etiology of chest pain. Taken together, all of these results strongly suggest that sp-selectin cannot reliably serve as a surrogate marker to indicate platelet activation in patients with AMI and noncardiac chest pain (4). Regarding CD-40L, despite the earlier enthusiasm about the potential of this marker as a diagnostic tool, there have been no reports that this marker has clinical importance. Its lack of utility may be related to artifacts associated with its measurement. Finally, in addition to platelets, endothelial cells and monocytes/macrophages express cyclooxygenase-2. In states of intense inflammation, such as pneumonia, in which cyclooxygenase-2 expression is high, elevated total serum TxB2 levels may be the result of increased TxA2 synthesis in leukocytes or caused by transcellular synthesis of TxA2 in platelets (5). Therefore, we suggest that the results of the current study must be interpreted with caution for 3 reasons: 1) the assessment of platelet activation by the proposed soluble markers; 2) the elevation of sp-selectin and TxB2 in noncardiac disease states; and 3) the prior evidence that both soluble and membrane-bound p-selectin are not robustly associated with proven MI.
Please note: Dr. Gurbel has served as a consultant for Daiichi-Sankyo/Lilly, Bayer, AstraZeneca, Merck, Boehringer, and CSL; and has received grants/support from the National Institutes of Health, Daiichi-Sankyo/Lilly, CSL, AstraZeneca, Harvard Clinical Research Institute, Bayer, Haemonetics, Duke Clinical Research Institute, Sinnowa, CORAMED, and Accumetrics. Dr. Gurbel has reported holding stock or stock options in Merck, Medtronic, and Pfizer; and holds patents in the area of personalized antiplatelet therapy and interventional cardiology. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- American College of Cardiology Foundation