Risk stratification of emergency department patients with acute coronary syndromes using P-selectin.

OBJECTIVES: We compared the predictive properties of P-selectin to creatine kinase, MB fraction (CK-MB) for detecting acute myocardial infarction (AMI), acute coronary syndromes (ACS) and serious cardiac events upon emergency department (ED) arrival. BACKGROUND: Practioners detecting early diagnosis of ACS have focused on cardiac markers of myocardial injury. Plaque rupture/platelet aggregation precedes myocardial ischemia. Therefore, markers of platelet aggregation may detect ACS earlier than cardiac markers. METHODS: Consecutive patients with potential ACS presenting to an urban university ED were identified by research assistants who screened all ED patients between November 12, 1997 and January 31, 1998. Whole blood was drawn at presentation and 1 h later and rapidly stained and fixed for membrane P-selectin assay and plasma was separated for soluble P-selectin assay. Creatine kinase, MB fraction values were determined using standard immunoassay techniques. Clinical history and hospital course were followed daily. Outcomes were AMI, ACS (AMI and unstable angina) and serious cardiac events. Receiver operator characteristic curves were derived for CK-MB, and soluble and membrane-bound P-selectin to determine the optimal cutoff values. Predictive properties were calculated with 95% confidence intervals. RESULTS: A total of 263 patients were enrolled. They had a mean age of 56.5+/-14 years; 52% were male. There were 22 patients with AMI; 87 patients with ACS and 54 patients with serious cardiac events. Creatine kinase, MB fraction had a higher specificity for detection of AMI, ACS and serious cardiac events than both soluble and membrane-bound P-selectin. At the time of ED presentation, the specificity of CK-MB, and soluble and membrane-bound P-selectin for AMI was 91% versus 76% versus 71%; for ACS, 95% versus 79% versus 71%, and for serious cardiac events, 91% versus 76% versus 72% (p < 0.05). The sensitivities for AMI were 50% versus 45% versus 32%; for ACS, 26% versus 35% versus 30%, and for serious cardiac events, 29% versus 35% versus 36%. CONCLUSIONS: Although theoretically attractive, the use of soluble and membrane-bound P-selectin for risk stratification of chest pain patients at the time of ED presentation does not appear to have any advantages over the use of CK-MB.

Inhibition of human vascular smooth muscle cell migration and proliferation by beta-cyclodextrin tetradecasulfate.

Smooth muscle cell migration and proliferation are important regulatory processes in the development of intimal thickening after vascular injury. beta-cyclodextrin tetradecasulfate, an orally active synthetic heparin mimic, is effective in inhibiting rabbit aortic smooth muscle cell proliferation in vitro and in limiting restenosis in an experimental angioplasty restenosis model in rabbits (Hermann et al., 1993). However, its effects on migration are unknown, as are its effects on human vascular smooth muscle cell biology in general. Using a Transwell assay system, we demonstrated a dose dependent inhibition of human vascular smooth muscle cell random migration for beta-cyclodextrin tetradecasulfate with half maximal inhibition between 100-500 micrograms/ml and 85 +/- 1% inhibition at 10(3) micrograms/ml (P < .001, n = 4). At this latter concentration, inhibition of migration was also demonstrable using a linear under-agarose assay, where the mean velocity for beta-cyclodextrin tetradecasulfate-treated cells (8 +/- 2 microns/h, +/- S.E.) was significantly less than for control cells (21 +/- 4, P < .01), but equaled that of control cells 48 h after drug withdrawal (21 +/- 1, P = NS). Single cell analysis over 17 h using time lapse video microscopy revealed significant inhibition of total migration pathway distance for beta-cyclodextrin tetradecasulfate-treated smooth muscle cells compared with control smooth muscle cells (0.40 +/- 0.03 mm vs. 0.73 +/- 0.03, P < .01). We also demonstrated a dose-dependent inhibition of serum-induced proliferation by beta-cyclodextrin tetradecasulfate in both cultured human umbilical vein and coronary artery smooth muscle cells. To assess whether beta-cyclodextrin tetradecasulfate had any direct cellular toxicity, we measured the release of intracellular LDH at 6 or 24 h. At 10(3) micrograms/ml or less, there was no increase in LDH release compared with untreated cultures. Thus, beta-cyclodextrin tetradecasulfate may be an effective agent in inhibiting intimal thickening after vascular injury by limiting both smooth muscle cell migration and proliferation.