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E-selectin as a plasma marker of acute coronary syndromes

Three Part Question

In [patients with suspected cardiac chest pain presenting to the Emergency Department] does [measurement of plasma E-selectin] enable [exclusion of acute coronary syndromes]?

Clinical Scenario

A fifty year-old lady with a severe needle phobia presents to the Emergency Department with a three-hour history of central tight chest pain. Baseline observations, chest radiograph and initial ECG are normal. You feel that you ought to exclude acute coronary syndrome before discharging her.
Particularly in view of her needle phobia, you would like to be able to exclude the diagnosis using her admission blood samples but you are aware that troponin will be insufficiently sensitive at this time. Serial CK-MBmass would necessitate serial venepuncture. You wonder if there is an early marker you could use. As e-selectin as been proposed as such an early marker, you wonder if its measurement would help in this situation.

Search Strategy

OVID Medline 1966 - Week 3 August 2005
OVID Embase 1980 - 2005 Week 35
[exp Myocardial Infarction/ OR exp Coronary Thrombosis/ OR exp Angina, Unstable/ OR (heart attack OR MI OR AMI O R unstable angina OR (acute adj coronary adj syndrome) OR ACS).mp. OR (myocard$ adj (infarct$ OR ischaem$ OR ischem$).mp.] AND [exp E-Selectin/ OR e selectin.mp. OR endothelial cell leucocyte adhesion molecule$.mp. OR ELAM$.mp.] limit to human and English language

Search Outcome

Altogether 98 papers were identified in Medline and 123 in Embase. One papers that appraised the use of E-selectin in an Emergency Department population with undifferentiated chest pain was identified. Several papers that investigated E-selectin levels in various acute coronary syndromes are discussed, together with other relevant papers.

Relevant Paper(s)

Author, date and country Patient group Study type (level of evidence) Outcomes Key results Study Weaknesses
Hope et al
2002
Australia
57 patients presenting to the Emergency Department with chest pain. 13 had AMI, 23 UA and 21 non-cardiac pain. Blood taken at mean 2 hours 17 minutes from symptom onset.Prospective diagnostic cohortE-selectin levels according to time of samplingLevels did not change with time from symptom onsetSmall numbers. Suboptimal gold standards: AMI diagnosis not according to WHO guidelines and used CK-MB not troponins as gold standard biochemical markers; UA diagnosis required a minimum of "typical chest pain at rest" with no objective verification; only "some" patients with non-cardiac chest pain underwent exercise testing. No clinical follow up, which is at least as important as comparing diagnosis with accepted gold standards. ROC curve analysis, sensitivity, specificity, PPV and NPV not reported.
E-selectin levels in AMI, UA and controlsNo significant differences between groups

Comment(s)

Leucocyte adhesion and subsequent migration across the endothelium is pivotal to the development of coronary atherosclerosis (Kher et al, 2004). Their initial attachment to endothelial cells is mediated by cell adhesion molecules, including the selectin family. E-selectin is synthesised by endothelial cells in response to stimulation by interleukin-1 and tumour necrosis factor-alpha (Price et al, 1999). It binds to a ligand on the cell surface of leucocytes, causing the leucocytes to 'roll' across the endothelium (Bevilacqua et al, 1987). If the leucocytes then encounter activating signals from other cell adhesion molecules, they adhere firmly to the endothelium and may transmigrate across the endothelium into the intima. From there, macrophages accumulate lipids and secrete proinflammatory and atherogenic cytokines, matrix metalloproteinases that destabilise the fibrous cap of atheroma and the procoagulant tissue factor (Szmitko et al, 2003; Libby et al, 1995; Davies et al, 1996). Inhibition of neutrophil adhesion has been shown to limit myocardial infarct size and reduce myocardial reperfusion injury in animal models (Curtis et al, 1993; Litt et al, 1989). Soluble E-selectin is potentially useful as a biochemical marker as it can be easily measured by ELISA techniques and is stable under laboratory conditions (Hope et al, 2002). Seven authors have reported raised E-selectin levels in AMI (Squadrito et al, 1996; Miyao et al, 1999; Zeitler et al, 1997; Li et al, 1997; Suefuji et al, 2000; Pellegatta et al, 1997; Siminiak et al, 1998). Two authors have demonstrated raised E-selectin in UA (Atalar et al, 2001; Ghaisas et al, 1997). Five authors have reported raised E-selectin in all ACS (Xie et al, 2000; Mulvihill et al, 1999; Mulvihill et al, 2000; Squadrito et al, 1995; Guray et al, 2004). Raised E-selectin levels have been reported following attacks of variant angina (Miwa et al, 1997), although Siminiak et al (1997) found no difference in E-selectin levels during angina attacks. Two authors have reported a reduction in E-selectin following successful reperfusion in AMI (Squadrito et al, 1995; Squadrito et al, 1996). Two authors have also shown a correlation between E-selectin levels and severity of atherosclerosis (Oishi et al, 2000; Parker et al, 2001). Further, Zeitler et al (1997) demonstrated higher E-selectin in those who died of AMI than in survivors. Suefuji et al (2000) found that E-selectin was higher in patients with AMI who had experienced a prodrome of UA. However, three authors have failed to find elevated E-selectin levels in ACS (Gurbel et al, 1998; Galvani et al, 2000; Shyu et al, 1996). There is no clear explanation for the discrepancy in the results. Only one study has investigated E-selectin levels in the Emergency Department population with undifferentiated chest pain. This study failed to demonstrate a difference in E-selectin levels between patients with AMI, UA and controls. However, the study had significant limitations, including small numbers, suboptimal gold standards and no clinical follow-up. The study was not designed to appraise the performance of E-selectin as a diagnostic test for use in the Emergency Department. The available research suggests that E-selectin has promising characteristics for use as a marker of ACS. A large prospective observational cohort study is necessary to evaluate its performance as a diagnostic test. Incorporation into a multimarker strategy with markers that may reflect other aspects of the pathophysiological evolution of ACS may be necessary to obtain sufficient sensitivity.

Editor Comment

Abbreviations: AMI: acute myocardial infarction; UA: unstable angina; ACS: acute coronary syndrome

Clinical Bottom Line

Available research suggests that E-selectin may be a promising marker of ACS but there is currently no available evidence to appraise its use as a diagnostic test in the Emergency Department.

References

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