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Prognostic value of increased soluble thrombomodulin and increased soluble E-selectin in ischaemic heart disease
A D Blann1, J Amiral, C N McCollum
1Thrombosis, Haemostasis and Vascular Biology Unit, The University Department of Medicine, The City Hospital, Birmingham, UK.
Insights
Raised soluble thrombomodulin levels in patients surviving myocardial infarction predict future cardiovascular events. Soluble E-selectin levels did not show predictive value for disease progression.
Area of Science:
- Cardiovascular Medicine
- Biomarkers
- Atherosclerosis Research
Background:
- Endothelial cell dysfunction is implicated in ischaemic heart disease.
- Elevated levels of soluble E-selectin and soluble thrombomodulin may indicate endothelial damage.
Purpose of the Study:
- To investigate if soluble E-selectin and soluble thrombomodulin levels predict cardiovascular disease progression after myocardial infarction.
Main Methods:
- Plasma samples from 54 myocardial infarction survivors were analyzed for soluble E-selectin and soluble thrombomodulin using ELISA.
- Patients were followed for 49 months for subsequent cardiovascular events.
Main Results:
- Soluble thrombomodulin levels were significantly higher in patients who experienced an event (65+/-24 ng/mL) compared to those who did not (49+/-19 ng/mL, p=0.009).
- Soluble E-selectin levels did not differ significantly between groups (p=0.43).
- Soluble thrombomodulin levels significantly impacted survival free of cardiovascular events (p=0.011).
Conclusions:
- Soluble thrombomodulin is a novel predictive marker for atherosclerosis progression in ischaemic heart disease patients.
- Soluble E-selectin measurement has limited value in epidemiological studies for this patient group.
Abstract:
Endothelial cell dysfunction is likely to be important in the pathophysiology of ischaemic heart disease and increased levels of endothelial cell markers soluble E-selectin and soluble thrombomodulin may reflect this damage. To determine whether increased levels of these markers were predictive of disease progression, we obtained plasma from 54 patients who had survived a myocardial infarction. Soluble E-selectin and soluble thrombomodulin were measured by ELISA. After 49 months, 24 patients had suffered an additional cardiovascular event such as a second myocardial infarction or requirement for arterial surgery. Soluble E-selectin was 60+/-30 ng/mL in patients who suffered an end-point and was 54+/-23 ng/mL in those without an end-point (p=0.43). Soluble thrombomodulin was 65+/-24 ng/mL in patients who suffered an end-point and was 49+/-19 ng/mL in patients who were free of an end-point (p=0.009). The major risk factors for atherosclerosis (hypercholesterolaemia, hypertension, smoking) or peak creatinine kinase levels were unable to predict the development of an end-point. Using life tables, soluble thrombomodulin had a significant effect on survival free of an end-point (p=0.011). We conclude that the measurement of soluble E-selectin is of limited value in epidemiological studies, and that raised soluble thrombomodulin is a new marker for the progression of atherosclerosis in patients with ischaemic heart disease.