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Circulating endostatin as a risk factor for cardiovascular events in patients with stable coronary heart disease: A
Toralph Ruge1, Axel C Carlsson2, Erik Kjøller3
1Department of Emergency Medicine, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
Insights
Higher serum endostatin levels may indicate increased cardiovascular event risk in stable coronary heart disease patients. However, its clinical utility for risk prediction requires further investigation.
Area of Science:
- Cardiovascular Medicine
- Biomarkers
- Clinical Trials
Background:
- Elevated serum endostatin, a collagen XVIII fragment, is linked to ischemic heart disease.
- The association between serum endostatin and incident cardiovascular events in stable coronary heart disease (CHD) is not well-established.
Purpose of the Study:
- To investigate the association between baseline serum endostatin levels and cardiovascular events in patients with stable coronary heart disease.
- To evaluate the predictive value of endostatin for cardiovascular and all-cause mortality over a 10-year follow-up period.
Main Methods:
- Utilized data from the CLARICOR trial, a randomized, placebo-controlled study of stable CHD patients.
- Analyzed 10-year follow-up data, using the placebo group (n=1998) as the discovery sample and the clarithromycin group (n=1979) as the replication sample.
- Employed Cox regression models, adjusting for cardiovascular risk factors, glomerular filtration rate, and current medications.
Main Results:
- Higher serum endostatin showed a statistically significant association with an increased risk of the composite cardiovascular outcome in the discovery sample (HR 1.11, p=0.004).
- This association was weaker and not statistically significant in the replication sample (HR 1.06, p=0.06).
- Consistent and strong associations were observed between endostatin and cardiovascular and all-cause mortality across all models and subgroups. Endostatin addition provided minimal improvement in risk prediction (<1%).
Conclusions:
- Elevated serum endostatin may be associated with cardiovascular events in patients with stable coronary heart disease.
- The clinical utility of serum endostatin measurements for risk stratification in this population remains uncertain and requires further validation.
Background And Aims:
Raised levels of serum endostatin, a biologically active fragment of collagen XVIII, have been observed in patients with ischemic heart disease but association with incident cardiovascular events in patients with stable coronary heart disease is uncertain.
Methods:
The CLARICOR-trial is a randomized, placebo-controlled trial of stable coronary heart disease patients evaluating 14-day treatment with clarithromycin. The primary outcome was a composite of acute myocardial infarction, unstable angina pectoris, cerebrovascular disease or all-cause mortality. In the present sub-study using 10-year follow-up data, we investigated associations between serum endostatin at entry (randomization) and the composite outcome and its components during follow-up. The placebo group was used as discovery sample (1204 events, n = 1998) and the clarithromycin-treated group as replication sample (1220 events, n = 1979).
Results:
In Cox regression models adjusting for cardiovascular risk factors, glomerular filtration rate, and current pharmacological treatment, higher serum endostatin was associated with an increased risk of the composite outcome in the discovery sample (hazard ratio per standard deviation increase 1.11, 95% CI 1.03-1.19, p = 0.004), but slightly weaker and not statistically significant in the replication sample (hazard ratio 1.06, 95% CI 1.00-1.14, p = 0.06). In contrast, strong and consistent associations were found between endostatin and cardiovascular and all-cause mortality in all multivariable models and sub-samples. Addition of endostatin to a model with established cardiovascular risk factors provided no substantial improvement of risk prediction (<1%).
Conclusions:
Raised levels of serum endostatin might be associated with cardiovascular events in patients with stable coronary heart disease. The clinical utility of endostatin measurements remains to be established.
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