Serum Endothelin-1 Level >2.0 pg/mL associates with High-Risk Duke Treadmill Score among Chronic Coronary Syndrome Patients

Muhammad Sarwansyah Putra (Department of Cardiology and Vascular Medicine, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada – Dr. Sardjito Hospital, Yogyakarta, Indonesia.)
Irsad Andi Arso (Department of Cardiology and Vascular Medicine, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada – Dr. Sardjito Hospital, Yogyakarta, Indonesia.)
Ira Puspitawati (Department of Clinical Pathology and Laboratory Medicine, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada–Dr. Sardjito Hospital, Yogyakarta, Indonesia)
Anggoro Budi Hartopo (Department of Cardiology and Vascular Medicine, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada – Dr. Sardjito Hospital, Yogyakarta, Indonesia.)

Indonesian Journal of Cardiology
Online First

Background: Chronic coronary syndrome (CCS) contributes to morbidity and increased risk of acute coronary syndrome within 5 years. Duke Treadmill Score (DTS) is the most robust risk stratification based on cardiac exercise stress test, which predicts 5-year survival. Those with high-risk DTS (DTS ≤11) had the least favorable survival. Endothelin-1, a potent vasoconstrictor peptide, affects the 5-year survival in CCS. This study aimed to investigate the association between serum endothelin-1 level and DTS risk stratification among Indonesian patients with CCS. Methods: This was a cross-sectional study that recruited consecutive patients with CCS after Coronary Angiography (CAG). The DTS data were collected from the previous Treadmill Test (TMT) and were classified into high-risk DTS (DTS ≤-11) and low-moderate-risk DTS (DTS >-11). A serum sample for measuring endothelin-1 was withdrawn during CAG and used in the ELISA protocol. A high endothelin-1 level was defined as > 2.0 pg/mL. An association between variables was assessed using statistical analysis (significance at p < 0.05). Results: Eighty subjects were enrolled. Median time interval of TMT and endothelin-1 measurement was 30 days. Mean age was 58.48±8.73 years old, with males predominant (82.5%). Hypertension (71.3%) and previous Acute Coronary Syndrome (ACS) (52.5%) were dominant. The proportion of subjects with high-risk DTS was 52.5%. Median endothelin-1 level was 1.8 pg/mL (range: 0.4 - 6.8 pg/mL). Serum endothelin-1 level > 2.0 pg/mL was observed in 34 subjects (42.5%), of whom 23 (67.6%) had high-risk DTS. There was a significantly increased risk of high-risk DTS in subjects with serum endothelin-1 >2.0 pg/mL (OR 2.97; 95% CI 1.18-7.51; p=0.020). Based on bivariate analysis, two variables, namely hypertension (p=0.052) and history of ACS (p=0.036), were also significantly associated with high-risk DTS. In multivariate analysis, endothelin-1 level >2.0 pg/mL had an adjusted OR of 1.75 (95% CI: 0.60-5.13, p=0.305), indicating no statistically significant independent association with high-risk DTS. Hypertension and a history of ACS had an independent and significant association with high-risk DTS. Conclusion: Among CCS patients, serum endothelin-1 level > 2.0 pg/mL was associated with high-risk DTS from TMT examination. However, this association was not independent, as in hypertension and history of ACS.