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Journals / Uludağ Üniversitesi Tıp Fakültesi Dergisi / 2026 / Cilt: 52

Modified Endothelial Activation and Stress Index (mEASIX) Predicts Long-Term Mortality in Patients with Acute Coronary Syndromes

Akut Koroner Sendrom ile Başvuran Hastalarda Modifiye Endotelyal Aktivasyon ve Stres İndeksinin (mEASIX) Uzun Dönem Mortaliteyi Öngörmedeki Değeri

Çetin Alak(Department of Cardiology, Faculty of Medicine, Bursa Uludag University, Bursa, Türkiye.)0000-0003-1875-2078
Kaan Turhan(Department of Cardiology, Faculty of Medicine, Bursa Uludag University, Bursa, Türkiye.)0009-0009-7333-3301
Fazıl Cagrı Hunutlu(Division of Hematology, Department of Internal Medicine, Bursa Sehir Training and Research Hospital, University of Health Sciences, Bursa, Türkiye.)0000-0002-4991-9830
Zeynep Kumral(Department of Cardiology, Unye State Hospital, Ordu, Türkiye.)0000-0003-2422-9363
Bülent Özdemir(Department of Cardiology, Faculty of Medicine, Bursa Uludag University, Bursa, Türkiye.)0000-0002-8886-7703
Pages
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Publication Date
2026-09-10
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AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

Further prospective validation is required before clinical implementation.

📌 3 Key Takeaways

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Objective & Hypothesis:Endothelial dysfunction, inflammation, and microvascular injury are key mechanisms involved in the development and progression of acute coronary syndrome (ACS).
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Key Findings & Data:The Endothelial Activation and Stress Index (EASIX) and its derivatives have emerged as readily available biomarkers of endothelial stress; however, the prognostic value of modified EASIX (m-EASIX), which incorporates C-reactive protein, remains uncertain.
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Conclusion & Impact:Further prospective validation is required before clinical implementation.
🔬Design:Modeling & Simulation
📍Scope:2019 Verileri
⚙️Variables:Akut koroner sendrom · endotelyal disfonksiyon · EASIX

Abstract

Endothelial dysfunction, inflammation, and microvascular injury are key mechanisms involved in the development and progression of acute coronary syndrome (ACS). The Endothelial Activation and Stress Index (EASIX) and its derivatives have emerged as readily available biomarkers of endothelial stress; however, the prognostic value of modified EASIX (m-EASIX), which incorporates C-reactive protein, remains uncertain. This study evaluated the prognostic performance of EASIX-derived indices and investigated whether high admission m-EASIX was independently associated with long-term post-discharge all-cause mortality in patients with ACS. Adult patients admitted with ACS between January 2019 and February 2020 who survived the index hospitalization and were discharged alive were retrospectively identified from a tertiary referral center. EASIX, simplified EASIX (s-EASIX), and m-EASIX were calculated from admission laboratory measurements, and their prognostic performance was evaluated using receiver operating characteristic analysis, Kaplan–Meier survival curves, and multivariable Cox proportional hazards models. Among 102 patients who survived the index ACS hospitalization, 29 (28.4%) died during a mean post-discharge follow-up of 68.2 ± 28.0 months. m-EASIX showed the numerically highest AUC for post-discharge all-cause mortality (AUC 0.730, 95% CI 0.617–0.843; p<0.001), followed by EASIX (AUC 0.715) and s-EASIX (AUC 0.629). However, paired DeLong comparisons showed no significant difference between m-EASIX and EASIX (p=0.809) or between m-EASIX and s-EASIX (p=0.158). Patients with m-EASIX ≥1.21 had significantly higher mortality than those with lower values (53.7% vs. 11.5%; p<0.001). After adjustment for age, hemoglobin concentration, and left ventricular ejection fraction, high m-EASIX remained independently associated with post-discharge all-cause mortality (HR 2.759, 95% CI 1.109–6.865; p=0.029). Among the evaluated indices, m-EASIX showed the numerically highest AUC, although its discriminatory performance was not statistically superior to that of EASIX or s-EASIX. Further prospective validation is required before clinical implementation.

Özet

Endotelyal disfonksiyon, inflamasyon ve mikrovasküler hasar, akut koroner sendromun (AKS) gelişim ve ilerlemesinde rol oynayan temel mekanizmalardır. Endotelyal Aktivasyon ve Stres İndeksi (EASIX) ve türevleri endotelyal stresi yansıtan kolay erişilebilir biyobelirteçlerdir. Ancak, C-reaktif proteini içeren modifiye EASIX'in (m-EASIX) prognostik değeri net değildir. Bu çalışmada, EASIX türevi indekslerin prognostik performansı değerlendirildi ve başvuru anındaki mEASIX düzeyinin AKS ile başvuran hastalarda uzun dönem tüm nedenlere bağlı mortalite ile bağımsız ilişkisi araştırıldı. Ocak 2019 ile Şubat 2020 tarihleri arasında üçüncü basamak bir merkezde AKS tanısıyla başvuran erişkin hastalar retrospektif olarak değerlendirildi. Başvuru laboratuvar verileri kullanılarak EASIX, basitleştirilmiş EASIX (s-EASIX) ve modifiye EASIX (m-EASIX) hesaplandı. İndekslerin prognostik performansı ROC analizi, Kaplan–Meier sağkalım eğrileri ve çok değişkenli Cox orantısal risk regresyon analizi ile değerlendirildi. m-EASIX, taburculuk sonrası tüm nedenlere bağlı mortaliteyi öngörmede sayısal olarak en yüksek AUC değerini gösterdi (AUC: 0,730; %95 GA: 0,617–0,843; p<0,001); bunu EASIX (AUC: 0,715) ve s-EASIX (AUC: 0,629) izledi. Bununla birlikte, eşleştirilmiş DeLong karşılaştırmalarında m-EASIX ile EASIX (p=0,809) veya s-EASIX (p=0,158) arasında anlamlı fark saptanmadı. m-EASIX ≥1,21 olan grupta mortalite oranı, m-EASIX <1,21 olan gruba kıyasla anlamlı olarak daha yüksekti (%53,7’ye karşı %11,5; p<0,001). Yaş, hemoglobin düzeyi ve sol ventrikül ejeksiyon fraksiyonu için düzeltme sonrasında yüksek m-EASIX, taburculuk sonrası tüm nedenlere bağlı mortalite ile bağımsız olarak ilişkiliydi (HR: 2,759; %95 GA: 1,109–6,865; p=0,029). Değerlendirilen indeksler arasında m-EASIX sayısal olarak en yüksek AUC değerini göstermekle birlikte, ayırt edici performansı EASIX veya s-EASIX’ten istatistiksel olarak üstün değildi. Klinik kullanıma geçilmeden önce prospektif çalışmalarda doğrulanması gerekmektedir.

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Cite This Article

Alak, Ç., Turhan, K., Hunutlu, F. C., Kumral, Z., Özdemir, B., *, Ç. A. (2026). Modified Endothelial Activation and Stress Index (mEASIX) Predicts Long-Term Mortality in Patients with Acute Coronary Syndromes. Uludağ Üniversitesi Tıp Fakültesi Dergisi, Cilt: 52. https://doi.org/10.32708/uutfd.2000692

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References (19)

  1. Byrne, R.A.; Rossello, X.; Coughlan, J.J.; Barbato, E.; Berry, C.; Chieffo, A.; Claeys, M.J.; Dan, G.-A.; Dweck, M.R.; Galbraith, M.; et al. 2023 ESC Guidelines for the management of acute coronary syndromes: Developed by the Task Force on the management of acute coronary syndromes of the European Society of Cardiology (ESC). Eur. Heart J. 2023, 44, 3720–3826. https://doi.org/10.1093/eurheartj/ehad191
  2. Bauer, D.; Toušek, P. Risk stratification of patients with acute coronary syndrome. J. Clin. Med. 2021, 10, 4574. https://doi.org/10.3390/jcm10194574
  3. Tsalamandris, S.; Koliastasis, L.; Miliou, A.; Oikonomou, E.; Papageorgiou, N.; Antonopoulos, A.; Hatzis, G.; Mourouzis, K.; Vogiatzi, G.; Siasos, G.; Xaplanteris, P.; Tousoulis, D. Endothelial function and pro-inflammatory cytokines as prognostic markers in acute coronary syndromes. Diagnostics 2025, 15, 1033. https://doi.org/10.3390/diagnostics15081033
  4. Xiong, X.; Wang, J.; Ren, L.; Li, Z.; Liu, Y.; Xia, P.; Duan, L. The emerging pathological mechanism of coronary microvascular dysfunction: A narrative review. Metab. Target Organ Damage 2025, 5, 54. https://doi.org/10.20517/mtod.2025.71
  5. Ziogos, E.; Chelko, S.P.; Harb, T.; Engel, M.; Vavuranakis, M.A.; Landim-Vieira, M.; Walsh, E.M.; Williams, M.S.; Lai, S.; Halushka, M.K.; Gerstenblith, G.; Leucker, T.M. Platelet activation and endothelial dysfunction biomarkers in acute coronary syndrome: The impact of PCSK9 inhibition. Eur. Heart J. Cardiovasc. Pharmacother. 2023, 9, 636–646. https://doi.org/10.1093/ehjcvp/pvad051
  6. Finke, D.; Hund, H.; Frey, N.; Luft, T.; Lehmann, L.H. EASIX(endothelial activation and stress index) predicts mortality inpatients with coronary artery disease. Clin. Res. Cardiol. 2025, 114, 1008–1018. https://doi.org/10.1007/s00392-024-02534-y
  7. Sang, M.; Ma, X.; Zhu, F.; Zhu, C.; Ying, Z. Association between endothelial activation and stress index and 30-day mortality risk in acute myocardial infarction patients: A study based on the Medical Information Mart for Intensive Care-IVdatabase. BMC Cardiovasc. Disord. 2024, 24, 699.https://doi.org/10.1186/s12872-024-04353-5
  8. Karauzum, K.; Tanık, V.O.; Taş, A.; Mirzamidinov, D.; Şimşek, U.; Gencer, E.; Çelik, F.; Badalova, N.; Büyükbaş, F.C.; Yılmaz, I.; et al. The role of endothelial activation and stress index (EASIX) for predicting contrast-induced nephropathy and in-hospital mortality in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. Diagnostics 2026, 16, 1123. https://doi.org/10.3390/diagnostics16081123
  9. Şahin, Y.B.; Tanık, V.O.; Boz, S.; Akdoğan, M.; Tunca, Ç.; Seçkin, Ö.; Taş, A.; Özlek, B. Admission EASIX score predictscoronary no-reflow and in-hospital mortality in STEMI patientsundergoing primary PCI. J. Clin. Med. 2026, 15, 1063.https://doi.org/10.3390/jcm15031063
  10. Faideci, E.M.; Hancıoğlu, E.; Ziyrek, M.; Özcan, S.; Güzel, S.; Alak, M.E.; Aslan, R.; Ardahanlı, İ.; Ertan, Ç.; Şahin, İ.;Okuyan, E. Endothelial activation and stress index (EASIX) asa novel index associated with no-reflow phenomenon inSTEMI: A bi-center retrospective study. BMC Cardiovasc.Disord. 2026, 26, 363. https://doi.org/10.1186/s12872-026-05719-7
  11. Tekin, I.; Büber, İ.; Avcı, E. Endothelial stress indices in acute coronary syndrome: Comparative prognostic performance ofEASIX and its variants. J. Lab. Med. 2026, 50, 120–127. https://doi.org/10.1515/labmed-2025-0275
  12. Wu, H.; Wu, Z.; Xin, Y.; Jiang, X.; Guo, C. Lactate dehydrogenase-to-albumin ratio for the severity of coronaryartery disease in acute myocardial infarction: A retrospective study. J. Int. Med. Res. 2026, 54, 3000605251409694.https://doi.org/10.1177/03000605251409694
  13. Libby, P. The changing landscape of atherosclerosis. Nature 2021, 592, 524–533. https://doi.org/10.1038/s41586-021-03392-8
  14. Ajoolabady, A.; Pratico, D.; Lin, L.; Mantzoros, C.S.; Bahijri,S.; Tuomilehto, J.; Ren, J. Inflammation in atherosclerosis: Pathophysiology and mechanisms. Cell Death Dis. 2024, 15, 817. https://doi.org/10.1038/s41419-024-07166-8
  15. Henein, M.Y.; Vancheri, S.; Longo, G.; Vancheri, F. The Roleof Inflammation in Cardiovascular Disease. Int. J. Mol.Sci. 2022, 23, 12906. https://doi.org/10.3390/ijms232112906
  16. Arnold, N.; Koenig, W. Inflammation in atheroscleroticcardiovascular disease: From diagnosis to treatment. Eur. J. Clin. Invest. 2025, 55, e70020.https://doi.org/10.1111/eci.70020
  17. Ridker, P.M. Residual inflammatory risk: Addressing the obverse side of the atherosclerosis prevention coin. Eur. HeartJ. 2016, 37, 1720–1722. https://doi.org/10.1093/eurheartj/ehw024
  18. Lin, Q.; Zhao, W.; Zhang, H.; Chen, W.; Lian, S.; Ruan, Q.;Qu, Z.; Lin, Y.; Chai, D.; Lin, X. Predicting the risk of heartfailure after acute myocardial infarction using an interpretablemachine learning model. Front. Cardiovasc. Med. 2025, 12, 1444323. https://doi.org/10.3389/fcvm.2025.1444323
  19. Zhang, H.; Kang, K.; Chen, S.; Su, Q.; Zhang, W.; Zeng, L.;Lin, X.; Peng, F.; Lin, J.; Chai, D. High serum lactatedehydrogenase as a predictor of cardiac insufficiency at follow-up in elderly patients with acute myocardial infarction. Arch. Gerontol. Geriatr. 2024, 117, 105253.https://doi.org/10.1016/j.archger.2023.105253