Endovasküler Girişim Uygulanan Periferik Arter Hastalarında MELD-Albumin Skorunun Öngörücü Değeri: İki Yıllık Takip

Öz

Amaç: Periferik arter hastalığı (PAH), sistemik aterosklerozun bir yansıması olup, hastaları hem majör advers kardiyak olaylar (MACE) hem de majör advers ekstremite olayları (MALE) açısından yüksek risk altında bırakmaktadır. Bu çalışmanın temel amacı, endovasküler girişim uygulanan bu yüksek riskli hasta popülasyonunda, rutin kan tetkiklerinden kolayca hesaplanabilen MELD-XI ve MELD-Albumin skorlarının, 24 aylık takipte MACE ve MALE'i öngörmedeki prognostik gücünü karşılaştırmalı olarak değerlendirmek ve bu skorların klinik karar mekanizmalarındaki potansiyel yerini aydınlatmaktır. Materyal ve metod: Çalışmamız, 2018 ile 2022 yılları arasında kliniğimizde alt ekstremite PAH tanısıyla endovasküler girişim uygulanmış 427 hastanın verilerinin retrospektif olarak analiz edildiği bir kohort çalışmasıdır. Hastalar, MELD-Albumin skorlarına göre beş eşit gruba (quintile) ayrılmıştır. Birincil sonlanım noktaları, 24 aylık takip süresince gelişen MACE (kardiyovasküler ölüm, ölümcül olmayan miyokart enfarktüsü, ölümcül olmayan inme) ve MALE (majör ampütasyon, tekrar endovasküler veya cerrahi revaskülarizasyon) olarak tanımlanmıştır. Skorların ayırt edicilik kapasiteleri Alıcı İşletim Karakteristiği (ROC) eğrisi analizi ile, bağımsız öngördürücü rolleri ise çok değişkenli Cox regresyon analizi ile incelenmiştir. Bulgular: Çalışma popülasyonumuzda, MELD-Albumin skoru arttıkça hastaların demografik ve klinik risk profillerinin ağırlaştığı gözlenmiştir. Yüksek MELD-Albumin skoruna sahip gruplarda ileri yaş, diyabet, hipertansiyon, kronik böbrek hastalığı ve daha karmaşık lezyon morfolojisi gibi faktörler istatistiksel olarak anlamlı düzeyde daha yaygındı (tümü için p<0.001). Klinik takip neticesinde, en yüksek MELD-Albumin skoruna sahip beşinci gruptaki (Q5) hastaların, en düşük skorlu gruba (Q1) kıyasla hem MACE hem de MALE oranlarının dramatik şekilde arttığı saptanmıştır (kardiyovasküler ölüm için %26.8'e karşılık %2.7; majör amputasyon için %18.6'ya karşılık %6.0; p<0.001). Prognostik performans analizinde, MELD-Albumin skorunun MACE'i öngörmede (Eğri Altında Kalan Alan [AUC]: 0.872; %95 GA: 0.785-0.892) ve MALE'i öngörmede (AUC: 0.803; %95 GA: 0.739-0.869) MELD-XI skoruna (sırasıyla AUC: 0.723 ve 0.583) kıyasla istatistiksel olarak anlamlı derecede üstün bir öngörü gücüne sahip olduğu kanıtlanmıştır. Cox regresyon analizi, MELD-Albumin skorunun yaş, diyabet ve diğer bilinen risk faktörlerinden bağımsız olarak hem MACE hem de MALE için güçlü bir bağımsız belirteç olduğunu ortaya koymuştur (p<0.001). Sonuç: MELD-Albumin skoru, karaciğer-böbrek aksının fonksiyonel durumunu ve hastanın nutrisyonel/enflamatuar statüsünü yansıtan biyobe-lirteçleri bir araya getirerek, endovasküler tedavi uygulanan PAH hastalarında gelecekteki kardiyovasküler ve ekstremiteye bağlı olumsuz olayları öngörmede basit, maliyet-etkin ve güçlü bir prognostik araçtır. Bulgularımız, bu skorun MELD-XI'e kıyasla daha üstün bir performansa sahip olduğunu ve klinisyenlerin risk sınıflandırması yaparak tedavi stratejilerini bireyselleştirmelerine yardımcı olabileceğini güçlü bir şekilde desteklemektedir. Anahtar Kelimeler: MELD-Albumin Skoru, Periferik Arter Hastalığı, Endovasküler Girişim, Majör Advers Kardiyak Olaylar, Majör Advers Ekstremite Olayları, Prognoz

Anahtar Kelimeler

• MELD-Albumin
• Periferik Arter Hastalığı
• MACE
• MALE

Etik Beyan

Çalışma, Helsinki Bildirgesi'ne uygun olarak yürütülmüş olup, Ordu Üniversitesi Klinik Araştırmalar Etik Kurulu'nun 05/04/2024 tarihli toplantısında 51 karar numarası ile onaylanmıştır. Hastalardan bilgilendirilmiş onam formu alınmıştır.

Predictive Value of MELD-Albumin Score in Patients with Peripheral Artery Disease Undergoing Endovascular Intervention: Two-Years Follow-Up

Öz

Background: Peripheral artery disease (PAD) is a manifestation of systemic atherosclerosis and places patients at high risk for both major adverse cardiac events (MACE) and major adverse limb events (MALE). The primary objective of this study is to compare the prognostic value of MELD-XI and MELD-Albumin scores, which can be easily calculated from routine blood tests, in predicting MACE and MALE at 24 months of follow-up in this high-risk patient population undergoing endovascular intervention, and to elucidate the potential role of these scores in clinical decision-making mechanisms. Materials and Methods: Our study is a retrospective cohort analysis of data from 427 patients who underwent endovascular intervention for lower extremity PAH at our clinic between 2018 and 2022. Patients were divided into five equal groups (quintiles) based on their MELD-Albumin scores. Primary endpoints were defined as MACE (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke) and MALE (major amputation, repeat endovascular or surgical revascularization) occurring during a 24-month follow-up period. The discriminatory capaci-ty of the scores was analyzed using Receiver Operating Characteristic (ROC) curve analysis, while their independent predictive roles were examined using multivariate Cox regression analysis. Results: In our study population, an increase in the MELD-Albumin score was associated with worsening demographic and clinical risk profiles. In groups with high MELD-Albumin scores, factors such as advanced age, diabetes, hypertension, chronic kidney disease, and more complex lesion morphology were statistically significantly more prevalent (p<0.001 for all). Following clinical follow-up, patients in the fifth group (Q5) with the highest MELD-Albumin scores had dramatically increased rates of both MACE and MALE compared to the lowest-scoring group (Q1) (26.8% vs. 2.7% for cardiovascular death; 18.6% vs. 6.0% for major amputation; p<0.001). In prognostic performance analysis, the MELD-Albumin score demonstrated statistically significantly superior predictive power for predicting MACE (Area Under the Curve [AUC]: 0.872; 95% CI: 0.785–0.892) and MALE (AUC: 0.803; 95% CI: 0.739–0.869) compared to the MELD-XI score (with AUC: 0.723 and 0.583), respectively. Cox regression analysis demonstrated that the MELD-Albumin score is a strong independent predictor of both MACE and MALE, independent of age, diabetes, and other known risk factors (p<0.001). Conclusions: The MELD-Albumin score, by combining biomarkers reflecting the functional status of the liver-kidney axis and the patient's nutritional/inflammatory status, serves as a simple, cost-effective, and robust prognostic tool for predicting future cardiovascular and limb-related adverse events in PAH patients undergoing endovascular therapy. Our findings strongly support that this score outperforms MELD-XI and may assist clinicians in risk stratification and individualization of treatment strategies. Keywords: MELD-Albumin Score, Peripheral Arterial Disease, Endovascular Intervention, Major Adverse Cardiac Events, Major Adverse Limb Events, Prognosis

Anahtar Kelimeler

• : MELD-Albumin
• Peripheral Artery Disease
• MACE
• MALE

Kaynakça

1. 1. Cook IO, Chung J. Contemporary Medical Management of Peripheral Arterial Disease. Cardiovasc Drugs Ther. 2023. Epub 20231102. doi: 10.1007/s10557-023-07516-2. PubMed PMID: 37914901.
2. 2. MOA A, MOA A, Tablet F, Tablet M, Tablet E, MOA A. Peripheral vascular disease. PHA FORMULARY. 2023:81.
3. 3. Dong Y, Liu Y, Cheng P, Liao H, Jiang C, Li Y, et al. Lower limb arterial calcification and its clinical relevance with peripheral arterial disease. Frontiers in Cardiovascular Medicine. 2023;10:1271100.
4. 4. Golledge J. Pathology, Progression, and Emerging Treatments of Peripheral Artery Disease–Related Limb Ischamia. Clinical Therapeutics. 2023.
5. 5. Yu X, Wang B, Qiu C, He Y, Chen T, Zhu Q, et al. A systematic review and meta-analysis of primary bypass surgery compared with bypass surgery after endovascular treatment in peripher-al artery disease patients. Journal of Vascular Surgery. 2023.
6. 6. Rahman ÖF, Özkısacık EA. Patency and Survival in Patients Undergoing Revascularization for Peripheral Arterial Disease. Sağlık Bilimlerinde Değer. 2024;14(2):215-23.
7. 7. Anılır E, Topcu FS, Oral A, Şahin E, Dirican A, Ünal B. Periopera-tive findings and postoperative complications in living donor liver transplantation recipients with high MELD scores. Akad-emik Gastroenteroloji Dergisi. 2023;22(3):150-4.
8. 8. Sungur A, Sungur MA, Yıldırımtürk Ö. Effect of Albumin-Bilirubin Score on Prognosis in Ambulatory Heart Failure Pa-tients with Reduced Ejection Fraction. Archives of the Turkish Society of Cardiology/Türk Kardiyoloji Derneği Arşivi. 2024;52(2).

9. 9. İdin K, Dereli S, Yenerçağ M, Kaya A. MELD-Albumin score predicts 30-day mortality in high-risk patients with acute pul-monary embolism admitted to intensive care units. 2020.
10. 10. Ludușanu A, Ciuntu BM, Tanevski A, Bernic V, Tinica G. Correla-tion between MELD Score and Postoperative Outcomes in Pa-tients Undergoing Coronary Artery Bypass Surgery: A Retro-spective Study. 2024.
11. 11. Krafcik BM, Farber A, Eslami MH, Kalish JA, Rybin D, Doros G, et al. The role of Model for End-Stage Liver Disease (MELD) score in predicting outcomes for lower extremity bypass. Journal of Vascular Surgery. 2016;64(1):124-30.
12. 12. Members WC, Gerhard-Herman MD, Gornik HL, Barrett C, Barshes NR, Corriere MA, et al. 2016 AHA/ACC guideline on the management of patients with lower extremity peripheral artery disease: executive summary. Vascular Medicine. 2017;22(3):NP1-NP43.
13. 13. Parvar SL, Thiyagarajah A, Nerlekar N, King P, Nicholls SJ. A systematic review and meta-analysis of gender differences in long-term mortality and cardiovascular events in peripheral artery disease. Journal of Vascular Surgery. 2021;73(4):1456-65. e7.
14. 14. Byrne RA, Rossello X, Coughlan JJ, Barbato E, Berry C, Chieffo A, et al. 2023 ESC Guidelines for the management of acute coronary syndromes: Developed by the task force on the man-agement of acute coronary syndromes of the European Society of Cardiology (ESC). European Heart Journal. 2023;44(38):3720-826. doi: 10.1093/eurheartj/ehad191.
15. 15. Murphy SJ, Werring DJ. Stroke: causes and clinical features. Medicine. 2020;48(9):561-6.
16. 16. Ruf A, Dirchwolf M, Freeman RB. From Child-Pugh to MELD score and beyond: Taking a walk down memory lane. Annals of Hepatology. 2022;27(1):100535.
17. 17. Kim WR, Mannalithara A, Heimbach JK, Kamath PS, Asrani SK, Biggins SW, et al. MELD 3.0: the model for end-stage liver dis-ease updated for the modern era. Gastroenterology. 2021;161(6):1887-95. e4.
18. 18. Kirov H, Caldonazo T, Audisio K, Rahouma M, Robinson NB, Cancelli G, et al. Association of liver dysfunction with out-comes after cardiac surgery—a meta-analysis. Interactive Car-dioVascular and Thoracic Surgery. 2022;35(6):ivac280.
19. 19. Dereli S, Yenerçağ M, Kaya A. Primer Perkütan Koroner Girişim Yapılan ST-Segment Elevasyonlu Miyokard Enfarktüsünde MELD-Albumin Skorunun Prediktif Rolü. Harran Üniversitesi Tıp Fakültesi Dergisi. 2020;17(3):389-96.
20. 20. Ziberna L, Martelanc M, Franko M, Passamonti S. Bilirubin is an endogenous antioxidant in human vascular endothelial cells. Sci Rep. 2016;6(1):29240.
21. 21. Sedlak TW, Snyder SH. Bilirubin benefits: cellular protection by a biliverdin reductase antioxidant cycle. Pediatrics. 2004;113(6):1776-82.
22. 22. Koca TT, Çetin GY, Göğebakan H, Nacitarhan V. The clinic importance of bilirubin parameters in ankylosing spondylitis: Case control study. Journal of Surgery and Medicine. 2018;2(3):330-3.
23. 23. Özden Ö, Avcı BK, İkitimur B, Cimci M, Ertürk E, Omar T, et al. Serum Bilirubin Level is Positively Correlated with Severity of Coronary Artery Disease in Patients with Non-St Elevation Acute Coronary Syndrome. Gazi Medical Journal. 2023;34(2).
24. 24. Demirel Y, Taş A, Taş F, Bolayır E, Topaktaş S. Evaluation of the effects of serum bilirubin levels on intimal medial hyperplasia of carotis vessels. Erciyes tıp dergisi= Erciyes Medical Journal. 2005;27(2):53.
25. 25. Tanaka M, Fukui M, Tomiyasu K-i, Akabame S, Nakano K, Haseg-awa G, et al. Low serum bilirubin concentration is associated with coronary artery calcification (CAC). Atherosclerosis. 2009;206(1):287-91.
26. 26. Wang H-Y, Han P, Zhang W-H, Liu B, Li H-L, Wang H-J, et al. Serum bilirubin level is negatively correlated with disease progression of peripheral arterial disease: an observational cohort study. Angiology. 2012;63(4):248-53.
27. 27. Kim K-M, Kim B-T, Park S-B, Cho D-Y, Je SH, Kim K-N. Serum total bilirubin concentration is inversely correlated with Fram-ingham risk score in Koreans. Archives of medical research. 2012;43(4):288-93.
28. 28. Dentali F, Douketis JD, Lim W, Crowther M. Combined aspi-rin–oral anticoagulant therapy compared with oral anticoagu-lant therapy alone among patients at risk for cardiovascular disease: a meta-analysis of randomized trials. Archives of in-ternal medicine. 2007;167(2):117-24.
29. 29. Giannini EG, Risso D, Caglieris S, Testa R. Longitudinal modifi-cations of the MELD score have prognostic meaning in patients with liver cirrhosis. Journal of clinical gastroenterology. 2005;39(10):912-4.
30. 30. Krafcik B, Rybin DV, Doros G, Farber A, Kalish J, Eslami MH, et al. The Role of Model of End-Stage Liver Disease (MELD) Score in Predicting Outcomes for Lower Extremity Bypass in Patients with Liver Disease. Journal of Vascular Surgery. 2015;61(6):78S.
31. 31. Wu N, Liu T, Tian M, Liu C, Ma S, Cao H, et al. Albumin, an interesting and functionally diverse protein, varies from ‘na-tive’to ‘effective’. Molecular Medicine Reports. 2024;29(2):1-15.
32. 32. Manolis AA, Manolis TA, Melita H, Mikhailidis DP, Manolis AS. Low serum albumin: a neglected predictor in patients with cardiovascular disease. European Journal of Internal Medicine. 2022;102:24-39.
33. 33. Bath J, Smith JB, Woodard J, Kruse RL, Vogel TR. Complex relationship between low albumin level and poor outcome af-ter lower extremity procedures for peripheral artery disease. Journal of vascular surgery. 2021;73(1):200-9.
34. 34. Ronit A, Kirkegaard-Klitbo DM, Dohlmann TL, Lundgren J, Sabin CA, Phillips AN, et al. Plasma albumin and incident cardiovas-cular disease: results from the CGPS and an updated meta-analysis. Arteriosclerosis, thrombosis, and vascular biology. 2020;40(2):473-82.
35. 35. Tran B. Assessment and management of peripheral arterial disease: what every cardiologist should know. Heart. 2021;107(22):1835-43.
36. 36. Mishra N. Use of ABI to detect peripheral arterial disease in diabetes–A recommendation for primary care physicians. Journal of Family Medicine and Primary Care. 2021;10(1):154-7.
37. 37. Porras CP, Teraa M, Damen JA, Hazenberg CE, Bots ML, Verhaar MC, et al. Prognostic Factors and Models to Predict Mortality Outcomes in Patients with Peripheral Arterial Disease: A Sys-tematic Review. Eur J Vasc Endovasc Surg. 2024;68(3):361-377.