Predictive Value of the Inflammatory Prognostic Index for Ischemic Stroke in Patients with HFpEF and Atrial Fibrillation

Öz

Aim: This study aimed to evaluate the predictive value of the inflammatory prognostic index (IPI) for ischemic cerebrovascular events in patients with heart failure with preserved ejection fraction (HFpEF) and atrial fibrillation (AF). Material and Methods: A total of 1,286 patients with HFpEF and AF followed between 2020 and 2024 were retrospectively included. The primary endpoint was the occurrence of ischemic stroke during follow-up. The mean follow-up duration was 651 ± 167 days. IPI and CHA₂DS₂-VA scores were calculated. Cox regression, receiver operating characteristic (ROC), and Kaplan–Meier analyses were performed. Results: Ischemic stroke occurred in 67 patients (5.2%). Patients with stroke were older and had higher rates of hypertension, coronary artery disease, and prior stroke/TIA, while oral anticoagulant use was lower. They also exhibited higher creatinine, CRP, and neutrophil levels and lower lymphocyte counts. Both IPI and CHA₂DS₂-VA scores were significantly higher in the stroke group. In multivariable analysis, creatinine (HR: 1.828), CHA₂DS₂-VA (HR: 2.081), and IPI (HR: 1.909) remained independent predictors of stroke. ROC analysis showed that IPI had superior discriminative ability compared to CHA₂DS₂-VA (AUC: 0.783 vs. 0.726). Kaplan–Meier analysis demonstrated a significantly higher incidence of stroke in patients with elevated IPI levels (log-rank p<0.001). Conclusion: IPI is a strong and independent predictor of ischemic stroke in patients with HFpEF and AF. Integration of inflammation-based biomarkers into conventional clinical risk scores may improve risk stratification, particularly in high-risk populations.

Anahtar Kelimeler

• Atrial fibrillation
• HFpEF
• Inflammatory prognostic index
• Ischemic stroke

Kaynakça

1. 1. Van Gelder IC, Rienstra M, Bunting KV, Casado-Arroyo R, Caso V, Crijns H, et al. 2024 ESC guidelines for the management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2024;45(36):3314–414. https://doi.org/10.1093/eurheartj/ehae176
2. 2. Hindricks G, Potpara T, Dagres N, Arbelo E, Bax JJ, Blomstrom-Lundqvist C, et al. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): the task force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Eur Heart J. 2021;42(5):373–498. https://doi.org/10.1093/eurheartj/ehaa612
3. 3. Zabierowski J, Hudzik B, Nowak J, Gasior M. Emerging risk factors for stroke and bleeding in patients with atrial fibrillation and heart failure-a narrative review. Curr Probl Cardiol. 2026;51(3):103231. https://doi.org/10.1016/j.cpcardiol.2025.103231
4. 4. Fauchier L, Bisson A, Bodin A. Heart failure with preserved ejection fraction and atrial fibrillation: recent advances and open questions. BMC Med. 2023;21(1):54. https://doi.org/10.1186/s12916-023-02764-3
5. 5. Hu YF, Chen YJ, Lin YJ, Chen SA. Inflammation and the pathogenesis of atrial fibrillation. Nat Rev Cardiol. 2015;12(4):230–243. https://doi.org/10.1038/nrcardio.2015.2
6. 6. Hazarapetyan L, Zelveian PH, Grigoryan S. Inflammation and coagulation are two interconnected pathophysiological pathways in atrial fibrillation pathogenesis. J Inflamm Res. 2023;16:4967–4975. https://doi.org/10.2147/JIR.S429892
7. 7. Tomita M, Ayabe T, Maeda R, Nakamura K. The inflammatory prognostic index predicts cancer-specific outcomes of patients with resected non-small cell lung cancer. Asian Pac J Cancer Prev. 2018;19(10):2867–2870. https://doi.org/10.22034/APJCP.2018.19.10.2867
8. 8. McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Bohm M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021;42(36):3599–3726. https://doi.org/10.1093/eurheartj/ehab368

9. 9. Benjamin EJ, Muntner P, Alonso A, Bittencourt MS, Callaway CW, Carson AP, et al. Heart disease and stroke statistics 2019 update: a report from the American Heart Association. Circulation. 2019;139(10):e56–e528. https://doi.org/10.1161/CIR.0000000000000659
10. 10. Melgaard L, Gorst-Rasmussen A, Lane DA, Rasmussen LH, Larsen TB, Lip GY. Assessment of the CHA2DS2-VASc score in predicting ischemic stroke, thromboembolism, and death in patients with heart failure with and without atrial fibrillation. JAMA. 2015;314(10):1030–1038. https://doi.org/10.1001/jama.2015.10725
11. 11. Patel RB, Greene SJ, Xu H, Alhanti B, Peterson P, Yancy CW, et al. Intersection of atrial fibrillation and heart failure with mildly reduced and preserved ejection fraction in >400 000 participants in the get with the guidelines-heart failure registry. Eur J Heart Fail. 2023;25(1):63–73. https://doi.org/10.1002/ejhf.2729
12. 12. Canepa M, Kapelios CJ, Benson L, Savarese G, Lund LH. Temporal trends of heart failure hospitalizations in cardiology versus noncardiology wards according to ejection fraction:16-year data from the SwedeHF registry. Circ Heart Fail. 2022;15(8):e009462. https://doi.org/10.1161/CIRCHEARTFAILURE.121.009462
13. 13. Ito T, Noda T, Nochioka K, Shiroto T, Yamamoto N, Sato H, et al. Clinical impact of atrial fibrillation progression in patients with heart failure with preserved ejection fraction: a report from the CHART-2 study. Europace. 2024;26(9):euae218. https://doi.org/10.1093/europace/euae218
14. 14. Zafrir B, Lund LH, Laroche C, Ruschitzka F, Crespo-Leiro MG, Coats AJS, et al. Prognostic implications of atrial fibrillation in heart failure with reduced, mid-range, and preserved ejection fraction: a report from 14 964 patients in the European Society of Cardiology Heart Failure long-term registry. Eur Heart J. 2018;39(48):4277–4284. https://doi.org/10.1093/eurheartj/ehy626
15. 15. Golla MSG, Shams P. Heart failure with preserved ejection fraction (HFpEF). StatPearls. Treasure Island (FL)2026.
16. 16. Paulus WJ, Tschope C. A novel paradigm for heart failure with preserved ejection fraction: comorbidities drive myocardial dysfunction and remodeling through coronary microvascular endothelial inflammation. J Am Coll Cardiol. 2013;62(4):263–271. https://doi.org/10.1016/j.jacc.2013.02.092
17. 17. Chang SN, Lai LP, Chiang FT, Lin JL, Hwang JJ, Tsai CT. C-reactive protein gene polymorphism predicts the risk of thromboembolic stroke in patients with atrial fibrillation: a more than 10-year prospective follow-up study. J Thromb Haemost. 2017;15(8):1541–1546. https://doi.org/10.1111/jth.13735
18. 18. Zhang S, Xu W, Xu J, Qiu Y, Wan Y, Fan Y. Association of C-reactive protein level with adverse outcomes in patients with atrial fibrillation: a meta-analysis. Am J Med Sci. 2024;367(1):41–48. https://doi.org/10.1016/j.amjms.2023.11.009
19. 19. Peng L, Liu L, Chai M, Cai Z, Wang D. Predictive value of neutrophil to lymphocyte ratio for clinical outcome in patients with atrial fibrillation: a systematic review and meta-analysis. Front Cardiovasc Med. 2024;11:1461923. https://doi.org/10.3389/fcvm.2024.1461923
20. 20. Wang Y, Du P, Xiao Q, Li J, Liu X, Tan J, et al. Relationship between serum albumin and risk of atrial fibrillation: a dose-response meta-analysis. Front Nutr. 2021;8:728353. https://doi.org/10.3389/fnut.2021.728353
21. 21. Dirican N, Dirican A, Anar C, Atalay S, Ozturk O, Bircan A, et al. A new inflammatory prognostic index, based on C-reactive protein, the neutrophil to lymphocyte ratio and serum albumin is useful for predicting prognosis in non-small cell lung cancer cases. Asian Pac J Cancer Prev. 2016;17(12):5101–5106. https://doi.org/10.22034/APJCP.2016.17.12.5101
22. 22. Ozveren A, Erdogan AP, Ekinci F. The inflammatory prognostic index as a potential predictor of prognosis in metastatic gastric cancer. Sci Rep. 2023;13(1):7755. https://doi.org/10.1038/s41598-023-34778-5
23. 23. Oflar E, Kalyoncuoglu M, Koyuncu A, Yildiz Erbas C, Sinoplu HA, Katkat F, et al. The role of the inflammatory prognostic index in patients with non-ST elevation myocardial infarction undergoing percutaneous coronary intervention. J Clin Med. 2025;14(13):4491. https://doi.org/10.3390/jcm14134491
24. 24. Saylik F, Cinar T, Tanboga IH. The predictive value of the inflammatory prognostic index for detecting no-reflow in ST-elevation myocardial infarction patients. Arq Bras Cardiol. 2024;121(4):e20230644. https://doi.org/10.36660/abc.20230644
25. 25. Jiang Y, Luo B, Chen Y, Peng Y, Lu W, Chen L, et al. Predictive value of inflammatory prognostic index for contrast-induced nephropathy in patients undergoing coronary angiography and/or percutaneous coronary intervention. Sci Rep. 2024;14(1):15861. https://doi.org/10.1038/s41598-024-66880-7
26. 26. Karabağ Y, Karahan T, Kina S, Erata Y, Demir Ö. The inflammatory prognostic index predicts new-onset atrial fibrillation in patients after primary percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction. Kafkas J Med Sci. 2025;15(1):112–118. https://doi.org/10.5505/kjms.2025.79282
27. 27. Ma F, Li L, Xu L, Wu J, Zhang A, Liao J, et al. The relationship between systemic inflammation index, systemic immune-inflammatory index, and inflammatory prognostic index and 90-day outcomes in acute ischemic stroke patients treated with intravenous thrombolysis. J Neuroinflammation. 2023;20(1):220. https://doi.org/10.1186/s12974-023-02890-y