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Dirençli hipertansiyon için yeni prediktif biyobelirteçler olarak Sistemik İmmün-Enflamasyon İndeksi ve Sistemik Enflamatuar Yanıt İndeksi: karşılaştırmalı kesitsel çalışma

Year 2026, Volume: 9 Issue: 1, 156 - 163, 05.01.2026
https://doi.org/10.32322/jhsm.1831025
https://izlik.org/JA43UN47EW

Abstract

Amaç: Bu çalışma, sistemik bağışıklık-inflamasyon indeksi (SII) ve sistemik inflamatuar yanıt indeksi (SIRI) gibi bileşik inflamasyon indeksleri ile dirençli hipertansiyon arasındaki ilişkiyi araştırarak, bunların öngörücü performansını ve klinik yararını değerlendirmiştir.

Materyal ve metod: Nisan 2022'den Ocak 2025'e kadar yürütülen bu karşılaştırmalı kesitsel çalışmaya, 256'sı kontrollü hipertansiyon (HT) ve 244'ü dirençli hipertansiyon (RHT) olan 500 hipertansif hasta dahil edilmiştir. SII ve SIRI, tam kan sayımlarından hesaplanmıştır. Çok değişkenli lojistik regresyon, çeyrek analiz, kısıtlı kübik spline modelleme ve alıcı işletim karakteristiği (ROC) eğrisi analizi gerçekleştirildi.

Bulgular: RHT hastaları, anlamlı olarak yüksek SII (480,2'ye karşı 361,7, P<0,001) ve SIRI (0,73'e karşı 0,46, P<0,001) değerleri gösterdi. Çok değişkenli analiz, SIRI'yi RHT'nin en güçlü bağımsız öngörücüsü olarak belirledi (OR=25,954, %95 CI: 7,382-91,253, P<0,001). Çeyrek analizinde, RHT prevalansının SIRI çeyrekleri arasında %20,0'dan %84,0'a çıktığı (trend için P<0,001) bir doz-yanıt ilişkisi ortaya çıktı. SIRI, 0,6071'lik optimal kesme değeriyle (duyarlılık %68,0, özgüllük %75,8) mükemmel bir tanı performansı (AUC=0,780, %95 CI: 0,739-0,820) sergilemiştir. Cinsiyete göre tabakalandırılmış analiz, erkeklerin yüksek inflamatuar indekslere daha duyarlı olduğunu göstermiştir.

Sonuç: SII ve SIRI, dirençli hipertansiyonda önemli ölçüde yükselir ve güçlü, maliyet etkin prediktif biyomarkerler olarak işlev görür. SIRI (kesme değeri ≥0,6071) mükemmel bir tanı performansı sergiler ve hipertansif hastalarda risk sınıflandırması, erken teşhis ve hedefe yönelik tedavi stratejilerine rehberlik edebilir.

Ethical Statement

Bu çalışma için Ordu Üniversitesi Klinik Araştırmalar Etik Kurulu'ndan 25.03.2022 tarihinde, 2022/71 sayılı karar ile etik onay alınmıştır. Çalışma, Helsinki Bildirgesi prensiplerine uygun olarak yürütülmüştür. Tüm katılımcılardan bilgilendirilmiş onam formu alınmıştır.

Supporting Institution

Yazarlar, bu çalışma için herhangi bir kurum veya kuruluştan finansal destek almadıklarını beyan ederler.

Thanks

Yazarlar, bu çalışmaya katılımlarından dolayı tüm hastalara ve veri toplama sürecindeki katkıları için klinik personele teşekkür eder.

References

  • Mills KT, Stefanescu A, He J. The global epidemiology of hypertension. Nat Rev Nephrol. 2020;16:223-237. doi:10.1038/s41581-019-0244-2
  • de la Sierra A, Ruilope LM, Staplin N, et al. Resistant hypertension and mortality: an observational cohort study. Hypertension. 2024;81:2350-2356. doi:10.1161/HYPERTENSIONAHA.124.23276
  • McEvoy JW, McCarthy CP, Bruno RM, et al. 2024 ESC Guidelines for the management of elevated blood pressure and hypertension. Eur Heart J. 2024;45:3912-4018. doi:10.1093/eurheartj/ehae178
  • Mancia G, Kreutz R, Brunström M, et al. 2023 ESH Guidelines for the management of arterial hypertension. J Hypertens. 2023;41:1874-2071. doi:10.1097/HJH.0000000000003480
  • Carey RM, Sakhuja S, Calhoun DA, Whelton PK, Muntner P. Prevalence of apparent treatment-resistant hypertension in the united states. Hypertension. 2019;73:424-431. doi:10.1161/HYPERTENSIONAHA.118. 12191
  • Parodi R, Brandani L, Romero C, Klein M. Resistant hypertension: diagnosis, evaluation, and treatment practical approach. Eur J Intern Med. 2024;123:23-28. doi:10.1016/j.ejim.2023.12.026
  • Daugherty SL, Powers JD, Magid DJ, et al. Incidence and prognosis of resistant hypertension in hypertensive patients. Circulation. 2012;125: 1635-1642. doi:10.1161/CIRCULATIONAHA.111.068064
  • Cardoso CRL, Salles GF. prognostic value of changes in aortic stiffness for cardiovascular outcomes and mortality in resistant hypertension. Hypertension. 2022;79:447-456. doi:10.1161/HYPERTENSIONAHA. 121.18498
  • Harrison DG, Guzik TJ, Lob HE, et al. Inflammation, immunity, and hypertension. Hypertension. 2011;57:132-140. doi:10.1161/HYPERTENS IONAHA.110.163576
  • Tsioufis C, Kordalis A, Flessas D, et al. Pathophysiology of resistant hypertension: the role of sympathetic nervous system. Int J Hypertens. 2011;2011:642416. doi:10.4061/2011/642416
  • Nishiyama A. Pathophysiological mechanisms of mineralocorticoid receptor-dependent cardiovascular and chronic kidney disease. Hypertens Res. 2019;42:293-300. doi:10.1038/s41440-018-0158-6
  • Madhur MS, Lob HE, McCann LA, et al. Interleukin 17 promotes angiotensin II-induced hypertension and vascular dysfunction. Hypertension. 2010;55:500-507. doi:10.1161/HYPERTENSIONAHA. 109.145094
  • Saco-Ledo G, Valenzuela PL, Ruilope LM, Lucia A. Physical exercise in resistant hypertension: a systematic review and meta-analysis. Front Cardiovasc Med. 2022;9:893811. doi:10.3389/fcvm.2022.893811
  • Wang A, Tian X, Zuo Y, et al. Monocyte-to-lymphocyte ratio is associated with the presence and severity of resistant hypertension. J Clin Hypertens. 2022;24:1022-1029.
  • Cicero AFG, Veronesi M, Fogacci F. Dietary intervention to improve blood pressure control: beyond salt restriction. High Blood Press Cardiovasc Prev. 2021;28:547-553. doi:10.1007/s40292-021-00474-6
  • Blumenthal JA, Hinderliter AL, Smith PJ, et al. Effects of lifestyle modification on patients with resistant hypertension: results of the TRIUMPH randomized clinical trial. Circulation. 2021;144:1212-1226. doi:10.1161/CIRCULATIONAHA.121.055329
  • Ozemek C, Tiwari S, Sabbahi A, Carbone S, Lavie CJ. Impact of therapeutic lifestyle changes in resistant hypertension. Prog Cardiovasc Dis. 2020;63:4-9. doi:10.1016/j.pcad.2019.11.012
  • Yamada T, Kimura-Koyanagi M, Sakaguchi K, Ogawa W, Tamori Y. Obesity and risk for its comorbidities diabetes, hypertension, and dyslipidemia. Sci Rep. 2023;13:2346. doi:10.1038/s41598-023-29276-7
  • Filippou C, Tatakis F, Polyzos D, et al. Overview of salt restriction in the Dietary Approaches to Stop Hypertension (DASH) and the mediterranean diet for blood pressure reduction. Rev Cardiovasc Med. 2022;23:36. doi:10.31083/j.rcm2301036
  • Noubiap JJ, Nansseu JR, Nyaga UF, Sime PS, Francis I, Bigna JJ. Global prevalence of resistant hypertension: a meta-analysis. Heart. 2019;105: 98-105. doi:10.1136/heartjnl-2018-313599
  • Tompson AC, Ward AM, McManus RJ, et al. Acceptability and psychological impact of out-of-office monitoring to diagnose hypertension. Br J Gen Pract. 2019;69:e389-e397. doi:10.3399/bjgp19X70 2221
  • Kasiakogias A, Tsioufis C, Dimitriadis K, et al. Cardiovascular morbidity of severe resistant hypertension among treated uncontrolled hypertensives. J Hum Hypertens. 2018;32:487-493. doi:10.1038/s41371-018-0065-y
  • Wei FF, Zhang ZY, Huang QF, Staessen JA. Diagnosis and management of resistant hypertension: state of the art. Nat Rev Nephrol. 2018;14:428-441. doi:10.1038/s41581-018-0006-6
  • Hu B, Yang XR, Xu Y, et al. Systemic Immune-Inflammation index predicts prognosis of patients after curative resection for hepatocellular carcinoma. Clin Cancer Res. 2014;20:6212-6222. doi:10.1158/1078-0432.CCR-14-0442
  • Qi X, Li J, Deng H, et al. Neutrophil-to-lymphocyte ratio for the prognostic assessment of hepatocellular carcinoma. Oncotarget. 2016;7: 45283-45301. doi:10.18632/oncotarget.9942
  • Dudenbostel T, Calhoun DA. Use of aldosterone antagonists for treatment of uncontrolled resistant hypertension. Am J Hypertens. 2017; 30:103-109. doi:10.1093/ajh/hpw105
  • Zhao D, Liu H, Dong P, Zhao J. A meta-analysis of add-on use of spironolactone in patients with resistant hypertension. Int J Cardiol. 2017;233:113-117. doi:10.1016/j.ijcard.2016.12.158
  • Bozkurt B, Aguilar D, Deswal A, et al. Contributory risk and management of comorbidities of hypertension, obesity, diabetes mellitus, hyperlipidemia, and metabolic syndrome in chronic heart failure. Circulation. 2016;134:e535-e578. doi:10.1161/CIR.0000000000000450
  • Rosa J, Zelinka T, Petrák O, et al. Should all patients with resistant hypertension receive spironolactone? Curr Hypertens Rep. 2016;18:81. doi:10.1007/s11906-016-0690-1
  • Fadl Elmula FE, Jin Y, Yang WY, et al. Meta-analysis of randomized controlled trials of renal denervation in treatment-resistant hypertension. Blood Press. 2015;24:263-274. doi:10.3109/08037051.2015.1058595

Systemic Immune-inflammation Index (SII) and Systemic Inflammatory Response Index (SIRI) as novel predictors of resistant hypertension

Year 2026, Volume: 9 Issue: 1, 156 - 163, 05.01.2026
https://doi.org/10.32322/jhsm.1831025
https://izlik.org/JA43UN47EW

Abstract

Aims: Resistant hypertension (RHT) accounts for 10-15% of hypertensive patients, and diagnosis and treatment are more complex in these cases, which means a higher risk of cardiovascular complications. Although the effect of chronic systemic inflammation on the pathophysiology of RHT is known, the effective use of biomarkers is limited. This study investigated the relationship between the Systemic Immune-Inflammation Index (SII) and the Systemic Inflammatory Response Index (SIRI), which are composite inflammatory indices that can be used as markers of chronic inflammation, and RHT, testing their clinical utility and predictive value.
Methods: Between April 2022 and January 2025, 256 hypertensive patients followed up at our clinic were defined as having controlled hypertension (CHT) and 244 as having RHT, for a total of 500 patients included in this cross-sectional study. SII and SIRI values were calculated from routine blood count results. Data were analyzed and compared using multivariate logistic regression, quartile analysis, limited cubic spline modeling, and receiver operating characteristic (ROC) curve analysis.
Results: Significantly higher SII (480.2 vs. 361.7, p<0.001) and SIRI (0.73 vs. 0.46, p<0.001) values were observed in RHT patients. According to multivariate analysis, SIRI stood out as the strongest independent predictor of RHT (OR=25.954, 95% CI: 7.382-91.253, p<0.001). Quartile analysis showed a linear relationship, with RHT prevalence increasing from 20.0% to 84.0% across SIRI quartiles (p<0.001 for trend). SIRI showed attractive diagnostic performance (AUC=0.780, 95% CI: 0.739-0.820) with an optimal cutoff value of 0.6071 (sensitivity 68.0%, specificity 75.8%). Analysis stratified by gender suggested that males may be more sensitive to chronic inflammatory indices.
Conclusion: SII and SIRI are significantly elevated in the RHT patient group. Furthermore, their cost-effectiveness may highlight the existence of biomarkers that can be used as markers of inflammation in the course of this disease. SIRI (cut-off value ≥0.6071), demonstrating superior diagnostic performance, may play a helpful role in the management of hypertensive patients, particularly in the diagnosis of RHT. Furthermore, risk classification may empower clinicians in early diagnosis and targeted treatment strategies.

Ethical Statement

The study protocol was approved by the Ordu University Clinical Research Ethics Committee (Date: 25.03.2022, Decision No: 2022/71). The study was conducted in accordance with the principles of the Declaration of Helsinki. Informed consent was obtained from all participants.

Supporting Institution

The authors declared that this study has received no financial support. Teşekkür (Türkçe):

Thanks

The authors thank all the participants and the clinical staff for their contribution to data collection in this study.

References

  • Mills KT, Stefanescu A, He J. The global epidemiology of hypertension. Nat Rev Nephrol. 2020;16:223-237. doi:10.1038/s41581-019-0244-2
  • de la Sierra A, Ruilope LM, Staplin N, et al. Resistant hypertension and mortality: an observational cohort study. Hypertension. 2024;81:2350-2356. doi:10.1161/HYPERTENSIONAHA.124.23276
  • McEvoy JW, McCarthy CP, Bruno RM, et al. 2024 ESC Guidelines for the management of elevated blood pressure and hypertension. Eur Heart J. 2024;45:3912-4018. doi:10.1093/eurheartj/ehae178
  • Mancia G, Kreutz R, Brunström M, et al. 2023 ESH Guidelines for the management of arterial hypertension. J Hypertens. 2023;41:1874-2071. doi:10.1097/HJH.0000000000003480
  • Carey RM, Sakhuja S, Calhoun DA, Whelton PK, Muntner P. Prevalence of apparent treatment-resistant hypertension in the united states. Hypertension. 2019;73:424-431. doi:10.1161/HYPERTENSIONAHA.118. 12191
  • Parodi R, Brandani L, Romero C, Klein M. Resistant hypertension: diagnosis, evaluation, and treatment practical approach. Eur J Intern Med. 2024;123:23-28. doi:10.1016/j.ejim.2023.12.026
  • Daugherty SL, Powers JD, Magid DJ, et al. Incidence and prognosis of resistant hypertension in hypertensive patients. Circulation. 2012;125: 1635-1642. doi:10.1161/CIRCULATIONAHA.111.068064
  • Cardoso CRL, Salles GF. prognostic value of changes in aortic stiffness for cardiovascular outcomes and mortality in resistant hypertension. Hypertension. 2022;79:447-456. doi:10.1161/HYPERTENSIONAHA. 121.18498
  • Harrison DG, Guzik TJ, Lob HE, et al. Inflammation, immunity, and hypertension. Hypertension. 2011;57:132-140. doi:10.1161/HYPERTENS IONAHA.110.163576
  • Tsioufis C, Kordalis A, Flessas D, et al. Pathophysiology of resistant hypertension: the role of sympathetic nervous system. Int J Hypertens. 2011;2011:642416. doi:10.4061/2011/642416
  • Nishiyama A. Pathophysiological mechanisms of mineralocorticoid receptor-dependent cardiovascular and chronic kidney disease. Hypertens Res. 2019;42:293-300. doi:10.1038/s41440-018-0158-6
  • Madhur MS, Lob HE, McCann LA, et al. Interleukin 17 promotes angiotensin II-induced hypertension and vascular dysfunction. Hypertension. 2010;55:500-507. doi:10.1161/HYPERTENSIONAHA. 109.145094
  • Saco-Ledo G, Valenzuela PL, Ruilope LM, Lucia A. Physical exercise in resistant hypertension: a systematic review and meta-analysis. Front Cardiovasc Med. 2022;9:893811. doi:10.3389/fcvm.2022.893811
  • Wang A, Tian X, Zuo Y, et al. Monocyte-to-lymphocyte ratio is associated with the presence and severity of resistant hypertension. J Clin Hypertens. 2022;24:1022-1029.
  • Cicero AFG, Veronesi M, Fogacci F. Dietary intervention to improve blood pressure control: beyond salt restriction. High Blood Press Cardiovasc Prev. 2021;28:547-553. doi:10.1007/s40292-021-00474-6
  • Blumenthal JA, Hinderliter AL, Smith PJ, et al. Effects of lifestyle modification on patients with resistant hypertension: results of the TRIUMPH randomized clinical trial. Circulation. 2021;144:1212-1226. doi:10.1161/CIRCULATIONAHA.121.055329
  • Ozemek C, Tiwari S, Sabbahi A, Carbone S, Lavie CJ. Impact of therapeutic lifestyle changes in resistant hypertension. Prog Cardiovasc Dis. 2020;63:4-9. doi:10.1016/j.pcad.2019.11.012
  • Yamada T, Kimura-Koyanagi M, Sakaguchi K, Ogawa W, Tamori Y. Obesity and risk for its comorbidities diabetes, hypertension, and dyslipidemia. Sci Rep. 2023;13:2346. doi:10.1038/s41598-023-29276-7
  • Filippou C, Tatakis F, Polyzos D, et al. Overview of salt restriction in the Dietary Approaches to Stop Hypertension (DASH) and the mediterranean diet for blood pressure reduction. Rev Cardiovasc Med. 2022;23:36. doi:10.31083/j.rcm2301036
  • Noubiap JJ, Nansseu JR, Nyaga UF, Sime PS, Francis I, Bigna JJ. Global prevalence of resistant hypertension: a meta-analysis. Heart. 2019;105: 98-105. doi:10.1136/heartjnl-2018-313599
  • Tompson AC, Ward AM, McManus RJ, et al. Acceptability and psychological impact of out-of-office monitoring to diagnose hypertension. Br J Gen Pract. 2019;69:e389-e397. doi:10.3399/bjgp19X70 2221
  • Kasiakogias A, Tsioufis C, Dimitriadis K, et al. Cardiovascular morbidity of severe resistant hypertension among treated uncontrolled hypertensives. J Hum Hypertens. 2018;32:487-493. doi:10.1038/s41371-018-0065-y
  • Wei FF, Zhang ZY, Huang QF, Staessen JA. Diagnosis and management of resistant hypertension: state of the art. Nat Rev Nephrol. 2018;14:428-441. doi:10.1038/s41581-018-0006-6
  • Hu B, Yang XR, Xu Y, et al. Systemic Immune-Inflammation index predicts prognosis of patients after curative resection for hepatocellular carcinoma. Clin Cancer Res. 2014;20:6212-6222. doi:10.1158/1078-0432.CCR-14-0442
  • Qi X, Li J, Deng H, et al. Neutrophil-to-lymphocyte ratio for the prognostic assessment of hepatocellular carcinoma. Oncotarget. 2016;7: 45283-45301. doi:10.18632/oncotarget.9942
  • Dudenbostel T, Calhoun DA. Use of aldosterone antagonists for treatment of uncontrolled resistant hypertension. Am J Hypertens. 2017; 30:103-109. doi:10.1093/ajh/hpw105
  • Zhao D, Liu H, Dong P, Zhao J. A meta-analysis of add-on use of spironolactone in patients with resistant hypertension. Int J Cardiol. 2017;233:113-117. doi:10.1016/j.ijcard.2016.12.158
  • Bozkurt B, Aguilar D, Deswal A, et al. Contributory risk and management of comorbidities of hypertension, obesity, diabetes mellitus, hyperlipidemia, and metabolic syndrome in chronic heart failure. Circulation. 2016;134:e535-e578. doi:10.1161/CIR.0000000000000450
  • Rosa J, Zelinka T, Petrák O, et al. Should all patients with resistant hypertension receive spironolactone? Curr Hypertens Rep. 2016;18:81. doi:10.1007/s11906-016-0690-1
  • Fadl Elmula FE, Jin Y, Yang WY, et al. Meta-analysis of randomized controlled trials of renal denervation in treatment-resistant hypertension. Blood Press. 2015;24:263-274. doi:10.3109/08037051.2015.1058595
There are 30 citations in total.

Details

Primary Language English
Subjects Cardiology
Journal Section Research Article
Authors

Ertan Aydın 0000-0002-7280-5137

Aslı Vural 0000-0002-6601-8778

Emre Yılmaz 0000-0002-1656-3778

Devrim Kurt 0000-0003-4230-3248

Sencer Çamcı 0000-0003-2152-0470

Gökhan Gök 0009-0001-9729-6391

Submission Date November 26, 2025
Acceptance Date December 21, 2025
Publication Date January 5, 2026
DOI https://doi.org/10.32322/jhsm.1831025
IZ https://izlik.org/JA43UN47EW
Published in Issue Year 2026 Volume: 9 Issue: 1

Cite

AMA 1.Aydın E, Vural A, Yılmaz E, Kurt D, Çamcı S, Gök G. Systemic Immune-inflammation Index (SII) and Systemic Inflammatory Response Index (SIRI) as novel predictors of resistant hypertension. J Health Sci Med / JHSM. 2026;9(1):156-163. doi:10.32322/jhsm.1831025

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