Laboratory Parameters Predicting Mortality in Heart Failure Patients treated with Implantable Cardioverter Defibrillator: Single Centre, Long-term Results

Year 2021, Volume: 74 Issue: 1, 83 - 89, 30.04.2021

Veysel Özgür Barış , Ahmet Büyük , Fatih Poyraz , Murat Can Güney Sedat Sakallı

Abstract

Objectives: Neutrophil/lymphocyte (NLR), Monocyte/HDL (MHR), lymphocyte/monocyte (LMR) and platelet/lymphocyte ratios (PLR) are inflammation markers with proven prognostic values in various cardiovascular diseases. However, a clinical study demonstrating the prognostic value of these markers in heart failure (HF) patients treated with an implantable cardioverter-defibrillator (ICD) is not yet available. It is aimed to demonstrate the relationship between NLR, MHR, LMR, PLR and mortality development in patients with HF with ICD.

Materials and Methods: One hundred and ninety-four patients who underwent ICD implantation due to systolic HF between January 2015 and December 2019 were included in the study.

Results: The mean age was 59.84±13.26 years. The female gender ratio was 25.3%. Death developed in 16 patients (8%) after a median follow-up of 27 months. While basal urea, uric acid, gamma-glutamyl transferase, C-reactive protein and neutrophil levels were found to be high, hemoglobin and lymphocyte levels were found to be low in the exitus developing group. While the rates of NLR, MHR and PLR were statistically significantly higher in the group with death during follow-up (p=0.001, p=0.049, p=0.020, respectively ), LMR was significantly lower (p<0.001). In ROC analyses, mortality was predicted with 81% sensitivity and 61% specificity (p=0.001 AUC=0.76) of values of NLR and above 3.06; 86% sensitivity and 61% specificity [p=0.046 Area under curve (AUC)=0.723] of values of MHR and above 0,0196; 81% sensitivity and 55% specificity (p<0.001 AUC=0.784) of values of LMR 3.22 and 113.59 and above of PLR with 75% sensitivity and 51% specificity (p=0.020 AUC=0.68). Multiple logistic regression analysis showed LMR was an independent factor for mortality (p=0.027).

Conclusion: In our study, it has been shown that NLR, MHR, PLR and LMR, which are inflammation markers, can predict mortality in patients with ICD implanted HF. In the multivariate analysis, LMR value has been found to be significant. This is the first study demonstrating the predictive power of these parameters in this patient group.

Key Words: Heart Failure, Neutrophil Lymphocyte Ratio, Monocyte HDL Ratio, Platelet Lymphocyte Ratio, Lymphocyte Monocyte Ratio

Keywords

Heart Failure , Neutrophil Lymphocyte Ratio , Monocyte HDL Ratio , Platelet Lymphocyte Ratio , Lymphocyte Monocyte Ratio

Ethical Statement

Ethics Committee Approval: The study protocol has been approved by the local ethics committee. Informed Consent: Totally, 194 patients, that signed informed consent, between January 2015 and December 2019 have been included in the study. Peer-review: Externally peer-reviewed. Authorship Contributions Surgical and Medical Practices: S.S., F.P., M.C.G., Concept: V.Ö.B., Design: V.Ö.B., Data Collection or Processing: V.Ö.B., Analysis or Interpretation: V.Ö.B., Literature Search: V.Ö.B., Writing: V.Ö.B., A.B. Conflict of Interest: No conflict of interest was declared by the authors. Financial Disclosure: The authors declared that this study received no financial support

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Takılabilir Kardiyoverter Defibrilatör ile Tedavi Edilen Kalp Yetersizliği Hastalarında Mortaliteyi Belirleyen Laboratuvar Paramaterleri: Tek Merkezli, Uzun Dönemli Sonuçlar

Abstract

Amaç: Nötrofil/lenfosit oranı (NLR), Monosit/HDL oranı (MHR), lenfosit/monosit oranı (LMR) ve platelet/lenfosit oranı (PLR) kardiyovasküler hastalıklarda prognostik değerleri kanıtlanmış olan enflamasyon belirteçleridir. Fakat bu belirteçlerin takılabilir kardiyoverter defibrillator (ICD) ile tedavi edilen kalp yetersizliği hastalarında prognostik değerini gösteren klinik çalışma henüz mevcut değildir. Bu çalışmada NLR, MHR, LMR, PLR oranları ile ICD’si olan kalp yetersizliği hastalarında mortalite gelişimi arasındaki ilişkinin gösterilmesi amaçlanmıştır.

Gereç ve Yöntem: Çalışmaya, Ocak 2015-Aralık 2019 tarihleri arasında sistolik kalp yetersizliği nedeniyle ICD implantasyonu yapılmış 194 hasta
dahil edildi

Bulgular: Hastaların ortalama yaşı 59,84±13,26 idi. Kadın cinsiyet oranı %25,3 idi. Medyan 27 aylık izlem sonrasında 16 hastada ölüm gelişti (%8). Exitus gelişen grupta bazal üre, ürik asit, gama-glutamil transferaz, C-reaktif protein, nötrofil düzeyleri yüksek saptanırken; hemoglobin ve lenfosit düzeyleri ise düşük saptandı. Takiplerde ölüm gelişen grupta NLR, MHR ve PLR oranları istatistiksel olarak anlamlı şekilde yüksek saptanırken (p=0,001, p=0,049, p=0,020, sırasıyla) LMR belirgin derecede düşük saptanmıştır (p<0,001). Yapılan ROC analizlerinde mortaliteyi NLR’nin 3,06 ve üzerindeki değerlerinin %81 sensitive ve % 61 spesifite [p=0,001 Eğri altında kalan alan (AUC)=0,76]; MHR’nin 0,0196 ve üzerindeki değerlerinin %86 sensitive ve %61 spesifite (p=0,046 AUC=0,723); LMR’nin 3,22 ve altındaki değerlerinin %81 sensitive ve %55 spesifite (p<0,001 AUC=0,784); PLR’nin 113,59 ve üzerindeki değerlerinin %75 sensitive ve %51 spesifite (p=0,020 AUC=0,68) ile öngördüğü saptandı. Bu oranların dahil edildiği multipl lojistik regresyon analizinde LMR değeri istatistiksel olarak anlamlı saptanmıştır (p=0,027).

Sonuç: Çalışmamızda enflamasyon belirteçleri olan NLR, MHR, PLR ve LMR oranlarının ICD implante edilmiş kalp yetersizliği hastalarında mortaliteyi predikte edebileceği gösterilmiştir. Yapılan çok değişkenli analizde LMR değeri anlamlı bulunmuştur. Bu çalışma bu hasta grubunda bu parametrelerin prediktör gücünü gösteren ilk çalışmadır.

Anahtar Kelimeler: Kalp Yetersizliği, Nötrofil Lenfosit Oranı, Monosit HDL Oranı, Trombosit Lenfosit Oranı, Lensofit Monosit Oranı

Keywords

Kalp Yetersizliği , Nötrofil Lenfosit Oranı , Monosit HDL Oranı , Trombosit Lenfosit Oranı , Lensofit Monosit Oranı

Ethical Statement

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References

• 1. Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J 2016;37:2129-2200.
• 2. Aukrust P, Ueland T, Lien E, et al. Cytokine network in congestive heartfailure secondary to ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol. 1999;83:376-382.
• 3. McMurray JJ, Packer M, Desai AS, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371:993-1004
• 4. Ganjali S, Gotto AM Jr, Ruscica M, et al. Monocyte-to-HDL-cholesterol ratio as a prognostic marker in cardiovascular diseases. J Cell Physiol. 2018;233:9237-9246.
• 5. Abdul-Rahim AH, Perez AC, Fulton RL, et al. Risk of Stroke in Chronic Heart Failure Patients Without Atrial Fibrillation: Analysis of the Controlled Rosuvastatin in Multinational Trial Heart Failure (CORONA) and the Gruppo Italiano per lo Studio della Sopravvivenza nell’Insufficienza Cardiaca-Heart Failure (GISSI-HF) Trials. Circulation. 2015;131:1486-1494.
• 6. Priori SG, Blomström-Lundqvist C, Mazzanti A, et al. 2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: The Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology (ESC). Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC). Eur Heart J. 2015;36:2793-2867.
• 7. Bardy GH, Lee KL, Mark DB, et al. Amiodarone or an implantable cardioverterdefibrillator for congestive heart failure. N Engl J Med. 2005;352:225-237.
• 8. Uthamalingam S, Patvardhan EA, Subramanian S, et al. Utility of the neutrophil to lymphocyte ratio in predicting long-term outcomes in acute decompensated heart failure. Am J Cardiol. 2011;107:433-438.
• 9. Ertem AG, Yayla C, Acar B, et al. Relation between lymphocyte to monocyte ratio and short-term mortality in patients with acute pulmonary embolism. Clin Respir J. 2018;12:580-586.
• 10. Villanueva DLE, Tiongson MD, Ramos JD, et al. Monocyte to High-Density Lipoprotein Ratio (MHR) as a predictor of mortality and Major Adverse Cardiovascular Events (MACE) among ST Elevation Myocardial Infarction (STEMI) patients undergoing primary percutaneous coronary intervention: a meta-analysis. Lipids Health Dis. 2020;19:55.
• 11. Demir V, Samet Y, Akboga MK. Association of lymphocyte-monocyte ratio and monocyte-to-high-density lipoprotein ratio with the presence and severity of rheumatic mitral valve stenosis. Biomark Med. 2017;11:657-663.
• 12. Pocock SJ, Ariti CA, McMurray JJ, et al. Predicting survival in heart failure: a risk score based on 39 372 patients from 30 studies. Eur Heart J. 2013;34:1404-1413.
• 13. Rahimi K, Bennett D, Conrad N, et al. Risk prediction in patients with heart failure: a systematic review and analysis. JACC Heart Fail. 2014;2:440-446.
• 14. Mann DL, Young JB. Basic mechanisms in congestive heart failure. Recognizing the role of proinflammatory cytokines. Chest. 1994;105:897- 904.
• 15. Torre-Amione G, Kapadia S, Benedict C, et al. Proinflammatory cytokine levels in patients with depressed left ventricular ejection fraction: a report from the Studies of Left Ventricular Dysfunction (SOLVD). J Am Coll Cardiol. 1996;27:1201-1206.
• 16. Engström G, Melander O, Hedblad B. Leukocyte count and incidence of hospitalizations due to heart failure. Circ Heart Fail. 2009;2:217-222.
• 17. Cooper HA, Exner DV, Waclawiw MA, et al. White blood cell count and mortality in patients with ischemic and nonischemic left ventricular systolic dysfunction (an analysis of the Studies Of Left Ventricular Dysfunction [SOLVD]). Am J Cardiol. 1999;84:252-257.
• 18. Baldus S, Heeschen C, Meinertz T, et al. Myeloperoxidase serum levels predict risk in patients with acute coronary syndromes. Circulation. 2003;108:1440-1445.
• 19. Mehta J, Dinerman J, Mehta P, et al. Neutrophil function in ischemic heart disease. Circulation. 1989;79:549-556.
• 20. Tousoulis D, Antoniades C, Koumallos N, et al. Pro-inflammatory cytokines in acute coronary syndromes: from bench to bedside. Cytokine Growth Factor Rev. 2006;17:225-233.
• 21. Reichlin T, Socrates T, Egli P, et al. Use of myeloperoxidase for risk stratification in acute heart failure. Clin Chem. 2010;56:944-951.
• 22. Curi R, de Siqueira Mendes R, de Campos Crispin LA, et al. A past and present overview of macrophage metabolism and functional outcomes. Clin Sci (Lond). 2017;131:1329-1342.
• 23. Açıkgöz SK, Açıkgöz E, Şensoy B, et al. Monocyte to high-density lipoprotein cholesterol ratio is predictive of in-hospital and five-year mortality in STsegment elevation myocardial infarction. Cardiol J. 2016;23:505-512.
• 24. Ammirati E, Moroni F, Magnoni M, et al. Circulating CD14+ and CD14highCD16- classical monocytes are reduced in patients with signs of plaque neovascularization in the carotid artery. Atherosclerosis. 2016;255:171-178.
• 25. Ossoli A, Remaley AT, Vaisman B, et al. Plasma-derived and synthetic highdensity lipoprotein inhibit tissue factor in endothelial cells and monocytes. Biochem J. 2016;473:211-219.
• 26. Swedberg K, Eneroth P, Kjekshus J, et al. Hormones regulating cardiovascular function in patients with severe congestive heart failure and their relation to mortality. CONSENSUS Trial Study Group. Circulation. 1990;82:1730- 1736.
• 27. Sciarretta S, Ferrucci A, Ciavarella GM, et al. Markers of inflammation and fibrosis are related to cardiovascular damage in hypertensive patients with metabolic syndrome. Am J Hypertens. 2007;20:784-791.
• 28. Gawaz M, Langer H, May AE. Platelets in inflammation and atherogenesis. J Clin Invest. 2005;115:3378-3384.
• 29. Ginsberg MH, Kozin F, O’Malley M, et al. Release of platelet constituents by monosodium urate crystals. J Clin Invest. 1977;60:999-1007.
• 30. Yucel H, Zorlu A, Kaya H, et al. Elevated Neutrophil/Lymphocyte Ratio is Associated with Appropriate Shock After ICD Implantation. J Clin Anal Med. 2016;7:772-776.
• 31. Gratchev A, Sobenin I, Orekhov A, et al. Monocytes as a diagnostic marker of cardiovascular diseases. Immunobiology. 2012;217:476-482.
• 32. Cetin MS, Ozcan Cetin EH, Kalender E, et al. Monocyte to HDL Cholesterol Ratio Predicts Coronary Artery Disease Severity and Future Major Cardiovascular Adverse Events in Acute Coronary Syndrome. Heart Lung Circ. 2016;25:1077-1086.
• 33. Balta S, Celik T, Ozturk C, et al. The relation between monocyte to HDL ratio and no-reflow phenomenon in the patients with acute ST-segment elevation myocardial infarction. Am J Emerg Med. 2016;34:1542-1547.
• 34. Çiçek G, Kundi H, Bozbay M, et al. The relationship between admission monocyte HDL-C ratio with short-term and long-term mortality among STEMI patients treated with successful primary PCI. Coron Artery Dis. 2016;27:176-184.
• 35. Ucar FM. A potential marker of bare metal stent restenosis: monocyte count- to- HDL cholesterol ratio. BMC Cardiovasc Disord. 2016;16:186.
• 36. Balta S, Demırer Z, Aparci M, et al. The lymphocyte-monocyte ratio in clinical practice. J Clin Pathol. 2016;69:88-89.
• 37. Silva N, Bettencourt P, Guimarães JT. The lymphocyte-to-monocyte ratio an added value for death prediction in heart failure. Nutr Metab Cardiovasc Dis. 2015;25:1033-1040.
• 38. Kurtul A, Murat SN, Yarlioglues M, et al. Association of platelet-tolymphocyte ratio with severity and complexity of coronary artery disease in patients with acute coronary syndromes. Am J Cardiol. 2014;114:972-978.
• 39. Gary T, Pichler M, Belaj K, et al. Platelet-to-lymphocyte ratio: a novel marker for critical limb ischemia in peripheral arterial occlusive disease patients. PLoS One. 2013;8:67688.
• 40. Ye GL, Chen Q, Chen X, et al. The prognostic role of platelet-to-lymphocyte ratio in patients with acute heart failure: A cohort study. Sci Rep. 2019;9:10639