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Assessment of the hemogram parameters in patients with paroxysmal supraventricular tachycardia: a retrospective study

SUMMARY

OBJECTIVE:

Inflammation has been suggested as a potential mechanism in the pathogenesis of arrhythmia. Hemogram parameters such as monocyte count to high-density lipoprotein cholesterol ratio (MHR), neutrophil/lymphocyte ratio (NLR), and monocyte/lymphocyte ratio (MLR) have been considered to be markers of inflammation and new cardiovascular risk predictors. This retrospective study aimed to investigate the relationship between MHR, NLR, and MLR in patients with paroxysmal supraventricular tachycardia (PSVT).

METHODS:

A retrospective study conducted at a university hospital in Bolu, Turkey, between 2017 and 2019. Our study included 196 patients who underwent electrophysiological study (EPS) due to palpitation or documented PSVT on electrocardiography (ECG). Patients having documented atrioventricular nodal re-entrant tachycardia (AVNRT) on ECG or inducible AVNRT on EPS were included in the PSVT group (n=130), and patients with palpitation but without inducible arrhythmia on EPS (n=66) were included in the control group. Routine biochemical and hemogram tests were performed before the EPS procedure.

RESULTS:

When hemogram parameters were compared, there was no statistically significant difference in MHR values [0.010 (0.001-0.030) vs 0.010 (0.001-0.020) p =0.67]. Additionally, both NLR [2.21(0.74-11.36) vs 1.98(0.72-24.87) p=0.13] and MLR [0.25 (0.03-1.05) vs 0.24(0.07-1.39) p=0.41] were not statistically significant between the two groups.

CONCLUSION:

There is no significant difference in PSVT patients regarding hemogram parameters including white blood cell subtypes, MLR, NLR, and MHR. Therefore the evaluation of hemogram parameters may not be clinically relevant for PSVT patients.

KEYWORDS:
Inflammation; Tachycardia, supraventricular; Blood cell count; Monocytes; Lipoproteins, HDL

RESUMO

OBJETIVO:

A inflamação tem sido sugerida como um mecanismo potencial na patogênese da arritmia. Parâmetros do hemograma, como contagem de monócitos e razão de colesterol lipoproteína de alta densidade (MHP), proporção de neutrófilos / linfócitos (NLP) e proporção de monócitos / linfócitos (MLR), foram considerados marcadores de inflamação e novos preditores de risco cardiovascular. Este estudo retrospectivo teve como objetivo investigar a relação entre MHP, NLP e MLP em pacientes com taquicardia paroxística supraventricular (PSVT).

MÉTODOS:

Estudo retrospectivo realizado em um hospital universitário em Bolu, Turquia, entre 2017 e 2019. Nosso estudo incluiu 196 pacientes submetidos a estudo eletrofisiológico (EPS) devido a palpitações ou PSVT documentada na eletrocardiografia (ECG). Os pacientes com taquicardia nodal atrioventricular reentrante (AVNRT) no ECG ou AVNRT indutível no EPS foram incluídos no grupo PSVT (n = 130) e os pacientes com palpitações sem arritmia induzível no EPS (n = 66) foram incluídos no grupo controle. Testes bioquímicos e de hemograma de rotina foram realizados antes do procedimento de EPS.

RESULTADOS:

Quando os parâmetros do hemograma foram comparados, não houve diferença estatisticamente significante nos valores de MHP (0,010 (0,001-0,030) vs 0,010 (0,001-0,020) p = 0,67). Além disso, tanto o NLP (2,21 (0,74-11,36) vs 1,98 (0,72-24,87) p = 0,13) quanto o MLP (0,25 (0,03-1,05) vs 0,24 (0,07-1,39) p = 0,41) não foram estatisticamente significantes entre os dois grupos.

CONCLUSÃO:

Não há diferença significativa nos pacientes com PSVT em relação aos parâmetros do hemograma, incluindo os subtipos de glóbulos brancos, MHP, NLP e MHP. Portanto, a avaliação dos parâmetros do hemograma pode não ser clinicamente relevante para pacientes com PSVT.

PALAVRAS-CHAVE:
Inflamação; Taquicardia supraventricular; Contagem de células sanguíneas; Monócitos; Lipoproteínas HDL

INTRODUCTION

Paroxysmal supraventricular tachycardia (PSVT) is characterized by the sudden onset and abrupt termination of tachycardia11. Page RL, Joglar JA, Caldwell MA, Calkins H, Conti JB, Deal BJ, et al. 2015 ACC/AHA/HRS guideline for the management of adult patients with supraventricular tachycardia: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2016;67(13):1575-623.. Most patients have no associated structural heart disease. Enhanced automaticity, triggered activity, and re-entry are among the mechanisms for PSVT22. Ferguson JD, DiMarco JP. Contemporary management of paroxysmal supraventricular tachycardia. Circulation. 2003;107(8):1096-9.. The mechanism for tachycardia may be induced by pharmacologic and pacing maneuvers33. Al-Zaiti SS, Magdic KS. Paroxysmal supraventricular tachycardia: pathophysiology, diagnosis, and management. Crit Care Nurs Clin North Am. 2016;28(3):309-16.. Atrioventricular nodal re-entrant tachycardia (AVNRT) is the most common type of PSVT22. Ferguson JD, DiMarco JP. Contemporary management of paroxysmal supraventricular tachycardia. Circulation. 2003;107(8):1096-9..

Inflammation has been suggested as a potential mechanism in the pathogenesis of arrhythmia44. Yalta K, Sivri N, Geyik B, Yetkin E. Tumour necrosis factor-α antagonism: a potential therapeutic target for prevention of arrhythmogenesis in the setting of acute myocardial infarction? Heart. 2014;100(3):263.,55. Demirel ME, Donmez I, Ucaroglu ER, Yuksel A. Acute coronary syndromes and diagnostic methods. Med Res Innov. 2019;3:1-8. doi:10.15761/MRI.1000167.
https://doi.org/10.15761/MRI.1000167...
. White blood cells (WBC) and their subtypes are among inflammatory markers and have been associated with cardiovascular disorders66. Tamhane UU, Aneja S, Montgomery D, Rogers EK, Eagle KA, Gurm HS, et al. Association between admission neutrophil to lymphocyte ratio and outcomes in patients with acute coronary syndrome. Am J Cardiol. 2008;102(6):653-7.. Recently, monocyte count to HDL-C ratio (MHR), which is obtained by dividing monocyte count by HDL cholesterol, has been reported to be a novel indicator in cardiovascular diseases77. Zhang Y, Li S, Guo YL, Wu NQ, Zhu CG, Gao Y, et al. Is monocyte to HDL ratio superior to monocyte count in predicting the cardiovascular outcomes: evidence from a large cohort of Chinese patients undergoing coronary angiography. Ann Med. 2016;48(5):305-12.. There are few and contradictory reports about the association of PSVT and hemogram parameters88. Küçük U, Arslan M. Assessment of the white blood cell subtypes ratio in patients with supraventricular tachycardia: retrospective cohort study. J Surg Med. 2019;3(4):297-9.1010. Aydın M, Yildiz A, Yuksel M, Polat N, Aktan A, İslamoğlu Y. Assessment of the neutrophil/lymphocyte ratio in patients with supraventricular tachycardia. Anatol J Cardiol. 2016;16(1):29-33.. And, as far as we know, there is no data for MHR and PSVT association.

OBJECTIVE

In this study, we aimed to investigate the relationship between PSVT and hemogram parameters and MHR.

METHODS

A retrospective cross-sectional design was used. After institutional approval, patients who underwent electrophysiological study (EPS) and catheter ablation of PSVT between December 2017 and September 2019 at our center were included. Patients' data were obtained from the computer records and files of our hospital. The study was approved by the institutional board (33443051-903.99).

We included 196 patients who underwent EPS due to palpitation or documented SVT on ECG. Patients having documented AVNRT on ECG or inducible AVNRT on EPS were included in the PSVT group, and patients with palpitation and without inducible arrhythmia on EPS were included in the control group.

The exclusion criteria included recent infection or surgery, morbid obesity (body mass index ≥35 kg/m2), severe renal or liver dysfunction, heart failure, coronary artery disease, moderate to severe valvular diseases, chronic obstructive pulmonary disease, peripheral or cerebral vascular disease, hematological disorders, malignancies, inflammatory diseases, and drug use (including antiarrhythmic agents).

Venous blood samples were drawn from the antecubital vein at the initial presentation before the EPS procedure. In order to determine hemogram parameter values, the blood samples were analyzed in the Beckman Coulter Device (Beckman Coulter In.; Bre CA) within 15 minutes. Basic biochemical tests and several hemogram parameters like WBC, leukocyte subtypes [neutrophil (NEU), monocyte (MONO), and lymphocyte (LYM) counts], hemoglobin (HGB), hematocrit (HCT), mean corpuscular volume (MCV), red blood cell distribution width (RDW), platelet (PLT) count, platelet distribution width (PDW), mean platelet volume (MPV), plateletcrit (PCT) were measured, and neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), RDW/platelet ratio (RPR), mean platelet volume/platelet ratio (MPR), and monocyte/lymphocyte ratio (MLR) and monocyte count/HDL cholesterol ratio (MHR) were calculated.

STATISTICAL ANALYSIS

Data were evaluated using SPSS version 16.0 (SPSS 16.0; SPSS Inc., Chicago, IL, USA). The normality of the variables was tested with the Kolmogorov-Smirnov method. The student t-test was used for the comparison of normally distributed variables, and these data were expressed as mean ± standard deviation (SD). The Mann-Whitney U test was used for the comparison of non-normally distributed variables, and these data were expressed as median (min-max). The Chi-square test was used for the comparison of categorical variables. P<0.05 values were considered statistically significant.

RESULTS

A total of 196 patients were included in the study. There were 130 patients in the PSVT group (Group 1) and 66 patients in the control group (Group 2). Baseline demographic variables including age, sex, frequencies of hypertension, and diabetes were not significantly different between the groups (Table 1).

TABLE 1
DEMOGRAPHICS AND CLINICAL

Laboratory findings and studied hemogram parameters were also not significantly different between the groups (Table 2, Figure 1).

TABLE 2
LABORATORY DATA OF THE STUDY COHORT
Figure 1
MHR, NLR, MPV AND MONOCYTE COUNT DISTRIBUTION OF THE SVT AND CONTROL GROUPS

DISCUSSION

In this study, we have found that hemogram parameters including MPV, NLR, monocyte count, and MHR were not significantly different in the PSVT patient and control groups. Inflammation is a common condition seen in many pathological states. Inflammatory pathogenesis has also been claimed for coronary artery disease, heart failure, and arrhythmias55. Demirel ME, Donmez I, Ucaroglu ER, Yuksel A. Acute coronary syndromes and diagnostic methods. Med Res Innov. 2019;3:1-8. doi:10.15761/MRI.1000167.
https://doi.org/10.15761/MRI.1000167...
,1111. Klein RM, Vester EG, Brehm MU, Dees H, Picard F, Niederacher D, et al. Inflammation of the myocardium as an arrhythmia trigger. Z Kardiol. 2000;89(Suppl 3):24-35.. Likewise, inflammation has been suggested to have an important role in PSVTs1212. Psychari SN, Apostolou TS, Sinos L, Hamodraka E, Liakos G, Kremastinos DT. Relation of elevated C-reactive protein and interleukin-6 levels to left atrial size and duration of episodes in patients with atrial fibrillation. Am J Cardiol. 2005;95(6):764-7..

Several mechanisms have been accused of an association between systemic inflammation and arrhythmogenesis. Inflammatory cytokines may play a particular role in arrhythmogenesis through a potential reduction in the arrhythmogenic threshold in arrhythmia-prone patients44. Yalta K, Sivri N, Geyik B, Yetkin E. Tumour necrosis factor-α antagonism: a potential therapeutic target for prevention of arrhythmogenesis in the setting of acute myocardial infarction? Heart. 2014;100(3):263.,1313. Yo CH, Lee SH, Chang SS, Lee MC, Lee CC. Value of high-sensitivity C-reactive protein assays in predicting atrial fibrillation recurrence: a systematic review and meta-analysis. BMJ Open. 2014;4(2):e004418.,1414. Sinner MF, Stepas KA, Moser CB, Krijthe BP, Aspelund T, Sotoodehnia N, et al. B-type natriuretic peptide and C-reactive protein in the prediction of atrial fibrillation risk: the CHARGE-AF Consortium of community-based cohort studies. Europace. 2014;16(10):1426-33.. For instance, TNF-α was suggested to exert its arrhythmogenic effects at the cellular level through electrophysiological abnormalities, which may be associated with enhanced automaticity and reentrant loops, like the hyperactivation of sodium channels with abnormal calcium handling and increased action potential duration1515. Xiao H, Liao YH, Chen ZJ. Tumor necrosis factor-alpha: a new mechanism of ischemic ventricular fibrillation? Chin Med J (Engl). 2008;121(18):1848-51..

Currently, hemogram parameters are, in general, recognized as inflammatory markers and prognostic determinants in a wide spectrum of diseases. These hemogram parameters have been evaluated as new predictors of cardiovascular risk66. Tamhane UU, Aneja S, Montgomery D, Rogers EK, Eagle KA, Gurm HS, et al. Association between admission neutrophil to lymphocyte ratio and outcomes in patients with acute coronary syndrome. Am J Cardiol. 2008;102(6):653-7.,77. Zhang Y, Li S, Guo YL, Wu NQ, Zhu CG, Gao Y, et al. Is monocyte to HDL ratio superior to monocyte count in predicting the cardiovascular outcomes: evidence from a large cohort of Chinese patients undergoing coronary angiography. Ann Med. 2016;48(5):305-12..

It has been suggested that increased MPV was correlated with inflammation in several conditions1616. Ege MR, Acikgoz S, Zorlu A, Sıncer I, Guray Y, Guray U, et al. Mean platelet volume: an important predictor of coronary collateral development. Platelets. 2013;24(3):200-4.. Ocak et al.99. Ocak T, Erdem A, Duran A, Tekelioglu U, Öztürk S, Ayhan S, et al. The importance of the mean platelet volume in the diagnosis of supraventricular tachycardia. Afr Health Sci. 2013;13(3):590-4. demonstrated that MPV was significantly higher in patients with documented SVT. In this retrospective study, 122 patients arriving at the emergency department with documented SVT on ECG and 100 healthy adults were analyzed. They found that, among hemogram parameters, hemoglobin, neutrophil count, MCV, RDW, platelet, WBC, and lymphocyte counts were similar to the control group, whereas MPV was significantly higher in SVT patients. However, we couldn't confirm their finding in the present study.

NLR has been suggested as an indicator of inflammation1717. Balta S, Demirkol S, Unlu M, Arslan Z, Celik T. Neutrophil to lymphocyte ratio may be predict of mortality in all conditions. Br J Cancer. 2013;109(12):3125-6.. Aydın et al.1010. Aydın M, Yildiz A, Yuksel M, Polat N, Aktan A, İslamoğlu Y. Assessment of the neutrophil/lymphocyte ratio in patients with supraventricular tachycardia. Anatol J Cardiol. 2016;16(1):29-33. studied 150 patients who underwent catheter ablation of SVT and 98 healthy subjects. In this retrospective cross-sectional study, they reported that higher values of NLR were associated with SVT. Furthermore, NLR values were higher in patients in whom tachycardia was induced during EPS than those in whom tachycardia was not induced. However, Küçük et al.88. Küçük U, Arslan M. Assessment of the white blood cell subtypes ratio in patients with supraventricular tachycardia: retrospective cohort study. J Surg Med. 2019;3(4):297-9. recently studied 33 SVT patients and 26 control subjects who underwent EPS and suggested that NLR and MLR values were not significantly different. In accordance with Küçük et al.88. Küçük U, Arslan M. Assessment of the white blood cell subtypes ratio in patients with supraventricular tachycardia: retrospective cohort study. J Surg Med. 2019;3(4):297-9., we have also found similar NLR values in PSVT patients and in the control group.

Monocytes are the largest type of WBC and have a major role in the inflammatory process of atherosclerosis1818. Takahashi K, Takeya M, Sakashita N. Multifunctional roles of macrophages in the development and progression of atherosclerosis in humans and experimental animals. Med Electron Microsc. 2002;35(4):179-203.. High-density lipoprotein cholesterol (HDL-C) shows anti-inflammatory and anti-oxidant properties by inhibiting the transmigration of monocytes. Higher levels of HDL-C are associated with reduced cardiovascular disease risk1919. Murphy AJ, Woollard KJ, Hoang A, Mukhamedova N, Stirzaker RA, McCormick SP, et al. High-density lipoprotein reduces the human monocyte inflammatory response. Arterioscler Thromb Vasc Biol. 2008;28(11):2071-7.. Therefore, the integration of these two measurements as MHR can be used as an indicator of inflammation6,20-23. Accordingly, MHR has been suggested as a new prognostic marker in several cardiovascular disorders2323. Kadihasanoglu M, Karabay E, Yucetas U, Erkan E, Ozbek E. Relation between monocyte to high-density lipoprotein cholesterol ratio and presence and severity of erectile dysfunction. Aktuelle Urol. 2018;49(3):256-61.2525. Cetin MS, Ozcan Cetin EH, Kalender E, Aydin S, Topaloglu S, Kisacik HL, 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(11):1077-86.. Regarding monocyte counts, Küçük et al.88. Küçük U, Arslan M. Assessment of the white blood cell subtypes ratio in patients with supraventricular tachycardia: retrospective cohort study. J Surg Med. 2019;3(4):297-9. have found no significant difference in SVT patients. In the present study, we have also found that MHR was not increased in SVT patients.

Limitations

This is a single-center, retrospective small study. Lack of measurement of other inflammation markers like CRP, TNF-α, and interleukins is another major limitation.

CONCLUSION

We have found no significant difference in PSVT patients regarding none of the hemogram parameters including WBC subtypes, MPV, NLR, and MHR. Therefore, the evaluation of hemogram parameters may not be clinically relevant for PSVT patients.

  • Sources of Funding/ Study Association
    There were no external funding sources for this study.
    This study is not associated with any thesis or dissertation work

REFERENCES

  • 1
    Page RL, Joglar JA, Caldwell MA, Calkins H, Conti JB, Deal BJ, et al. 2015 ACC/AHA/HRS guideline for the management of adult patients with supraventricular tachycardia: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2016;67(13):1575-623.
  • 2
    Ferguson JD, DiMarco JP. Contemporary management of paroxysmal supraventricular tachycardia. Circulation. 2003;107(8):1096-9.
  • 3
    Al-Zaiti SS, Magdic KS. Paroxysmal supraventricular tachycardia: pathophysiology, diagnosis, and management. Crit Care Nurs Clin North Am. 2016;28(3):309-16.
  • 4
    Yalta K, Sivri N, Geyik B, Yetkin E. Tumour necrosis factor-α antagonism: a potential therapeutic target for prevention of arrhythmogenesis in the setting of acute myocardial infarction? Heart. 2014;100(3):263.
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    Demirel ME, Donmez I, Ucaroglu ER, Yuksel A. Acute coronary syndromes and diagnostic methods. Med Res Innov. 2019;3:1-8. doi:10.15761/MRI.1000167.
    » https://doi.org/10.15761/MRI.1000167
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    Tamhane UU, Aneja S, Montgomery D, Rogers EK, Eagle KA, Gurm HS, et al. Association between admission neutrophil to lymphocyte ratio and outcomes in patients with acute coronary syndrome. Am J Cardiol. 2008;102(6):653-7.
  • 7
    Zhang Y, Li S, Guo YL, Wu NQ, Zhu CG, Gao Y, et al. Is monocyte to HDL ratio superior to monocyte count in predicting the cardiovascular outcomes: evidence from a large cohort of Chinese patients undergoing coronary angiography. Ann Med. 2016;48(5):305-12.
  • 8
    Küçük U, Arslan M. Assessment of the white blood cell subtypes ratio in patients with supraventricular tachycardia: retrospective cohort study. J Surg Med. 2019;3(4):297-9.
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    Ocak T, Erdem A, Duran A, Tekelioglu U, Öztürk S, Ayhan S, et al. The importance of the mean platelet volume in the diagnosis of supraventricular tachycardia. Afr Health Sci. 2013;13(3):590-4.
  • 10
    Aydın M, Yildiz A, Yuksel M, Polat N, Aktan A, İslamoğlu Y. Assessment of the neutrophil/lymphocyte ratio in patients with supraventricular tachycardia. Anatol J Cardiol. 2016;16(1):29-33.
  • 11
    Klein RM, Vester EG, Brehm MU, Dees H, Picard F, Niederacher D, et al. Inflammation of the myocardium as an arrhythmia trigger. Z Kardiol. 2000;89(Suppl 3):24-35.
  • 12
    Psychari SN, Apostolou TS, Sinos L, Hamodraka E, Liakos G, Kremastinos DT. Relation of elevated C-reactive protein and interleukin-6 levels to left atrial size and duration of episodes in patients with atrial fibrillation. Am J Cardiol. 2005;95(6):764-7.
  • 13
    Yo CH, Lee SH, Chang SS, Lee MC, Lee CC. Value of high-sensitivity C-reactive protein assays in predicting atrial fibrillation recurrence: a systematic review and meta-analysis. BMJ Open. 2014;4(2):e004418.
  • 14
    Sinner MF, Stepas KA, Moser CB, Krijthe BP, Aspelund T, Sotoodehnia N, et al. B-type natriuretic peptide and C-reactive protein in the prediction of atrial fibrillation risk: the CHARGE-AF Consortium of community-based cohort studies. Europace. 2014;16(10):1426-33.
  • 15
    Xiao H, Liao YH, Chen ZJ. Tumor necrosis factor-alpha: a new mechanism of ischemic ventricular fibrillation? Chin Med J (Engl). 2008;121(18):1848-51.
  • 16
    Ege MR, Acikgoz S, Zorlu A, Sıncer I, Guray Y, Guray U, et al. Mean platelet volume: an important predictor of coronary collateral development. Platelets. 2013;24(3):200-4.
  • 17
    Balta S, Demirkol S, Unlu M, Arslan Z, Celik T. Neutrophil to lymphocyte ratio may be predict of mortality in all conditions. Br J Cancer. 2013;109(12):3125-6.
  • 18
    Takahashi K, Takeya M, Sakashita N. Multifunctional roles of macrophages in the development and progression of atherosclerosis in humans and experimental animals. Med Electron Microsc. 2002;35(4):179-203.
  • 19
    Murphy AJ, Woollard KJ, Hoang A, Mukhamedova N, Stirzaker RA, McCormick SP, et al. High-density lipoprotein reduces the human monocyte inflammatory response. Arterioscler Thromb Vasc Biol. 2008;28(11):2071-7.
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    Acikgoz N, Kurtoğlu E, Yagmur J, Kapicioglu Y, Cansel M, Ermis N. Elevated monocyte to high-density lipoprotein cholesterol ratio and endothelial dysfunction in Behçet disease. Angiology. 2017;69(1):65-70.
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    Bolayir A, Gokce SF, Cigdem B, Bolayir HA, Yildiz OK, Bolayir E, et al. Monocyte/high-density lipoprotein ratio predicts the mortality in ischemic stroke patients. Neurol Neurochir Pol. 2018;52(2):150-5.
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    Kundi H, Gok M, Kiziltunc E, Cetin M, Cicekcioglu H, Cetin ZG, et al. Relation between monocyte to high-density lipoprotein cholesterol ratio with presence and severity of isolated coronary artery ectasia. Am J Cardiol. 2015;116(11):1685-9.
  • 23
    Kadihasanoglu M, Karabay E, Yucetas U, Erkan E, Ozbek E. Relation between monocyte to high-density lipoprotein cholesterol ratio and presence and severity of erectile dysfunction. Aktuelle Urol. 2018;49(3):256-61.
  • 24
    Karataş MB, Çanga Y, Özcan KS, İpek G, Güngör B, Onuk T, et al. Monocyte to high-density lipoprotein ratio as a new prognostic marker in patients with STEMI undergoing primary percutaneous coronary intervention. Am J Emerg Med. 2016;34(2):240-4.
  • 25
    Cetin MS, Ozcan Cetin EH, Kalender E, Aydin S, Topaloglu S, Kisacik HL, 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(11):1077-86.

Publication Dates

  • Publication in this collection
    06 Nov 2020
  • Date of issue
    Oct 2020

History

  • Received
    04 Feb 2020
  • Accepted
    21 Apr 2020
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