ABSTRACT

Conclusion:

As inexpensive and easily available new inflammatory markers, MPVLR and MPVPR were significantly higher in patients with GFR <60 and in those who died from AMI. In addition, MPVLR and MPVPR could predict mortality from MI.

Results:

The mean age of the survivor group was 64.3±10.4. In the mortality group, the mean age was 70.02±9.3. MPVLR levels were statistically significantly higher in the mortality group (8.39±5.9) compared to the survivor group (6.58±5.4) (p=0.011). However, MPVPR levels were statistically significantly lower in the mortality group (0.041±0.01) compared to the survivor group (0.044±0.01) (p=0.048). According to the results of ROC analysis in patients with mortality, sensitivity was 50.0% and specificity was 68.6% for MPVLR (p=0.010); sensitivity was 41.0% and specificity was 47.9% for MPVPR. The risk factors found to be significantly associated with mortality in the regression analysis included MPVPR [β: 0.045, odds ratio (95% confidence interval): 0.945 (0.899- 1.001), p=0.032].

Method:

This study was designed as a retrospective cohort study. Two hundred myocardial infarction (MI) patients over the age of 18 years and with GFR <60, who were hospitalized in our hospital between January 01, 2018 and January 01, 2021, were included in the study. The patients were divided into 2 groups, as the survivor and mortality groups. The two groups were compared in terms of demographic characteristics and clinical data (symptoms, comorbidities, laboratory findings, GFR, coronary angiography, drugs used and complications). MPVLR was found by dividing the mean platelet volume to lymphocyte count. MPVPR was found by dividing the mean platelet volume to platelet count.

Objective:

In this study, we aimed to evaluate the relationship between the laboratory parameters of mean platelet volume/lymphocyte ratio (MPVLR) and mean platelet volume/platelet ratio (MPVPR) with prognosis and mortality in patients with hospitalized glomerular filtration rate (GFR) <60 and a diagnosis of acute myocardial infarction (AMI).

Keywords:

Acute myocardial infarction, mortality, MPV-to-lymphocyte ratio, MPV-to-platelet ratio

Introduction

Heart failure (HF) is a major public health problem, affecting more than 23 million individuals worldwide, and its incidence increases with age. After the diagnosis of HF, the average life expectancy is 50% in 5 years and 10% in 10 years. Despite advanced modern treatment approaches, mortality rates are still high. Moreover, HF patients need long-term care, as it is a chronic disease that can be exacerbated by acute exacerbations (1). It is known that inflammation has an important role in the pathogenesis of atherosclerosis and thus cardiovascular diseases (CVDs) (2). The role of inflammation in HF has been demonstrated in many previous studies. HF syndrome is largely due to the imbalance between inflammatory and anti-inflammatory forces (3).

Mean platelet volume (MPV) blood test measures the average size of your platelets. The test can help diagnose bleeding disorders and diseases of the bone marrow. In recent years, MPV-to-lymphocyte ratio (MPVLR) and MPV-platelet ratio (MPVPR) have been shown to be important indicators of systemic inflammation (1,4-6). Recently, the MPV-to-lymphocyte ratio (MPVLR) has arisen as a prognostic marker in patients with CVDs (4). However, it was reported that elevated MPVPR values at admission are independently associated with the development of no-reflow phenomenon after primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) (4,7). However, there is no study investigating the association of MPVLR and MPVPR with the severity and complexity of acute myocardial infarction (AMI). In addition, MPV-platelet ratio (MPVPR) has also been shown to vary in various diseases and are associated with prognosis (8-11).

In this study, we aimed to evaluate the relationship between the laboratory parameters of MPVLR and MPVPR with prognosis and mortality in patients with hospitalized glomerular filtration rate (GFR) <60 mL/min and a diagnosis of AMI.

Materials and Methods

This study was designed as a retrospective cohort study. Before the study started, the study protocol was approved by Local Ethics Committee of İstanbul Medipol University (approval no: E-10840098-772.02-3976). This study was conducted in accordance with the ethical principles of the Declaration of Helsinki. Two hundred myocardial infarction (MI) patients over the age of 18 years and with GFR <60 mL/min, who were hospitalized in our hospital between January 01, 2018 and January 01, 2021, were included in the study. The demographic characteristics of the patients and clinical data (symptoms, comorbidities, laboratory findings, GFR, coronary angiography, medications and complications that developed in the patients) were scanned.

The patients were divided into 2 groups, as the survivor and mortality groups. The two groups were compared in terms of demographic characteristics and clinical data. Fasting morning blood samples of the patients and control healthy subjects were collected through vein puncture. The MPVLR was found by dividing MPV to lymphocyte count. The MPVPR was found by dividing MPV to platelet count.

Statistical Analysis

The data obtained in this study were analyzed using SPSS v.25 (SPSS, Chicago, USA) statistical program. Descriptive statistics such as frequency distribution, mean and standard deviation were used to evaluate the data. The differences between the means of two independent groups were compared with the student’s t-test, and the differences between more than two groups were compared with the analysis of variance with the parametric test. The Mann-Whitney U and Kruskal-Wallis tests, which are non-parametric alternatives of these tests, were used in cases where parametric test assumptions were not met. Categorical data were analyzed using the chi-square or Fisher’s Exact test. Variables with a p-value ≤0.05 were entered in the regression model. Values of p<0.05 were considered statistically significant at 95% confidence interval (CI).

Results

Comparison of laboratory and socio-demographic findings between the mortality and survivor groups was shown in Table 1. The mean age of the survivor group was 64.3±10.4 years. In the mortality group, the mean age was 70.02±9.3 years. MPVLR levels were statistically significantly higher in the mortality group (8.39±5.9) compared to the survivor group (6.58±5.4) (p=0.011). However, MPVPR levels were statistically significantly lower in the mortality group (0.041±0.01) compared to the survivor group (0.044±0.01) (p=0.048).There was not any statistical significance between the groups in terms of gender, length of hospitalization, coronary artery disease, HF, STEMI, non-STEMI, hypertension, hyperlipidemia, diabetes mellitus, cigarette, nephropathy, acetyl salicylic acid, beta blocker, statins, angiotensin converting enzyme (ACE) inhibitors, GFR, hemoglobin (g/dL), creatinine (mg/dL), lymphocytes (10⁹/L), and platelet (10⁹/L) (Table 1).

ROC analysis results in patients with mortality are shown in Table 2. According to the results of ROC analysis in patients with mortality, sensitivity was 50.0% and specificity was 68.6% for MPVLR (p=0.010); and sensitivity was 41.0% and specificity was 47.9% for MPVPR (p=0.048) (Table 2, Figure 1).

Multiple logistic regression analysis of factors used for mortality was shown in Table 3. The risk factors found to be significantly associated with mortality in the regression analysis included MPVLR [b: 0.067, odds ratio (OR) 95% confidence interval (CI): 1.069 (1.016-1.125), p=0.010] and MPVPR [b: 0.045, OR (95% CI): 0.945 (0.899-1.001), p=0.032] (Table 3).

Discussion

In this study, the effects of retrospective clinical and laboratory data on mortality were evaluated in 200 MI patients over 18 years of age and with GFR <60, who were hospitalized in coronary intensive care unit. There was a significant relationship between the laboratory markers obtained, especially MPVLR and MPVPR, and those who died from MI. MI is a disease with significant morbidity and mortality. While 145 (72.5%) patients survived in our study, 55 (27.5%) patients died in the hospital. MPVLR levels were statistically significantly higher in the mortality group compared to the survivor group. However, MPVPR levels were statistically significantly lower in the mortality group compared to the survivor group. The risk factors found to be significantly associated with mortality in the regression analysis included only MPVPR.

Increased inflammatory marker levels in the blood are associated with poor outcome in HF as in many chronic diseases. An increased inflammatory stimulus causes the secretion of many inflammatory cytokines. These inflammatory cytokines show detrimental effects on the myocardium, leading to decreased left ventricular function and thus HF (1,2,12-14). In one study, high neutrophil-lymphocyte ratio (NLR) values were associated with high mortality rates in individuals with acute decompensated HF, and the value of NLR in predicting death was superior to that of neutrophil count, total white blood cell count, and partially low lymphocyte count (15). Therefore, NLR has an important prognostic value in HF. On the other hand, previous studies have shown that high platelet and low lymphocyte counts are associated with poor cardiovascular outcomes (16-18). The value recently found and shown as one of the complete blood count parameters is the MPVLR. It was first reported by Hudzik et al. (5) in 2016 as a potential prognostic marker in patients with diabetes and MI. Życzkowski et al. (19) reported that prognostic relationship between high pre-operative MPVLR and higher long-term mortality of patients with clear cell renal cell carcinoma. In the study of Sut et al. (20) in 78 patients with breast cancer, they reported that MPVLR, NLR, and PLR levels were significantly higher in breast cancer patients compared to controls. In addition, a significant association was found between NLR and PLR but not MPVLR and low dietary polyphenol intake in breast cancer patients (20). In our study, MPVLR levels were statistically significantly higher in the mortality group compared to the survivor group. According to the results of ROC analysis in patients with mortality, sensitivity was 50.0% and specificity was 68.6% for MPVLR. However, in the regression analysis, risk factors were not found to be associated with mortality and MPVLR.

In the literature, studies examining the relationship of diseases with MPVPR are limited (7,8). Tezcan et al. (8) reported a prognostic relationship between MPVPR and Behçet’s disease (BD), which determines the diagnosis and severity of BD. Bernardi et al. (7) reported a prognostic relationship between MPVPR and predictive markers of CVD. In a study conducted by Karakurt et al. (21) in complexity of coronary artery disease (CCAD) in patients with acute coronary syndrome (ACS), MPVPR and MPVLR were not independent predictors of CCAD in patients with ACS. In our study, MPVPR levels were statistically significantly lower in the mortality group compared to the survivor group. According to the results of ROC analysis in patients with mortality, sensitivity was 41.0% and specificity was 47.9% for MPVPR. However, the risk factors found to be significantly associated with mortality in the regression analysis included MPVPR [b: 0.043, OR (95% CI): 0.435 (0.353-0.516), p=0.048].

Study Limitations

There were some limitations in our study. First, our study is a single-center and retrospective study. The small sample size of patients was the second limitation. Moreover, multi-center and prospective studies should be planned to support these pre-liminary results. However, the strengths of our study included that our sample was larger and our results were supported by logistic regression analysis.

Conclusion

As inexpensive and easily available new inflammatory markers, higher MPVLR and lower MPVPR were significantly in patients with GFR <60 and in those who died from MI. However, MPVLR levels may predict hemodynamically severe coronary obstruction better than MPVPR. The utility of this new marker warrants to be investigated in various cardiac situations. Large-scale, prospective, and multicenter studies will be necessary to clarify the relationship between MPVLR, MPVPR and MI.

Ethics

Ethics Committee Approval: The study protocol was approved by Local Ethics Committee of İstanbul Medipol University (approval no: E-10840098-772.02-3976).

Informed Consent: Informed consent was obtained.

Peer-review: Externally peer-reviewed.

Authorship Contributions

Concept: S.K., E.O., M.R.Y., Design: S.K., E.O., M.R.Y., Data Acquisition: S.K., F.K., S.V., O.İ., Data Collection or Processing: S.K., İ.Ş., Analysis or Interpretation: S.K., İ.Ş., Drafting Manuscript: S.K., E.O., M.R.Y., Critical Revision of Manuscript: S.K., F.K., S.V., O.İ., İ.Ş., Final Approval and Accountability: S.K., F.K., S.V., O.İ., İ.Ş., E.O., M.R.Y.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study received no financial support.

References

Carrabba M, Madeddu P. Current Strategies for the Manufacture of Small Size Tissue Engineering Vascular Grafts. Front Bioeng Biotechnol 2018;6:41.

Budzianowski J, Pieszko K, Burchardt P, Rzezniczak J, Hiczkiewicz J. The Role of Hematological Indices in Patients with Acute Coronary Syndrome. Dis Markers 2017;2017:3041565.

Karahan S, Okuyan E. Systemic Inflammatory Index and Platelet-to-Lymphocyte Ratio Predicted Mortality in patients with Acute Myocardial Infarction. Experimental Applied Medical Science 2021;2(2):146-153.

Kurtul A, Acikgoz SK. Usefulness of Mean Platelet Volume-to-Lymphocyte Ratio for Predicting Angiographic No-Reflow and Short-Term Prognosis After Primary Percutaneous Coronary Intervention in Patients With ST-Segment Elevation Myocardial Infarction. Am J Cardiol 2017;120(4):534-541.

Hudzik B, Szkodzinski J, Lekston A, Gierlotka M, Polonski L, Gąsior M. Mean platelet volume-to-lymphocyte ratio: a novel marker of poor short- and long-term prognosis in patients with diabetes mellitus and acute myocardial infarction. J Diabetes Complications 2016;30(6):1097-1102.

Inanir M. Evaluation of Platelet Indices in Diabetic Patients with Myocardial Bridges. Dicle Med J 2020;47(2):286-292.

Bernardi M, Fedullo AL, Di Giacinto B, Squeo MR, Aiello P, Dante D, et al. Cardiovascular Risk Factors and Haematological Indexes of Inflammation in Paralympic Athletes with Different Motor Impairments. Oxidative Medicine and Cellular Longevity 2019;2019:6798140.

Tezcan D, Körez MK, Gülcemal S, Hakbilen S, Akdağ T, Yılmaz S. Evaluation of diagnostic performance of haematological parameters in Behçet’s disease. Int J Clin Pract 2021;75(10):e14638.

Bilgin S, Aktas G, Kahveci G, Atak BM, Kurtkulagi O, Duman TT. Does mean platelet volume/lymphocyte count ratio associate with frailty in type 2 diabetes mellitus? Bratisl Lek Listy 2021;122(2):116-119.

Wang H, Xing Y, Yao X, Li Y, Huang J, Tang J, et al. Retrospective Study of Clinical Features of COVID-19 in Inpatients and Their Association with Disease Severity. Med Sci Monit 2020;26:e927674.

Tekin YK, Tekin G. Mean Platelet Volume-to-Platelet Count Ratio, Mean Platelet Volume-to-Lymphocyte Ratio, and Red Blood Cell Distribution Width-Platelet Count Ratio as Markers of Inflammation in Patients with Ascending Thoracic Aortic Aneurysm. Braz J Cardiovasc Surg 2020;35(2):175-180.

Durmus E, Kivrak T, Gerin F, Sunbul M, Sari I, Erdogan O. Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio are Predictors of Heart Failure. Arq Bras Cardiol 2015;105(6):606-613.

Yang YL, Wu CH, Hsu PF, Chen SC, Huang SS, Chan WL, et al. Systemic immune-inflammation index (SII) predicted clinical outcome in patients with coronary artery disease. Eur J Clin Invest 2020;50(5):e13230.

Mirza AJ, Taha AY, Khdhir BR. Risk factors for acute coronary syndrome in patients below the age of 40 years. Egypt Heart J 2018;70(4):233-235.

Uthamalingam S, Patvardhan EA, Subramanian S, Ahmed W, Martin W, Daley M, et al. Utility of the neutrophil to lymphocyte ratio in predicting long-term outcomes in acute decompensated heart failure. Am J Cardiol 2011;107(3):433-438.

Yildiz A, Yuksel M, Oylumlu M, Polat N, Akyuz A, Acet H, et al. The Utility of the Platelet-Lymphocyte Ratio for Predicting No Reflow in Patients With ST-Segment Elevation Myocardial Infarction. Clin Appl Thromb Hemost 2015;21(3):223-228.

Gary T, Pichler M, Belaj K, Hafner F, Gerger A, Froehlich H, et al. Platelet-to-lymphocyte ratio: a novel marker for critical limb ischemia in peripheral arterial occlusive disease patients. PLoS One 2013;8(7):e67688.

Oylumlu M, Yıldız A, Oylumlu M, Yüksel M, Polat N, Bilik MZ, et al. Platelet-to-lymphocyte ratio is a predictor of in-hospital mortality patients with acute coronary syndrome. Anatol J Cardiol 2015;15(4):277-283.

Życzkowski M, Kaletka Z, Rajwa P, Rempega G, Stelmach P, Bogacki R, et al. Mean platelet volume-to-lymphocyte ratio: a novel biomarker associated with overall survival in patients with nonmetastatic clear cell renal cell carcinoma treated with nephrectomy. Int Urol Nephrol 2020;52(5):885-891.

Sut A, Pytel M, Zadrozny M, Golanski J, Rozalski M. Polyphenol-rich diet is associated with decreased level of inflammatory biomarkers in breast cancer patients. Rocz Panstw Zakl Hig 2019;70(2):177-184.

Karakurt A, Yildiz C. Predictive values of inflammatory cell ratios for complexity of coronary artery disease in patients with acute coronary syndrome. Int J Cardiovasc Acad 2018;4(4):70.

The Role of MPV-to-Lymphocyte Ratio and MPVto- Platelet Ratio in Predicting Mortality in Patients with Acute Myocardial Infarction