Clinical Significance of Platelet Volume and Other Platelet Parameters in Acute Myocardial Infarction and Stable Coronary Artery Disease

Abstract

Background:

Platelets are important in the initiation of thrombosis, and their morphological and functional changes are closely related with the occurrence and development of coronary artery thrombosis. Platelet parameters might be valuable in distinguishing between acute myocardial infarction (AMI) and stable coronary artery disease (SCAD).

Objective:

This study was designed to detect and compare changes in platelet parameters, such as mean platelet volume (MPV) in patients with acute myocardial infarction (AMI) and stable coronary artery disease (SCAD) and to investigate their roles in these diseases.

Methods:

Specimen collection: Between January 2011 and December 2013, 2 mL of elbow vein blood was drawn from each of 31 patients primarily diagnosed with AMI, 34 SCAD patients and 50 healthy subjects; and placed in EDTA-K2 anticoagulant tubes. Platelet count (PLT), MPV, plateletcrit (PCT), platelet distribution width (PDW), white blood cell (WBC) and neutrophil (NEU) counts were determined using an STKS automated hematology analyzer (Beckman Courter).

Results:

Compared with the control group, MPV levels were significantly higher in the AMI and SCAD groups (p < 0.05), while PLT was significantly lower (p < 0.05).

Conclusion:

These results suggest that MPV and other related parameters have a certain value in the diagnosis of SCAD and AMI.

Keywords:
Acute Coronary Syndrome/physiopathology; Coronary Thrombosis; Mean Platelet Volume; Myocardial Infarction

Resumo

Fundamento:

As plaquetas são importantes no início da trombose e suas alterações morfológicas e funcionais estão intimamente relacionadas com a ocorrência e o desenvolvimento de trombose da artéria coronária. Os parâmetros plaquetários podem ser valiosos na distinção entre infarto agudo do miocárdio (IAM) e doença arterial coronariana estável (DACE).

Objetivo:

O objetivo desse estudo foi detectar e comparar alterações nos parâmetros plaquetários, como o volume plaquetário médio (VPM) em pacientes com infarto agudo do miocárdio (IAM) e doença arterial coronariana estável (DACE) e investigar seu papel nessas doenças.

Métodos:

Coleta de amostras: Entre janeiro de 2011 e dezembro de 2013, foram retirados 2 mL de sangue da veia do antebraço de cada um dos 31 pacientes diagnosticados principalmente com IAM, 34 pacientes com DACE e 50 indivíduos saudáveis; e colocado em tubos com anticoagulante EDTA-K2. As contagens de plaquetas (PQT), VPM, massa total de plaquetas (MTP), Amplitude de Distribuição de Plaquetas (PDW, do inglês platelet distribution width), contagem de glóbulos brancos (WBC, do inglês white blood cells) e neutrófilos (NEU) foram determinadas utilizando-se um analisador de hematologia automatizado STKS (Beckman Courter).

Resultados:

Comparado com o grupo controle, os níveis de VPM foram significativamente maiores nos grupos IAM e DACE (p < 0,05), enquanto os níveis de PQT foram significativamente menores (p < 0,05).

Conclusão:

Esses resultados sugerem que o VPM e outros parâmetros associados têm um certo valor no diagnóstico de DACE e IAM.

Palavras-chave:
Síndrome Coronariana Aguda/fisiopatologia; Trombose Coronária; Volume Plaquetário Médio; Infarto do Miocárdio

Introduction

Acute coronary syndromes (ACS) are a group of clinical syndromes, of which pathological bases are coronary atherosclerosis plaques rupture or erosion,¹ followed by complete or incomplete occlusive thrombosis. ACS include acute myocardial infarction (AMI) and unstable angina pectoris. Among these, AMI refers to acute focal myocardial necrosis caused by prolonged and severe myocardial ischemia.²

In 2013, the European Society of Cardiology issued the management guidelines for stable coronary artery disease (SCAD).³ These guidelines clearly pointed out that SCAD also include situations of no symptoms or stable symptoms after the stabilization of acute coronary syndrome, besides stable angina pectoris. These situations cannot be clearly distinguished from ACS. Previous studies have revealed that platelet is an important medium in the initiation of thrombosis, and its morphological and functional changes are closely correlated with the occurrence and development of coronary artery thrombosis.^4,5

Additionally, mean platelet volume (MPV), one of the platelet parameters in AMI, is significantly higher than in normal subjects, hence MPV is considered as a predictor for AMI.⁶ However, the value of platelet parameters in distinguishing between AMI and SCAD has not been reported in China. It has been reported that the supersensitive troponin level was elevated in patients with SCAD.⁷ Although it did not reach the threshold for the diagnosis of myocardial infarction, the prognosis was poorer, when compared with SCAD patients without an elevated troponin level. In our study, differences in platelet parameters such as MPV in AMI patients, SCAD patients and healthy subjects were analyzed, and the significance of these parameters for predicting the disease was investigated.

Methods

General Information

A total of 31 patients primarily diagnosed with AMI were enrolled in this study. All patients had been diagnosed for the first time, did not undergo anticoagulation or stent percutaneous coronary intervention, and met the international and Chinese guidelines for the diagnosis of AMI. Of these patients, 23 patients were males and eight patients were females; and the mean age of these patients was 64.4 ± 11.6 years. Thirty-four patients were diagnosed with SCAD. These patients were required to meet the following criteria: (1) patients diagnosed with AMI for more than two months; (2) patients without pectoralgia; (3) patients who were receiving anticoagulation drug treatment. Of these patients, 28 patients were males and six patients were females; the mean age of these patients was 60.6 ± 13.1 years. The control group comprised 50 healthy subjects who underwent physical examinations at the Outpatient Department. Among these subjects, 38 were males and 12 were females, and their mean age was 60.9 ± 6.9 years.

None of the abovementioned patients had severe liver or kidney disease, malignant tumors, idiopathic thrombocytopenia, or thrombocytopenia caused by other primary diseases.

Sample collection

In the early morning, 2 mL of elbow vein blood was withdrawn from each of these subjects under a fasting state, without receiving any hemostasis, coagulation and anticoagulation drugs. The collected blood was placed in EDTA-K2 anticoagulant tubes.

Detection method

Platelet count (PLT), plateletcrit (PCT), MPV, platelet distribution width (PDW), white blood cell (WBC) and neutrophil (NEU) counts were determined using an STKS automated hematology analyzer (Beckman Courter).

Statistical analysis

Statistical analysis was performed using the GraphPad Prism 5 software. Measurement data were presented as mean± standard deviation (x ± SD). Comparison of the means in multiple samples was performed using unpaired t-test. p < 0.05 was considered statistically significant. The prediction value of platelet parameters and the total leukocyte count for AMI and SCAD were evaluated using the receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC). Correlations between parameters were analyzed using Pearson’s correlation statistical method.

Results

Results of the four platelet parameters and the total WBC count in AMI patients, SCAD patients and normal healthy subjects (Table 1).

Table 1
Platelet parameters and total number of white blood cells and neutrophils in the AMI, SCAD and the control groups

Parameters	AMI (n = 31)	SCAD (n = 34)	control group (n = 50)
PLT (x 109)	185.84 ± 61.26	193.62 ± 47.1	206.28 ± 36.17
MPV (fL)	10.42 ± 1.26	9.16 ± 1.28	8.42 ± 0.72
PCT (%)	0.1777 ± 0.0464	0.1709 ± 0.0393	0.1693 ± 0.0287
PDW (%)	16.2 ± 0.65	16.0 ± 1.37	16.5 ± 0.32
WBC (x 109/L)	10.60 ± 2.53	6.61 ± 1.54	6.37 ± 1.25
NEU (x 109/L)	8.34 ± 2.66	3.99 ± 1.25	3.79 ± 0.93

• Compared with the control group, the MPV levels were significantly higher (p < 0.01), while the PLT and the PDW were significantly lower (p < 0.05) in the AMI and SCAD groups. Besides, compared to the control group, the WBC and NEU levels were also significantly higher (p < 0.01) in the AMI group, but there was no significant difference in the SCAD group. However, the PCT levels showed no significant difference between the patient groups and the control group.

As shown in Table 1, compared with the control group, the MPV levels were significantly higher (p < 0.01), while the PLT and the PDW were significantly lower (p < 0.05) in the AMI and SCAD groups. Moreover, compared to the control group, the WBC and NEU levels were also significantly higher (p < 0.01) in the AMI group, but there was no significant difference in the SCAD group. However, the PCT levels had no significant difference between the patient groups and the control group.

Evaluation of the diagnostic efficacy of each index by the diagnostic test

As shown in Figure 1, in the AMI group, the AUC of PLT (95% CI) was 0.6474 (0.5206-0.7742) and the p-value compared with controls was < 0.05, which shows that the differences were statistically significant. The AUC of MPV (95%Cl) was 0.9032 (0.8232-0.9832) and the p-value compared with controls was < 0.01, which revealed that the differences were statistically significant. Furthermore, the AUC of PDW (95% CI) was 0.6529 (0.5239-0.7819) and the p-value compared with controls was < 0.05; the AUC of PCT (95% CI) was 0.5687 (0.4364-0.701) and the p-value compared with controls was < 0.05, and the AUC of WBC (95% CI) was 0.9190 (0.8475-0.9906) and the p-value compared with controls was < 0.01. Finally, the AUC of NEU (95% CI) was 0.9310 (0.8678-0.9942) and the p-value compared with controls was < 0.01. These differences were all statistically significant. These results imply that the diagnostic value of PLT, MPV, WBC and NEU was significantly higher in the AMI group.

Figure 1
ROC curves of PLT, PDW, MPV, PCT, WBC and NEU for predicting AMI. PLT: platelet count; MPV: mean platelet volume; PCT: plateletcrit; PDW: platelet distribution width; WBC: white blood cell; NEU: neutrophils; AMI: acute myocardial infarction.

As shown in Figure 2, in the SCAD group, the AUC of PLT (95% CI) was 0.6176 (0.4907-0.7445) and the p-value compared with controls was > 0.05. The AUC of PDW (95% CI) was 0.6818 (0.5554-0.8081) and the p-value compared with controls was < 0.01, with the differences being statistically significant. The AUC of PDW (95% CI) was 0.5609 (0.4268-0.6949) and the p-value compared with controls was >0.05, whereas the AUC of PCT (95% CI) was 0.5332(0.3994-0.6671) and the p-value compared with controls was > 0.05, and the AUC of WBC (95% CI) was 0.5635 (0.4368-0.6903) and the p-value compared with controls was > 0.05. Finally, the AUC of NEU (95% CI) was 0.5447 (0.4138-0.6756) and the p-value compared with controls was > 0.05. These results imply that the diagnostic value of MPV was significantly higher in the SCAD group.

Figure 2
ROC curves of PLT, PDW, MPV, PCT, WBC and NEU for predicting SCAD. ROC, receiver operating characteristics; PLT: platelet count; MPV: mean platelet volume; PCT: plateletcrit; PDW: platelet distribution width; WBC: white blood cell; NEU: neutrophils; SCAD: stable coronary artery disease.

Correlation analysis of MPV with PLT, PCT and PDW in patients with myocardial infarction

Pearson’s correlation coefficient between MPV and PLT was 0.3817; Pearson’s correlation coefficient between MPV and PCT was 0.1103. Pearson’s correlation coefficient between MPV and PDW was 0.0726. It indicates that the MPV and PLT in patients with myocardial infarction have a strong correlation.

Discussion

The key mechanisms of ACS include coronary plaque rupture, platelet aggregation and thrombus formation. Mounting evidence has revealed that inflammation is an important precipitating event in the pathogenesis of ACS.⁸ Inflammatory response plays an important role in the process of the occurrence, development and prognosis of coronary heart diseases. As markers of inflammatory response, WBC and NEU are closely correlated to cardiovascular system diseases. Studies have revealed that both can directly reflect the level of inflammation in coronary artery lesions, thereby further reflecting the severity of coronary artery lesions.^9,10 Studies have confirmed that the NEU/lymphocyte ratio could serve as a predictor of major adverse cardiovascular events.^11-13 This study revealed that there was a leukocyte-mediated inflammatory response in patients with AMI and that serum leukocyte levels were higher in SCAD and AMI patients than in normal healthy subjects. Furthermore, serum NEU levels were significantly abnormal in AMI patients, suggesting that inflammatory response is more intense in AMI patients. Hence, we consider that the reason may be that the range of inflammation is broader in myocardial infarction.

MPV reflects the degree of activation of platelets to a certain extent and is considered an important marker of cardiovascular disease.¹⁴ Furthermore, it can be used in risk prediction, diagnosis and prognosis assessment of cardiovascular diseases.^15-17

A recent study revealed that MPV significantly increased in patients with AMI, and the increase in MPV was correlated to the long-term prognosis of AMI patients to a certain extent.¹⁸ Our study also revealed that MPV was significantly increased in patients in the AMI and SCAD groups. The increase in MPV is likely correlated to the intensity of inflammatory response in the body.

MPV has important significance in the evaluation of arterial thrombotic diseases such as cardiovascular thrombotic diseases. Therefore, MPV can act as an independent factor for the diagnosis and assessment of conditions and the curative effect of ACS. MPV levels in both the AMI and SCAD groups were significantly higher than normal levels, while PLT levels were significantly lower. These indicators are worthwhile in practice for disease diagnosis. In addition, based on the assessment of the diagnostic efficacy of the ROC curve for these parameters, the predicting value of MPV and PLT in AMI was superior to that in SCAD. In summary, the present study revealed that MPV- and PLT-related indicators are valuable for AMI and SCAD diagnostic prediction. However, there are two shortcomings of our study: one is that the study design is cross-sectional, because of the difficulty in keeping contact with these patients; the other is that there are only about 30 patients in the AMI and SCAD groups. There is no doubt that these two problems constitute limitations of our study. Further studies need to be carried out in a larger cohorts of patients with AMI and SCAD, with a more appropriate design to confirm its value as a diagnostic marker.

• Sources of Funding
  There were no external funding sources for this study.
• Study Association
  This study is not associated with any thesis or dissertation work.
• Ethics approval and consent to participate
  This study was approved by the Ethics Committee of the Jinshan Hospital, Fudan University under protocol number 785. All the procedures in this study were in accordance with the 1975 Helsinki Declaration, updated in 2013. Informed consent was obtained from all participants included in the study.

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Publication Dates

• Publication in this collection
  01 Apr 2019
• Date of issue
  June 2019

History

• Received
  21 May 2018
• Reviewed
  28 Sept 2018
• Accepted
  14 Nov 2018