Increased Platelet Volume Indices is associated with the severity of Coronary Artery Disease

 

Maya Alkhateeb¹, Tagrid Kaddar²

¹Postgraduate Student, Department of Microbiology and Biochemistry, Faculty of Pharmacy, Tishreen University, Lattakia, Syria.

²Associate Professor, Department of Laboratory Medicine, Faculty of Medicine, Tishreen University, Lattakia, Syria

 

ABSTRACT:

Platelets play key roles both in the pathogenesis of atherosclerosis and in the development of acute thrombotic events. Platelet size correlates with platelet activity and can be assessed by platelet volume indices, which are mean platelet volume (MPV), platelet distribution width (PDW), and Platelet-large cell ratio (P-LCR). We enrolled 101 patients with stable angina, unstable angina or myocardial infarction undergoing coronary angiography. Patients were divided into three groups according to their degree of stenosis and the number of stenotic vessels; Non-significant coronary artery disease (CAD) was defined as a stenosis <50% in coronary vessel, significant coronary artery disease was defined as a stenosis >50% in at least 1 coronary vessel, while severe coronary artery disease was defined as left main and/or three-vessel disease >50%. Blood samples were run through the automated blood analyzer to obtain the platelet indices. As a result, a statistically significant increase in all three platelet volume indices was observed in patients with severe CAD compared to those with non-significant CAD. We concluded that platelet volume indices, MPV, PDW, and P-LCR, are useful markers for the diagnosis of severe coronary artery disease.

 

 

 

 

 

 

 

INTRODUCTION:

The importance of coronary artery disease (CAD) and atherosclerosis in particular has emerged recently as it is the leading cause of mortality among developed countries¹ and in Syria². Despite the significant improvement in survival in the treatment of acute myocardial infarction in the last decades by the great improvements in mechanical devices and antithrombotic therapies³, the outcome is still unsatisfactory in high-risk subsets of patients⁴.

 

Therefore, large interests have been focused on the identification of new risk factors and prognostic markers in order to achieve a better prevention⁵. Particular attention has been paid to platelets which have an important role in the initiation of atherosclerotic lesions and subsequent complications⁶, by secreting cytokines, chemokines, and other inflammatory mediators in the site of injury⁷. Atherosclerosis is not merely the passive accumulation of lipids within artery walls, it is also a chronic progressive inflammatory disease⁸.

 

Circulating platelets are heterogeneous with respect to their size, density and reactivity. Large platelets contain more dense granules, are metabolically and enzymatically more active than small platelets, and have higher thrombotic potential^9,10. Increased platelet activity is associated with atherosclerotic disease, including CAD¹¹. Platelet activity may be assessed by platelet volume indices such as mean platelet volume (MPV), platelet distribution width (PDW), and platelet-large cell ratio (P-LCR). It is unclear yet whether these indices can be considered as risk factors for CAD¹².

 

The aim of this study was to evaluate the relationship between these easily measured parameters and clinical features of CAD in patients undergoing coronary angiography.

 

MATERIAL AND METHODS:

Our population is represented by 101 consecutive patients with stable angina, unstable angina or myocardial infarction undergoing coronary angiography at Al-Assad university hospital, Lattakia, Syria from February, 2015 to April, 2016. All demographic and clinical data were collected from the patients and included in a dedicated database. The study was approved by the local ethics committee.

 

Basic demographic data were collected including age, gender, presence of diabetes mellitus, hypertension, hyperlipidaemia, family history of coronary artery disease (CAD), current smoking, and medications.

 

Exclusion criteria were renal dysfunction, hematological disorders, malignant disease and acute or chronic infection, thyroid dysfunction and current pregnancy.

 

Hematological measurements:

Blood samples were collected in tubes with tripotassium ethylenediaminetetraacetate (K3 EDTA) as an anticoagulant. Then they were analyzed by automatic blood counter (Sysmex XP-300, Kobe, Japan) within 15 minutes of collection. The following hematological parameters were studied in all blood samples: platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), platelet-large cell ratio (P-LCR) which represents the percentage of platelets larger than 12 fL, and plateletcrit (Pct). The expected value for platelet count in our laboratory ranges from 150 to 400*10⁹/L, for MPV from 8 to 12 fL, for PDW between 9-14 fL, and for P-LCR between 15-35%. The study population was divided into quartiles based on P-LCR values. We also examined some blood smears microscopically to exclude any platelets aggregation in the samples.

 

Coronary angiography:

Femoral, brachial or radial artery cannulation was used for arterial access site and Judkins technique using 5 or 6 French right and left heart catheters was applied for cannulation of the left and right coronary arteries. All angiograms were evaluated by two experienced physicians blinded to the study.

 

Non atherosclerotic patients and patients with Coronary stenotic lesions with <50% luminal stenosis were defined as nonsignificant CAD (group 1). Significant CAD was defined by 1 or 2 coronary stenosis more than 50% (group2). Severe CAD was defined as three-vessel disease and/or left main disease (group 3). In case of patients who had previously undergone percutaneous coronary intervention, even though no restenosis was observed, the treated vessel was counted as significantly diseased. In previously bypassed patients, native arteries and grafts were taken into account in the evaluation of extension of artery disease (number of diseased vessels).

 

Statistical analysis:

Continuous variables were given as mean ± standard deviation, categorical variables were expressed as percentages. The Shapiro–Wilk test was used for normality tests. The Student’s t test and the one way analysis of variance test were used for comparing continuous variables. The chi-square test and Fisher exact test were used for categorical variables. Receiver operating characteristic (ROC) curve analysis was performed to determine the predictive value of P-LCR regarding coronary stenosis. Odd ratios were measured to assess the risk of CAD in the P-LCR quartiles.

 

Statistical analysis was performed using Microsoft Excel 2016 along with XLSTAT 2016 software. Results were considered statistically significant when p value < 0.05.

 

RESULTS:

In this study, we enrolled 101 patients (65 men and 36 women), the mean age was 55±8.9 years (range from 34 to 83 years). Considering the risk factors, of the 101 patients, 31% had diabetes mellitus, 54% had hypertension, 47% had family history of CAD, 37% were obese and 59% were current smokers. Patients were divided in three groups according to the coronary angiography reports. The main demographic and clinical features of the study population are displayed in (table 1)

 

 

Table1: Demographic and clinical features of patients and their treatments

	Group 1 (n=29) Nonsignificant CAD	Group 2 (n=36) Significant CAD	Group 3 (n=36) Severe CAD	P value
Age (years ± SD)	51.8 ±9.2	55 ±7.1	58.3 ±9.3	0.01*
Male sex	11 (38%)	28 (78%)	26 (72%)	0.001*
Diabetes mellitus	6 (21%)	8 (22%)	17 (47%)	0.02*
Hypertension	18 (62%)	16 (44%)	21 (58%)	0.3
Current smokers	16 (55%)	22 (61%)	22 (61%)	0.85
Obesity	8 (28%)	19 (53%)	10 (28%)	0.04*
Family history of CAD	10 (34%)	17 (47%)	20 (56%)	0.23
Dyslipidemia	8 (28%)	13 (36%)	11 (31%)	0.75
ASA	15 (52%)	20 (56%)	32 (89%)	0.001*
Clopidogrel	10 (34%)	12 (33%)	18 (50%)	0.28
Statins	10 (34%)	17 (47%)	21 (58%)	0.15
Beta-blockers	13 (45%)	20 (56%)	24 (67%)	0.2
ACE-inhibitors	5 (17%)	8 (22%)	9 (25%)	0.75
ARBs	7 (24%)	5 (14%)	6 (17%)	0.54
Ca-antagonists	8 (28%)	8 (22%)	8 (22%)	1
Diurectis	8 (28%)	6 (17%)	15 (42%)	0.06

 

 

Data expressed as frequency (percentage). CAD: coronary artery disease, ASA: acetyl salicylic acid, ACE: angiotensin converting enzyme, ARB; Angiotensin-receptor blockers, *statistical significance:

Patients were older in group 3 than the two other groups (p=0.01). There were also statistically significant differences between groups in terms of gender, diabetes mellitus, obesity (p=0.001, p=0.02, p=0.04 respectively).

There were no statistically significant differences between groups according to presence of hypertension or smoking habit, family history for coronary artery disease, and dyslipidemia (p >0.05). Patients in group 3 were more often on aspirin (p=0.001). However, there were no significant differences regarding other treatments.

 

 

 

 

The hematological parameters of study population are shown in (table 2). Although values of  PDW, MPV and P-LCR increased gradually from group 1 to the group 3, there were no statistically significant differences in the platelet indices values between the groups. But when we compare the indices between each two groups separately we found that PDW, MPV, and P-LCR were significantly higher in group 3 than group 1. On the other hand, there were no significant difference between group 2 and group 1 or between group 2 and group 3 regarding any of the platelet parameters (table 3).

 

Patients were also divided into four groups according to quartiles values of P-LCR (1st quartile; ≤ 21.1%, 2nd quartile; 21.2-25.4%, 3rd quartile; 25.5- 32.2%, 4th quartile; ≥32.3%). The main demographic, clinical, and angiographic characteristics of the quartiles are reported on (table 4).

 

 

 

 

Table 2: Hematological parameter in three angiographic groups

	Group 1 (n=29)	Group 2 (n=36)	Group 3 (n=36)	P value
Platelet count (*103)	236 ± 63	226 ± 63	247 ± 112	0.57
PDW (fL)	12.3 ± 1.8	12.8 ± 2.2	13.2 ± 2.4	0.22
MPV(fL)	9.8 ± 0.8	10.1 ± 1.1	10.3 ± 1.1	0.18
P-LCR (%)	24.2 ± 6.2	26.8 ± 8.2	28 ± 8.5	0.155
Plateletcrit	0.23 ± 0.06	0.22 ± 0.04	0.25 ± 0.12	0.13

Data expressed as mean ± SD. PDW: platelet distribution width, MPV: mean platelet volume, P-LCR: platelet large cell ratio

 

 

Table 3: significance of platelet indices differences between each two angiographic groups

	Group 3 vs group 2	Group 2 vs group 1	Group 3 vs group 1
Platelet count	0.16	0.26	0.32
PDW	0.2	0.16	0.04*
MPV	0.27	0.09	0.03*
P-LCR	0.26	0.08	0.02*
Plateletcrit	0.09	0.34	0.17

PDW: platelet distribution width, MPV: mean platelet volume, P-LCR: platelet large cell ratio. *statistical significance

 

Table 4: Baseline characteristics according to quartiles of (P-LCR)

	1st quartile (n=27)	2nd quartile (n=24)	3rd quartile (n=25)	4th quartile (n=25)	P value
Age (years) ± SD	53.8 ± 7.6	54.5 ± 10.3	56.1 ± 9.6	56.6 ± 8.1	0.65
Male sex	17 (62%)	16 (67%)	16 (64%)	16 (64%)	0.99
Diabetes mellitus	8 (30%)	7 (29%)	7 (28%)	9 (36%)	0.92
Hypertension	15 (56%)	12 (50%)	12 (48%)	16 (64%)	0.67
Current smokers	19 (70%)	13 (54%)	16 (64%)	12 (48%)	0.36
Obesity	9 (33%)	11 (46%)	9 (36%)	8 (32%)	0.74
Family history of CAD	11 (41%)	11 (46%)	10 (10%)	15 (60%)	0.45
Dyslipidemia	10 (37%)	8 (33%)	9 (36%)	5 (20%)	0.53
Extent of CAD
Severe CAD	9 (33%)	6 (25%)	7 (28%)	14 (56%)	0.09
Significant CAD	7 (26%)	12 (50%)	9 (36%)	8 (32%)
Nonsignificant CAD	11 (41%)	6 (25%)	9 (36%)	3 (12%)

 

Data expressed as frequency (percentage). P-LCR: Platelet-Large Cell Ratio, CAD: coronary artery disease

ROC curve analysis was performed to determine the predictive value of P-LCR in patients with CAD regarding the degree and the number of stenotic vessels. The cutoff value for P-LCR for identifying patients with significant or severe CAD was 28.7% (p= 0.04), the area under the curve (AUC: 0.615 [sensitivity 43.1%, specificity 82.8%]) is shown in (figure 1).

 

 

Figure 1: ROC curve of P-LCR for identifying patients with significant or severe CAD. P-LCR, platelet-large cell ratio; ROC, receiver operating characteristic.

 

The odds of CAD risk according to each quartile of P-LCR is shown in (Table 5). Patient within the fourth quartile of P-LCR (≥32.3%) had a 2.55-fold increased odds of CAD as compared with the reference group (quartile 1: ≤ 21.1%,) (95% CI: 0.89-7.28). However, no significance was found across increasing quartiles of P-LCR (P trend=0.088).

 

Table 5: Relationship between P-LCR and CAD 

DISCUSSION:

Platelets represent an important link between inflammation, thrombosis, and atherogenesis¹³. Platelet volume indices are easily available during routine blood counts by automated blood analyzer, and could be used as a marker of platelet activity.

 

We found that platelet volume indices, including MPV, PDW, and P-LCR, increased significantly in patients with severe CAD compared with those with significant and nonsignificant CAD. These indices were higher in patients with significant coronary stenosis than in nonsignificant CAD, although this increase was not statistically significant. These findings are in agreement with previous studies that showed a prognostic and diagnostic value for that the elevated platelet volume indices in patients with CAD.

 

Murat et al. found that MPV may be an independent factor correlating with the severity of coronary artery atherosclerosis¹⁴. Ekici at al. concluded that MPV could be used to determine cardiovascular disease burden besides other risk factors during routine clinical practice¹⁵. Furthermore, a meta-analysis by Chu et al. stated that MPV was a potentially useful prognostic biomarker in patients with cardiovascular disease, and it was associated with recurrent MI, and coronary restenosis following stenting¹⁶.

 

On the other hand, some reports came up with confliction results. Turk et al. reported that PDW and MPV may not be related to the clinical features or extent of CAD¹⁷. However, Güvenç at al. showed that there is no linear relationship between MPV and extent of coronary artery disease, while patients with lower than normal mean platelet volume had reduced extent of coronary artery disease¹⁸. In a large scale study, De Luca et al. found that there were no correlations between MPV or P-LCR and the extension of CAD according to coronary angiography^{19, 20}.

 

 

 

Despite the fact that most of the studies focused on MPV and some included PDW and P-LCR as well, we believe that the diagnostic and prognostic values of platelet volume indices may be similar to each other. On top of that, P-LCR may potentially provides better prognostic information as compared to MPV or PDW, because it represents the percentage of platelets larger than 12 fl²¹.

 

Even though, significantly more patients in group 3 were taking aspirin, previous reports revealed that aspirin or dual antiplatelet therapy may not significantly affect MPV^{22, 23}

 

We can say that patients with P-LCR>28.7% are more likely to have significant stenosis in their coronary arteries. And the odds of CAD risk rise with higher P-LCR values.

 

Male sex is considered a risk factor for CAD. Accordingly, we showed that there were a significant difference regarding the prevalence of CAD between both sexes (table 1).

 

In conclusion we found that platelet volume indices, MPV, PDW, and P-LCR, are useful tools for diagnosis of patients with severe stenotic lesions in their coronary arteries.

 

LIMITATIONS:

The main limitation of this study was relatively small sample size. A larger study population would provide a higher statistical power.

 

CONFLICT OF INTEREST:

The authors declare no conflict of interest.

 

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Accepted on 28.11.2016           © RJPT All right reserved

Research J. Pharm. and Tech 2018; 11(6): 2168-2172.