Li-Guo , Hong , Zhen-Jun , Ling-Guang , Li-Jun , Shao-Jing , and Tao: Prognostic value of post-procedural mean platelet volume on one-year major cardiac outcomes in ST-elevation myocardial infarction after percutaneous coronary intervention.

Platelet-induced inflammation may play a critical role in atherothrombosis1, and is thought to be the major cause of unstable coronary syndromes2. STEMI is a major and clinically important event. Platelet activity is a major culprit in contributing to thrombus formation or apposition after coronary plaque rupture3. MPV, a simple and reliable parameter used to measure the platelet, is a potential marker of platelet reactivity. Larger platelets are metabolically and enzymatically more active than smaller platelets and have an increased production of vasoactive and prothrombotic factors4-7, including increased platelet aggregation, increased thromboxane synthesis β-thromboglobulin release, and increased expression of adhesion molecules8. Few studies have evaluated the prognostic value of MPV in patients suffering from myocardial infarction (MI)9-12 and recent studies have focused on ST-segment elevation MI11,12.

Balloon injury and stent implantation can also injury vascular endothelium and activate platelets. Recently, it has been confirmed that the circulating WBC count is altered after PCI13,14. Increased post-procedural WBC is an independent predictor of poor clinical outcomes in STEMI patients who underwent PCI15. However, whether MPV is altered after PCI and whether post-procedural MPV is associated with MCO following PCI remains unknown. Therefore, this study was designed to investigate whether mean platelet volume is associated with 1-year MCO in patients with STEMI after PCI.

Methods

A total of 301 consecutive patients with acute STEMI were recruited to the study from January 2011 to June 2012. All patients were treated with successful primary PCI. They were divided into 2 groups (G) according to their mean platelet volume (G1≤ 9.9 fl, n=101; G2 > 9.9 fl, n=200) measured within 12 hours after PCI. STEMI was defined as ST-elevation of ≥0.1mV in >limb lead or ≥0.2mV in contiguous chest leads or left bundle branch block (LBBB) at presentation. Patients with concomitant infectious diseases, neoplastic disease or hematological disorders were excluded from this study. The time interval from the onset of chest pain to vascular reperfusion was less than 12 hours. All patients had taken Aspirin, Alopidogrel, Atorvastatin, ACEIs or ARBs, Beta blockers, and Calcium antagonists (according to their required blood pressure, and heart rate adjustments). All patients were continuously followed using telephone contact or clinical interview for one year. MCO was defined as death from any cause, non-fatal MI, re-angina, re-hospital and stroke. This study was approved by the Ethics Committee of Ningxia People’s Hospital.

Statistical Analysis

All data were analyzed using SPSS18.0. Descriptive statistics were presented as the mean±standard deviation (SD) for continuous variables. Comparison between groups was performed by means of independent samples t test. Categorical variables were compared by the chi-square test. The independent effect of variables on prognosis was calculated using Binary logistic regression analysis. A 2-tailed P <0.05 was considered significant.

Results

Table 1 shows the demographic, clinical characteristics and laboratory characteristics of the 2 groups. Age, gender, smoking, diabetes, hypertension, oral drugs, Low-density lipoprotein (LDL) cholesterol and creatinine were similar in the 2 groups. Platelet count was significantly higher in the low MPV group than that in the high MPV group (222±50x106 vs. 205±45x106; p=.003). Compared with the low MPV group, White Blood Cell (WBC) was higher in the high MPV group (p<0.001)

Table 1

Demographic, clinical characteristics, laboratory and outcomes in patients with low and high MPV groups

Variables Low MPV≤9.9(n=101) High MPV>9.9fl(n=200) P
Age 63.33±11.7 62.92±11.70 0.747
Male sex 67(66.3%) 145(72.5%) 0.286
Smoking 60(59.4%) 128(64%) 0.452
Hypertension 53(52.5%) 119(59.5%) 0.268
Diabetes mellitus 47(46.5%) 75(37.5%) 0.138
Aspirins 71(70.3%) 151(75.5%) 0.335
Statins 27(26.7%) 41(20.5%) 0.244
ACEIs OR ARBs 41(40.6%) 82(41%) 1.0
Beta blockers 25(24.8%) 59(29.5%) 0.417
Calcium antagonists 44(43.6%) 110(55%) 0.068
Diuretics 9(8.9%) 17(8.5%) 1.0
Creatinine (umol/l) 79.5±24.8 79.9±22.5 0.908
WBC (×109/l) 10.15±1.61 11.27±2.07 <0.001
Platelet count (×109/l) 222±50 205±45 0.003
LDL-C(mmol/l) 2.7±0.8 2.9±0.9 0.053
Hours 5.3±1.0 5.3±0.9 0.003
Culprit vessel: LAD30(29.7%)
LCX26(25.7%)
LAD92(46%)
LCX20(10%)
<0.001
RCA 45(44.6%) 144/56
Multi/single vessel disease 80/31 RCA 88(44%) 1.000
MCO 14(13.9%) 50(25%) 0.026
Death 1(1%) 8(4%) 0.281
MI 3(3%) 10(5%) 0.554
Re-angina 8(7.9%) 35(17.5%) 0.024
Re-hospital 10(9.9%) 39(19.5%) 0.033
Stroke 2(2%) 1(0.5%) 0.261

WBC, White blood cells; LDL-C, low-density lipoprotein cholesterol; MCO, major cardiac outcomes; hours = symptom-onset-to-balloon time.

Target vessels differed significantly between the high MPV group (LAD 46%, LCX 10%, RCA 44%) and the low MPV group (LAD 29.7%, LCX 25.7%,RCA 44.6%) (P <0.001) .However, the number of diseased vessels (P=1.00) did not. MCO rate was higher in G2 than that in G1 (25% vs. 13.9%; P =0.026), recurrent-angina (17.5% vs. 7.9%; P =.024), re-hospitalization (19.5% vs.9.9%; P=0.033) .Death, MI, stroke were not significant between groups.

Table 2

clinical characteristics and laboratory outcomes in patients with and without MCO at 1-year

Variables MCO(-) n=237 MCO(+) n=64 P
Age 62.6±11.0 64.7±12.0 0.175
Male sex 172(72.6%) 40(62.5%) 0.125
Smoking 152(64.1%) 36(56.3%) 0.249
Hypertension 128(54%) 44(68.7%) 0.046
Diabetes mellitus 89 (37.6%) 33(51.6%) 0.046
Aspirins 165(69 .6%) 57(89.1%) 0.001
Statins 51(21.5%) 17(26.6%) 0.402
ACEIs OR ARBs 91(39.2%) 30(46.9%) 0.253
Beta blockers 6326.6%) 21(32.8%) 0.348
Calcium antagonists 116(48.9%) 38(59.4%) 0.159
Diuretics 18(7.6%) 8(12.5%) 0.216
Creatinine (umol/l) 78.9±22.4 83.1±26.4 0.02
WBC(x109/l) 10.68±1.98 11.67±1.87 <0.001
Platelet count(x109/l) 213±49 201±42 0.089
LDL-C (mmol/l) 2.8±0.9 3.0±0.8 0.122
MPV 10.2±1.1 10.7±1.1 0.005
Hours 5.2±0.9 5.9±0.8 <0.001
Culprit vessel: LAD93(39.2%)
LCX35(14.8%)
LAD29(45.3%)
LCX11(17.2%)
0.479
RCA109(46.0%) RCA24(37.5%)
Multi/single vessel disease 158/79 56/8 0.001

WBC, White blood cells; LDL-C, low-density lipoprotein cholesterol; MPV, mean platelet volume; hours, symptom-onset-to-balloon time.

For further analysis of the prognostic effect of MPV, the study population was also divided into two groups with and without MCO. In these groups, the demographic, clinical, and procedural characteristics are shown in Table 2. Hypertension, Diabetes mellitus, oral aspirin use and multivessel disease were more prevalent in patients with MCO than those without MCO. The mean MPV was higher in patients with MCO compared with patients without MCO (10.7±1.1fl vs. 10.2±1.1fl; P=0.005). The mean WBC was also higher in patients with MCO compared with patients without MCO (11.67±1.87x106 vs. 10.68±1.98x106; P<0.001). There was a difference in creatinine between the 2 groups (p=0.002), and symptom onset to balloon time was also different between the 2 groups(p<0.001)

Table 3

independent variables associated with presence of major cardiac outcomes at 1-year

B Wlad P OR 95% CI
Diabetes mellitus 1.13 10.02 0.002 3.11 1.54-6.30
Statins -0.86 5.58 0.018 0.42 0.20-0.86
WBC 0.16 4.90 0.027 1.18 1.01-1.37
MPV 0.26 4.03 0.045 1.30 1.01-1.69
Hours 0.45 7.92 0.005 1.58 1.14-2.17

OR , Odds ratios; CI, confidence intervals; WBC, White blood cells; MPV, mean platelet volume; hours= symptom-onset-to-balloon time.

In Binary logistic regression analysis, independent predictors of MCO at 1-year are presented in Table 3. MPV was an independent predictor of 1-year MCO (OR 1.30, 95%CL 1.01-1.69, p=0.045). Other independent predictors were diabetes mellitus WBC, oral Statins, and symptom onset to balloon time.

Discussion

In the present study, high MPV was independently associated with the presence of WBC, platelet count, symptom onset to balloon time and culprit vessels in patients with STEMI after PCI. Moreover, it had prognostic value for MCO in addition to diabetes mellitus, WBC, oral Statins, and symptom onset to balloon time at 1-year follow-up.

Platelets have a pivotal role in the development of thrombus in the ACS setting16. Platelet activation is associated with altered shape and expanded volume, with aggregation and the release of various active contents. Activated platelets release several prothrombotic substances such as thromboxan A2, beta-thromboglobulin, P-selectin, and glycoprotein Ib and II/IIIa 5. Larger platelets, characterized by high MPV, are associated with increased platelet reactivity. MPV is a marker of platelet size, function and activation. Several studies have showed the MPV was higher in patients with MI than controls or those with stable angina9,17.

Previous reports showed that there is a close relationship between MPV and other prognostic factors, such as smoking, diabetes, hypertension, and hypercholesterolemia18-20. But we do not have clear information about an association between MPV and those risk factors, so the mechanisms underlying the relationship between elevated MPV and adverse events remains uncertain. We did not find any association between MPV and smoking, diabetes, hypertension, gender or LDL-C. We observed that platelet count, symptom onset to balloon time, and culprit vessel were significantly associated with larger platelets.

At 1-year follow-up, MCO was poorer in patients with high MPV compared to those with low MPV in our study. The difference was mainly due to recurrent-angina and re-hospitalization. One study has found no significant difference in cardiac death among NSTEACS patients with and without high MPV at 6 months although mean MPV was higher in such patients compared to healthy controls21. Similarly, another study has reported no significant relation between MPV level and re-infarction rate at 2-year follow-up22. In our study, cardiac death, stroke and re-infarction rates were comparable in high and low MPV groups as well.

We observed that MCO was independently associated with high MPV, diabetes mellitus, oral stains, WBC and symptom onset to balloon time. Diabetes mellitus, oral stains and WBC have been known as high risk markers for adverse cardiac events23-25. Symptom onset to balloon time has been reported to relate significantly to mortality in patients with AMI26.

Several studies have reported elevated MPV which has been proposed as a cardiovascular risk factor and has been recognized as an independent risk factor for myocardial infarction and adverse cardiovascular events such as recurrent ischemia or death27,28. Several reports have also reported that MPV was associated with restenosis after primary coronary intervention16,21. But, previous studies on MPV have looked at admission MPV. In our study, the result supported an association between elevated MPV that was measured within 12 hours in patients with STEMI after PCI post 1-year MCO. however, there were mainly differences between recurrent-angina and re-hospitalization rates.

There are several limitations in this study. First, all cases were recuited from the same hospital, which may lead to selection bias. Second, LVEDV and other echocardiographic indices were not collected. Third, the number of patients enrolled was relatively small, and follow-up time was only one year.

In conclusion, post-procedural MPV above 9.9fl was associated with platelet counts, symptom onset to balloon time and culprit vessel in the STEMI patients treated with successful primary PCI. Moreover, post-procedural MPV was predictive of 1-year MCO. These findings provide a simple, feasible and economical indices to stratify the STEMI patients who underwent primary PCI.

Statement of ethical publishing

The authors state that they abide by the statement of ethical publishing of the International Cardiovascular Forum Journal29.

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