Larger size platelets have enhanced reactivity. The mean platelet volume (MPV) is a marker of platelet activation and is usually measured as part of blood testing. The aim of the present study was to investigate the utility of the MPV as a biomarker in prognosticating the long-term outcomes after percutaneous coronary intervention (PCI). The baseline MPV values from consecutive patients undergoing PCI were screened. Of the 1,432 patients, the composite primary end point of mortality or myocardial infarction at 1 year occurred in 80 (5.6%). The patients in the highest tertile (MPV >9.1 fL) had an increased frequency of the primary end point compared to those in the mid (8.1 to 9.1 fL) and lowest (<8.1 fL) tertiles (9.0%, 4.5%, and 3.5%, respectively; p <0.01). Logistic regression analysis demonstrated diabetes (odds ratio 2.44, 95% confidence interval 1.48 to 4.00) and highest tertile of MPV (odds ratio 2.42, 95% confidence interval 1.47 to 3.99) as the best predictors of adverse outcomes. In patients with acute coronary syndrome, the preprocedural MPV and troponin levels demonstrated a comparable predictive relation to the primary end point (receiver operator characteristics curve analysis, area under the curve 0.64, p = 0.01; and 0.63, p = 0.01, respectively). In conclusion, an elevated MPV was a strong independent predictor of long-term outcomes after PCI. The preprocedural MPV had prognostic value similar to that of troponin in patients with acute coronary syndrome. These findings could be of importance in the clinical evaluation of patients before PCI and the design of future studies assessing antiplatelet therapies.
Large platelets have enhanced reactivity compared with normal-size platelets. The mean platelet volume (MPV) has been associated with clinical and angiographic outcomes. Patients with a high MPV before balloon angioplasty have been more likely to develop restenosis. In patients undergoing primary percutaneous coronary intervention (PCI), a high MPV has been associated with impaired angiographic reperfusion and increased 6-month mortality. The predictive value of the MPV for clinical outcomes in undifferentiated patients undergoing PCI has not been investigated in the current era of drug-eluting stents and prolonged dual antiplatelet therapy. Unlike more expensive or time-consuming methods of assessing platelet function, the determination of platelet size by quantification of the MPV, using automated hemograms, is simple and inexpensive. The biologic rationale linking the MPV to clinical outcomes, along with its universal availability, have made it a promising indirect marker of platelet reactivity in the PCI setting. Our study sought to evaluate the effect of the preprocedural MPV level on the long-term clinical outcomes in patients undergoing PCI for a variety of indications.
Methods
The present analysis was a cohort within the University of Ottawa Heart Institute PCI Registry. The registry has included patients treated at a tertiary cardiac center, with a referral base of 30 peripheral hospitals servicing a population of >1 million. The study cohort included patients who had undergone PCI from December 1, 2003 to November 30, 2004. The patients were identified retrospectively from the registry and then followed prospectively for a 1-year period. The patients referred for elective and urgent PCI procedures, including primary PCI, were screened for the study. The patients were included if a baseline MPV measurement before PCI was available. The patients were excluded from the study if PCI had failed and they had undergone emergent coronary bypass surgery or if death had occurred during the index hospital admission. In the event that patients required more than one PCI during the study period, the entry date was recorded as the date of the index procedure. The study complied with the Declaration of Helsinki, and the Human Research Ethic Review Board of the University of Ottawa Heart Institute approved the study.
Trained research nurses collected the data from the PCI reports and hospital charts during the study period. All pre-PCI medication and PCI-related data were documented. The medications and dosages before PCI had been prescribed by the initial treating physician. The choice of stent and periprocedural antithrombotic therapy was at the discretion of the treating interventional cardiologist. A telephone interview was conducted 1 year after the index PCI. If a patient had been rehospitalized for possible cardiac symptoms, the records from the admitting hospital were obtained. For patients who had undergone repeat angiography or revascularization, the procedural reports and in-hospital charts were evaluated for the outcomes. Explicit definitions for the data elements had been predetermined. Recurrent myocardial infarction was defined as ischemic symptoms with new or recurrent elevation of ST-segments in ≥2 contiguous leads and/or the elevation of cardiac biomarkers to >2 times the upper limit of normal. Stent thrombosis included only angiographically or autopsy-confirmed cases ≤1 year after the index PCI procedure (Academic Research Consortium definite). Pretreatment with aspirin was defined as taking aspirin >12 hours before PCI. Pretreatment with clopidogrel was defined as a cumulative dosage of the drug of ≥300 mg >12 hours before PCI. For all patients, peripheral venous blood samples were used. The MPV measurements were determined from the first available blood sample within the preceding 2 weeks before PCI for elective patients. For nonelective patients, the MPV measurements were obtained from the admission blood work. All samples were obtained in standardized dipotassium ethylenedinitrotetraacetic acid (EDTA) tubes. The measurements were performed using automated hemograms (Bayer Advia 2120, Bayer Diagnostics, Tarrytown, New York). After the determination of the baseline MPV values, the study population was divided into tertiles according to the MPV.
The primary outcome was a combined end point of all-cause mortality and nonfatal myocardial infarction at 1 year. For patients with >1 myocardial infarction, only the first event was counted as an end point. Statistical analysis for the study was conducted using the Statistical Package for Social Sciences software, version 16.0 (SPSS, Chicago, Illinois). The patients were separated into tertiles of MPV. The primary hypothesis, that patients with the highest MPV tertile would have a greater event rate than those in the other tertiles, was tested using a chi-square test and adjusted odds ratio (OR). All p values are reported as 2-tailed, with an accepted significance at ≤0.05. The ORs are reported with the 95% confidence intervals (CIs). The patient characteristics among the different tertiles of MPV were compared using the chi-square test. For continuous variables, Student’s t test or one-way analysis of variance and Tukey’s post hoc test was used. A logistic regression model to determine the predictors for the primary outcome was created. The covariates in the model included highest MPV tertile, age, gender, diabetes mellitus, previous myocardial infarction, hypertension, smoking, aspirin therapy, clopidogrel pretreatment, statin therapy, acute coronary syndrome (ACS), history of heart failure, platelet count, and creatinine on admission. Using the highest MPV tertile as the dependent variable, a separate regression analysis was conducted to establish the possible determinants of the MPV. Multiple separate logistic regression models were constructed using these variables to determine the influence of a high MPV in the subgroups of interest. To further delineate the role of MPV as a biomarker in patients with ACS, a receiver operating characteristic (ROC) curve was constructed to analyze the relation between the baseline MPV and death or myocardial infarction at 1 year. The same ROC curves were constructed for the pre-PCI troponin T and creatine kinase levels for patients with ACS. A logistic model using the previous variables, elevated troponin (>0.1 μg/L), and elevated MPV was created for the patients with ACS.
Results
During the study period, 1,984 patients underwent PCI procedures. From the original cohort, 1,432 (72.2%) met the inclusion criteria and had MPV values available. The mean age of the cohort was 62.8 ± 11.5 years, with 1,102 patients (77.0%) presenting with ACS. The division by tertile was as follows: first tertile, MPV <8.1 fL (n = 460); second tertile, MPV 8.1 to 9.1 fL (n = 492); and third tertile, MPV >9.1 fL (n = 480). The baseline demographics of the study population stratified into MPV tertiles are listed in Table 1 . With the exception of an expected inverse association with the platelet count, no significant differences were found for the baseline characteristics among the MPV tertiles. A trend was seen for patients with the highest tertile to be older and more prone to present with ACS. Subgroups stratified by gender, smoking status, hypertension, hypercholesterolemia, a history of heart failure, ACS, and a history of myocardial infarction did not demonstrate significant differences in the mean MPV values.
| Characteristic | Total (n = 1,432) | Tertile | p Value ⁎ | ||
|---|---|---|---|---|---|
| Lower (n = 460) | Mid (n = 492) | Upper (n = 480) | |||
| Age (years) | 62.8 ± 11.5 | 62.2 ± 11.7 | 62.3 ± 11.2 | 63.8 ± 11.7 | 0.061 |
| Men | 1,043 (72.8%) | 343 (74.6%) | 360 (73.2%) | 340 (70.8%) | 0.428 |
| Diabetes mellitus | 399 (27.9%) | 111 (24.1%) | 145 (29.5%) | 143 (29.8%) | 0.095 |
| Current smoker | 228 (15.9%) | 73 (15.9%) | 83 (16.9%) | 72 (15.0%) | 0.728 |
| Hypertension | 862 (60.2%) | 268 (58.3%) | 296 (60.2%) | 298 (62.1%) | 0.489 |
| Hypercholesterolemia | 1,024 (71.5%) | 332 (72.2%) | 350 (71.1%) | 342 (71.2%) | 0.928 |
| Previous aspirin | 960 (67.0%) | 312 (67.8%) | 332 (67.5%) | 316 (65.8%) | 0.783 |
| Acute coronary syndrome | 1,102 (77.0%) | 350 (76.1%) | 365 (74.2%) | 387 (80.6%) | 0.051 |
| History of heart failure | 86 (6.0%) | 23 (5.0%) | 29 (5.9%) | 34 (7.1%) | 0.402 |
| Previous myocardial infarction | 354 (24.7%) | 117 (25.4%) | 119 (24.2%) | 118 (24.6%) | 0.092 |
| Platelet count (×10 9 /L) | 247 ± 74.1 | 261 ± 75.4 | 251 ± 75.0 | 228 ± 68.0 | 0.001 † |
| Hemoglobin (g/L) | 138.2 ± 16.3 | 137.7 ± 17.0 | 138.3 ± 16.4 | 138.6 ± 15.6 | 0.726 |
| Creatinine (μmol/L) | 100.4 ± 64.1 | 100.3 ± 75.7 | 101.5 ± 66.8 | 99.4 ± 47.1 | 0.879 |
⁎ Analyses done using chi-square test for categorical data or one-way analysis of variance for continuous data and Tukey’s post hoc test, as appropriate.
† Intergroup differences with Tukey’s test (p <0.05); difference lies between tertiles 1 and 3 and 2 and 3.
Logistic regression analysis demonstrated a previous use of clopidogrel to be inversely associated with the highest MPV tertile (OR 0.63, 95% CI 0.48 to 0.83, p = 0.001; Table 2 ).
| Characteristic | p Value | OR | 95% CI |
|---|---|---|---|
| Age (years) | 0.136 | 1.009 | 0.997–1.020 |
| Male gender | 0.046 | 0.744 | 0.557–0.995 |
| Diabetes mellitus | 0.299 | 1.149 | 0.884–1.492 |
| Current smoker | 0.944 | 1.012 | 0.728–1.406 |
| Hypertension | 0.577 | 1.073 | 0.838–1.373 |
| Hypercholesterolemia | 0.707 | 0.951 | 0.732–1.236 |
| Acute coronary syndrome | 0.011 | 1.458 | 1.092–1.947 |
| History of heart failure | 0.280 | 1.305 | 0.805–2.115 |
| Previous myocardial infarction | 0.691 | 0.946 | 0.719–1.245 |
| Platelet count (×10 9 /L) | 0.000 | 0.994 | 0.992–0.996 |
| Hemoglobin (g/L) | 0.249 | 1.005 | 0.997–1.013 |
| Creatinine (μmol/L) | 0.755 | 1.000 | 0.998–1.002 |
| Previous statin use | 0.868 | 1.022 | 0.791–1.320 |
| Previous aspirin use | 0.730 | 1.049 | 0.798–1.380 |
| Previous clopidogrel use | 0.001 | 0.632 | 0.483–0.827 |
At 1 year of follow-up, 80 patients (5.6%) had died or experienced a myocardial infarction. In these patients, the mean baseline MPV was greater than that in those without a primary outcome (9.3 ± 1.5 vs 8.7 ± 1.3 fL, p <0.001). When the 1-year incidence of outcomes was stratified by MPV tertile, the incidence of death or myocardial infarction was significantly more frequent with increasing MPV tertiles ( Figure 1 ).
Of the high-risk subgroups of patients with diabetes or ACS, those with the highest MPV tertile had an increased incidence of death and myocardial infarction compared to those with the lower 2 tertiles ( Figure 1 ). The results of the univariate analysis of the primary end point by subgroup of interest are shown in Figure 2 . In patients with diabetes, those with an elevated MPV had a threefold increase in the event rate compared to those without an elevated MPV (17.5% vs 5.9%, p <0.001). Patients with diabetes without an elevated MPV had an incidence of events similar to that of nondiabetic patients (5.9% vs 3.9%, respectively, p = 0.17). Comparable trends were present for patients with ACS versus those with stable angina.
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