Clinical Usefulness Of Mean Platelet Volume In Acute Coronary Syndromes

Acute coronary syndromes (ACS) represent a major source of morbidity and mortality worldwide. Despite advances in the ACS diagnosing and implementing therapies, the residual mortality of ACS patients remains high. ACS comprise a spectrum of patients with different clinical features, baseline risks, and prognoses. Platelet aggregation and subsequent thrombus formation are key steps in the progression of ACS. Mean platelet volume (MPV), a simple, quick, easy and cheap indicator, is correlated with platelet reactivity. Recently, the significance of MPV in patients with ACS has been investigated in many studies. However, these studies have yielded contrasting results, and the quality of the studies was not systematically assessed or expressed as a quality score. Therefore, a further meta-analysis is needed to better define the relationship between MPV and clinical outcome in patients with ACS.Guidelines at home and abroad recommend using a validated scoring system such as the Global Registry of Acute Coronary Events (GRACE) score to evaluate the risk profile and prognosis of ACS patients. However, because the laboratory-based variables included in the GRACE risk score are limited to serum creatinine and cardiac marker enzymes, it is plausible that variables, such as MPV, which reflect other pathophysiological aspects of ACS could provide additional predictive value.Accordingly, the present study consisted of the following 2 parts to discuss the clinical usefulness of MPV in ACS. First, we undertook a systematic review and meta-analysis to summarize the published literature on the relationship between MPV and ACS. Second, we conducted a case-observational study to confirm the relationship between MPV and prognosis in patients with ACS, and to assess whether the addition of MPV to the GRACE score adds incremental predictive information.Part 1:A systematic review on the role of mean platelet volume in patients with acute coronary syndromesPart 1:A systematic review on the role of mean platelet volume in patients with acute coronary syndromesBackground:Platelets play a key role in atherothrombosis leading to acute coronary syndromes (ACS), and patients with increased platelet activation are at higher risk of cardiovascular events in the setting of ACS. Mean platelet volume (MPV), a readily available laboratory test, is correlated with platelet reactivity. However, the role of MPV in patients with ACS remains uncertain.Objective:We undertook a systematic review and meta-analysis examining the association between MPV and all-cause mortality, high on-treatment platelet reactivity (HTPR), and no-reflow after percutaneous coronary intervention (PCI).Methods:Studies were retrieved by systematically searching the PubMed and Web of Science databases. We screened the reports for eligibility against the inclusion and exclusion criteria and then extracted data from the shortlisted studies using pre-specified forms. The methodological quality of included study was also assessed using defined criteria. The mean difference (MD) and hazard ratio (HR) [and their corresponding 95% confidence intervals (CIs)] were calculated for the continuous or dichotomous outcome data, respectively. A random-effect model via generic inverse variance weighting was used to provide a more conservative summary estimate of treatment effect. Statistical heterogeneity was evaluated with the x2 test and the I2 statistic (P values< 0.1 and I2 values> 50% represented significant inconsistency). Meta-regression and subgroup analyses were used to examine whether any had an impact on the results of the meta-analysis. Statistical computations were performed with STATA 11.0 and RevMan 5.1 software.Results:Twenty RCTs, including 18 860 patients, were analyzed. Compared to ACS patients in the lower MPV group, those with a high MPV had a 1.65-fold higher increase in the risk of death (HR 1.65,95% CI 1.41-1.92, P< 0.001). The heterogeneity test across the studies was statistically significant (P< 0.001,I2= 88%). The subsequent meta-regression and subgroup analyses did not identify factors that affect the prognostic accuracy of MPV in ACS patients, including study design, disease type, mean age, male, various cut-off values of MPV, adjusting confounding factors, study quality score, and follow-up time. Moreover, MPV was significantly higher in patients who developed no-reflow following PCI than in those who did not develop no-reflow (MD 0.54 fL,95%CI 0.16-0.92, P= 0.006). MPV was significantly larger in patients with HTPR than those without HTPR (MD 0.76 fL,95%CI 0.44-1.08, P< 0.001).Conclusion:An elevated MPV on admission was associated with the risk of no-reflow after PCI and high on-treatment platelet reactivity in ACS patients. MPV levels could predict the risk of death in patients with ACS. Further research is needed to evaluate the additive predictive value of MPV to a validated scoring system.Part 2:Adjustment of the GRACE score by mean platelet volume offers incremental predictive value in patients with acute coronary syndromesPart 2:Adjustment of the GRACE score by mean platelet volume offers incremental predictive value in patients with acute coronary syndromesBackground:An elevated mean platelet volume (MPV) is a risk marker in patients with acute coronary syndromes (ACS); however, current Global Registry of Acute Coronary Events (GRACE) risk scoring systems do not consider this factor.Objective:The aim of this study were:(1) to assess the association between baseline MPV and clinical outcomes in patients with ACS and (2) to evaluate the incremental predictive value of adding MPV to the GRACE risk score.Methods:The MPV and GRACE score were determined on admission in 509 consecutive patients with ACS. The study endpoint was major adverse cardiac events (MACE), defined as a composite of all-cause mortality and non-fatal myocardial infarction at 6-month clinical follow-up. Receiver operating characteristic curve analysis was undertaken to determine the use of MPV for distinguishing patients with and without events during follow up. The optimal cut-off was calculated by determining the MPV that provided the greatest sum of sensitivity and specificity. Cumulative event-free survival curves were constructed by the Kaplan-Meier method, and the difference between the curves was assessed using the log-rank test. The relationship of MPV with the prognosis in patients with ACS was assessed by the Cox proportional hazard regression model. The additional contribution of MPV to GRACE score for the prediction of study end points was evaluated in terms of global model fit, discrimination (C-statistic) and classification accuracy [net reclassification improvement (NRI) and integrated discrimination improvement (IDI)].Results:61 patients (12%) reached the combined endpoint. We used a cut-off point of 11.9 fL, which was established by receiver-operator characteristic curve analysis. Kaplan-Meier analysis revealed that the higher MPV group (≥11.9 fL) had a significantly increased event rate compared to the lower MPV group (27% vs.6%, log-rank P< 0.001). Cox multivariate analysis indicated that patients with a high MPV were at higher risk of 6-month MACE [hazard ratio (HR)= 4.14,95% confidence interval (CI):2.36-7.27, P< 0.001]. As a continuous variable (per fL), MPV was independently associated with the endpoint (HR= 1.66,95%CI:1.32-2.09, P< 0.001). The addition of MPV to the GRACE model improved its global fit and discriminatory capacity (the c-statistic increased from 0.747 to 0.806). The patients were categorized into the following three groups based on the GRACE risk score prediction:<12%,12%to 21%, and>21%. The new model including MPV allowed adequate reclassification of 16%of the patients. The NRI was estimated at 15%(P= 0.038) after the addition of MPV, and the IDI was estimated as 0.06 (P<0.001).Conclusion:An elevated MPV on admission is an independent predictor of 6-month MACE in ACS patients. Combined with the GRACE risk score, information regarding MPV improves risk classification.