AF is the most common major cardiac arrhythmia, and it is associated with significant morbidity and mortality from ischemic stroke [8,9]. There is a positive association between MPV and the severity of acute ischemic stroke [10], and MPV is useful for predicting the risk of ischemic stroke in patients with AF [11-15]. A recent case-control study showed that stroke patients with AF have a higher MPV than AF patients without a stroke history [13]. The precise mechanism underlying the supposed relationship (cardiac embolism caused by increased platelet reactivity) remains to be fully elucidated. However, Providencia et al. [16] recently suggested an association between MPV and markers of left atrial stasis, reinforcing the notion that a cardioembolic mechanism may be in play when AF is associated with stroke. In that study, MPV independently predicted the development of a left-atrial appendage thrombus. The MPV cutoff values for predicting ischemic stroke in AF patients were 7.85 to 8.85 fL (Table 1).

Anticoagulant therapy reduces the risk of stroke by 40% in patients with AF, and is more effective than antiplatelet therapy [17]. Hence, identifying patients at higher risk for ischemic stroke is essential to optimize treatment. The MPV has been shown to enhance the predictive value of the clinical variables employed when calculating CHADS₂ or CHA₂DS₂ VASc scores [11,12]. One study found that the cutoff MPV better predicted ischemic stroke in those with a lower CHADS₂ score (< 2) than in those with a higher score (≥ 2) [11]. In addition, those with a high MPV who were not on anticoagulation therapy experienced poorer stroke-free survival than did others; this was true even for patients with CHADS₂ scores < 2. It was suggested that anticoagulation therapy was required by patients with high MPVs, even those in the low to intermediate risk groups. Similarly, another study suggested that measurement of MPV may help physicians to decide whether to administer anticoagulants to patients with CHA₂DS₂ VASc scores of 1, who are thus at intermediate risk of stroke [12].

Treatment of AF with rhythm or rate control therapy is tailored to patient inclinations and characteristics [18]. Many randomized controlled clinical trials have compared rhythm and rate control strategies in patients with AF, and have found no differences in mortality [19-23]. Nevertheless, the appropriate choice of patients who need rate or rhythm control treatment (to prevent ischemic stroke) among those with AF remains a matter of contention [24,25]. To the best of our knowledge, only one study, which was both retrospective in nature and had a small sample size, has explored whether MPV could potentially guide the provision of rhythm or rate control therapy to AF patients [14]. In this work, the rate control strategy used to treat AF, and a high MPV, were independent predictors of ischemic stroke, as was a high CHADS₂ score (≥ 2). Such an association was also evident in patients at high risk for ischemic stroke as indicated by their MPVs and CHADS₂ scores. This suggests that implementation of a rhythm control strategy might be necessary in patients with a high MPV or CHADS₂ score (≥ 2).

MPV increases during AMI and in the weeks thereafter [50-52]. MPV is associated with markers of platelet activity, particularly the expression levels of the glycoprotein Ib and glycoprotein IIb/IIIa receptors [53,54]. An elevated MPV correlates with poor clinical outcomes among survivors of MI in the era of thrombolysis, and an impaired response to thrombolysis in those with ST segment elevation myocardial infarction (STEMI) [28,55]. MPV is also a strong independent predictor of impaired angiographic reperfusion, in-hospital major adverse cardiovascular events, and 30-day, 6-month, 12-month, and 2-year mortality from STEMI treated via primary PCI [26,30-33,36-38,56]. In addition, a higher MPV on admission is independently associated with impaired microvascular perfusion, a poor postintervention myocardial blush grade, decreased post-PCI thrombolysis, and a poorer myocardial infarction flow grade (thrombolysis in myocardial infarction [TIMI]) in STEMI patients treated via primary PCI [33-36,57]. In one study, a higher MPV on admission was strongly associated with greater microvascular resistance, a steeper diastolic deceleration time, a lower thermodilution-derived coronary flow reserve, and a higher coronary wedge pressure [57]. MPV seems to play a role in mediating reperfusion injury. In patients with STEMI scheduled for PCI, MPV at admission may be a valuable discriminator of a higher-risk patient subgroup, and a useful guide when deciding whether adjunctive therapy may be necessary to improve outcomes [27]. MPV cutoff values for predicting poor clinical outcomes in STEMI patients treated via PCI are 8.9 to 11.7 fL; thus, somewhat higher than those predictive of ischemic stroke in AF patients (Table 1).

Duygu et al. [40] suggested a role for MPV as a useful hematological marker allowing early and simple identification of patients with stable coronary artery disease at high risk for post-PCI low-reflow. MPV independently predicted the post-PCI-corrected TIMI frame count. Another study found that MPV predicted in-stent restenosis in patients undergoing PCI [58]. Similar to the effects of MPV on AMI, several studies have found that an elevated MPV is a strong independent predictor of long-term outcomes after PCI [41-47]. However, one study found that mortality increased when the MPV rose over time after PCI, but the pre-procedural MPV was not predictive in this context [59]. It was suggested that monitoring of MPV after PCI might aid risk stratification. MPV cutoffs for predicting poor clinical outcomes in patients with unselected coronary artery disease treated via PCI are 8.00 to 9.25 fL (Table 1) [11,14,16,26,30,31,33,36-38,43-48,56,60,61].

Antiplatelet therapy reduces the incidence of both procedure-related complications and ischemic cardiovascular events after PCI [62,63]. Particularly, dual antiplatelet therapy (aspirin and an ADP receptor inhibitor) is the present standard of care after implantation of drug-eluting stents. Nevertheless, high residual platelet reactivity can limit the utility of antiplatelet therapy, increasing the frequency of cardiovascular events both during the procedure and during long-term follow-up [64-67]. Recently, however, Paulu et al. [68], in a prospective observational study, showed that clopidogrel resistance was not of prognostic utility in an unselected cohort of 378 patients who underwent PCI. In addition, Collet et al. [69] observed no significant improvement in clinical outcomes when platelet function was monitored and adjusted in patients who underwent coronary stenting, compared to those who received standard antiplatelet therapy (without monitoring); this was a large, randomized open-label study on 2,440 patients. Platelet activity testing can be time-consuming, expensive, and technically complex [70]. However, MPV can be readily measured before PCI using automated hematology analyzers. Recently, Kim et al. [48] suggested that a high MPV was associated with reduced responses to aspirin and clopidogrel. Some investigators have suggested that an increase in MPV over time after PCI is associated with high on-treatment platelet reactivity [49]. Moreover, Choi et al. [47] suggested that MPV was superior to platelet function testing in terms of predicting cardiac death or cardiovascular events in patients who had undergone PCI, particularly those in an acute coronary syndrome subgroup.