Platelet size, measured as mean platelet volume (MPV), is associated with platelet reactivity. MPV has been identified as an independent risk factor for future stroke and myocardial infarction. The aim of this study was to determine the association of MPV with the development of stoke in patients with atrial fibrillation (AF). MPV, N-terminal pro B-type natriuretic peptide (NT-proBNP), and high-sensitivity C-reactive protein (hsCRP) were analysed in 200 patients with AF (mean age 69 years; 56% male). The primary endpoint was ischaemic stroke event. The mean MPV was 8.5 ± 1.0 fL and the median NT-proBNP was 1916.5 (IQR 810-4427) pg/mL. The median hsCRP was 0.47 (IQR 0.32-2.46) mg/dL. There were 14 stroke events during a mean of 15.1 months of follow up. Kaplan-Meier analysis revealed that the higher tertile MPV group (≥8.9 fL) had a significantly higher stroke rate compared to the lower tertile MPV group (<8.0 fL) (14.7% vs. 3.1%, log-rank: P = 0.01). A higher MPV was an independent predictor of stroke risk after adjusting for age, gender, and other CHADS(2) (congestive heart failure, hypertension, diabetes, and previous stroke or transient ischemic attack (TIA) history) score components (hazard ratio: 5.03, 95% CI 1.05-24.05, P = 0.043) in Cox proportional hazard analysis. When the MPV cut-off level was set to 8.85 fL using the receiver operating characteristic curve, the sensitivity was 71% and the specificity was 69% for differentiating between the group with stroke and the group without stroke. This value was more useful in patients with a low to intermediate traditional thromboembolic risk (CHADS(2) score <2). Furthermore, AF patients with an MPV over 8.85 fL had high stroke risk without anticoagulation, especially in the low thromboembolic risk group (Log-Rank <0.0001). The results of this study show that MPV was a predictive marker for stroke; its predictive power for stroke was independent of age, gender, and other CHADS(2) score components in patients with AF. These findings suggest that anticoagulation may be needed in patients with a high MPV, even if they have low to intermediate traditional thromboembolic risk (CHADS(2) score <2).

The aim of this study was to determine the associations of the mean platelet volume (MPV) with the development of adverse outcomes after percutaneous coronary intervention (PCI) and platelet reactivity. MPV and platelet function testing were analysed in 208 patients who underwent PCI. The primary endpoint was cardiac death. The secondary endpoint analysed was cardiovascular events (CVE): the composite of myocardial infarction (MI), target vessel revascularization (TVR), and stent thrombosis (ST). The median MPV level, aspirin reaction unit (ARU), P2Y12 reaction units (PRU) and P2Y12% inhibition (PI%) of clopidogrel were 8.55 (IQR 8.00-9.18) fl, 401.0 (IQR 389.3-442.0) ARU, 222.0 (IQR 169.0-272.3) PRU and 22 (IQR 9-38) %, respectively. We observed that high values of MPV were associated with elevated ARU (r = 0.165, p = 0.017) and decreased PI% (r = -0.167, p = 0.016). There were 10 events of cardiac death, 3 MI (including 1 event of ST), and 8 TVR during a mean of 7.6 months of follow-up. The Kaplan-Meier analysis revealed that the higher MPV group (≥8.55 fl, median) had a significantly higher cardiac death rate compared to the lower MPV group (<8.55 fl) (7.7% vs. 1.9%, log-rank: p = 0.035). However, aspirin or clopidogrel resistance (>550 ARU, <40 PI%, respectively) did not predict cardiac death. When the MPV cut-off level was set to 8.55 fl using the receiver operating characteristic curve, the sensitivity was 80% and the specificity was 51.5% for differentiating between the group with cardiac death and the group without cardiac death. This value was more useful in patients with clinical diagnosis of acute coronary syndrome (ACS). Furthermore, ACS patients with an MPV over 8.55 fl had high cardiac death and CVE risk without atorvastatin loading before PCI (Log-Rank = 0.0031, 0.0023, respectively). The results of this study show that MPV was a predictive marker for cardiac death after PCI; its predictive power for cardiac death was more useful in patients with ACS.

The aim of this study was to determine the associations of the mean platelet volume (MPV) high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B type natriuretic peptide (NT-proBNP) with the development of adverse outcomes after percutaneous coronary intervention (PCI). MPV hs-cTnT and NT-proBNP were analyzed in 372 patients who underwent PCI. The primary endpoint was cardiac death. The secondary endpoint analyzed was cardiovascular events (CVE): the composite of cardiac death, myocardial infarction (MI), target vessel revascularization (TVR), ischemic stroke and stent thrombosis (ST). The median MPV hs-cTnT and NT-proBNP levels were 8.20 (IQR 7.70-8.70) fL, 0.291 (IQR 0.015-3.785) ng/mL, and 105.25 (IQR 50.84-1128.5) pg/mL, respectively. There were 21 events of cardiac death, 10 MI (including 4 events of ST), 7 ischemic strokes and 29 TVR during a mean of 25.8 months of follow-up. The Kaplan-Meier analysis revealed that the higher MPV group (>8.20 fL, median) had a significantly higher cardiac death rate than the lower MPV group (≤8.20 fL; 9.4% vs. 2.1%, log-rank: p = 0.0026). When the MPV cut-off level was set to 8.20 fL using the receiver operating characteristic curve, the sensitivity was 81% and the specificity was 53.3% for differentiating between the group with cardiac death and the group without cardiac death. This value was more useful in patients with myocardial injury (hs-cTnT ≥ 0.1 ng/mL) or heart failure (NT-proBNP ≥ 450 pg/mL). The results of this study show that MPV is a predictive marker for cardiac death after PCI; its predictive power for cardiac death is more useful in patients with myocardial injury or heart failure.

It might be considered that lovastatin resulted in reducing the first-pass metabolism in the intestine and/or in the liver via inhibition of CYP3A4 and increasing the absorption of diltiazem in the intestine via inhibition of P-gp by lovastatin.

-The aim of this study was to investigate the effect of atrovasatatin on the pharmacokinetics of nicardipine after oral and intravenous administration of nicardipine to rats. Nicardipine was administered orally (12 mg/kg) or intravenously (i.v., 4 mg/kg) without or with oral administration of atrovasatatin (0.3 or 1.0 mg/kg) to rats. The effect of atorvastatin on the P-glycoprotein (P-gp) as well as CYP3A4 activity was also evaluated. Atorvastatin inhibited CYP3A4 enzyme activity in a concentration-dependent manner with 50% inhibition concentration (IC50) of 48 μM. Compared to the controls (nicardipine alone), the area under the plasma concentration-time curve (AUC) of nicardipine was significantly (1.0 mg/kg, p＜0.05) greater by 16.8-45.4%, and the peak plasma concentration (C max ) was significantly (1.0 mg/kg, p＜0.05) higher by 28.0% after oral administration of nicardipine with atorvastatin, respectively. Consequently, the relative bioavailability (R.B.) of nicardipine was increased by 1.17-to 1.45-fold and the absolute bioavailability (A.B.) of nicardipine with atrovasatatin was significantly greater by 16.7-20.9% compared to that of the controls (14.3%). Compared to the i.v. control, atrovasatatin did not significantly change pharmacokinetic parameters of i.v. administration nicardipine. The enhanced oral bioavailability of nicardipine by atorvastatin suggests that CYP3A subfamily-mediated metabolism were inhibited in the intestine and/or in the liver rather than P-gp-mediated efflux of nicardipine. Based on these results, modification of nicardipine of dosage regimen is required in the patients. Human studies are required to prove the above hypothesis.

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