Vascular endothelial dysfunction is part of the underlying pathophysiology of heart failure. However, there are no reports in which vascular endothelial function of both conduit arteries and microvasculature was assessed in patients with heart failure. This study was aimed to assess vascular endothelial function separately in heart failure with reduced (HFrEF) and preserved ejection fraction (HFpEF). We performed simultaneous measurement of both flow-mediated vasodilation for endothelial function of conduit arteries and reactive hyperemia-peripheral arterial tonometry for that of microvasculature in 88 consecutive patients with chronic heart failure. In 55 patients with ischemic heart disease as an underlying cause of heart failure, flow-mediated vasodilation value was comparable between the two groups of HFrEF (left ventricular ejection fraction < 50%, n = 31) and HFpEF (left ventricular ejection fraction ≥ 50%, n = 24). Reactive hyperemia index measured by reactive hyperemia peripheral arterial tonometry, however, was lower in HFrEF patients compared to HFpEF patients (P = 0.014). In contrast, among 33 patients with non-ischemic heart disease, the degree of flow-mediated vasodilation was lower in HFpEF patients (n = 18) compared with HFrEF patients (n = 15) (P = 0.009), while reactive hyperemia index was comparable between the two groups. The clinical and pathophysiological significance of endothelial function in heart failure differs between conduit artery and microvasculature, and these differences may contribute to the underlying pathophysiology of HFpEF and HFrEF, as well as in ischemic heart disease and non-ischemic heart disease.

Compared to clopidogrel, prasugrel has a lower incidence of ischemic events following percutaneous coronary intervention (PCI) because of an early reduction during the acute phase in P2Y12 reaction units (PRU). The objective of this study was to compare the antiplatelet effect and vascular endothelial function of both drugs during the chronic phase after PCI. Patients who had undergone PCI and were confirmed to have no restenosis by follow-up coronary angiography under dual anti-platelet therapy with clopidogrel (75 mg/day) and aspirin (100 mg/day) were randomized to either continue clopidogrel or switch to prasugrel (3.75 mg/day). At baseline, prior to randomization we determined the CYP2C19 genotype. At the baseline and 24 weeks after randomization, the P2Y12 reactivity unit (PRU) was measured using the VerifyNow™ P2Y12 assay. Endothelial function was evaluated by flow-mediated vasodilation (FMD) and reactive hyperemia peripheral arterial tonometry (RH-PAT), while and circulating CD34+/CD133+/CD45low progenitor cells were measured by flow cytometric analysis. Serum high-sensitivity C-reactive protein (hsCRP) level was also measured. The PRU was reduced significantly in the prasugrel group (P = 0.0008), especially in patients who were intermediate or poor metabolizers based on the CYP2C19 genotype (P < 0.0001). This reduction was not observed in the clopidogrel group. The number of CD34+/CD133+/CD45low cells increased in the clopidogrel group (P = 0.008), but not in the prasugrel group. The hsCRP, FMD and reactive hyperemia index measured by RH-PAT did not change in either group. Prasugrel is potentially better than clopidogrel for preventing thrombotic events, although clopidogrel may have an advantage over prasugrel in terms of preventing atherosclerotic events. Proper use of thienopyridine drugs based on the CYP2C19 genotype has promising clinical potential.

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