Preloading with atorvastatin before percutaneous coronary intervention in statin-naïve Asian patients with non-ST elevation acute coronary syndromes: A randomized study

BackgroundData on atorvastatin pretreatment in Asian patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI) are limited. However, there have been studies in other populations in Asia which demonstrated that statins can reduce the risk of periprocedural myocardial infarction (MI).Methods and resultsStatin-naïve patients with non-ST-segment-elevation (NSTE)-ACS scheduled for PCI were randomized to usual care or atorvastatin preloading groups. All patients received usual care including atorvastatin 40 mg/day. The atorvastatin group received atorvastatin 80 mg 12 h and 40 mg 2 h pre-PCI. Of 499 patients randomized, 247 were assigned to atorvastatin preloading. Following coronary angiography, 335 patients (163 atorvastatin) received PCI. During the 30 days post-PCI, major adverse cardiac events (death, MI, and target vessel revascularization) occurred in 24 (15%) atorvastatin and 27 (16%) usual care patients (p = NS). Post hoc analyses showed that at 8 h post-PCI, 3.82% of the atorvastatin group and 7.22% of the usual care group had a post-procedural creatine kinase-myocardial band (CK-MB) above 3 times the upper limit of normal (p = 0.27) and at 24 h post-PCI, the rate was 7.64% versus 9.47% (p = 1.0). Safety profile suggests that high-dose atorvastatin (40 mg) for up to 1 month, in conjunction with usual care, is relatively safe and well tolerated.ConclusionsThis study of statin-naïve Korean and Chinese patients with NSTE-ACS who received additional atorvastatin loading doses of 80 mg at 12 h, and 40 mg at 2 h, pre-PCI did not find a beneficial effect compared with usual post-PCI atorvastatin 40 mg/day treatment. Atorvastatin was found to be well tolerated in Asian patients with NSTE-ACS undergoing PCI. Results of the current study merit further investigation of the early use of statins in patients with NSTE-ACS to delineate patient subgroups who may benefit from this therapy.     

Mitophagy Receptors and Mediators: Therapeutic Targets in the Management of Cardiovascular Ageing

Mitophagy serves as a cardinal regulator in the maintenance of mitochondrial integrity, function, and cardiovascular homeostasis, through the fine control and governance of cellular metabolism, ATP production, redox balance, and mitochondrial quality and quantity control. As a unique form of selective autophagy, mitophagy specifically recognizes and engulfs long-lived or damaged (depolarized) mitochondria through formation of the double-membraned intracellular organelles - mitophagosomes, ultimately resulting in lysosomal degradation. Levels of mitophagy are reported to be altered in pathological settings including cardiovascular diseases and biological ageing although the precise nature of mitophagy change in ageing and ageing-associated cardiovascular deterioration remains poorly defined. Ample clinical and experimental evidence has depicted a convincing tie between cardiovascular ageing and altered mitophagy. In particular, ageing perturbs multiple enigmatic various signal machineries governing mitophagy, mitochondrial quality, and mitochondrial function, contributing to ageing-elicited anomalies in the cardiovascular system. This review will update novel regulatory mechanisms of mitophagy especially in the perspective of advanced ageing, and discuss how mitophagy dysregulation may be linked to cardiovascular abnormalities in ageing. We hope to pave the way for development of new therapeutic strategies against the growing health and socieconomical issue of cardiovascular ageing through targeting mitophagy.     

Multimodal SPION-CREKA peptide based agents for molecular imaging of microthrombus in a rat myocardial ischemia-reperfusion model

Microthrombosis plays a key role in many cardiovascular diseases. Although it is not difficult to localize thrombus within large or middle-sized vessels, the noninvasive diagnostic regimen for the detection of microthrombus remains scarce. Here we developed a nanoagent by conjucting superparamagnetic iron-oxide nanoparticle with fluorophore and a targeting element, CREKA, a peptide with special affinity for fibrin. In a rat model of myocardial ischemia–reperfusion (MI/R), the multimodal nanoagents were readily and selectively accumulated within microthrombosis, which was detectable by both magnetic resonance and optical imaging modalities. The fibrin-targeted nanoagent could be expected to have utility not only in molecular imaging of fibrin, understanding the mechanisms of microcirculation disorders, but also in targeted therapy with fibrinolytic agents.