LDL cholesterol levels and in-hospital bleeding in patients on high-intensity antithrombotic therapy: findings from the CCC-ACS project.

AIMS: Emerging evidence has linked cholesterol metabolism with platelet responsiveness. We sought to examine the dose-response relationship between low-density lipoprotein cholesterol (LDL-C) and major in-hospital bleeds in acute coronary syndrome (ACS) patients. METHODS AND RESULTS: Among 42 378 ACS patients treated with percutaneous coronary intervention (PCI) enrolled in 240 hospitals in the Improving Care for Cardiovascular Disease in China-ACS project from 2014 to 2019, a total of 615 major bleeds, 218 ischaemic events, and 337 deaths were recorded. After controlling for baseline variables, a non-linear relationship was observed for major bleeds, with the higher risk at lower LDL-C levels. No dose-response relationship was identified for ischaemic events and mortality. A threshold value of LDL-C <70 mg/dL was associated with an increased risk for major bleeds (adjusted odds ratio: 1.49; 95% confidence interval: 1.21-1.84) in multivariable-adjusted logistic regression models and in propensity score-matched cohorts. The results were consistent in multiple sensitivity analyses. Among ticagrelor-treated patients, the LDL-C threshold for increased bleeding risk was observed at <88 mg/dL, whereas for clopidogrel-treated patients, the threshold was <54 mg/dL. Across a full spectrum of LDL-C levels, the treatment effect size associated with ticagrelor vs. clopidogrel on major bleeds favoured clopidogrel at lower LDL-C levels, but no difference at higher LDL-C levels. CONCLUSIONS: In a nationwide ACS registry, a non-linear association was identified between LDL-C levels and major in-hospital bleeds following PCI, with the higher risk at lower levels. As the potential for confounding may exist, further studies are warranted. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02306616.

Highly Monodisperse Cu-Sn Alloy Nanoplates for Efficient Nitrophenol Reduction Reaction via Promotion Effect of Tin.

The hexagonal copper-tin alloy (Cu-Sn) nanoplates were synthesized using a high temperature solvent method, the length of six equilateral edges of hexagonal Cu-Sn nanoplates was 23 nm, and the thickness was 13 nm. The obtained hexagonal Cu-Sn nanoplates were highly monodisperse and allowed the formation of nanoarrays arranged with long-range order. The hexagonal Cu-Sn nanoplates exhibited high catalytic activity on catalytic hydrogenation of 4-nitrophenol to 4-aminophenol. Due to the promotion effect of Sn, the apparent rate constant (ka) of hexagonal Cu-Sn nanoplates was three times that of Cu nanoparticles. The density functional theory (DFT) calculations and experimental results demonstrated that Sn could promote the coordination process of -NO2 of 4-nitrophenol with Cu-Sn nanoplates and contribute to activation of 4-nitrophenol. In addition, the hexagonal Cu-Sn nanoplates showed high stability and reusability for the reduction reaction, good adaptability in different pH and the ionic strength, and wide applicability for the degradation of methylene blue, methyl orange, and rhodamine B, even in the industrial wastewater, suggesting that the Cu-Sn nanoplates are promising catalysts in organic industry wastewater treatment.

Antithrombotic therapy and bleeding risk in the era of aggressive lipid-lowering: current evidence, clinical implications, and future perspectives.

ABSTRACT: The clinical efficacy of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) in reducing major cardiovascular adverse events related to atherosclerotic cardiovascular disease (ASCVD) has been well established in recent large randomized outcome trials. Although the cardiovascular and all-cause mortality benefit of PCSK9i remains inconclusive, current cholesterol management guidelines have been modified toward more aggressive goals for lowering low-density lipoprotein cholesterol (LDL-C). Consequently, the emerging concept of "the lower the better" has become the paradigm of ASCVD prevention. However, there is evidence from observational studies of a U-shaped association between baseline LDL-C levels and all-cause mortality in population-based cohorts. Among East Asian populations, low LDL-C was associated with an increased risk for hemorrhagic stroke in patients not on antithrombotic therapy. Accumulating evidence showed that low LDL-C was associated with an enhanced bleeding risk in patients on dual antiplatelet therapy following percutaneous coronary intervention. Additionally, low LDL-C was associated with a higher risk for incident atrial fibrillation and thereby, a possible increase in the risk for intracranial hemorrhage after initiation of anticoagulation therapy. The mechanism of low-LDL-C-related bleeding risk has not been fully elucidated. This review summarizes recent evidence of low-LDL-C-related bleeding risk in patients on antithrombotic therapy and discusses potential measures for reducing this risk, underscoring the importance of carefully weighing the pros and cons of aggressive LDL-C lowering in patients on antithrombotic therapy.