Tse-Min Lu

Hyperuricemia is closely associated with the mobility and mortality of patients with cardiovascular diseases. However, how hyperuricemia accelerates atherosclerosis progression is not well understood. The balance between asymmetric dimethylarginine (ADMA) and dimethylarginine dimethylaminotransferases (DDAHs) is crucial to regulate vascular homeostasis. Therefore, we investigated the role of the ADMA/DDAH pathway in hyperuricemia-induced endothelial dysfunction and atherosclerosis and the underlying molecular mechanisms in endothelial cells (ECs) and apolipoprotein E–knockout (apoe−/−) mice. Our results demonstrated that uric acid at pathological concentrations increased the intracellular levels of ADMA and downregulated DDAH-2 expression without affecting DDAH-1 expression. Excess uric acid also reduced NO bioavailability and increased monocyte adhesion to ECs, which were abolished by using the antioxidant N-acetylcysteine, the nicotinamide adenine dinucleotide phosphate oxidase inhibitor apocynin, or DDAH-2 overexpression. In apoe−/− mice, treatment with oxonic acid, a uricase inhibitor, increased the circulating level of uric acid, cholesterol, and lipid peroxidation; exacerbated systemic and aortic inflammation; and worsened atherosclerosis compared with vehicle-treated apoe−/− mice. Furthermore, oxonic acid–treated apoe−/− mice exhibited elevated ADMA plasma level and downregulated aortic expression of DDAH-2 protein. Notably, DDAH-2 overexpression in the ECs of apoe−/− mice prevented hyperuricemia-induced deleterious effects from influencing ADMA production, lipid peroxidation, inflammation, and atherosclerosis. Collectively, our findings suggest that hyperuricemia disturbs the balance of the ADMA/DDAH-2 axis, results in EC dysfunction, and, consequently, accelerates atherosclerosis.

BACKGROUND: The benefit of utilizing an invasive strategy in elderly Chinese patients with non-ST-elevation myocardial infarction (NSTEMI) remains unclear. The aim of this study was to determine whether in-hospital revascularization is associated with long-term prognosis in elderly Chinese patients with NSTEMI, as compared with younger patients. METHODS: All patients were followed up for at least 3 years or until the occurrence of a major event. The primary endpoint was all-cause mortality, and the secondary endpoint was the combined occurrence of major adverse cardiovascular events (MACE), including death, nonfatal MI, and ischemic stroke. RESULTS: A total of 343 consecutive NSTEMI patients (148 over the age of 75 years and 195 aged < 75 years) were enrolled. Coronary angiography was performed less frequently in elderly patients (66% vs. 76%; p = 0.027). Multiple logistic regression analysis confirmed the benefit of in-hospital revascularization in the elderly and younger patients, with a statistically significant reduction in the odds of all-cause death and MACE at 1 year and 3 years, respectively. In a multivariable Cox regression analysis, in-hospital revascularization was an independent predictor of future MACE not only in elderly patients [hazard ratio (HR), 0.61; 95% confidence interval (CI), 0.38-0.97] but also in younger patients as well (HR, 0.51; 95% CI, 0.31-0.84). CONCLUSIONS: In Chinese patients with NSTEMI, in-hospital revascularization was associated with significant benefits at 1 year and 3 years in both younger and elderly groups. These results are consistent with the published literature and suggest that advanced age alone should not be regarded as a contraindication to invasive management following presentation with NSTEMI. KEY WORDS: Elderly; Invasive strategy; Myocardial infarction.

Background The role of routine intravascular imaging in percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) remains unclear. This study evaluated the clinical outcomes of PCI guided by different imaging modalities in AMI patients. Materials and methods Data from AMI patients who had undergone PCI between 2012 and 2022 were analyzed. The mean follow-up was 12.9 ± 1.73 months. The imaging modality-either intravascular ultrasound (IVUS), optical coherence tomography (OCT), or angiography alone-was selected at the operator's discretion. The primary endpoint was major adverse cardiac events (MACEs), including cardiovascular (CV) death, myocardial infarction (MI), target vessel revascularization. Results Of the 1,304 PCIs performed, 47.5% ( n = 620) were guided by angiography alone, 37.0% ( n = 483) by IVUS, and 15.4% ( n = 201) by OCT. PCI guided by intravascular imaging modalities was associated with lower 1-year rates of MI (1.3%, P = 0.001) and MACE (5.2%, P = 0.036). OCT-guided PCI was linked to lower rates of 1-year CV death (IVUS vs. OCT: 6.2% vs. 1.5%, P = 0.016) and MACE (IVUS vs. OCT: 6.4% vs. 2.5%, P = 0.032). Intravascular imaging modalities and diabetes were identified as predictors of better and worse 1-year MACE outcomes, respectively. Conclusion PCI guided by intravascular imaging modalities resulted in improved 1-year clinical outcomes compared to angiography-guided PCI alone in AMI patients. OCT-guided PCI was associated with lower 1-year MACE rates compared to IVUS-guided PCI. Therefore, intravascular imaging should be recommended for PCI in AMI, with OCT being particularly considered when appropriate.