Circulation Journal最新文献

Background: The pathogenesis of aortic aneurysm (AA) is characterized by chronic inflammation of the aortic wall, the associated accumulation of macrophages, and degradation of the extracellular matrix, including elastin. Colchicine (COL) has long been known for its anti-inflammatory effects, so in this study we investigated its effects on AA.

Methods and results: In vitro, tumor necrosis factor (TNF)-α-stimulated macrophages and vascular smooth muscle cells (VSMCs) were treated with and without COL for 24 h. Unstimulated cells were used as controls. COL significantly reduced interleukin (IL)-1β, TNF-α, monocyte chemotactic protein (MCP)-1, nuclear factor kappa B (NF-κB), matrix metalloproteinase (MMP)-9, and activated caspase-1 in macrophages, and increased lysyl oxdase (Lox) and tissue inhibitor of metalloproteinase (TIMP)-2 expression in VSMCs. In vivo, aged male apolipoprotein E-deficient (ApoE^-/^-) mice were infused with angiotensin II (Ang II) for 28 days. The mice received either normal saline (NS) or COL orally. The control group of ApoE^-/^-mice did not receive Ang II infusion or treatment. COL significantly suppressed aortic enlargement and reduced AA incidence by preserving elastin and decreasing IL-1β, TNF-α, MCP-1, NLRP3 inflammasome, neutrophil elastase, and myeloperoxidase expression. No significant differences were observed in the enzymatic activities of MMP-2 and MMP-9 between the 2 groups.

Conclusions: The results suggested that COL prevents AA progression in a clinically relevant model and is expected to be a novel preventive agent for AA.

Background: Several cross-sectional studies have implicated gut dysbiosis caused by an abundance of oral commensals in stroke, but the effect on long-term prognosis is still unknown. Therefore, we longitudinally investigated oral pathobionts in the gut and their clinical relevance to stroke.

Methods and results: We analyzed the salivary and gut microbiomes collected from 189 acute stroke and 55 non-stroke subjects, and found that Streptococcus anginosus was significantly more abundant in both the saliva (median [IQR], 0.01 [0.00-0.14] vs. 0.00 [0.00-0.03], P=0.02) and gut (0.09 [0.00-0.28] vs. 0.00 [0.00-0.02], P<0.001) of the stroke patients compared with their non-stroke counterparts. Network analysis revealed S. anginosus as a central hub in gut dysbiosis. After adjusting for vascular risks, S. anginosus (odds ratio 1.20, 95% confidence interval 1.06-1.36, P<0.01), Anaerostipes hadrus (0.82, [0.73-0.93], P<0.01), and Bacteroides plebeius (0.86, [0.86-0.93], P=0.01) in the gut were independent predictors of stroke. Longitudinally, S. anginosus in the gut was significantly associated with increased rates of death and major cardiovascular events (P=0.04; log-rank test), whereas A. hadrus and B. plebeius were not (P=0.45 and P=0.19). After adjusting for vascular risks, S. anginosus in the gut was a residual risk for increased rates of death and major cardiovascular events (hazard ratio 4.78, 95% confidence interval 1.08-21.18, P=0.04)Conclusions: S. anginosus in the gut may increase the risk of stroke and a poor prognosis.

Background: The antiplatelet effect of prasugrel for acute ischemic stroke or transient ischemic attack (TIA) remains unclear. This study compared platelet reactivity between prasugrel and clopidogrel, considering cytochrome P450 family 2 subfamily C member 19 (CYP2C19) gene polymorphisms (extensive metabolizers [EM], intermediate metabolizers [IM], and poor metabolizers [PM]), in patients with acute large artery atherosclerosis (LAA) or high-risk TIA.

Methods and results: In this multicenter open-label randomized controlled study, patients with acute LAA or high-risk TIA received prasugrel or clopidogrel with aspirin. The primary endpoint was platelet reaction units (PRU) 5 days after the start of drug administration, stratified according to CYP2C19 polymorphism. In all, 176 patients participated (88 in each group). Compared with the clopidogrel group, PRU on Day 5 in the prasugrel group were significantly lower in the overall population (adjusted mean 136.0 vs. 169.9; estimated difference -33.9; 95% confidence interval [CI] -49.0, -18.8), EM group (118.5 vs. 144.8; estimated difference -26.2; 95% CI -48.0, -4.4), and IM group (140.3 vs. 173.1; estimated difference -32.8; 95% CI -56.6, -9.0), and tended to be lower in the PM group (164.7 vs. 196.2; estimated difference -31.6; 95% CI -68.3, 5.1). The prevalence of new infarct lesions was comparable between the prasugrel and clopidogrel groups, as was the incidence of adverse events (30.7% vs. 26.1%, respectively) and bleeding events up to Day 5 of administration.

Conclusions: In patients with acute LAA or high-risk TIA, prasugrel resulted in stable inhibition of platelet aggregation 5 days after starting drug administration compared with clopidogrel, regardless of CYP2C19 polymorphisms.

Background: Direct oral anticoagulants (DOACs) are commonly used oral anticoagulants for patients with venous thromboembolism (VTE). Sometimes these patients receive concomitant antiplatelet therapy, with limited data supporting the practice. This study investigated the effect of concomitant antiplatelet therapy (CAT) on clinical outcomes in VTE patients treated with anticoagulants.

Methods and results: The COMMAND VTE Registry-2 is a multicenter registry that enrolled 5,197 consecutive patients with acute symptomatic VTE across 31 centers in Japan between January 2015 and August 2020. After excluding 407 patients without oral anticoagulants, there were 4,790 VTE patients treated with oral anticoagulants. After propensity score matching, 676 patients (338 matched pairs in the CAT and anticoagulant only [AC] groups) were included for analysis. There were no significant differences between the CAT and AC groups in the cumulative 3-year incidence of recurrent VTE (4.9% vs. 7.3%, respectively; P=0.50), major bleeding (9.4% vs. 12.4%, respectively; P=0.36), or stroke (6.7% vs. 4.1%, respectively; P=0.24). However, the cumulative 3-year incidence of clinically relevant non-major bleeding (CRNMB) was significantly higher in the CAT group than in the AC group (17.7% vs. 10.0%; P=0.047).

Conclusions: In a large VTE registry in the DOAC era, concomitant antiplatelet and anticoagulant therapy, compared with anticoagulant alone, was not significantly associated with risks of recurrent VTE, major bleeding, or stroke, but did increase the risk of CRNMB.

Time-space network hypertension is a data science approach that connects diverse information related to hypertension within a time-space framework. This field of academic research aims to predict disease onset and direct effective, individualized, optimized treatments by integrating and analyzing the variability of multiple internal biological and external environmental signals as they relate to blood pressure variability across different time phases. By linking time series changes in blood pressure and biological distribution with multi-environmental and physiological information, enabled by advances in digital technology, the time-space network hypertension approach contributes to "digital hypertension" research. This article from Jichi Medical University provides an update on research relating to the time-space network hypertension approach, which is designed to progress hypertension management towards achieving net zero cardiovascular events.

Background: Non-home discharge (NHD) after endovascular therapy (EVT) for chronic limb-threatening ischemia (CLTI) signals frailty and higher healthcare costs.

Methods and results: The nationwide J-EVT Registry (2021-2023) captured data for 31,025 patients with CLTI who underwent EVT. NHD, defined as transfer to chronic-care hospitals, occurred in 12.9%. Independent predictors of NHD were age ≥70 years, non-ambulatory status, and perioperative complications.

Conclusions: Because 1 in 8 Japanese CLTI patients required NHD after EVT, risk stratification and minimizing procedural invasiveness are essential to improve home-discharge rates.

Background: Emerging evidence highlights the clinical significance of lipid variability in cardiovascular disease and adverse outcomes. This study investigated the relationship between lipid variability and incident peripheral artery disease (PAD) risk.

Methods and results: We identified 93,948 patients in the Chang Gung Research Database in Taiwan who had been diagnosed with hyperlipidemia between 2007 and 2013 and had annual lipid measurements over 4 consecutive years. Lipid levels, including total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), and triglycerides, as well as their visit-to-visit variability, were assessed over the 4-year period. Patients were followed until December 31, 2019 for incident PAD development. Over a mean 5.9-year follow-up, 2,735 patients (2.5%) developed PAD. Mean lipid levels were significantly associated with incident PAD. Of note, the average real variability (ARV) in HDL-C was independently associated with increased PAD risk (adjusted hazard ratio 1.13; 95% confidence interval 1.004-1.27 for highest vs. lowest quartile of HDL-C ARV; P for trend=0.002). Sensitivity analysis using variability independent of the mean as the HDL-C variability index confirmed this finding. Consistency was observed across all subgroup analyses.

Conclusions: In this multi-institutional database analysis, visit-to-visit variability in HDL-C was significantly associated with the risk of incident PAD, independent of traditional risk factors for atherosclerosis, mean lipid levels, and the use of lipid-lowering therapy.

Background: Transcatheter aortic valve implantation (TAVI) is an alternative to surgical aortic valve replacement in hemodialysis patients; however, contemporary outcomes and risk stratifications remain unreported.

Methods and results: Using data from a multicenter database, this study included 2,888 patients who underwent TAVI between 2021 and 2024: 336 (11.6%) on hemodialysis and 2,552 (88.4%) not. The primary outcome was all-cause death after TAVI; the median follow-up was 527 days. Hemodialysis patients were younger, predominantly male, and had more comorbidities with higher surgical risk. Hemodialysis and non-hemodialysis patients had similar 30-day mortality (2.9% vs. 1.5%, respectively) and major procedural complications. Hemodialysis patients had 2- to 3-fold higher rates of all-cause death (14.4% vs. 6.5% at 1-year; 21.5% vs. 11.0% at 2 years), cardiovascular death, and the composite of all-cause death and heart failure hospitalization. After adjusting for confounders, hemodialysis had no significant effect on all-cause death and the composite endpoint. Body mass index, Clinical Frailty Scale, and albumin levels were associated with all-cause death in hemodialysis patients, allowing risk stratification into low-, intermediate-, and high-risk groups.

Conclusions: In this study, hemodialysis patients were younger and had more comorbidities, but 30-day mortality and complications were similar to the non-hemodialysis group. Although hemodialysis patients had higher all-cause mortality, the worse outcomes in this group were attributed to comorbidities rather than the hemodialysis itself.