Vascular Medicine最新文献

Rare vascular diseases are a diverse group of life-threatening conditions defined by their low prevalence but profound impact on patient morbidity and quality of life. Diagnosing these disorders remains a significant clinical challenge due to their genetic heterogeneity, overlapping phenotypes, and limited patient populations. As such, the development of robust and human-relevant disease models is critical for elucidating pathogenic mechanisms and guiding therapeutic discovery. The advent of human induced pluripotent stem cell (iPSC) technology has opened new avenues for modeling rare vascular diseases by enabling the generation of patient-specific vascular cell types, including endothelial cells, smooth muscle cells, and fibroblasts, and the creation of both two-dimensional cultures and three-dimensional vascular organoids. Together with genome editing and next-generation multiomics, these platforms represent new approach methodologies (NAMs) that allow for detailed investigation of disease biology, facilitate the correction of pathogenic mutations, and enable high-throughput drug screening in a personalized context. In this review, we highlight the advancements in iPSC-derived vascular modeling, discuss the integration of gene editing and multiomics technologies, and explore their transformative potential for uncovering mechanisms and developing precision therapies for rare vascular diseases.

Introduction: Vascular contributions to cognitive impairment and dementia are potentially modifiable. Early detection of reversible arterial injury may improve risk stratification and provide treatment monitoring. We hypothesized that carotid ultrasound grayscale median (GSM), a novel imaging biomarker of early arterial injury, would predict incident all-cause dementia in the Multi-Ethnic Study of Atherosclerosis (MESA).

Methods: The MESA enrolled adults free of atherosclerotic cardiovascular disease. Common carotid GSM was measured at baseline. Incident all-cause dementia events were identified by hospital and death records. Cox proportional hazards models with natural cubic splines investigated the association of baseline GSM and all-cause dementia.

Results: The 1788 participants were a mean (SD) 63.1 (10.3) years old and 53% were women. Over a median 13.7 years, 157 all-cause dementia events occurred. In fully adjusted models, with additional adjustment for carotid intima-media thickness, lower (worse) GSM independently predicted incident all-cause dementia (hazard ratio, 1st to 3rd tertile, 1.45 [95% CI, 1.11-1.90], p = 0.021).

Conclusions: Lower GSM independently predicts all-cause dementia, beyond traditional arterial injury measures, suggesting it may serve as an early marker of dementia risk.

Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have demonstrated cardiovascular benefits in patients with type 2 diabetes mellitus (T2DM), but their effect on the risk of cardiovascular events and amputation in patients with chronic limb-threatening ischemia (CLTI) remains underexplored. This retrospective cohort study evaluated the association between GLP-1RA use and the 5-year risk of major amputation, all-cause mortality, and cardiovascular events in diabetic patients with CLTI.

Methods: The TriNetX real-world clinical data platform was used to identify patients with T2DM and CLTI, categorized by GLP-1RA prescription records. Propensity score matching was applied based on demographics, comorbidities, concurrent medications, and laboratory values. Cox proportional hazards, Kaplan-Meier curves, and the log-rank test were used for analysis.

Results: Among 139,173 patients with T2DM and CLTI, 17,306 patients were GLP-1RA users and 121,867 were non-GLP-1RA users. Following propensity score matching, 15,743 patients remained in each group (91% match rate). The mean age was 65.4 ± 11 years and 58.9% were men. The mean follow-up duration was 753.7 days. GLP-1RA users had a significantly lower rate of major amputation (hazard ratio [HR]: 0.745; 95% CI: 0.679-0.816; log-rank p < 0.001), all-cause mortality (HR: 0.7; 95% CI: 0.663-0.738; log-rank p < 0.001), and myocardial infarction (MI) (HR: 0.838; 95% CI: 0.792-0.886; log-rank p < 0.001). There was no difference in the risk of ischemic stroke (HR: 0.969; 95% CI: 0.906-1.036; log-rank p = 0.353).

Conclusion: The use of GLP-1RA medications is associated with a significant decrease in the 5-year risk of major amputations, all-cause mortality, and MI in diabetic patients with CLTI.