Sociodemographic Heterogeneity in the Associations of Social Isolation With Mortality.

Importance: There are limited data on whether the vulnerabilities and impacts of social isolation vary across populations. Objective: To explore the association between social isolation and mortality due to all causes, cardiovascular diseases (CVD), and malignant neoplasms focusing on heterogeneity by sociodemographic factors. Design, Setting, and Participants: This cohort study used a moderator-wide approach to examine the heterogeneity in the association of social isolation with all-cause, CVD, and malignant neoplasm mortality using baseline data from the Japan Gerontological Evaluation Study in 2010 and 2011. Eligible participants were adults aged 65 years or older without heart disease, stroke, cancer, or impaired activity of daily living across 12 Japanese municipalities. Follow-up continued until December 31, 2017, identifying 6-year all-cause, cardiovascular disease (CVD), and malignant neoplasm mortality. Logistic regression assessed effect modification by age, gender, education, income, population density, marital status, and employment on mortality associations. Data analysis was performed from September 13, 2023, to March 17, 2024. Exposure: Social isolation, determined by a 3-item scale (scores of 2 or 3 indicating isolation) was the primary exposure variable. Main Outcomes and Measures: Six-year all-cause, CVD, and malignant neoplasms mortality. Results: This study included 37 604 older adults, with a mean (SD) age of 73.5 (5.9) years (21 073 women [56.0%]). A total of 10 094 participants (26.8%) were classified as experiencing social isolation. Social isolation was associated with increased all-cause (odds ratio [OR], 1.20 [95% CI, 1.09-1.32]), CVD (OR, 1.22 [95% CI, 0.98-1.52]), and malignant neoplasm mortality (OR, 1.14 [95% CI, 1.01-1.28]). Stratified analysis showed associations of social isolation with all-cause and malignant neoplasm mortality among people with high income (highest tertile all cause: OR, 1.27 [95% CI, 1.06-1.53]; malignant neoplasm: OR, 1.27 [95% CI, 1.02-1.60]), living in areas with high population density (highest tertile all cause: OR, 1.47 [95% CI, 1.26-1.72]; malignant neoplasm: OR, 1.38 [95% CI, 1.11-1.70]), not married (all cause: OR, 1.33 [95% CI, 1.15-1.53]; malignant neoplasm: OR, 1.25 [95% CI, 1.02-1.52]), and retirees (all cause: OR, 1.27 [95% CI, 1.14-1.43]; malignant neoplasm: OR, 1.27 [95% CI, 1.10-1.48]). Formal testing for effect modification indicated modification by population density and employment for all-cause mortality and by household income and employment for neoplasm mortality. Conclusions and Relevance: Social isolation was associated with increased risks of all-cause, CVD, and malignant neoplasm mortality, with associations varying across populations. This study fills an important gap in research on social isolation, emphasizing its varied associations across demographic and socioeconomic groups.

Synergistic Effects of 1 h Post-Load Plasma Glucose and Smoking on Arterial Stiffness in Apparently Healthy Men: A Cross-sectional Study.

AIM: One-hour post-load plasma glucose (1h-PG) during an oral glucose tolerance test and smoking are associated with arterial stiffness. However, it remains unknown whether there are synergistic effects of these two factors on arterial stiffness. This study aimed to investigate the interaction between 1h-PG and smoking in relation to brachial-ankle pulse wave velocity (baPWV) in young men with normal glucose tolerance (NGT). METHODS: The study included 25-, 30-, 35-, 40-, and 45-year-old non-industrial male workers (n=2189) who underwent a detailed health check-up. Normotensive participants with NGT and taking no medication were included. RESULTS: A univariate linear regression analysis showed that 1h-PG correlated with baPWV (r=0.13, p＜0.001), but the correlation was not significant in the multivariate analysis (ß=0.02, p=0.24). However, we found a significant interaction between 1h-PG levels and smoking status in relation to baPWV (p=0.048). Therefore, further analyses were conducted in nonsmokers and smokers. A multivariate linear regression analysis revealed that 1h-PG significantly correlated with baPWV in smokers (ß=0.11, p=0.02), but not in nonsmokers (ß=0.01, p=0.79). The correlation remained significant even after adjustment for the number of cigarettes smoked per day (ß=0.096, p=0.048) or the Brinkman index (ß=0.097, p=0.043). CONCLUSION: A significant interaction between 1h-PG and smoking in relation to baPWV was found in apparently healthy men younger than 50 years old.

Inhibition of endothelial p53 improves metabolic abnormalities related to dietary obesity.

Accumulating evidence has suggested a role for p53 activation in various age-associated conditions. Here, we identified a crucial role of endothelial p53 activation in the regulation of glucose homeostasis. Endothelial expression of p53 was markedly upregulated when mice were fed a high-calorie diet. Disruption of endothelial p53 activation improved dietary inactivation of endothelial nitric oxide synthase that upregulated the expression of peroxisome proliferator-activated receptor-γ coactivator-1α in skeletal muscle, thereby increasing mitochondrial biogenesis and oxygen consumption. Mice with endothelial cell-specific p53 deficiency fed a high-calorie diet showed improvement of insulin sensitivity and less fat accumulation, compared with control littermates. Conversely, upregulation of endothelial p53 caused metabolic abnormalities. These results indicate that inhibition of endothelial p53 could be a novel therapeutic target to block the vicious cycle of cardiovascular and metabolic abnormalities associated with obesity.