Association between the trajectory of ideal cardiovascular health metrics and incident chronic kidney disease among 27,635 older adults in northern China-a prospective cohort study.

BACKGROUND: There is a lack of relevant studies evaluating the long-term impact of cardiovascular health factor (CVH) metrics on chronic kidney disease (CKD). OBJECTIVE: This study investigates the long-term change in CVH metrics in older people and explores the relationship between CVH metrics trajectory and CKD. METHODS: In total, 27,635 older people aged over 60 from the community-based Tianjin Chronic Kidney Disease Cohort study were enrolled. The participants completed five annual physical examinations between January 01, 2014, and December 31, 2018, and a subsequent follow-up between January 01, 2019, and December 31, 2021. CVH metrics trajectories were established by the group-based trajectory model to predict CKD risk. The relationships between baseline CVH, CVH change (ΔCVH), and CKD risk were also explored by logistic regression and restricted cubic spline regression model. In addition, likelihood ratio tests were used to compare the goodness of fit of the different models. RESULTS: Six distinct CVH metrics trajectories were identified among the participants: low-stable (11.19%), low-medium-stable (30.58%), medium-stable (30.54%), medium-high-decreased (5.46%), medium-high-stable (18.93%), and high-stable (3.25%). After adjustment for potential confounders, higher CVH metrics trajectory was associated with decreased risk of CKD (P for trend < 0.001). Comparing the high-stable with the low-stable group, the risk of CKD decreased by 46%. All sensitivity analyses, including adjusting for baseline CVH and removing each CVH component from the total CVH, produced consistent results. Furthermore, the likelihood ratio test revealed that the model established by the CVH trajectory fit better than the baseline CVH and Δ CVH. CONCLUSION: The higher CVH metrics trajectory and improvement of CVH metrics were associated with decreased risk of CKD. This study emphasized the importance of improving CVH to achieve primary prevention of CKD in older people.

The impact of prolonged exposure to air pollution on the incidence of chronic non-communicable disease based on a cohort in Tianjin.

Evidence on the associations of prolonged ambient pollutants exposure with chronic non-communicable diseases among middle-aged and elderly residents is still limited. This prospective cohort study intends to investigate the long-term effects of ambient pollution on hypertension and diabetes incidence among relatively older residents in China. Individual particulate matter exposure levels were estimated by satellite-based model. Individual gaseous pollutants exposure levels were estimated by Inverse Distance Weighted model. A Cox regression model was employed to assess the risks of hypertension and diabetes morbidity linked to air pollutants exposures. The cross-product term of ambient pollutants exposure and covariates was further added into the regression model to test whether covariates would modify these air pollution-morbidity associations. During the period from 2014 to 2018, a total of 97,982 subjects completed follow-up. 12,371 incidents of hypertension and 2034 of diabetes occurred. In the multi-covariates model, the hazard ratios (HR) and 95% confidence interval (CI) were 1.49 (1.45-1.52), 1.28 (1.26-1.30), 1.17 (1.15-1.18), 1.21 (1.17-1.25) and 1.33 (1.31-1.35) for hypertension morbidity per 10 µg/m3 increment in PM1, PM2.5, PM10, NO2 and SO2, respectively. For diabetes onsets, the HR (95% CI) were 1.17 (1.11-1.23), 1.09 (1.04-1.13), 1.06 (1.02-1.09), 1.02 (0.95-1.10), and 1.24 (1.19-1.29), respectively. In addition, for hypertension analyses, the effect estimates were more pronounced in the participants with age <60 years old, BMI ≥24 kg/m2, and frequent alcohol drinking. These findings provided the evidence on elevated risks of morbidity of hypertension and diabetes associated with prolonged ambient pollutants exposure at relatively high levels.

Joint exposure to outdoor ambient air pollutants and incident chronic kidney disease: A prospective cohort study with 90,032 older adults.

Objectives: There is paucity of studies to investigate the association between combined and long-term exposure to air pollution and the risk of incident chronic kidney disease (CKD) in older adults. Methods: A prospective cohort of 90,032 older adults who did not have CKD at baseline were followed up from January 1, 2017, to December 31, 2019. Various pollutant data, including particulate matter with diameters ≤ 2.5 mm (PM2.5), ≤ 10 mm (PM10), nitrogen dioxide (NO2), sulfur dioxide (SO2), Ozone (O3), and carbon monoxide (CO), from all monitoring stations in Binhai New Area, Tianjin were considered in calculating the mean exposure concentration of each pollutant over 2 years. By summing each pollutant concentration weighted by the regression coefficients, we developed an air pollution score that assesses the combined exposure of these air pollutants. Due to the strong correlation between air pollutants, Principal Component Analysis (PCA) score was also developed. The association between air pollutants and incident CKD in the elderly was analyzed. Results: A total of 90,032 subjects participated in this study with a median follow-up of 545 days. Among them, 22,336 (24.8%) developed CKD. The HR (95% CI) for air pollution score and incidence of CKD was 1.062 (1.060-1.063) and p <0.001 after adjusting for all confounders. The adjusted HRs for the quartile subgroups of combined air pollution score were: Q2: 1.064 (1.013-1.117); Q3: 1.141 (1.088-1.198); and Q4: 3.623 (3.482-3.770), respectively (p for trend <0.001). The adjusted HRs for the quartile subgroups of air quality index (AQI) were: Q2: 1.035 (0.985-1.086); Q3: 1.145 (1.091-1.201); and Q4: 3.603 (3.463-3.748), respectively (p for trend <0.001). When the risk score was over 86.9, it significantly rose in a steep curve. The subgroup analysis showed that male, younger or exercise were more likely to develop CKD. Conclusion: Combined air pollution score, AQI, and PCA score were associated with an increased risk of CKD in an exposure-response relationship. Our current results might also provide evidence for developing environmental protection policies.

Rosmarinic Acid Induces Proliferation Suppression of Hepatoma Cells Associated with NF-κB Signaling Pathway.

BACKGROUND: Rosmarinic acid (RA) is a natural phenolic compound that acts as a Fyn inhibitor by 53 homology modeling of the human Fyn structure. Therefore, the apoptosis mechanism related to  NF-κB signaling pathway induced by RA in HepG2 was investigated. METHODS: The cell growth, apoptosis, and proliferation of HepG2 regulated by various concentrations of RA were studied. The proteins expression of MMP-2, MMP-9, PI3K, AKT, NF-κB, and apoptosis-related proteins Bax, Bcl-2, cleaved caspase-3 were detected. RESULTS: RA significantly reduced proliferation rates, inhibited migration and invasion, and decreased the expressions of invasion-related factors, such as matrix metalloproteinase (MMP)-2 and MMP-9. TUNEL staining revealed that RA resulted in a dose-dependent increase of HepG2 cell apoptosis. In line with this finding, the expression of apoptosis suppressor protein Bcl-2 was downregulated and that of the pro-apoptotic proteins Bax and cleaved caspase-3 was increased. In addition, we found that the phosphatidylinositol 3-kinase (PI3K)/Akt/nuclear factor kappa B (NF-κB) signaling pathway was involved in RA-mediated inhibition of HepG2 cell metastasis. CONCLUSION: Our study identified that  RA as a drug candidate for the treatment of HCC.

Fluctuations in waist circumference increase diabetes risk: a 4-year cohort study in 61,587 older adults.

PURPOSE: To evaluate the effect of fluctuations in waist circumference (WC), weight, and body mass index (BMI) on the incidence of diabetes in older adults. PATIENTS AND METHODS: A prospective cohort of 61,587 older adults (age, 60-96 years) who did not have diabetes at study initiation was examined. Data on weight, BMI, and WC were collected, and participants were followed up until 31 December 2018. The main end point was new-onset diabetes. A Cox regression model was used to estimate the risk of diabetes (hazard ratios [HRs] and confidence intervals [CI]) in these participants. RESULTS: During a mean follow-up of 3.6 years, being overweight (HR [95% CI] 1.87 [1.62-2.17]), obesity (1.41 [1.26-1.59]), abdominal obesity (1.42 [1.28-1.58]), and obesity plus abdominal obesity at baseline (1.93 [1.66-2.25]) increased the risk of diabetes onset. Compared with older adults who "maintained normal WC", those who "remained abdominally obese" (HR = 1.66), "became abdominally obese" (HR = 1.58), or "achieved normal WC" (HR = 1.36) were at a higher risk of diabetes onset, as well as those with an increase in WC > 3 cm or > 5% compared with the baseline level. Weight gain or loss > 6 kg or weight gain > 5%, increase or decrease in BMI > 2 kg/m2, or an increase in BMI > 10% were associated with a higher diabetes risk. The diabetes risk was reduced by 19% in overweight older adults who exercised daily. CONCLUSION: For older adults, WC, BMI, and healthy weight maintenance reduce the diabetes risk. The findings may provide evidence for developing guidelines of proper weight and WC control for older adults.

Risk Analysis of Air Pollution and Meteorological Factors Affecting the Incidence of Diabetes in the Elderly Population in Northern China.

BACKGROUND: Research investigating the effect of air pollution on diabetes incidence is mostly conducted in Europe and the United States and often produces conflicting results. The link between meteorological factors and diabetes incidence remains to be explored. We aimed to explore associations between air pollution and diabetes incidence and to estimate the nonlinear and lag effects of meteorological factors on diabetes incidence. METHODS: Our study included 19,000 people aged ≥60 years from the Binhai New District without diabetes at baseline. The generalized additive model (GAM) and the distributed lag nonlinear model (DLNM) were used to explore the effect of air pollutants and meteorological factors on the incidence of diabetes. In the model combining the GAM and DLNM, the impact of each factor (delayed by 30 days) was first observed separately to select statistically significant factors, which were then incorporated into the final multivariate model. The association between air pollution and the incidence of diabetes was assessed in subgroups based on age, sex, and body mass index (BMI). RESULTS: We found that cumulative RRs for diabetes incidence were 1.026 (1.011-1.040), 1.019 (1.012-1.026), and 1.051 (1.019-1.083) per 10 µg/m3 increase in PM2.5, PM10, and NO2, respectively, as well as 1.156 (1.058-1.264) per 1 mg/m3 increase in CO in a single-pollutant model. Increased temperature, excessive humidity or dryness, and shortened sunshine duration were positively correlated with the incidence of diabetes in single-factor models. After adjusting for temperature, humidity, and sunshine, the risk of diabetes increased by 9.2% (95% confidence interval (CI):2.1%-16.8%) per 10 µg/m3 increase in PM2.5. We also found that women, the elderly (≥75 years), and obese subjects were more susceptible to the effect of PM2.5. CONCLUSION: Our data suggest that PM2.5 is positively correlated with the incidence of diabetes in the elderly, and the relationship between various meteorological factors and diabetes in the elderly is nonlinear.

The Diabetes Risk and Determinants of Transition from Metabolically Healthy to Unhealthy Phenotypes in 49,702 Older Adults: 4-Year Cohort Study.

OBJECTIVE: This study aimed to assess whether metabolically healthy obesity (MHO) increases the risk of diabetes and to explore how the occurrence of metabolic disorders affects the risk of diabetes and which factors determine metabolic health. METHODS: This study examined 49,702 older people without diabetes via the Binhai Health Screening Program in Tianjin. RESULTS: Compared with individuals with metabolic health and normal weight, the risk of diabetes was increased in older adults with MHO (hazard ratio [HR]: 1.786, 95% CI: 1.407-2.279) but was not significantly increased when metabolic health was characterized by the absence of metabolic abnormalities. The older adults who were initially affected by MHO and then converted to having an unhealthy phenotype had a higher diabetes risk than older individuals with stable and healthy normal weight (HR: 3.727, 95% CI: 2.721-5.105). Waist circumference was an independent predictor of the transition from a metabolically healthy status to an unhealthy status in all BMI categories (odds ratio: 1.059, 95% CI: 1.026-1.032). CONCLUSIONS: The MHO phenotype was associated with an increased incidence of diabetes in older adults. The presence of metabolic disorders in the group with MHO was associated with an increased diabetes risk and was predicted by the waist circumference at baseline.