Yan-Feng Zhou

This study aimed to examine the longitudinal associations of estimated pulse wave velocity (ePWV) and its longitudinal change with incident frailty in older adults. A total of 2,016 older adults (≥60 years, baseline non-frail) were included in baseline analysis, selected from an initial cohort of 4,129. Of these, 1,137 had repeated ePWV data for change analysis. Arterial stiffness was measured using ePWV, and its longitudinal change from baseline to follow-up was defined as ΔePWV. Frailty was assessed using a frailty index (FI), analyzed as both continuous and binary outcome (FI ≥ 0.25). Multivariable regression models evaluated associations of baseline ePWV and ΔePWV with incident frailty. After a mean follow-up of 7 years, 394 of 2,016 participants (19.5%) developed frailty. Each 1 m/s increase in baseline ePWV was associated with higher frailty risk (OR = 1.21, 95% CI: 1.10–1.33); the highest quartile had more than twice the risk of the lowest (OR = 2.11, 95% CI: 1.36–3.28). Among 1,137 participants with repeated measures, each 1 m/s increase in ΔePWV was associated with 21.4% higher frailty odds (OR = 1.21, 95% CI: 1.03–1.43), and rapid increase group had higher risk than decline/stable group (OR = 1.91, 95% CI: 1.13–3.23). Results were consistent in continuous FI and most sensitivity analyses. However, after excluding hypertension and cardiovascular disease from the FI, the associations were attenuated and no longer statistically significant. These findings indicate that higher baseline ePWV and increases in ePWV over follow-up were associated with an increased risk of incident frailty, although part of this association may be related to the cardiovascular components within the FI. ePWV may serve as a useful indicator for identifying individuals at elevated risk of frailty.

Aims/hypothesis The relationship between the progression of arterial stiffness and the risk of chronic kidney disease (CKD) remains unclear. This study aimed to evaluate the time-dependent association between the progression of arterial stiffness and the risk of CKD. Methods We followed 10,567 individuals in the Kailuan Study, who were free of CKD and CVD at baseline. Arterial stiffness was repeatedly measured by brachial–ankle pulse wave velocity (baPWV) from baseline to the subsequent follow-ups. Time-dependent Cox models were used to estimate the association between progression of arterial stiffness (△baPWV/years) and incident CKD, defined as an eGFR below 60 ml/min per 1.73 m² and/or the presence of albuminuria. Results During a mean follow-up of 5.32 years, 1108 participants developed CKD. Lower quintiles in baPWV at baseline and the progression of baPWV over time were associated with a lower risk of CKD in a dose-dependent manner (p-trend C statistic from 0.690 to 0.709, p<0.001). Conclusions/interpretation In this cohort study, improvement in arterial stiffness, as indicated by a consistently low or decreased baPWV, might be associated with a lower risk of CKD. These findings underscore the potential importance of coordinated actions targeting cardiovascular health to improve kidney health in the general population. Graphical Abstract

Environmental metal mixtures can cause combined neurotoxicity, but the underlying mechanism remains unclear. Mitochondria are crucial for energy metabolism in the nervous system, and their dysfunction leads to neurodegeneration. Zinc (Zn) is a coenzyme of many mitochondrial enzymes that controls mitochondrial function. This study investigated the role of Zn in the neurotoxicity induced by Mn + Pb and Pb + As mixtures. Zn supplementation improved the survival rate and learning ability of Caenorhabditis elegans following their exposure to mixtures of Mn + Pb and Pb + As by enhancing their mitochondrial morphology, membrane potential, and respiratory chain. Similarly, in HT22 cells, Zn mitigated the decrease in cellular activity and increase in apoptosis induced by the Mn + Pb and Pb + As mixtures by improving mitochondrial morphology and function. Mechanistically, Zn activated the PINK1 and MFN-2/OPA-1 pathways, promoting mitophagy and mitochondrial fusion. However, inhibition of mitophagy reversed the protective effect of Zn, indicating its reliance on mitophagy for neuroprotection. Our study demonstrated that Zn alleviates the combined neurotoxicity of Mn + Pb and Pb + As mixtures by enhancing mitophagy and mitochondrial fusion, suggesting that Zn supplementation is a potential treatment for metal-induced neurotoxicity. Graphical Abstract

Background: In 2009, a workplace‐based hypertension management program was launched among men with hypertension in the Kailuan study. This program involved monitoring blood pressure semimonthly, providing free antihypertensive medications, and offering personalized health consultations. However, the cost‐effectiveness of this program remains unclear. Methods and Results: This analysis included 12 240 participants, with 6120 in each of the management and control groups. Using a microsimulation model derived from 10‐year follow‐up data, we estimated costs, quality‐adjusted life years (QALYs), life‐years, and incremental cost‐effectiveness ratios (ICERs) for workplace‐based management compared with routine care in both the study period and over a lifetime. Analyses are conducted from the societal perspective. Over the 10‐year follow‐up, patients in the management group experienced an average gain of 0.06 QALYs with associated incremental costs of $633.17 (4366.85 RMB). Projecting over a lifetime, the management group was estimated to increase by 0.88 QALYs or 0.92 life‐years compared with the control group, with an incremental cost of $1638.64 (11 301.37 RMB). This results in an incremental cost‐effectiveness ratio of $1855.47 per QALY gained and $1780.27 per life‐year gained, respectively, when comparing workplace‐based management with routine care. In probabilistic sensitivity analyses, with a threshold willingness‐to‐pay of $30 765 per QALY (3 times 2019 gross domestic product per capita), the management group showed a 100% likelihood of being cost‐effective in 10 000 samples. Conclusions: Workplace‐based management, compared with routine care for Chinese men with hypertension, could be cost‐effective both during the study period and over a lifetime, and might be considered in working populations in China and elsewhere.

The definition of hypertension has been a hot topic of debate over the last few years. In 2017, the American College of Cardiology/American Heart Association (ACC/AHA) published new guidelines for treatment strategies for hypertension and stage 1 hypertension was defined as a systolic/diastolic blood pressure (SBP/DBP) of 130-139 / 80-89 millimetres of mercury (mm Hg) [1]. Conversely, […]

Context: Younger onset of type 2 diabetes (T2D) was associated with higher risks of vascular complications and mortality. Objective: To prospectively assess risk profiles for incident T2D stratified by age at onset. Methods: A total of 471 269 participants free of T2D at baseline were included from the UK Biobank. Approximately 70 clinical, lipid, lipoprotein, inflammatory, and metabolic markers, and genetic risk scores (GRSs) were analyzed. Stratified Cox proportional-hazards regression models were used to estimate hazard ratios (HRs) for T2D with age of diagnosis divided into 4 groups (≤50.0, 50.1-60.0, 60.1-70.0, and >70.0 years). Results: During 11 years of follow-up, 15 805 incident T2D were identified. Among clinical risk factors, obesity had the highest HR at any age, ranging from 13.16 (95% CI, 9.67-17.91) for 50.0 years and younger to 4.13 (3.78-4.51) for older than 70.0 years. Other risks associated with T2D onset at age 50.0 years and younger included dyslipidemia (3.50, 2.91-4.20), hypertension (3.21, 2.71-3.80), cardiovascular disease (2.87, 2.13-3.87), parental history of diabetes (2.42, 2.04-2.86), education lower than college (1.89, 1.57-2.27), physical inactivity (1.73, 1.43-2.10), smoking (1.38, 1.13-1.68), several lipoprotein particles, inflammatory markers, liver enzymes, fatty acids, amino acids, as well as GRS. Associations of most risk factors and biomarkers were markedly attenuated with increasing age at onset (P interaction <.05), and some were not significant for onset at age older than 70.0 years, such as smoking, systolic blood pressure, and apolipoprotein B. Conclusion: Most risk factors or biomarkers had stronger relative risks for T2D at younger ages, which emphasizes the necessity of promoting primary prevention among younger individuals. Moreover, obesity should be prioritized.

Background: Nutrition plays a key role in modulating the likelihood of healthy ageing. In the present study, we aimed to conduct a systematic review to assess the impact of nutrition on healthy ageing in Asia. Methods: The systematic review was registered in the International Prospective Register of Systematic Reviews database (CRD42023408936) and conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The PubMed, Web of Science, and Embase databases were searched up to February 2023 without language restrictions. We included prospective cohort studies that evaluated the associations of intake of a single food or consumption of a single nutrient at midlife; adherence to various dietary patterns at midlife; and improved adherence to dietary patterns from mid- to late life with the likelihood of healthy ageing and its components. Results: Out of 16,373 records, we included 71 papers comprising 24 cohorts from Singapore, China, Japan, and Thailand. The healthy ageing components included cognitive function, physical function, and depression. The majority of studies supported the observation that the likelihood of healthy ageing and its components in late life was positively increased by a higher consumption of healthy foods, such as vegetables, fruits, fish, nuts, legumes, tea, milk, and dairy, at midlife, and also by greater adherence to dietary patterns with high diversity scores or high total antioxidant capacities. Furthermore, improved adherence to healthy dietary patterns from mid- to late life also increased the likelihood of healthy ageing in late life. Conclusion: Consuming healthy foods and adhering to healthy dietary patterns at midlife can promote the likelihood of healthy ageing. Moreover, improving diet quality from mid- to late life can still be beneficial.

Background and aims: Very high levels of high-density lipoprotein cholesterol (HDL-C) have been paradoxically linked to increased mortality risk. The present study aimed to examine associations of HDL-C and varied sizes of the HDL particle (HDL-P) with mortality risk stratified by hypertension. Methods and results: This prospective cohort study included 429 792 participants (244 866 with hypertension and 184 926 without hypertension) from the UK Biobank. During a median follow-up of 12.7 years, 23 993 (9.8%) and 8142 (4.4%) deaths occurred among individuals with and without hypertension, respectively. A U-shaped association of HDL-C with all-cause mortality was observed in individuals with hypertension after multivariable adjustment, whereas an L-shape was observed in individuals without hypertension. Compared with individuals with normal HDL-C of 50–70 mg/dL, those with very high HDL-C levels (>90 mg/dL) had a significantly higher risk of all-cause mortality among individuals with hypertension (hazard ratio, 1.47; 95% confidence interval, 1.35–1.61), but not among those without hypertension (1.05, 0.91–1.22). As for HDL-P, among individuals with hypertension, a larger size of HDL-P was positively whereas smaller HDL-P was negatively associated with all-cause mortality. After additional adjustment for larger HDL-P in the model, the U-shaped association between HDL-C and mortality risk was altered to an L-shape among individuals with hypertension. Conclusions: The increased risk of mortality associated with very high HDL-C existed only in individuals with hypertension, but not in those without hypertension. Moreover, the increased risk at high HDL-C levels in hypertension was likely driven by larger HDL-P.