Changes in sleep score and leisure-time physical activity, their combination, and all-cause mortality in middle-aged and older Chinese adults: The Dongfeng-Tongji cohort study.

OBJECTIVES: To prospectively investigate the associations of longitudinal changes in sleep score and LTPA and their combination with all-cause mortality. METHODS: Among 12,543 participants (mean age: 66.1 years) from the Dongfeng-Tongji cohort, we calculated sleep score (range, 0-4, integrating bedtime, sleep duration, sleep quality, and midday napping, higher score indicating healthier sleep) and LTPA at baseline (2008-2010) and the first follow-up (2013) surveys and their 5-year changes (defining stable sleep score as no change and stable LTPA as change within 150 min/week). We prospectively documented deaths from the first follow-up survey (2013) through December 31, 2018. RESULTS: During a mean 5.5-year follow-up, 792 deaths occurred. The 5-year changes in sleep score and LTPA were inversely associated with all-cause mortality risk, regardless of their initial values. When assessing 5-year changes in sleep score and LTPA jointly, compared with the stable sleep score-stable LTPA group, the decreased sleep score-decreased LTPA group had a 40 % (5-85 %) higher all-cause mortality risk, whereas the increased sleep score-increased LTPA group had a 34 % (9-52 %) lower risk. The direction of the joint association was mainly driven by sleep score change. Participants maintaining sleep scores ≥ 3 and LTPA ≥ 150 min/week over 5 years had a 44 % (28-56 %) lower all-cause mortality risk. CONCLUSIONS: Promoting sleep hygiene and LTPA together may benefit efforts in reducing mortality risk, with particular attention to monitoring long-term sleep health.

Changes in Sleep Patterns, Genetic Susceptibility, and Incident Cardiovascular Disease in China.

Importance: The associations of changes in sleep patterns with incident cardiovascular disease (CVD) are not fully elucidated, and whether these associations are modified by genetic susceptibility remains unknown. Objectives: To investigate the associations of 5-year changes in sleep patterns with incident CVD and whether genetic susceptibility modifies these associations. Design, Setting, and Participants: This prospective cohort study of the Dongfeng-Tongji cohort was conducted from 2008 to 2018 in China. Eligible participants included those with complete sleep information at baseline survey (2008-2010) and the first follow-up survey (2013); participants who had no CVD or cancer in 2013 were prospectively assessed until 2018. Statistical analysis was performed in November 2023. Exposures: Five-year changes in sleep patterns (determined by bedtime, sleep duration, sleep quality, and midday napping) between 2008 and 2013, and polygenic risk scores (PRS) for coronary heart disease (CHD) and stroke. Main Outcomes and Measures: Incident CVD, CHD, and stroke were identified from 2013 to 2018. Cox proportional hazards regression models were applied to estimate hazard ratios (HRs) and 95% CIs. Results: Among 15 306 individuals (mean [SD] age, 65.8 [7.4] years; 8858 [57.9%] female and 6448 male [42.1%]), 5474 (35.78%) had persistent unfavorable sleep patterns and 3946 (25.8%) had persistent favorable sleep patterns. A total of 3669 incident CVD cases were documented, including 2986 CHD cases and 683 stroke cases, over a mean (SD) follow-up of 4.9 (1.5) years. Compared with those with persistent unfavorable sleep patterns, individuals with persistent favorable sleep patterns over 5 years had lower risks of incident CVD (HR, 0.80; 95% CI, 0.73-0.87), CHD (HR, 0.84; 95% CI, 0.76-0.92), and stroke (HR, 0.66; 95% CI, 0.54-0.82) in the subsequent 5-year period. No significant effect modification by PRS was observed for sleep pattern change and CHD or stroke risk. However, sleep pattern changes and PRS were jointly associated with the CHD and stroke risk in a dose-dependent manner, with the lowest risk being among those with persistent favorable sleep patterns combined with low PRS (HR for CHD, 0.65; 95% CI, 0.52-0.82 and HR for stroke, 0.48; 95% CI, 0.29-0.79). Conclusions and Relevance: In this cohort study of middle-aged and older Chinese adults, individuals with persistent favorable sleep patterns had a lower CVD risk, even among those with higher genetic risk. These findings highlight the importance of maintaining favorable sleep patterns for CVD prevention.

Global, regional, and national burden of stroke attributable to extreme low temperatures, 1990-2019: A global analysis.

BACKGROUND: Extreme ambient temperatures have been linked to increased risks of stroke morbidity and mortality. However, global estimates of the burden of stroke due to extreme low temperatures are not well-defined. AIMS: This study aimed to determine the global burden of stroke due to extreme low temperatures and its spatiotemporal trend from 1990 to 2019. METHODS: Based on the Global Burden of Disease Study 2019, we obtained global, regional, and national data on deaths, disability-adjusted life years (DALYs), age-standardized mortality rate (ASMR), and age-standardized rate of DALYs (ASDR) of stroke attributed to extreme low temperatures, further stratified by age, sex, and sociodemographic index (SDI). RESULTS: Globally, in 2019, an estimated 474,000 stroke deaths with the corresponding ASMR (6.2 (95% uncertainty interval (UI): 4.6-7.9)) and ASDR (103.9 (95% UI: 77.0-134.5)) per 100,000 population, were attributable to extreme low temperatures. The most significant burden was observed in Central Asia, followed by Eastern Europe and East Asia. From 1990 to 2019, the global burden of stroke and its subtypes (ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage) attributable to extreme low temperatures exhibited a decrease in both ASMR and ASDR. Significant decreases in stroke burden occurred in the high-SDI regions, high-income Asia Pacific, and subarachnoid hemorrhage cases. Moreover, the ASMR and ASDR increased with age and were higher in males than females. CONCLUSION: The global stroke burden due to extreme low temperatures remains high despite a decreasing trend over the past three decades. The stroke burden due to extreme low temperatures was more notable for Central Asia, older people, and the male sex.

Bedtime, sleep pattern, and incident cardiovascular disease in middle-aged and older Chinese adults: The dongfeng-tongji cohort study.

OBJECTIVES: To investigate the associations of bedtime and a low-risk sleep pattern with incident cardiovascular disease (CVD). METHODS: A total of 31,500 retirees were included from the Dongfeng-Tongji cohort in 2008-2010 and 2013. Sleep information was collected by questionnaires. CVD events were identified through the health care system until December 31, 2018. Cox proportional hazards regression models were performed to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: During an average follow-up of 7.2 years, 8324 cases of incident CVD, including 6557 coronary heart disease (CHD) and 1767 stroke, were documented. U-shaped associations of bedtime with the risks of incident CVD and stroke were observed. Compared with bedtime between 10:01 p.m.-11:00 p.m., the HR (95% CI) for CVD was 1.10 (1.01-1.20) for ≤9:00 p.m., 1.07 (1.01-1.13) for 9:01 p.m.-10:00 p.m., and 1.32 (1.11-1.58) for >12:00 a.m., respectively, mainly driven by stroke risk (22%, 14%, and 70% higher for ≤9:00 p.m., 9:01 p.m.-10:00 p.m., and >12:00 a.m., respectively). The number of low-risk sleep factors, namely bedtime between 10:01 p.m.-12:00 a.m., sleep duration of 7-< 8 h/night, good/fair sleep quality, and midday napping ≤60 min, exhibited dose-dependent relationships with CVD, CHD, and stroke risks. Participants with 4 low-risk sleep factors had a respective 24%, 21%, and 30% lower risk of CVD, CHD, and stroke than those with 0-1 low-risk sleep factor. CONCLUSIONS: Individuals with early or late bedtimes had a higher CVD risk, especially stroke. Having low-risk sleep habits is associated with lower CVD risks.

Bedtime, sleep duration, and sleep quality and all-cause mortality in middle-aged and older Chinese adults: The Dongfeng-Tongji cohort study.

OBJECTIVE: This study aims to investigate the associations of bedtime and its combination with sleep duration and sleep quality with all-cause mortality. METHODS: We conducted a prospective cohort study using data collected from 2008 to 2018 in the Dongfeng-Tongji cohort. Among 40,097 participants aged 62.1 on average at baseline, we applied Cox regression models to assess hazard ratios and 95% confidence intervals for mortality risk. RESULTS: During a mean follow-up of 8.2years, 4345 deaths were documented. U-shaped associations of bedtime and sleep duration with all-cause mortality were observed. Compared with bedtime between 10:01 PM and 11:00 PM, the hazard ratio (95% confidence interval) for all-cause mortality was 1.34 (1.20-1.49) for ≤9:00 PM, 1.18 (1.09-1.27) for 9:01-10:00 PM, and 1.50 (1.13-2.00) for >12:00 AM, respectively. Participants with sleep duration of <6, 6-<7, 8-<9, and ≥9 h/night had a respective 39%, 21%, 11%, and 25% higher all-cause mortality risk than those sleeping 7-<8 h/night. Additionally, participants with a healthy sleep score of 3, characterized as proper bedtime (10:01 PM-12:00 AM), moderate sleep duration (7-<8h/night), and good/fair sleep quality, had a significantly 36% (hazard ratio, 0.64; 95% confidence interval, 0.56-0.74) lower all-cause mortality risk than those with a score of 0. CONCLUSIONS: Individuals with early or late bedtimes and short or long sleep duration were at higher all-cause mortality risks. Having healthy sleep habits may significantly reduce death risk.

Residential greenness alleviated the adverse associations of long-term exposure to ambient PM1 with cardiac conduction abnormalities in rural adults.

BACKGROUND: Ambient air pollution was linked to elevated risks of adverse cardiovascular events, and alterations in electrophysiological properties of the heart might be potential pathways. However, there is still lacking research exploring the associations between PM1 exposure and cardiac conduction parameters. Additionally, the interactive effects of PM1 and residential greenness on cardiac conduction parameters in resource-limited areas remain unknown. METHODS: A total of 27483 individuals were enrolled from the Henan Rural Cohort study. Cardiac conduction parameters were tested by 12-lead electrocardiograms. Concentrations of PM1 were evaluated by satellite-based spatiotemporal models. Levels of residential greenness were assessed using Enhanced Vegetation Index (EVI) and Normalized difference vegetation index (NDVI). Logistic regression models and restricted cubic splines were fitted to explore the associations of PM1 and residential greenness exposure with cardiac conduction abnormalities risk, and the interaction plot method was performed to visualize their interaction effects. RESULTS: The 3-year median concentration of PM1 was 56.47 (2.55) µg/m3, the adjusted odds rate (ORs) and 95% confidence intervals (CIs) for abnormal HR, PR, QRS, and QTc interval risk in response to 1 µg/m3 increase in PM1 were 1.064 (1.044, 1.085), 1.037 (1.002, 1.074), 1.061 (1.044, 1.077) and 1.046 (1.028, 1.065), respectively. Participants exposure to higher levels of PM1 had increased risks of abnormal HR (OR = 1.221, 95%CI: 1.144, 1.303), PR (OR = 1.061, 95%CI: 0.940, 1.196), QRS (OR = 1.225, 95%CI: 1.161, 1.294) and QTc interval (OR = 1.193, 95%CI: 1.121, 1.271) compared with lower levels of PM1. Negative interactive effects of exposure to PM1 and residential greenness on abnormal HR, QRS, and QTc intervals were observed (Pfor interaction < 0.05). CONCLUSION: Long-term PM1 exposure was associated with elevated cardiac conduction abnormalities risks, and this adverse association might be mitigated by residential greenness to some extent. These findings emphasize that controlling PM1 pollution and increasing greenness levels might be effective strategies to reduce cardiovascular disease burdens in resource-limited areas.

Effect of prior anticoagulation therapy on stroke severity and in-hospital outcomes in patients with acute ischemic stroke and atrial fibrillation.

BACKGROUND: We aimed to assess the prevalence of prior anticoagulation therapy (warfarin or non-vitamin K antagonist oral anticoagulants [NOACs]) among patients with acute ischemic stroke (AIS) and atrial fibrillation (AF) in China and investigate the associations between prior anticoagulation therapy and initial stroke severity and in-hospital outcomes. METHODS: We included consecutive patients with AIS and known history of AF admitted to hospitals in the China Stroke Center Alliance (CSCA) program from January 2019 to July 2019. Multivariate logistic regression analyses were performed to determine the associations between prior anticoagulation therapy and initial stroke severity and in-hospital outcomes. RESULTS: Of 7181 patients (median [IQR] age, 75.0 [68.0-81.0] years; 48.7% men), 700 (9.7%), 129 (1.8%), and 255 (3.6%) patients received prior subtherapeutic warfarin (international normalized ratio [INR] <2.0), therapeutic warfarin (INR ≥2.0), and NOACs therapy, respectively. A total of 6499 patients had a preadmission CHA2DS2-VASc score ≥ 2, among whom 94.6% were not adequately anticoagulated. Compared with no prior anticoagulation therapy, prior NOACs therapy was associated with reduced risk of moderate or severe stroke at admission (odds ratio [95% CI], 0.64 [0.43-0.94], P = 0.023) and in-hospital mortality or discharge against medical advice (DAMA) (0.46 [0.24-0.86], P = 0.015). However, no significant association was observed between prior therapeutic warfarin therapy and stroke severity or in-hospital mortality or DAMA. CONCLUSIONS: Among patients with AIS and AF in China, the proportion of patients with inadequate anticoagulation prior to stroke remained substantially high. Prior NOACs therapy was associated with reduced stroke severity and less in-hospital mortality or DAMA.

Efficient thin-film perovskite solar cells from a two-step sintering of nanocrystals.

Creating semiconductor thin films from sintering of colloidal nanocrystals (NCs) represents a very important technology for high throughput and low cost thin-film photovoltaics. Here we report the creation of all-inorganic cesium lead bromide (CsPbBr3) polycrystalline films with grain size exceeding 1 µm from the bottom up by sintering of CsPbBr3 NCs terminated with short and low-boiling-point alky ligands that are ideal for use in sintered photovoltaics. The grain growth behavior during the sintering process was carefully investigated and correlated to the solar cell performance. To achieve precise control over the microstructural development we propose a facile two-step sintering process involving the grain growth via coarsening at a relative low temperature followed by densification at a high temperature. Compared with the one-step sintering, the two-step process yields a more uniform CsPbBr3 bulk film with larger grain size, higher density and lower trap density. Consequently, the photovoltaic device based on the two-step sintering process demonstrates a significant enhancement of efficiency with reduced hysteresis that approaches the best reported CsPbBr3 solar cells using a similar configuration. Our study specifies a rarely addressed perspective concerning the sintering mechanism of perovskite NCs and should contribute to the development of high-performance bulk perovskite devices based on the building blocks of perovskite NCs.

Sleep Duration, Midday Napping, and Serum Homocysteine Levels: A Gene-Environment Interaction Study.

The associations of sleep duration and midday napping with homocysteine (Hcy) levels, and whether these sleep behaviors modify the association between genetic predisposition and Hcy levels, has yet to be investigated. We included 19,426 participants without severe health conditions at baseline from the Dongfeng−Tongji cohort. In a subgroup of 15,126 participants with genetic data, a genetic risk score (GRS) based on 18 Hcy-related loci was constructed to test the gene−sleep interactions in Hcy. Hcy levels were higher in subjects with a long sleep duration (≥9 h) and midday napping (>90 min), as compared to those who reported a moderate sleep duration (7 to <8 h) and midday napping (1−30 min) (all p values < 0.05). A long sleep duration and midday napping showed a joint effect in increasing Hcy (p for trend < 0.001). Significant interactions regarding Hcy levels were observed for a long sleep duration with GRS and MTHFR rs1801133, and long midday napping with DPEP1 rs12921383 (all p values for interaction < 0.05). Overall findings indicated that a long sleep duration and midday napping were associated with elevated serum Hcy levels, independently and jointly, and amplified the genetic susceptibility to higher Hcy.

Elevated Levels of Serum Alkaline Phosphatase are Associated with Increased Risk of Cardiovascular Disease: A Prospective Cohort Study.

AIM: We aimed to investigate the associations of serum alkaline phosphatase (ALP) levels with incident cardiovascular disease (CVD), coronary heart disease (CHD), and stroke, as well as their subtypes, among men and women in a prospective cohort study. METHODS: A total of 11,408 men and 14,981 women were included to evaluate the associations between ALP levels and incident CVD. Participants were divided into four groups according to the quartiles of serum ALP levels in men and women separately. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: During an average follow-up of 7.3 years, 7,015 incident CVDs (5,561 CHDs and 1,454 strokes) were documented. After adjustments for age, body mass index, smoking status, drinking status, diabetes, hyperlipidemia, hypertension, physical activity, aspirin usage, anticoagulants usage, menopausal status (women only), family history of CVD, estimated glomerular filtration rate, white blood cell counts, and admission batch and comparing the lowest quartile of ALP, the adjusted HRs (95% CIs) of participants in the highest quartile were 1.22 (1.11-1.34) for CVD, 1.14 (1.02-1.28) for CHD, 1.43 (1.18-1.73) for stroke, 1.31 (1.09-1.57) for acute coronary syndrome (ACS), 1.37 (1.11-1.70) for ischemic stroke, and 1.75 (1.10-2.79) for hemorrhagic stroke in men and 1.12 (1.01-1.23) for CVD, 1.10 (0.99-1.23) for CHD, 1.18 (0.92-1.51) for stroke, 1.23 (1.03-1.47) for ACS, 1.10 (0.83-1.45) for ischemic stroke, and 1.54 (0.90-2.65) for hemorrhagic stroke in women. The ALP-CVD associations remained significant even within the normal ranges of ALP levels (40-150 U/L). Moreover, linear dose-response relationships were found between ALP levels and incident CVD. CONCLUSIONS: Higher ALP levels, even within the normal range, were significantly associated with increased risks of CVD, in a dose-dependent manner. These findings suggested that regular monitoring of ALP levels may help in improving the early identification of the population at higher CVD risk.

Distribution of risk factors differs from coronary heart disease and stroke in China: a national population survey.

OBJECTIVES: This study aimed to explore the distribution differences of common risk factors between coronary heart disease (CHD) and stroke in China. SETTING: The China National Stroke Screening Survey is a cluster sampling survey based on a nationwide general community population, adopting multistage stratified sampling method and covering all 31 provinces in China mainland. PARTICIPANTS: A total number of 725 707 people aged 40 years and above were included in the study. PRIMARY AND SECONDARY OUTCOME MEASURES: The basic demographic information, lifestyle behaviour, physical examination, traditional risk factors, family history of cardiovascular disease (CVD) and CVD events were collected. Risk factors of CHD and stroke were explored and analysed in the whole investigated population to identify the common risk factors. Multivariate logistic regression analysis was used to analyse the distribution difference of risk factors between CHD and stroke. RESULTS: There were 13 variables associated with CHD and stroke, in which 11 variables revealed differences in the distribution between CHD and stroke. Family history of stroke (OR: 2.30; 95% CI 2.15 to 2.45), men (OR: 1.92; 95% CI 1.80 to 2.05), rural areas (OR: 1.70; 95% CI 1.60 to 1.80), transient ischaemic attack (OR: 1.41; 95% CI 1.30 to 1.54) and hypertension (OR: 1.28; 95% CI 1.19 to 1.38) indicated significantly stronger association with stroke, while family history of CHD (OR: 0.25; 95% CI 0.23 to 0.27), atrial fibrillation (OR: 0.60; 95% CI 0.51 to 0.71), diabetes (OR: 0.76; 95% CI 0.71 to 0.81), dyslipidaemia (OR: 0.76; 95% CI 0.72 to 0.81), smoking (OR: 0.79; 95% CI 0.73 to 0.85) and overweight/obesity (OR: 0.90; 95% CI 0.86 to 0.93) had closer relationship with CHD. CONCLUSIONS: The distribution of risk factors for CHD and stroke were substantial differences. More specific prevention and control measures should be formulated according to the distribution differences of risk factors related to CVD.

Solution-Processed Synaptic Memristors Based on Halide Perovskite Nanocrystals.

Exploring new materials and structures to construct synaptic devices represents a promising route to fundamentally approach novel forms of computing. Nanocrystals (NCs) of halide perovskites possess unique charge transport characteristics, i.e., ionic-electronic coupling, holding considerable promise for energy-efficient and reconfigurable artificial synapses. Herein, we report solution-processed thin-film memristors from all-inorganic CsPbBr3 perovskite NCs, functioning as an electrically programmable analog memory with good stability. The devices are demonstrated to successfully emulate a number of essential synaptic functions with low power consumption, including reversible potentiation and depression, short-term plasticity (STP), paired-pulse facilitation (PPF), and long-term plasticity (LTP), such as spike-number-dependent plasticity (SNDP), spike-rate-dependent plasticity (SRDP), spike-timing-dependent plasticity (STDP), and spike-voltage-dependent plasticity (SVDP). It is proposed that a coupled capacitive and inductive phenomenon originating from charge trapping and ion migration in CsPbBr3 NC films, controlled by the amplitude and timing of the programming pulses, defines the degree of synaptic plasticity. A transition emerges from the fast trap-related capacitive regime to a slow ionic inductive regime, which enables continuous change of the film resistance and the magnitude of the electronic current, analogous to the synaptic weight modulation in biological synapses.

Non-HDL-C/HDL-C ratio is associated with carotid plaque stability in general population: A cross-sectional study.

Background: Carotid atherosclerosis, especially the rupture of unstable plaques, plays an important role in the development of stroke. A novel lipid ratio, the non-high-density lipoprotein cholesterol (non-HDL-C)/high-density lipoprotein cholesterol (HDL-C) ratio, contains both atherogenic and anti-atherogenic particle information, and has been shown to be associated with carotid atherosclerosis. However, there is no data on evaluating the association between non-HDL-C/HDL-C ratio and carotid plaque stability. Methods: This study was carried out on 27,436 urban workers aged 20 years or older who participated in a comprehensive health screening between January 2016 and December 2017. Carotid plaque stability was assessed using ultrasonography. Multinomial logistic regression models were used to explore the relationship between the non-HDL-C/HDL-C ratio and carotid plaque stability by odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup and sensitivity analyses were performed to verify the robustness of the results. Results: Carotid plaque was detected in 7,161 (26.1%) participants, with stable and unstable plaque accounting for 3,277 (11.9%) and 3,884 (14.2%), respectively. The prevalence of stable carotid plaque substantially increased with increasing non-HDL-C/HDL-C ratio quartile levels (p for trend < 0.001) and with a similar association for unstable carotid plaque (p for trend < 0.001). The mean non-HDL-C/HDL-C ratios (mean ± SD) of non-carotid plaque (2.9 ± 1.1), stable carotid plaque (3.2 ± 1.2), and unstable carotid plaque (3.4 ± 1.4) gradually increased (p < 0.001). In multinomial logistic regression, ORs (95% CIs) for the highest vs. lowest quartile of the non-HDL-C/HDL-C ratio were 1.70 (1.48-1.95) between stable carotid plaques and no carotid plaque, 2.34 (2.06-2.67) between unstable carotid plaques and no carotid plaque, and 1.38 (1.18-1.61) between unstable carotid plaques and stable carotid plaque, after adjusting for common cardiovascular risk factors. The results of subgroup analysis and sensitivity analysis were similar. Conclusion: Our findings suggested that the non-HDL-C/HDL-C ratio was significantly associated with carotid plaque stability and might be a useful indicator for the early identification of high-risk carotid plaque.

Analysis of Changes in Weight, Waist Circumference, or Both, and All-Cause Mortality in Chinese Adults.

Importance: Although numerous studies have separately investigated the associations of changes in weight or waist circumference with mortality risk, few studies have examined the associations of concurrent changes in these 2 anthropometric parameters with all-cause mortality. Objective: To assess the associations of changes in body weight, waist circumference, or both, combined with all-cause mortality. Design, Setting, and Participants: This cohort study used data from 2 longitudinal cohort studies in Dongfeng-Tongji and Kailuan, China. Participants included 58 132 adults (aged 40 years and older) with measures of weight and waist circumference at baseline and follow-up visit. Statistical analysis was performed from June 2020 to September 2021. Exposures: Changes in weight and waist circumference between 2 visits (2008-2010 to 2013 in the Dongfeng-Tongji cohort, and 2006-2007 to 2010-2011 in the Kailuan study). Stable weight was defined as change in weight within 2.5 kg between the 2 visits and stable waist circumference was defined as changes within 3.0 cm. Changes were categorized as loss, stable, or gain for weight and waist circumference separately, and created a 9-category variable to represent the joint changes. Main Outcomes and Measures: All-cause mortality from follow-up visit (2013 in Dongfeng-Tongji cohort and 2010-2011 in Kailuan study) until December 31, 2018. Cox proportional hazard regression models were used to estimate the associations with adjustment for potential confounders. Results were obtained in the 2 cohorts separately and pooled via fixed-effect meta-analysis. Results: A total of 10 951 participants in the Dongfeng-Tongji cohort (median [IQR] age, 62 [56-66] years; 4203 [38.4%] men) and 47 181 participants in the Kailuan study (median [IQR] age, 51 [46-58] years; 36 663 [77.7%] men) were included in the analysis. During 426 072 person-years of follow-up, 4028 deaths (523 in the Dongfeng-Tongji cohort and 3505 in the Kailuan study) were documented. When changes in weight and waist circumference were examined separately, U-shape associations were found: both gain and loss in weight (weight loss: pooled hazard ratio [HR], 1.33; 95% CI, 1.23-1.43; weight gain: HR, 1.10; 95% CI, 1.02-1.19) or waist circumference (waist circumference loss: HR, 1.14; 95% CI, 1.05-1.24; waist circumference gain: HR, 1.11; 95% CI, 1.03-1.21) were associated with higher mortality risk compared with stable weight or waist group. When changes in weight and waist circumference were jointly assessed, compared with participants with stable weight and waist circumference (16.9% of the total population [9828 of 58 132] with 508 deaths), participants with different combinations of weight and waist circumference change all had higher mortality risks except for those with stable weight but significant loss in waist. Notably, those who lost weight but gained waist circumference (6.4% of the total population [3698 of 58 132] with 308 deaths) had the highest risk of all-cause mortality (HR, 1.69; 95% CI, 1.46-1.96; absolute rate difference per 100 000 person-years in the Dongfeng-Tongji cohort: 414; 95% CI, 116-819; and in the Kailuan study: 333; 95% CI, 195-492) among the joint subgroups. Conclusions and Relevance: In this cohort study, weight loss with concurrent waist circumference gain was associated with a higher mortality risk in middle-aged and older Chinese adults. This study's findings suggest the importance of evaluating the changes in both body weight and waist circumference when assessing their associations with mortality.

A Lipid Signature with Perturbed Triacylglycerol Co-Regulation, Identified from Targeted Lipidomics, Predicts Risk for Type 2 Diabetes and Mediates the Risk from Adiposity in Two Prospective Cohorts of Chinese Adults.

BACKGROUND: The roles of individual and co-regulated lipid molecular species in the development of type 2 diabetes (T2D) and mediation from metabolic risk factors remain unknown. METHODS: We conducted profiling of 166 plasma lipid species in 2 nested case-control studies within 2 independent cohorts of Chinese adults, the Dongfeng-Tongji and the Jiangsu non-communicable disease cohorts. After 4.61 (0.15) and 7.57 (1.13) years' follow-up, 1039 and 520 eligible participants developed T2D in these 2 cohorts, respectively, and controls were 1:1 matched to cases by age and sex. RESULTS: We found 27 lipid species, including 10 novel ones, consistently associated with T2D risk in the 2 cohorts. Differential correlation network analysis revealed significant correlations of triacylglycerol (TAG) 50:3, containing at least one oleyl chain, with 6 TAGs, at least 3 of which contain the palmitoyl chain, all downregulated within cases relative to controls among the 27 lipids in both cohorts, while the networks also both identified the oleyl chain-containing TAG 50:3 as the central hub. We further found that 13 of the 27 lipids consistently mediated the association between adiposity indicators (body mass index, waist circumference, and waist-to-height ratio) and diabetes risk in both cohorts (all P < 0.05; proportion mediated: 20.00%, 17.70%, and 17.71%, and 32.50%, 28.73%, and 33.86%, respectively). CONCLUSIONS: Our findings suggested notable perturbed co-regulation, inferred from differential correlation networks, between oleyl chain- and palmitoyl chain-containing TAGs before diabetes onset, with the oleyl chain-containing TAG 50:3 at the center, and provided novel etiological insight regarding lipid dysregulation in the progression from adiposity to overt T2D.

Triglyceride-Glucose Index Is Related to Carotid Plaque and Its Stability in Nondiabetic Adults: A Cross-Sectional Study.

Background: Carotid plaque plays an important role in the development of stroke. The triglyceride-glucose (TyG) index is a reliable alternative marker of insulin resistance. However, there are limited data regarding the relationship between TyG index and carotid plaque and its stability in nondiabetic adults. Methods: This study was carried out on 24,895 urban workers (10,978 men and 13,917 women) aged 20 years or older who participated in a comprehensive health screening between January 2016 and December 2017 at the First Affiliated Hospital of Zhengzhou University, China. Carotid plaque was assessed using ultrasonography. TyG index was calculated as ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL) /2]. Logistic regression models and restricted cubic spline (RCS) models were used to estimate the association of the TyG index with carotid plaque and its stability by odds ratios (ORs) and 95% confidence intervals (CIs). Results: Carotid plaque was detected in 5,668 (22.8%) respondents, with stable and unstable plaque accounting for 2,511 (10.1%) and 3,158 (12.7%), respectively. There was a significant positive association between the prevalence of carotid plaque and TyG index quartile levels, and the same associations were observed for the prevalence of stable and unstable carotid plaque (P for trend <0.0001). The multivariable-adjusted ORs (95% CIs) for the highest vs. lowest quartile of TyG index were 1.30 (1.15-1.47) for carotid plaque, 1.38 (1.17-1.63) for stable carotid plaque, and 1.24 (1.07-1.43) for unstable carotid plaque. The RCS analysis showed a linear association between TyG index and carotid plaque, and linear associations were also observed between TyG index and both stable carotid plaque and unstable carotid plaque (P for linearity<0.05). Conclusion: Our findings suggested that the TyG index was significantly associated with carotid plaque and might be a useful indicator for the early identification of carotid plaque in nondiabetic subjects.

Associations of Baseline and Changes in Leukocyte Counts with Incident Cardiovascular Events: The Dongfeng-Tongji Cohort Study.

AIM: The aim of the present study was to investigate the associations of baseline and longitudinal changes in leukocyte counts with incident cardiovascular disease (CVD). METHODS: We conducted a prospective study to investigate the associations of baseline and 5-year changes in leukocyte counts with incident CVD and its subtypes in middle-aged and elderly Chinese. We estimated the hazard ratios (HRs) and 95% confidence intervals (CIs) for CVD using the Cox proportional-hazards models. RESULTS: In the analyses of baseline total leukocyte count of 26,655 participants, compared with the lowest quartile (＜4.71×109/L), participants in the fourth quartile (＞6.70×109/L) had 11% higher risk for CVD. Consistent with total leukocyte count, neutrophil count also exhibited a significant positive association with the risk of CVD. In the analyses of 5-year changes in total leukocyte count of 11,594 participants, the changes in leukocyte count were categorized into three groups, i.e., the decreased group (＜25%), stable group (25%-75%), and increased group (＞75%). Compared with participants in the stable group (-1.18 to 0.44×109/L), participants in the increased group (＞0.44×109/L) had 14% higher risk for CVD. We also observed significant positive associations of the changes in neutrophil and monocyte counts with the risk of CVD. Furthermore, the total leukocyte count in the second or third tertile at the first follow-up with a 5-year increase was related to higher CVD risk. CONCLUSION: High baseline total leukocyte count and a 5-year increase in total leukocyte count were related to higher CVD risk.

Hearing loss is associated with increased risk of incident stroke but not coronary heart disease among middle-aged and older Chinese adults: the Dongfeng-Tongji cohort study.

Hearing loss has been associated with increased risk of cardiovascular disease (CVD) prevalence in cross-sectional studies. However, little is known about the prospective association between hearing loss and CVD incidence. We aimed to examine the associations of hearing loss with risk of incident CVD, coronary heart disease (CHD), and stroke in a Chinese population. We included 13,880 individuals aged 63.3 years from the Dongfeng-Tongji cohort study (2013-2018). Hearing loss was categorized into normal, mild, moderate, severe, or greater by the pure-tone average of thresholds at speech and high frequency in both ears. Cox proportional hazard models and linear regression models were used for multivariate longitudinal analyses. After multivariate adjustments, we observed suggestive dose-response associations of increased high-frequency hearing loss with elevated risk of CVD and stroke incidence. Compared with normal hearing loss at high frequency, those with moderate and severe or greater hearing loss had a 4% (95% CI: 0.92, 1.18) or 13% (95% CI: 0.98, 1.30) higher risk of CVD and 52% (95% CI: 1.06, 2.17) or 51% (95% CI: 1.03, 2.20) higher risk of stroke, while the associations were almost consistent across most subgroups. No significant associations were observed for CHD and high-frequency hearing loss, as well as CVD and speech-frequency hearing loss. In addition, higher high-frequency hearing loss was related to unfavorably altered lipid profiles and fasting glucose. Our data suggested that increased hearing loss might increase the risk of incident CVD and stroke among middle-aged and older Chinese, which was partially explained by altered CVD-related biomarkers.

Alternations in the gut microbiota and metabolome with newly diagnosed unstable angina.

Gut microbiota plays an important role in coronary heart disease, but its compositional and functional changes in unstable angina (UA) remain unexplored. We performed metagenomic sequencing of 133 newly diagnosed UA patients and 133 sex- and age-matched controls, and profiled the fecal and plasma metabolomes in 30 case-control pairs. The alpha diversity of gut microbiota was increased in UA patients: the adjusted odds ratios (ORs) per standard deviation increase in Shannon and Simpson indices were 1.30 (95% confidence interval, 1.01-1.70) and 1.36 (1.05-1.81), respectively. Two common species (depleted Klebsiella pneumoniae and enriched Streptococcus parasanguinis; P ≤ 0.002) and three rare species (depleted Weissella confusa, enriched Granulicatella adiacens and Erysipelotrichaceae bacterium 6_1_45; P ≤ 0.005) were associated with UA. The UA-associated gut microbiota was depleted in the pathway of L-phenylalanine degradation (P = 0.001), primarily contributed by Klebsiella pneumoniae. Consistently, we found increased circulating phenylalanine in UA patients (OR = 2.76 [1.17-8.16]). Moreover, Streptococcusparasanguinis was negatively correlated with fecal citrulline (Spearman's rs = -0.470, P = 0.009), a metabolite depleted in UA patients (OR = 0.26 [0.08-0.63]). These findings are informative to help understand the metabolic connection between gut microbiota and UA.

Multiple plasma metals, genetic risk and serum complement C3, C4: A gene-metal interaction study.

Exposure to metals and metalloids is widely related with human health, and could affect the function of immune system. The complement system links innate and adaptive immunity, and is critically involved in the pathogenesis of inflammatory and immune diseases. The third and fourth components of complement (C3, C4) play key roles in the complement system. However, few studies have examined the relations between multiple metals and complement levels. In this study, based on a total of 2977 participants from the Dongfeng-Tongji cohort, China, we investigated 17 plasma metals and serum C3, C4 levels, and calculated C3/C4-associated genetic risk scores (GRSs) using established single nucleotide polymorphisms. We further explored the potential gene-metal interactions on C3 and C4. After multivariable adjustment, an increment of 10-standard deviation increase in natural log-transformed exposure concentrations of plasma copper was associated with 0.549 (0.489, 0.608) (FDR <0.0001), and 1.146 (0.999, 1.294) (FDR <0.0001) higher natural log-transformed serum C3 and C4 levels, respectively. While each increment of 10-standard deviation of natural log-transformed zinc was associated with a difference of 0.083 (0.024, 0.143) (FDR = 0.049) and 0.007 (-0.138, 0.152) (FDR = 0.935) in log-transformed C3 and C4 levels, respectively. Participants with higher GRS had higher C3 and C4 levels. Furthermore, we found a significant interaction between arsenic exposure and C3-GRS in relation to C3 level (Pinteraction = 0.0096). Our results suggested that plasma arsenic would modify the association between C3 genetic predisposition and serum C3 level. We provide new insight into metals exposure on the human immune system. These findings require replication in future research.