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.

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.

Association of Complement C3 With Incident Type 2 Diabetes and the Mediating Role of BMI: A 10-Year Follow-Up Study.

CONTEXT: Impairment of immune and inflammatory homeostasis is reported to be one of the causal factors of diabetes. However, the association of complement C3 levels with incident diabetes in humans remains unclear. OBJECTIVE: This study aimed to examine the association between C3 levels and incident type 2 diabetes mellitus (T2DM), and further explore the potential mediating role of body mass index (BMI) in C3-T2DM associations. METHODS: We determined serum C3 levels of 2662 nondiabetic middle-aged and elderly (64.62 ± 7.25 years) individuals from the Dongfeng-Tongji cohort at baseline. Cox regression was employed to examine the incidence of T2DM in relationship to C3 levels during 10 years of follow-up. Mediation analysis was further applied to assess potential effect of BMI on the C3-T2DM associations. RESULTS: Overall, 711 (26.7%) participants developed T2DM during 23 067 person-years of follow-up. Higher serum C3 was significantly associated with higher risk of incident T2DM after full adjustment (HR [95% CI] = 1.16 [1.05, 1.27]; per SD higher). Compared with the first quartile of C3 levels, the HR in the fourth quartile was 1.52 (95% CI = [1.14, 2.02]; Ptrend = 0.029). Robust significant linear dose-response relationship was observed between C3 levels and BMI (Poverall < 0.001, Pnonlinear = 0.96). Mediation analyses indicated that BMI might mediate 41.0% of the associations between C3 and T2DM. CONCLUSION: The present prospective study revealed that C3 could be an early biomarker for incident T2DM, and that BMI might play a potential mediating role in the C3-T2DM associations, which provided clues for the pathogenesis of diabetes.

Polycyclic aromatic hydrocarbons exposure and plasma lncRNA signature: A profile and functional analysis.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants that pose detrimental effects on human health, and the exploration of the associations of PAHs exposure with long non-coding RNA (lncRNA) may provide novel clues to the underlying mechanisms. In the present study, we detected 10 urinary PAHs metabolites by GC-MS and plasma lncRNAs levels by Human LncRNA Array v4 among 230 participants from two panels (160 in the Shiyan panel and 70 in the Wuhan-Zhuhai panel). We applied linear regression models to assess the associations between PAHs metabolites and lncRNAs separately in each panel and combined the results using fixed-effect meta-analysis. To explore the potential origin of PAHs-related lncRNAs in plasma, we estimated their tissue-specificity and associations between lncRNAs levels in plasma and leukocytes. Leukocytes mRNA sequencing data and RNA binding proteins were utilized to explore implicated pathways of identified lncRNAs. We found that urinary 1-hydroxyphenanthrene (1-OH-Phe) was inversely associated with 8 lncRNAs and positively associated with 1 lncRNA, as well as 9-hydroxyphenanthrene (9-OH-Phe) was inversely associated with 11 lncRNAs (FDR < 0.1). Tissue specificity analysis using Genome Tissue Expression database suggested that several identified lncRNAs might specifically express in organs targeted by PAHs exposure (lung, liver, heart, kidney, and brain). Besides, plasma levels of 1-OH-Phe related ENSG00000260616 and 9-OH-Phe related STARD4-AS1 were inversely associated with their intra-leukocytes levels (P value < 0.05). Notably, STARD4-AS1 was positively associated with the expression levels of its neighboring protein-coding gene (CAMK4 and STARD4) in leukocytes and were involved in pathways related to cellular response to DNA damage, which we further confirmed using DNA damage biomarker, 8-hydroxydeoxyguanosine. Functional analysis also revealed vital pathways related to cytokine-mediated signaling and glucose homeostasis. Our findings provided novel insights into plausible biological mechanisms underlying the adverse effects of PAHs exposure.

Neutralization against SARS-CoV-2 Delta/Omicron variants and B cell response after inactivated vaccination among COVID-19 convalescents.

Emerging SARS-CoV-2 variants have made COVID-19 convalescents susceptible to re-infection and have raised concern about the efficacy of inactivated vaccination in neutralization against emerging variants and antigen-specific B cell response. To this end, a study on a long-term cohort of 208 participants who have recovered from COVID-19 was conducted, and the participants were followed up at 3.3 (Visit 1), 9.2 (Visit 2), and 18.5 (Visit 3) months after SARS-CoV-2 infection. They were classified into three groups (no-vaccination (n = 54), one-dose (n = 62), and two-dose (n = 92) groups) on the basis of the administration of inactivated vaccination. The neutralizing antibody (NAb) titers against the wild-type virus continued to decrease in the no-vaccination group, but they rose significantly in the one-dose and two-dose groups, with the highest NAb titers being observed in the two-dose group at Visit 3. The NAb titers against the Delta variant for the no-vaccination, one-dose, and two-dose groups decreased by 3.3, 1.9, and 2.3 folds relative to the wild-type virus, respectively, and those against the Omicron variant decreased by 7.0, 4.0, and 3.8 folds, respectively. Similarly, the responses of SARS-CoV-2 RBD-specific B cells and memory B cells were boosted by the second vaccine dose. Results showed that the convalescents benefited from the administration of the inactivated vaccine (one or two doses), which enhanced neutralization against highly mutated SARS-CoV-2 variants and memory B cell responses. Two doses of inactivated vaccine among COVID-19 convalescents are therefore recommended for the prevention of the COVID-19 pandemic, and vaccination guidelines and policies need to be updated.

Long-term outcomes of COVID-19 convalescents: An 18.5-month longitudinal study in Wuhan.

OBJECTIVES: This study aimed to describe the full scope of long-term outcomes and the ongoing pathophysiological alterations among COVID-19 survivors. METHODS: We established a longitudinal cohort of 208 COVID-19 convalescents and followed them at 3.3 (interquartile range [IQR]: 1.3, 4.4, visit 1), 9.2 (IQR: 9.0, 9.6, visit 2), and 18.5 (IQR: 18.2, 19.1, visit 3) months after infection, respectively. Serial changes in multiple physical and psychological outcomes were comprehensively characterized. We, in addition, explored the potential risk factors of SARS-CoV-2 antibody response and sequelae symptoms. RESULTS: We observed continuous improvement of sequelae symptoms, lung function, chest computed tomography (CT), 6-minute walk test, and the Borg dyspnea scale, whereas sequelae symptoms (at least one) and abnormal chest CT patterns still existed in 45.2% and about 30% of participants at 18.5 months, respectively. Anxiety and depression disorders were alleviated for the convalescents, although depression status was sustained for a longer duration. CONCLUSIONS: Most COVID-19 convalescents had an overall improved physical and psychological health status, whereas sequelae symptoms, residual lesions on lung function, exercise impairment, and mental health disorders were still observed in a small proportion of participants at 18.5 months after infection. Implementing appropriate preventive and management strategies for the ever-growing COVID-19 population is warranted.

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.