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Abstract Aims This study aimed to investigate the impact of different estimated glomerular filtration rate (eGFR) values like cystatin C-based eGFR (eGFRcys), creatinine-based eGFR (eGFRcr), and their difference (eGFRdiff; eGFRcys -eGFRcr), on the incidence of heart failure (HF) in patients with type 2 diabetes(T2D). Methods Being a prospective cohort study, it included 7,967 patients with T2D who underwent serum creatinine and cystatin C tests as part of the Kailuan Group’s 6th annual health examination (2016). Subsequently, eGFRcys, eGFRcr, and eGFRdiff were calculated. Patients were categorized into three groups: negative ( 15 mL/min/1.73 m2) eGFRdiff groups, respectively. Furthermore, the relationship between the various eGFR measurements and new-onset HF were studied using Cox proportional hazards regression, and the potential improvement in predictive capability was evaluated by adding these eGFR metrics to established HF risk models. Results Among 7967 participants with mean age of 60.51 years, there were 20.92% women and 79.08% men. At baseline, eGFRcys and eGFRcr values differed by more than 15 mL/min/1.73m2 in 41.3% of participants. During a median follow-up period of 3.76 years, there were 172 (2.16%) new HF cases and 517 (6.49%) all-cause deaths. The cumulative incidence of HF in the midrange, negative, and positive eGFRdiff groups was 1.74%, 4.10%, and 0.61%, respectively (p

Abstract Background Menopause significantly impacts the immune system. Postmenopausal women are more susceptible to infection. Nonetheless, the pattern of change in peripheral white blood cell counts around the menopause remains poorly understood. Methods We conducted a prospective longitudinal cohort study with repeated measurements using Kailuan cohort study of 3632 Chinese women who participated in the first checkup (2006–2007) and reached their final menstrual period (FMP) by the end of the seventh checkup (2018–2020). Peripheral WBC count indicators included total white blood cells (TWBC), neutrophils (NEUT), lymphocytes (LYM), and monocytes (MON). Multivariable mixed effects regressions fitted piece-wise linear models to repeated measures of WBC count indicators as a function of time before or after the final menstrual period (FMP). Interaction and subgroup analysis were used to explore the effects of age and body mass index (BMI) on changes in WBC indicators around FMP. Results WBC count indicators decreased before the FMP, and the reduction in TWBC, NEUT, and MON continued for 2 years following the FMP. LYM and NEUT declined during < -1 years and − 4 ∼ + 2 years relative to FMP, respectively. A reduction in MON was observed pre-FMP, extending continuously through the two-year period post-FMP. TWBC declined from − 3 to + 2 years relative to FMP, but both MON and TWBC increased during > + 2 years. The baseline age had an interaction effect on changes in WBC indicators during specific menopausal stages, except for TWBC. Individuals in different age subgroups showed distinct trajectories for NEUT, LYM and MON around the FMP. High baseline BMI had a synergistic effect on changes in specific menopause segments for TWBC, LYM, and MON. The impact of menopause on TWBC and LYM was postponed or counterbalanced in high BMI individuals. Individuals in three BMI subgroups experienced similar MON changes around FMP, and there were slight variations during < -4 years. Conclusions Menopause was associated with count changes of peripheral WBC. The trajectories of various WBC types differ around menopause. Age and BMI affected WBC trajectory around menopause. The menopause period may represent a window of opportunity to promote immune health in middle-aged women.

Abstract Background The health effects of Life’s Essential 8 (LE8) on chronic diseases have been disclosed, but its association with hypertension remains unknown. The current study aimed to explore the potential link between 10-year LE8 trajectory and the incidence of hypertension. Methods LE8 was constructed from four behaviors and four metabolic factors, ranging from 0 to 100. Latent mixture models were used to identify trajectories of LE8 scores during 2006 to 2016. Incident hypertension was diagnosed based on self-reported clinical diagnoses and physical examinations from 2016 to 2020. Cox models were employed to assess the association of LE8 trajectories with hypertension. In addition to incorporating the mean hs-CRP levels from 2006 to 2016, age, sex, monthly income, educational level, and occupation at recruitment were adjusted for as confounding factors. Results 7500 participants aged 40.28 ± 10.35 years were included in the study, of whom 2907 (38.76%) were women. Five LE8 trajectory patterns were identified. After around four-year follow-up, 667 hypertension events were observed. Compared to the Low-Stable trajectory, the hazard ratios and 95% confidence intervals for the Moderate-Increasing, Moderate-Decreasing, Moderate-Stable, and High-Stable trajectories were 0.51 (0.40, 0.65), 0.81 (0.64, 1.02), 0.45 (0.36, 0.58), 0.23 (0.16, 0.33), respectively. The risk of incident hypertension decreased as participants improved their LE8 status. The robustness of the primary results was confirmed through several sensitivity analyses. Conclusions LE8 trajectories were associated with the incident hypertension. People who improved their LE8 scores over time experienced a decreased risk of hypertension, even if they started with lower LE8 scores initially.

Background: The incidence of early-onset colorectal cancer (EOCRC), which exhibits differential clinical, pathological, and molecular features compared to late-onset CRC (LOCRC), is rising globally. The potential differential effects of blood glucose on EOCRC compared to LOCRC have not been investigated. Methods: This study analyzed 374,568 participants from the UK Biobank cohort and 172,809 participants from the Kailuan cohort. The linear associations between blood glucose and EOCRC/LOCRC were estimated using Cox regression models. Restricted cubic spline (RCS) analysis and non-linear Mendelian randomization (MR) analysis using a 70-SNPs genetic instrument for fasting glucose were used to explore the potential non-linear associations. Results: Participants in the highest quintile of blood glucose had higher overall CRC risk compared to the lowest quintile (HR = 1.10 in the UK Biobank cohort, 95% CI: 1.01–1.21, P-trend = 0.012; HR = 1.23 in the Kailuan cohort, 95% CI: 1.01–1.51, P-trend = 0.036). Elevated glucose (>7.0 mmol/L) was more strongly associated with increased risk of EOCRC (HR = 1.61, 95% CI: 1.07–2.44) than with LOCRC (HR = 1.14, 95% CI: 1.02–1.27) in the UK Biobank cohort (P-heterogeneity = 0.014). Elevated glucose (>7.0 mmol/L) was associated with increased risk of LOCRC (HR = 1.25, 95% CI: 1.04–1.65) in the Kailuan cohort as well. There was no evidence for non-linear associations between blood glucose and risks of EOCRC/LOCRC. Conclusions: This study showed a positive association between blood glucose and CRC risk in a dose-response manner, particularly for EOCRC, suggesting that tighter glucose control should be a priority for younger age groups.

Abstract To explore the effect of different levels of systolic blood pressure (SBP) control on new-onset chronic kidney disease in hypertension multimorbidity. The hypertensive patients with multimorbidity information were enrolled from the Kailuan Study. The isolated hypertension patients undergoing physical examination during the same period were selected in a 1:1 ratio as control. Finally, 12,897 participants were divided into six groups: Group SBP

Abstract Background A high triglyceride-glucose index (TyG) is associated with a higher risk of incident heart failure. However, the effects of longitudinal patterns of TyG index on the risk of heart failure remain to be characterized. Therefore, in the present study, we aimed to characterize the relationship between the trajectory of TyG index and the risk of heart failure. Methods We performed a prospective study of 56,149 participants in the Kailuan study who attended three consecutive surveys in 2006–2007, 2008–2009, and 2010–2011 and had no history of heart failure or cancer before the third wave survey (2010–2011). The TyG index was calculated as ln [fasting triglycerides (mg/dL) × fasting plasma glucose (mg/dL)/2], and we used latent mixture modeling to characterize the trajectory of the TyG index over the period 2006–2010. Additionally, Cox proportional risk models were used to calculate the hazard ratio (HR) and 95% confidence interval (CI) for incident heart failure for the various TyG index trajectory groups. Results From 2006 to 2010, four different TyG trajectories were identified: low-stable (n = 13,554; range, 7.98–8.07), moderate low-stable (n = 29,435; range, 8.60–8.65), moderate high-stable (n = 11,262; range, 9.31–9.30), and elevated-stable (n = 1,898; range, 10.04–10.25). A total of 1,312 new heart failure events occurred during a median follow-up period of 10.04 years. After adjustment for potential confounders, the hazard ratios (HRs) and 95% confidence intervals (CIs) for incident heart failure for the elevated-stable, moderate high-stable, and moderate low-stable groups were 1.55 (1.15, 2.08), 1.32 (1.08, 1.60), and 1.17 (0.99, 1.37), respectively, compared to the low-stable group. Conclusions Higher TyG index trajectories were associated with a higher risk of heart failure. This suggests that monitoring TyG index trajectory may help identify individuals at high risk for heart failure and highlights the importance of early control of blood glucose and lipids for the prevention of heart failure.

Abstract Background The atherogenic index of plasma (AIP) has been shown to be positively correlated with cardiovascular events. However, it remains unclear whether hypertensive patients with long-term high AIP levels are at greater risk of developing heart failure (HF). Therefore, the aim of this study was to investigate the association between AIP trajectory and the incidence of HF in hypertensive patients. Methods This prospective study included 22,201 hypertensive patients from the Kailuan Study who underwent three waves of surveys between 2006 and 2010. Participants were free of HF or cancer before or during 2010. The AIP was calculated as the logarithmic conversion ratio of triglycerides to high-density lipoprotein cholesterol. Latent mixed modeling was employed to identify different trajectory patterns for AIP during the exposure period (2006–2010). Cox proportional hazard models were then used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for incident HF among different trajectory groups. Results Four distinct trajectory patterns were identified through latent mixture modeling analysis: low-stable group (n = 3,373; range, -0.82 to -0.70), moderate-low stable group (n = 12,700; range, -0.12 to -0.09), moderate-high stable group (n = 5,313; range, 0.53 to 0.58), and elevated-increasing group (n = 815; range, 1.22 to 1.56). During a median follow-up period of 9.98 years, a total of 822 hypertensive participants experienced HF. After adjusting for potential confounding factors, compared with those in the low-stable group, the HR and corresponding CI for incident HF in the elevated-increasing group, moderate-high stable group, and moderate-low stable group were estimated to be 1.79 (1.21,2.66), 1.49 (1.17,1.91), and 1.27 (1.02,1.58), respectively. These findings remained consistent across subgroup analyses and sensitivity analyses. Conclusion Prolonged elevation of AIP in hypertensive patients is significantly associated with an increased risk of HF. This finding suggests that regular monitoring of AIP could aid in identifying individuals at a heightened risk of HF within the hypertensive population.

Abstract Background The Chinese visceral adiposity index (CVAI) is a new index to evaluate visceral adipose tissue in the Chinese population. Arterial stiffness (AS) is a kind of degeneration of the large arteries, and obesity is an essential contributing factor to AS. Our study aimed to explore the longitudinal association between CVAI and the risk of AS and to compare the predictive power of CVAI, body mass index (BMI), and waist circumference (WC) for AS. Methods Between 2010 and 2020, a total of 14,877 participants participating in at least two brachial-ankle pulse wave velocity (baPWV) measurements from the Kailuan study were included. The Cox proportional hazard regression models were performed to evaluate the longitudinal association between CVAI and the risk of AS. The area under the receiver operating characteristic (ROC) curve was calculated to compare the predictive power of CVAI, BMI, and WC for AS. Results After adjusting for potential confounding factors, CVAI was significantly associated with the risk of AS. Compared with the first CVAI quartile, the hazard ratios (HR) and 95% CI of the second, third, and fourth quartiles were 1.30 (1.09–1.56), 1.37 (1.15–1.63), and 1.49 (1.24–1.78), respectively. The area under ROC curve of CVAI was 0.661, significantly higher than BMI (AUC: 0.582) and WC (AUC: 0.606). Conclusion CVAI may be a reliable indicator to identify high-risk groups of AS in the Chinese general population, and the predictive power of CVAI for AS was better than BMI and WC.

Abstract Background Cardiovascular disease (CVD) is a chronic disease with a serious prognosis, and obesity is a risk factor for CVD. Lipid accumulation product index (LAP) is a new indicator of obesity, waist circumference, and triglycerides were included in the formula, but its association with CVD is inconsistent. Therefore, this study researched the effect of LAP levels on CVD. Methods This prospective cohort study was based on the Kailuan cohort. A total of 95,981 participants who completed the first physical examination in 2006 and had no history of CVD or LAP absence were included. The participants were divided into four groups according to the LAP quartile (Q1 - Q4). Up until December 31, 2022, incidence density was calculated for each group. The hazard ratio (HR) and 95% confidence interval (CI) of CVD in each group were calculated by the Cox proportional hazards model. Results During a median follow-up period of 15.95 years, 9925 incident CVD events occurred (2123 myocardial infarction and 8096 stroke). There were differences in potential confounders among the four groups (P

Abstract Background The Triglyceride-glucose (TyG) index, a surrogate marker of insulin resistance, has been implicated in the risk of ischemic stroke. However, the interplay between TyG levels, lifestyle factors, and their collective impact on stroke risk in non-diabetic populations remains inadequately explored. This study aims to evaluate the association of ischemic stroke with the joint development of the TyG index and lifestyle in the non-diabetic population. Methods In this prospective cohort study, data was collected across three consecutive biennial surveys of the Kailuan Study from 2006 to 2011. The dual-trajectory model was used to determine the temporal development of TyG levels and lifestyle scores. Statistical analysis involved Cox regression models to evaluate the association between TyG-lifestyle trajectories and ischemic stroke risk, adjusting for potential confounders. Results A total of 44,403 participants were included, with five distinct TyG levels and lifestyle scores trajectory subtypes identified. In the multivariable-adjusted analyses, significant differences in ischemic stroke risk among the trajectory subtypes. Group 5, characterized by the highest TyG levels and moderate lifestyle scores, exhibited the greatest ischemic stroke risk (HR = 1.81, 95% CI: 1.51–2.18), while group 4, with moderate TyG levels and higher lifestyle scores, demonstrated the lowest risk (HR = 1.19, 95% CI: 1.04–1.37), compared with group 3. Participants with elevated TyG levels were at an increased risk of ischemic stroke in cases of pronounced insulin resistance, even with a healthy lifestyle. Conclusions This study reveals the significant associations between the identified TyG and lifestyle trajectories and the stratification of ischemic stroke risk among non-diabetics. The TyG index is a valuable indicator for assessing insulin resistance. However, the potential benefits of lifestyle changes for those with significantly high TyG levels need to be clarified by more research to develop more effective stroke prevention strategies.

Abstract Objective To investigate the association between cumulative exposure to low-density lipoprotein cholesterol (LDL-C) and carotid intima-media thickness (IMT) in the young adulthood population. Methods Young adult subject (18-45 year old) from the Kailuan Study group who participated in the same period of follow-up and received carotid artery ultrasound were selected as the observation subjects. Among them, 3651 cases met the inclusion criteria, which required that carotid artery color ultrasound examinations be completed from 2010 to 2016, with complete IMT measurements, LDL-C data collected at least twice before carotid ultrasound, and participants’ age to be ≤ 45 years at the time of carotid artery color ultrasound examination. Linear regression was used to analyze the correlation between time-weighted average (TWA) to LDL-C cumulative exposure and IMT the young population. Logistic regression was used to analyze the effects of different TWA groups on IMT thickening. Considering that the use of anti hypertensive drugs and lipid-lowering drugs may affect TWA LDL-C, this study excluded people taking antihypertensive drugs and lipid-lowering drugs, and conducted a repeat analysis of the main results. Results There was a positive correlation between TWA LDL-C and IMT, with IMT increasing by 0.017 mm when TWA LDL-C increased by 1 mmol/L * year. The TWA LDL-C in the highest group was identified as a risk factor for IMT thickening, with odds ratio (OR) values of 1.812(1.027 ~ 3.200) in the T3 group. After excluding patients taking antihypertensive drugs and lipid-lowering drugs, the results still showed that the T3 group with the highest TWA LDL-C was a risk factor for IMT thickening, with an OR value of 1.850(0.988–3.464), P for trend is 0.043. Conclusion This cohort study revealed that TWA LDL-C is positively correlated with IMT in young adulthood for risk stratification, and control LDL-C levels at an earlier age may reduce the lifetime risk of developing atherosclerotic disease. Trial registration ChiCTR-TNC-11001489.

Abstract Background Triglyceride glucose (TyG) index and its related parameters have been introduced as cost-effective surrogate indicators of insulin resistance, while prospective evidence of their effects on atherosclerotic cardiovascular disease (ASCVD) remained scattered and inconsistent. We aimed to evaluate the association of TyG and its related parameters with new-onset ASCVD, and the predictive capacity were further compared. Method A total of 95,342 ASCVD-free participants were enrolled from the Kailuan study. TyG and its related parameters were defined by fasting blood glucose, triglyceride, body mass index (BMI), waist circumstance (WC) and waist-to-height ratio (WHtR). The primary outcome was incident ASCVD, comprising myocardial infarction (MI) and ischemic stroke (IS). Cox proportional hazard models and restricted cubic spline (RCS) analyses were adopted to investigate the association between each index and ASCVD. The C-index, integrated discrimination improvement (IDI), and net reclassification improvement (NRI) were used for comparison of their predictive value for ASCVD. Results During a median follow-up of 15.0 years, 8,031 new cases of ASCVD were identified. The incidence rate of ASCVD increased along with elevated levels of each index, and the relationships were found to be nonlinear in the RCS analyses. The hazard ratio (HR) and 95% confidence interval (95% CI) for ASCVD was 1.39 (1.35, 1.43), 1.46 (1.41, 1.50), 1.50 (1.46, 1.55), and 1.52 (1.48, 1.57) per 1 IQR increase of baseline TyG, TyG-BMI, TyG-WC, and TyG-WHtR, respectively, and the association were more pronounced for females and younger individuals aged

Abstract Background The relationship between variation in serum uric acid (SUA) levels and brain health is largely unknown. This study aimed to examine the associations of long-term variability in SUA levels with neuroimaging metrics and cognitive function. Methods This study recruited 1111 participants aged 25–83 years from a multicenter, community-based cohort study. The SUA concentrations were measured every two years from 2006 to 2018. We measured the intraindividual SUA variability, including the direction and magnitude of change by calculating the slope value. The associations of SUA variability with neuroimaging markers (brain macrostructural volume, microstructural integrity, white matter hyperintensity, and the presence of cerebral small vessel disease) and cognitive function were examined using generalized linear models. Mediation analyses were performed to assess whether neuroimaging markers mediate the relationship between SUA variation and cognitive function. Results Compared with the stable group, subjects with increased or decreased SUA levels were all featured by smaller brain white matter volume (beta = − 0.25, 95% confidence interval [CI] − 0.39 to − 0.11 and beta = − 0.15, 95% CI − 0.29 to − 0.02). Participants with progressively increased SUA exhibited widespread disrupted microstructural integrity, featured by lower global fractional anisotropy (beta = − 0.24, 95% CI − 0.38 to − 0.10), higher mean diffusivity (beta = 0.16, 95% CI 0.04 to 0.28) and radial diffusivity (beta = 0.19, 95% CI 0.06 to 0.31). Elevated SUA was also associated with cognitive decline (beta = − 0.18, 95% CI − 0.32 to − 0.04). White matter atrophy and impaired brain microstructural integrity mediated the impact of SUA increase on cognitive decline. Conclusions It is the magnitude of SUA variation rather than the direction that plays a critical negative role in brain health, especially for participants with hyperuricemia. Smaller brain white matter volume and impaired microstructural integrity mediate the relationship between increased SUA level and cognitive function decline. Long-term stability of SUA level is recommended for maintaining brain health and preventing cognitive decline.

Abstract Time in target range (TTR) and blood pressure variability (BPV) of systolic blood pressure (SBP) are independent risk factors for major adverse cardiovascular events (MACE) and all‐cause mortality in hypertensive patients. However, the association of the combination of low TTR and high BPV of SBP with the risk of MACE and all‐cause mortality is unclear. This study sought to investigate the combined effect of the TTR and BPV on the risk of MACE and all‐cause mortality in patients with hypertension. A total of 11 496 hypertensive patients from the Kailuan cohort study were included in our study. All participants were divided into four groups according to their TTR and BPV levels. Cox proportional hazards regression models were used to calculate the hazard ratios (HRs) and 95% confidence interval (CI) for incident MACE and all‐cause mortality. During a median follow‐up of 5.64 years, 839 MACEs (included 99 cases of myocardial infarction, 591 cases of stroke, and 191 cases of heart failure) and 621 deaths occurred. Compared with the high‐TTR and low‐BPV group, the HRs (95% CI) of MACE and all‐cause mortality were 1.309 (1.025–1.671) and 1.842 (1.373–2.473) for the high‐TTR and high‐BPV group, 1.692 (1.347–2.125) and 1.731 (1.298–2.309) for the low‐TTR & low‐BPV group, 2.132 (1.728–2.629) and 2.247 (1.722–2.932) for the low‐TTR & high‐BPV group. Our study suggests that the combination of low TTR and high BPV of SBP was associated with a higher risk of MACE and all‐cause mortality in patients with hypertension.

Abstract Background Stroke is a common complication of hypertension, but the predictive value of metabolic syndrome parameters' variability on stroke risk in individuals with hypertension remains unclear. Therefore, our objective was to investigate the relationship between metabolic syndrome parameters' variability and the risk of total stroke and its subtypes in hypertensive patients. Methods This prospective cohort study included 17,789 individuals with hypertension from the Kailuan study since 2006. Metabolic syndrome parameters, including waist circumference (WC), fasting blood glucose (FBG), systolic blood pressure (SBP), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG), were collected at three follow-up visits in the 2006, 2008, and 2010 surveys. We assess the variability utilizing the coefficient of variation (CV), standard deviation (SD), average real variation (ARV), and variability independent of the mean (VIM), with CV initially assessed. Participants were categorized based on the number of high-variability metabolic syndrome parameters (0, 1, 2, ≥ 3). Stroke cases were identified by reviewing medical records. The associations between variability in metabolic syndrome parameters and the risk of total stroke and its subtypes were analyzed using Cox proportional hazard regression models. Results During a median follow-up of 9.32 years, 1223 cases of stroke were recorded. Participants with ≥ 3 high-variability metabolic syndrome parameters had an increased risk of total stroke (HR: 1.29, 95%CI 1.09–1.52), as well as an increased risk of ischemic stroke (HR: 1.31, 95%CI 1.05–1.63) compared to those without high-variability parameters. The study also examined variability in each metabolic syndrome parameter, and significant associations with an increased risk of total stroke were observed for variability in SBP (HR: 1.24, 95%CI 1.05–1.46) and HDL-C (HR: 1.34, 95%CI 1.09–1.64). Conclusions Long-term fluctuations in metabolic syndrome parameters significantly increase the risk of total stroke, especially ischemic stroke. Maintaining low variability in metabolic syndrome parameters could benefit health, and hypertensive individuals must be regularly monitored.

Abstract Background and objective Gender disparities in mortality among individuals with early-onset cardiovascular disease (CVD) remain uncertain. This study aimed to investigate gender differences in all-cause mortality and identify influencing factors. Methods Data extracted from the Kailuan Study, a prospective cohort study initiated in 2006, were analyzed. A total of 2,829 participants with early-onset CVD were included. Cox proportional hazard models were used to assess hazard ratios (HR) and 95% confidence intervals (CI) for gender disparities in all-cause mortality, adjusting for various factors. Results Males experienced a median follow-up duration of 7.54 years with 276 recorded deaths, and females had a median follow-up of 6.45 years with 105 recorded deaths. Gender disparities in all-cause mortality were observed, with men experiencing a higher all-cause mortality risk compared to women (HR: 1.42, 95% CI: 1.04, 1.92) in the fully adjusted model. Both in men and women with early-onset CVD, elevated hs-CRP levels and an eGFR

Abstract Background No study has concentrated on the association of LE8 with cancer risk and death. We aim to examine the association of LE8 with death and cancer. Methods A total of 94733 adults aged 51.42 ± 12.46 years and 77551 participants aged 54.09±12.06 years were enrolled in longitudinal and trajectory analysis respectively. Baseline LE8 was divided into three groups based on the American Heart Association criteria and three trajectory patterns by latent mixture models. We reviewed medical records and clinical examinations to confirm incident cancer during the period from 2006 to 2020. Death information was collected from provincial vital statistics offices. Cox models were used. Results 12807 all-cause deaths and 5060 cancers were documented during a 14-year follow-up. Relative to participants with high LE8 at baseline, participants with lower levels of LE8 have a significantly increased risk of mortality and incident cancer. All these risks have an increasing trend with LE8 level decreasing. Meanwhile, the trajectory analysis recorded 7483 all-cause deaths and 3037 incident cancers after approximately 10 years. The associations of LE8 with death and cancer were identical to the longitudinal study. In the subtype cancer analysis, LE8 has a strong effect on colorectal cancer risk. Moreover, the cut point is 56.67 in the association between LE8 and death, while the cut point altered to 64.79 in the association between LE8 and incident cancers. These associations were enhanced among younger adults. Conclusions There was a significant association of LE8 with death and cancer risk, especially for the young population.

Abstract. Background:. Arterial stiffening increases with age and blood pressure and is associated with cardiovascular disease (CVD), but the relationship between blood pressure lowering and arterial stiffening is still uncertain, especially in older people. This study aimed to evaluate the effect of intensive blood pressure treatment on the progression of arterial stiffness and risk of CVD in older patients with hypertension. Methods:. The Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial was a multicenter, randomized, controlled trial performed at 42 clinical centers throughout China, and 8511 patients aged 60–80 years with essential hypertension were enrolled and randomly assigned to systolic blood pressure (SBP) target of 110 mmHg to

Abstract Background The association between the triglyceride glucose (TyG) index and the risk of early-onset atherosclerotic cardiovascular disease (ASCVD) events or all-cause mortality in young and middle-aged people is not fully elucidated. Methods The present study included 64,489 young and middle-aged people who participated in the 2006 Kailuan Study physical examination. Multivariate Cox proportional hazards models and restricted cubic spline curves were used to assess the association of TyG index with early-onset ASCVD events and all-cause mortality. Results During a median of 11-year follow-up, 1984 (3.08%) participants experienced at least one ASCVD event and 1,392 (2.16%) participants experienced all-cause death. A higher TyG index was significantly associated with a higher risk of early-onset ASCVD events (HR: 1.61, 95% CI 1.38–1.89) and all-cause mortality (HR: 1.39, 95% CI 1.17–1.65), respectively. For each unit increase in TyG index, the risk of early-onset ASCVD events increased by 20%. In addition, there was a non-linear association between the TyG index and early-onset ASCVD events (P for non-linear

Abstract Background The association of longitudinal uric acid (UA) changes with cardiac conduction block risk is unclear. We aimed to identify the trajectories of UA and explore its association with cardiac conduction block. Methods A total of 67,095 participants with a mean age of 53.12 years were included from the Kailuan cohort in Tangshan, China, who were free of cardiac conduction block and with repeated measurements of UA from 2006 to 2012. UA trajectories during 2006 to 2012 were identified by group-based trajectory modeling. Cox proportional hazard regression models were used to assess the association of UA trajectories with cardiac conduction block. Results We categorized three observed discrete trajectories of UA during 2006–2012 period: low-stable, moderate-stable, and high-stable. Over a median follow-up of 6.19 years, we identified 1405 (2.09%) incident cardiac conduction block. Compared to those in the low-stable trajectory, the adjusted hazard ratios (HRs) (95% confidence interval [CI]) of cardiac conduction block in the moderate-stable and high-stable trajectory were 1.30 (1.16–1.47) and 1.86 (1.56–2.22), and HRs of atrioventricular block were 1.39 (1.12–1.72) and 2.90 (2.19–3.83), and HRs of bundle branch blocks were 1.27 (1.10–1.47) and 1.43 (1.13–1.79). Notably, although the average UA level in the moderate-stable UA trajectory group is within the normal range, the risk of cardiac conduction block has increased. Conclusions The moderate-stable and high-stable trajectories are associated with increased risk for new-onset cardiac conduction block. Monitoring UA trajectories may assist in identifying subpopulations at higher risk for cardiac conduction block.

Abstract Background The current literature shows a strong relationship between retinal neuronal and vascular alterations in dementia. The purpose of the study was to use NFN+ deep learning models to analyze retinal vessel characteristics for cognitive impairment (CI) recognition. Methods We included 908 participants from a community-based cohort followed for over 15 years (the prospective KaiLuan Study) who underwent brain magnetic resonance imaging (MRI) and fundus photography between 2021 and 2022. The cohort consisted of both cognitively healthy individuals (N = 417) and those with cognitive impairment (N = 491). We employed the NFN+ deep learning framework for retinal vessel segmentation and measurement. Associations between Retinal microvascular parameters (RMPs: central retinal arteriolar / venular equivalents, arteriole to venular ratio, fractal dimension) and CI were assessed by Pearson correlation. P

Abstract Background Converging data have suggested that monocytic inflammation and C-reactive protein (CRP) are biologically intertwined processes and are involved in diabetogenesis. This study aimed to investigate the association between systemic inflammation assessed by joint cumulative high-sensitivity C-reactive protein (CumCRP) and monocyte to high-density lipoprotein ratio (CumMHR) and incident type 2 diabetes (T2D) and their predictive value for T2D in a general population. Methods A total of 40,813 nondiabetic participants from a prospective real-life cohort (Kailuan Study, China) were followed biennially from 2010/2011 until December 31, 2020. Multivariable Cox regression analyses were conducted to evaluate the adjusted hazard ratios (aHRs) of incident diabetes. Results During a median follow-up of 7.98 (IQR: 5.74–8.87) years, 4848 T2D cases developed. CumMHR and CumCRP were alone or jointly associated with incident T2D after adjusting for potential confounders. Elevated CumMHR levels significantly increased the risk of incident diabetes in each CumCRP strata (P-interaction: 0.0278). Participants with concomitant elevations in CumMHR and CumCRP levels had the highest risk (aHR: 1.71, 95% CI 1.52–1.91) compared to both in the low strata. Notably, the coexposure-associated T2D risk was modified by age, sex, hypertension, dyslipidemia, and prediabetes status. C-statistics increased from 0.7377 to 0.7417 when CumMHR and CumCRP were added into the multivariable-adjusted model, with a net reclassification improvement (%) of 12.39 (9.39–15.37) (P

Abstract Aims We aimed to explore the associations between urine albumin-to-creatinine ratio (uACR) and cardia-cerebrovascular disease (CVD) in Chinese population with type 2 diabetes(T2D). Methods We included 8975 participants with T2D but free of prevalent CVD (including myocardial infarction, ischemic and hemorrhagic stroke) at baseline from Kailuan study who were assessed with uACR between 2014 and 2016. The participants were divided into three groups based on their baseline uACR: normal (

Abstract. Background:. The 2017 American College of Cardiology/American Heart Association (ACC/AHA) blood pressure (BP) guideline lowered the threshold defining hypertension to 130/80 mmHg. However, how stage 1 hypertension defined using this guideline is associated with cardiovascular events in Chinese adults remains unclear. This study assessed the association between stage 1 hypertension defined by the 2017 ACC/AHA guideline and clinical outcomes in the Chinese population. Methods:. Participants with stage 1 hypertension (n = 69,509) or normal BP (n = 34,142) were followed in this study from 2006/2007 to 2020. Stage 1 hypertension was defined as a systolic blood pressure of 130-139 mmHg or a diastolic blood pressure of 80-89 mmHg. None were taking antihypertensive medication or had a history of myocardial infarction (MI), stroke, or cancer at baseline. The primary outcome was a composite of MI, stroke, and all-cause mortality. The secondary outcomes were individual components of the primary outcome. Cox proportional hazards models were used for the analysis. Results:. During a median follow-up of 11.09 years, we observed 10,479 events (MI, n = 995; stroke, n = 3408; all-cause mortality, n = 7094). After multivariable adjustment, the hazard ratios for stage 1 hypertension vs. normal BP were 1.20 (95% confidence interval [CI], 1.13-1.25) for primary outcome, 1.24 (95% CI, 1.05-1.46) for MI, 1.45 (95% CI, 1.33-1.59) for stroke, and 1.11 (95% CI, 1.04-1.17) for all-cause mortality. The hazard ratios for participants with stage 1 hypertension who were prescribed antihypertensive medications compared with those without antihypertensive treatment during the follow-up was 0.90 (95% CI, 0.85-0.96). Conclusions:. Using the new definition, Chinese adults with untreated stage 1 hypertension are at higher risk for MI, stroke, and all-cause mortality. This finding may help to validate the new BP classification system in China.

Background: Retinal health indices were suggested to be related to psychopathological symptoms, such as depressive symptoms. However, large-scale studies using optical coherence tomography (OCT) are missing to investigate the associations among them. Methods: In the META-KLS cohort study, 1456 participants (mean age [standard deviation]= 54.6 [11.91] years; n= 680 [47.8%] women) completed the Patient Health Questionnaire (PHQ-9) to measure depressive symptoms and underwent OCT. Poor-quality OCTs and multivariate outliers were excluded, and principal component analysis was performed to obtain retinal health indices separately for macular (n= 930) and optic nerve head (ONH) thicknesses (n= 800). Linear regressions were run controlling for covariates. Exploratory interaction models were run with demographic, lifestyle and health markers. Results: Although there were no direct significant associations between the retinal indices and depressive symptoms (macular: B= −0.05, 95% CI= [-0.15, 0.05], p= 0.32; ONH index: B= -0.02, 95% CI= [-0.11, 0.08], p= 0.71), their associations were moderated by demographic and health factors, e.g., C-reactive protein (CRP) (macular index: B= −0.03, 95% CI= [-0.05, −0.01], p= 0.002; ONH index: B= 0.05, 95% CI= [0.02, 0.08], p= 0.002). Limitations: Study was cross-sectional and there were no functional assessments of vision. Conclusions: In a large cohort, we observed associations between retinal indices and self-reported depressive symptoms depending on demographic and health factors, notably CRP. Following up, the study will investigate the prospective prediction of retinal health on depressive symptoms, especially in persons who may have chronic inflammation.

Introduction: The association between the longitudinal patterns of estimated glomerular filtration rate (eGFR) and risk of atrial fibrillation (AF) in populations with normal or mildly impaired renal function is not well-characterized. We sought to explore the eGFR trajectories in populations with normal or mildly impaired renal function and their association with AF. Methods: This prospective cohort study included 62,407 participants who were free of AF, cardiovascular diseases, and moderate to severe renal insufficiency (eGFR

Background Overweight and obesity represent critical modifiable determinants in the prevention of cardiometabolic disease (CMD). However, the long‐term impact of prior overweight/obesity on the risk of CMD in later life remains unclear. We aimed to investigate the association between longitudinal transition of body mass index (BMI) status and incident CMD. Methods and Results This prospective cohort study included 57 493 CMD‐free Chinese adults from the Kailuan Study. BMI change patterns were categorized according to the BMI measurements obtained during the 2006 and 2012 surveys. The primary end point was a composite of myocardial infarction, stroke, and type 2 diabetes. Cox regression models were used to evaluate the associations of transitions in BMI with overall CMD events and subtypes, with covariates selected on the basis of the directed acyclic graph. During a median follow‐up of 7.62 years, 8412 participants developed CMD. After considering potential confounders, weight gain pattern (hazard ratio [HR], 1.34 [95% CI, 1.23–1.46]), stable overweight/obesity (HR, 2.12 [95% CI, 2.00–2.24]), and past overweight/obesity (HR, 1.73 [95% CI, 1.59–1.89]) were associated with the incidence of CMD. Similar results were observed in cardiometabolic multimorbidity, cardiovascular disease, and type 2 diabetes. Additionally, triglyceride and systolic blood pressure explained 8.05% (95% CI, 5.87–10.22) and 12.10% (95% CI, 9.19–15.02) of the association between past overweight/obesity and incident CMD, respectively. Conclusions A history of overweight/obesity was associated with an increased risk of CMD, even in the absence of current BMI abnormalities. These findings emphasize the necessity for future public health guidelines to include preventive interventions for CMD in individuals with past overweight/obesity.

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.

Abstract Background Adiposity and elevated inflammation are two hallmarks of hyperglycemia. However, it is unknown whether clustering of elevated inflammation and adiposity interact act on diabetogenesis and lead to a greater risk for incident type 2 diabetes (T2D). Methods Adiposity was indicated by body mass index, waist circumference and ultrasonography-measured fatty liver degrees. Elevated inflammation was indicated as high-sensitivity C-reactive protein levels ≥ 2 mg/L. Time-to-event survival analyses were conducted to investigate the joint effect of adiposity and inflammation on incident T2D on both multiplicative and additive scales. Results Among 82,172 non-diabetic participants from a prospective cohort in China, 14,278 T2D occurred over a median follow-up of 11 years. In the multivariable-adjusted model, elevated inflammation [1.12 (1.08‒1.16)] and adiposity [1.76 (1.69‒1.83) for overweight/obesity, 1.49 (1.44‒1.55) for central obesity, and 2.02 (1.95‒2.09) for fatty liver] were significantly associated with incident diabetes. Higher adiposity-associated risks and incidence rates of diabetes were observed with elevated inflammation. When studying the joint effect, the adjusted HRs were 1.77 (1.69‒1.85) for overweight/obesity, 1.14 (1.06‒1.23) for elevated inflammation, and 2.08 (1.97‒2.19) for their joint effect, with a relative excess risk due to interaction of 0.17 (0.05‒0.28). The attributable proportions were 71.30% for overweight/obesity, 12.96% for elevated inflammation, and 15.74% for their interaction. Similar results were observed when adiposity was assessed as waist circumference or fatty liver. Conclusions Adiposity and elevated inflammation synergically lead to greater risks of incident diabetes than addition of each individual exposure. Strategies simultaneously targeting both risks should produce more benefits for diabetes prevention than through initiatives directed at each separate risk.

Abstract Background High cardiovascular health (CVH) was associated with lower risk of cardiovascular disease (CVD) and longer life expectancy. However, whether life years lived without CVD could increase faster than or at least at the same pace as total lifespan remains unknown. We aimed to explore the associations of CVH status with total life expectancy and life years lived with and without CVD among middle-aged and elderly men and women. Methods We included 65,587 participants aged ≥ 45 years from Kailuan study, who were recruited during June 2006 to October 2007. CVH was scored and classified (low [0–49 points], moderate [50–79 points] and high [80–100 points]) with Life’s Essential 8, incorporating evaluations of health behaviors and factors. All-cause mortality and incident non-fatal CVD were recorded from baseline to December 31, 2020. The multi-state life table was adopted to explore the associations of CVH status with total life expectancy and life years lived with and without CVD. Results Six thousand fifty eight cases of incident non-fatal CVD and 10,580 cases of deaths were identified. Men aged 45 years with low, moderate, and high CVH had a life expectancy of 33.0, 36.5 and 38.5 years, of which 7.8 (23.6%), 6.0 (16.3%) and 3.7 years (9.6%) were spent with CVD. For women, the corresponding life expectancy was 36.6, 43.6 and 48.6 years, and the remaining life years lived with CVD were 7.8 (21.3%), 6.0 (13.7%) and 4.5 years (9.3%), respectively. The benefits of high CVH were persistent across lifespan from age 45 to 85 years and consistent when CVH was evaluated with health behaviors and factors alone. Conclusions High CVH compared with low CVH was associated with longer total life expectancy and fewer years spent with CVD, indicating that promoting CVH is of great importance for CVD prevention and healthy ageing in China.

Abstract Background Although many studies have investigated the association between body composition, cancer risk and mortality, predicting these risks through a single body composition measurement undoubtedly increases the limitations of the study. Few studies have explored the association between the trajectory of changes in body composition and the risk of cancer and death. We aimed to explore the association of predicted lean mass trajectories with cancer risk, cancer‐specific mortality and all‐cause mortality. Methods The participants in this study were all from the Kailuan cohort, a prospective, periodic, resurvey cohort study initiated in 2006. Latent mixture modelling was used to identify predicted lean mass trajectories for 2006–2010. The hazard ratios (HRs) and 95% confidence intervals (95% CIs) of the Cox proportional hazard models were used to describe the association between predicted lean mass trajectories and cancer risk and cancer‐specific and all‐cause mortality during follow‐up (2010–2021). Results A total of 44 374 participants (average age, 53.01 ± 11.41 years, 78.99% men and 21.01% women) were enrolled in this study. Five distinct trajectories were identified: low‐stable (n = 12 060), low‐increasing (n = 8027), moderately stable‐decreasing (n = 4725), moderately stable‐increasing (n = 8053) and high‐stable (n = 11 509). During the 11‐year follow‐up period, 2183 cancer events were recorded. After adjusting for age, predicted fat mass in 2010, sex, BMI, sedentary, physical activity, smoke, alcohol use, salt consumption, high‐fat diet, high‐sensitivity C‐reactive protein, serum creatinine, family history of tumour, hypertension, diabetes mellitus, compared with the low‐stable group, participants in the low‐increasing group (HR = 0.851, 95% CI, 0.748–0.969), moderately stable‐increasing group (HR = 0.803, 95% CI, 0.697–0.925) and high‐stable group (HR = 0.770, 95% CI, 0.659–0.901) had a lower cancer risk, but not in the moderately stable‐decreasing group (HR = 0.864, 95% CI, 0.735–1.015). Compared with the low‐stable group, the risk of cancer‐specific mortality was reduced by 25.4% (8.8–38.9%), 36.5% (20.3–49.4%) and 35.4% (17.9–49.2%), and the risk of all‐cause mortality was reduced by 24.2% (16.9–30.8%), 37.0% (30.0–43.2%) and 47.4% (41.0–53.1%) in the low‐increasing, moderately stable‐increasing group and high‐stable groups, respectively. Conclusions Predicted lean mass trajectories may be closely associated with cancer risk and cancer‐specific and all‐cause mortality. Regular monitoring of body composition is necessary.

Abstract Background Previous studies using trajectory models focused on examining the longitudinal changes in triglyceride-glucose (TyG) levels and lifestyle scores separately, without exploring the joint evolution of these two factors. This study aimed to identify the multi-trajectories of TyG levels and lifestyle scores and assess their association with the risk of cardiovascular disease (CVD). Methods The study enrolled 47,384 participants from three health surveys of the Kailuan Study. The TyG index was computed as Ln [fasting triglycerides (mg/dL) × fasting blood glucose (mg/dL)/2], and the lifestyle scores were derived from five factors, including smoking, alcohol consumption, physical activity, sedentary behaviors, and salt intake. A group-based multi-trajectory model was adopted to identify multi-trajectories of TyG levels and lifestyle scores. The association of identified multi-trajectories with incident CVD was examined using Cox proportional hazard model. Results Five distinct multi-trajectories of TyG levels and lifestyle scores were identified. During a median follow-up period of 10.98 years, 3042 participants developed CVD events (2481 strokes, 616 myocardial infarctions, and 55 co-current stroke and myocardial infarctions). In comparison to group 3 with the lowest TyG levels and the best lifestyle scores, the highest CVD risk was observed in group 5 characterized by the highest TyG levels and moderate lifestyle scores (HR = 1.76, 95% CI: 1.50–2.05). Group 2 with higher TyG levels and the poorest lifestyle scores had a 1.45-fold (95% CI 1.26–1.66) risk of CVD, and group 1 with lower TyG levels and poorer lifestyle scores had a 1.33-fold (95% CI 1.17–1.50) risk of CVD. Group 4, with moderate TyG levels and better lifestyle scores, exhibited the lowest CVD risk (HR = 1.32, 95% CI: 1.18–1.47). Conclusions Distinct multi-trajectories of TyG levels and lifestyle scores corresponded to differing CVD risks. The CVD risk caused by a high level TyG trajectory remained increased despite adopting healthier lifestyles. These findings underscored the significance of evaluating the combined TyG and lifestyle patterns longitudinally, and implementing early interventions to reduce CVD risk by lowering TyG levels.

Abstract Background The risk of cardiovascular disease (CVD) depended on the magnitude and exposure duration of insulin resistance (IR). This study aimed to investigate the associations of cumulative metabolic score for IR (cumMETS-IR) with incident CVD, and to further explore the modulated effects of time course of METS-IR accumulation. Methods We enrolled 47,270 participants without CVD and underwent three examinations during 2006–2010 from the Kailuan study. CumMETS-IR from 2006 to 2010 were calculated as the mean values of METS-IR between consecutive examinations multiplying by time intervals between visits. Time course of METS-IR accumulation was calculated as the slope of METS-IR versus time. Hazard ratios (HRs) and 95% confidence intervals (CIs) for CVD risk were calculated with multivariable-adjusted Cox regressions. Results During a median follow-up of 10.99 years, we identified 3184 cases of incident CVD. The risk of incident CVD increased with increasing cumMETS-IR (HR, 1.77; 95% CI 1.58–1.98 for the Q4 versus Q1 group), exposure duration (HR, 1.60; 95% CI 1.45–1.77 for 6 years versus 0 years), and cumulative burden (HR, 1.49; 95% CI 1.37–1.61 for burden ≥ 0 versus

Abstract Objective To investigate the correlation between anthropometric indexes [cardiometabolic index (CMI), lipid accumulation products (LAP), waist triglyceride index (WTI), and body mass index (BMI)] and acute pancreatitis (AP) in a Chinese adult population. Methodology The present investigation consisted of a prospective group including 117,326 subjects who were enrolled in the Kailuan investigation. The individuals were categorized into quartiles based on their baseline levels of CMI, LAP, and WIT. BMI was categorized into three distinctive groups: normal weight group (BMI

Abstract Background Concurrent insulin resistance and elevated blood pressure are commonly observed in cardiovascular disease (CVD) and have long been proposed to contribute to CVD. However, the temporal relationship between them and the effect of their cumulative co-exposure on future incident CVD remains unclear. Methods Longitudinal analysis of data on 57,192 participants from a real-world, prospective cohort study (Kailuan Study) was performed to address the temporal relationship between Triglyceride-Glucose Index (TyG, calculated as ln [TG (mg/dL) × FBG (mg/dL)/2]) and blood pressure (BP) assessed by cross-lagged analyses in an approximately 4-year exposure period (2006/2007 to 2010/2011). After excluding 879 participants with known diabetes, 56,313 nonCVD participants were included for further analysis of the CVD outcome. Cox regression models were used to examine the hazard ratios (HRs) upon the cumulative TyG (CumTyG) and BP(CumBP) in the exposure period. Results The standard regression coefficient from baseline TyG to follow-up systolic BP was 0.0142 (95% CI 0.0059–0.0226), which was greater than the standard regression coefficient from baseline systolic BP to follow-up TyG (− 0.0390; 95% CI − 0.0469 to − 0.0311). The same results were observed in the cross-lag between TyG and diastolic blood pressure [0.0271 (0.0185 to 0.0356) vs. − 0.0372 (− 0.0451 to − 0.0293)]. During a median follow-up of 9.98 years, 3981 CVD cases occurred. Significant interactions were observed between the median CumTyG (8.61) and CumSBP thresholds (130, 140 mmHg) (P = 0.0149), the median CumTyG (8.61) and CumDBP thresholds (80, 90 mmHg) (P = 0.0441). Compared to CumTyG

Abstract Background Atherogenic index of plasma (AIP) has been demonstrated as a surrogate marker for ischemic stroke, but there is limited evidence for the effect of long-term elevation of AIP on ischemic stroke. Therefore, we aimed to characterize the relationship between cumulative exposure to AIP and the risk of ischemic stroke. Methods A total of 54,123 participants in the Kailuan Study who attended consecutive health examinations in 2006, 2008, and 2010 and had no history of ischemic stroke or cancer were included. The time-weighted cumulative AIP (cumAIP) was calculated as a weighted sum of the mean AIP values for each time interval and then normalized to the total duration of exposure (2006–2010). Participants were divided into four groups according to quartile of cumAIP: the Q1 group, ≤−0.50; Q2 group, − 0.50 to − 0.12; Q3 group, − 0.12 to 0.28; and Q4 group, ≥ 0.28. Cox proportional hazard models were used to evaluate the relationship between cumAIP and ischemic stroke by calculating hazard ratios (HRs) and 95% confidence intervals (95% CIs). Results After a median follow-up of 11.03 years, a total of 2,742 new ischemic stroke events occurred. The risk of ischemic stroke increased with increasing quartile of cumAIP. After adjustment for potential confounders, Cox regression models showed that participants in the Q2, Q3, and Q4 groups had significantly higher risks of ischemic stroke than those in the Q1 group. The HRs (95% CIs) for ischemic stroke in the Q2, Q3, and Q4 groups were 1.17 (1.03, 1.32), 1.33 (1.18, 1.50), and 1.45 (1.28, 1.64), respectively. The longer duration of high AIP exposure was significantly associated with increased ischemic stroke risk. Conclusions High cumulative AIP is associated with a higher risk of ischemic stroke, which implies that the long-term monitoring and maintenance of an appropriate AIP may help prevent such events.

Objective: The association between serum alanine aminotransferase (ALT) concentrations and the incidence of hypertension remains unclear. To explore the association between serum ALT levels and the risk of incident hypertension based on the Kailuan cohort study. Methods: People who had participated in health check-ups in 2006–2007 without hypertension, cardiovascular, or liver diseases were enrolled and received follow-ups every two years until December 2017. Hypertension was defined as systolic blood pressure/diastolic blood pressure ≥140/90 mmHg or using anti-hypertensive medication. A multivariable-adjusted Cox regression model was used to estimate the hazard ratio (HR) and its corresponding 95 % confidence intervals (95 % CIs). Results: During 10.5 years of follow-up, 24,023 (50.7 %) participants were diagnosed with hypertension. The HR of incident hypertension was 1.02 (95 % CI=1.01–1.03) for each 10 U/L increment of ALT concentrations. Participants with elevated ALT levels (>40 U/L) had an increased incidence of hypertension by 7 % (HR =1.07; 95 % CI=1.01–1.13). Besides, the HR was 1.10 (95 % CI=1.06–1.15), 1.13 (95 % CI=1.08–1.18), and 1.22 (95 % CI=1.16–1.30) (P for trend

Background The association of the severity of hepatic steatosis in metabolic dysfunction–associated fatty liver disease (MAFLD)/metabolic dysfunction–associated steatotic liver disease (MASLD) and the remission of MAFLD/MASLD with CKD occurrence is unclear. Methods and Results The study enrolled 79 540 participants from the Kailuan cohort. Hepatic steatosis was diagnosed by ultrasound. MAFLD/MASLD was defined as hepatic steatosis combined with metabolic dysfunction and MASLD further excluded alcohol or other causes of liver disease. Chronic kidney disease (CKD) was defined as estimated glomerular filtration rate

Summary: Background: The relationship between the fluctuation in body size and brain health is poorly understood. This study aimed to examine the associations of long-term variability in body mass index (BMI) and waist-to-hip ratio (WHR) with neuroimaging metrics that approximate brain health. Methods: This cohort study recruited 1114 participants aged 25–83 years from a multicenter, community-based cohort study in China. We modeled the BMI and WHR trajectories of participants during 2006–2018 and assessed the BMI and WHR variability (direction and speed of change) by calculating the slope. Generalized linear models were applied to investigate the associations of BMI and WHR variability with MRI markers of brain tissue volume, white matter microstructural integrity, white matter hyperintensity (WMH), and cerebral small vessel disease (CSVD). Findings: Progressive weight gain during follow-up was associated with lower global fractional anisotropy (beta = −0.18, 95% confidence interval [CI] −0.34 to −0.02), higher mean diffusivity (beta = 0.15, 95% CI 0.01–0.30) and radial diffusivity (beta = 0.17, 95% CI 0.02–0.32). Weight loss was also associated with a lower burden of periventricular WMH (beta = −0.26, 95% CI −0.48 to −0.03) and a lower risk of moderate-to-severe basal ganglia enlarged perivascular spaces (BG-EPVS, odds ratio [OR] = 0.41, 95% CI 0.20–0.83). Among overweight populations, weight loss was linked with smaller volumes of WMH (beta = −0.47, 95% CI −0.79 to −0.15), periventricular WMH (beta = −0.57, 95% CI −0.88 to −0.26), and deep WMH (beta = −0.36, 95% CI −0.69 to −0.03), as well as lower risk of CSVD (OR = 0.22, 95% CI 0.08–0.62), lacune (OR = 0.12, 95% CI 0.01–0.91) and moderate-to-severe BG-EPVS (OR = 0.24, 95% CI 0.09–0.61). In adults with central obesity, WHR loss was positively associated with larger gray matter volume (beta = 0.50, 95% CI 0.11–0.89), hippocampus volume (beta = 0.62, 95% CI 0.15–1.09), and parahippocampal gyrus volume (beta = 0.85, 95% CI 0.34–1.37). The sex-stratification and age-stratification analyses revealed similar findings with the main results, with the pattern of associations significantly presented in the individuals at mid-life and late-life. Interpretation: Long-term stability of BMI level is essential for maintaining brain health. Progressive weight gain is associated with impaired white matter microstructural integrity. Weight and WHR losses are associated with improved general brain health. Our results contribute to a better understanding of the integrated associations between variations in obesity measures and brain health. Funding: This study was supported by grants No. 62171297 (Han Lv) and 61931013 (Zhenchang Wang) from the National Natural Science Foundation of China, No. 7242267 from the Beijing Natural Science Foundation (Han Lv), and No. [2015] 160 from the Beijing Scholars Program (Zhenchang Wang).

BackgroundBaseline sleep duration is associated with cancer risk and cancer-specific mortality; however, the association between longitudinal patterns of sleep duration and these risks remains unknown. ObjectiveThis study aimed to elucidate the association between sleep duration trajectory and cancer risk and cancer-specific mortality. MethodsThe participants recruited in this study were from the Kailuan cohort, with all participants aged between 18 and 98 years and without cancer at baseline. The sleep duration of participants was continuously recorded in 2006, 2008, and 2010. Latent mixture modeling was used to identify shared sleep duration trajectories. Furthermore, the Cox proportional risk model was used to examine the association of sleep duration trajectory with cancer risk and cancer-specific mortality. ResultsA total of 53,273 participants were included in the present study, of whom 40,909 (76.79%) were men and 12,364 (23.21%) were women. The average age of the participants was 49.03 (SD 11.76) years. During a median follow-up of 10.99 (IQR 10.27-11.15) years, 2705 participants developed cancers. Three sleep duration trajectories were identified: normal-stable (44,844/53,273, 84.18%), median-stable (5877/53,273, 11.03%), and decreasing low-stable (2552/53,273, 4.79%). Compared with the normal-stable group, the decreasing low-stable group had increased cancer risk (hazard ratio [HR] 1.39, 95% CI 1.16-1.65) and cancer-specific mortality (HR 1.54, 95% CI 1.18-2.06). Dividing the participants by an age cutoff of 45 years revealed an increase in cancer risk (HR 1.88, 95% CI 1.30-2.71) and cancer-specific mortality (HR 2.52, 95% CI 1.22-5.19) only in participants younger than 45 years, rather than middle-aged or older participants. Joint analysis revealed that compared with participants who had a stable sleep duration within the normal range and did not snore, those with a shortened sleep duration and snoring had the highest cancer risk (HR 2.62, 95% CI 1.46-4.70). ConclusionsSleep duration trajectories and quality are closely associated with cancer risk and cancer-specific mortality. However, these associations differ with age and are more pronounced in individuals aged

BackgroundThe level at which cumulative blood pressure (BP) can increase the risk of ASCVD in different age groups remains unclear. This study aimed to investigate the association of 10-year cumulative BP levels with the long-term risk of ASCVD of different age groups.MethodsCumulative BP exposure was assessed using the time-weighted average (TWA) BP divided into four BP groups. The participants were also divided into four groups according to their baseline age (

Background: The cumulative effect of body mass index (BMI) on brain health remains ill-defined. The effects of overweight on brain health across different age groups need clarification. We analyzed the effect of cumulative BMI on neuroimaging features of brain health in adults of different ages. Methods: This study was based on a multicenter, community-based cohort study. We modeled the trajectories of BMI over 16 years to evaluate cumulative exposure. Multimodality neuroimaging data were collected once for volumetric measurements of the brain macrostructure, white matter hyperintensity (WMH), and brain microstructure. We used a generalized linear model to evaluate the association between cumulative BMI and neuroimaging features. Two-sample Mendelian randomization analysis was performed using summary level of BMI genetic data from 681,275 individuals and neuroimaging genetic data from 33,224 individuals to analyze the causal relationships. Results: Clinical and neuroimaging data were obtained from 1,074 adults (25 to 83 years). For adults aged under 45 years, brain volume differences in participants with a cumulative BMI of >26.2 kg/m2 corresponded to 12.0 years [95% confidence interval (CI), 3.0 to 20.0] of brain aging. Differences in WMH were statistically substantial for participants aged over 60 years, with a 6.0-ml (95% CI, 1.5 to 10.5) larger volume. Genetic analysis indicated causal relationships between high BMI and smaller gray matter and higher fractional anisotropy in projection fibers. Conclusion: High cumulative BMI is associated with smaller brain volume, larger volume of white matter lesions, and abnormal microstructural integrity. Adults younger than 45 years are suggested to maintain their BMI below 26.2 kg/m2 for better brain health. Trial Registration: This study was registered on clinicaltrials.gov (Clinical Indicators and Brain Image Data: A Cohort Study Based on Kailuan Cohort; No. NCT05453877; https://clinicaltrials.gov/ct2/show/NCT05453877).

Summary: Background: The most recent updated hypertension guidelines recommend individuals with systolic blood pressure (SBP)/diastolic blood pressure (DBP) of 130–139/80–89 mmHg and high cardiovascular risk should receive antihypertensive drug treatment. This study aimed to assess the benefits and cost-effectiveness of medication for people aged ≥35 years with this blood pressure stratum and high cardiovascular risk in China. Methods: The benefits of drug treatment in adults aged ≥35 years with SBP/DBP of 130–139/80–89 mmHg and high cardiovascular risk were evaluated in decision-analytic simulation models. Decreasing numbers of cardiovascular disease (CVD) events and premature deaths from all causes and increasing quality-adjusted life-years (QALYs) from drug treatment were estimated in 10-year and lifetime horizons. The incremental cost-effectiveness ratios (ICER) for drug treatment were calculated. Findings: Among approximately 106.60 million Chinese adults aged ≥35 years with this blood pressure stratum and high cardiovascular risk, drug treatment was estimated to prevent 2,060,000 strokes and 660,000 myocardial infarctions over a 10-year time horizon. Adults prescribed antihypertensive drugs could gain 0.034 incremental QALYs. Over a lifetime horizon, adults who start treatment earlier could benefit more in preventing CVD and gaining incremental QALYs. The medication treatment is cost-effective either over a 10-year time horizon with an ICER of Int$13321.29 per QALY gained or over the remaining lifetime. Interpretation: Antihypertensive treatment of adults with SBP/DBP of 130–139/80–89 mmHg and high cardiovascular risk would gain substantial benefits with cost-effectiveness. The young and middle-aged population would derive the most benefit. Funding: National Natural Science Foundation of China, and Beijing Natural Science Foundation.

Abstract Background Previous studies have reported that inflammatory responses can promote the onset of cardiovascular diseases; however, its association with cardiac conduction disorders remains unclear. The present community-based cohort study aimed to elucidate the effects of inflammatory responses on the risk of developing cardiac conduction disorders. Methods After the exclusion of participants failing to meet the inclusion criteria, 86,234 eligible participants (mean age: 50.57 ± 11.88 years) were included. The participants were divided into high-sensitivity C-reactive protein (hsCRP) ≤ 3 mg/L, and hsCRP > 3 mg/L groups based on hsCRP values. Multivariate Cox proportional hazard model was used to analyze the relationship between inflammatory responses and various cardiac conduction disorders. Results After adjusting for confounding factors, we observed that compared with the hsCRP ≤ 3 mg/L group, the hsCRP > 3 mg/L group exhibited increased risks of atrioventricular block (hazard ratio [HR]:1.64, 95%confidence interval [CI] 1.44–1.87) and left (HR:1.25, 95% CI 1.07–1.45) and right bundle branch block (HR:1.31, 95% CI 1.17–1.47). Moreover, the risk of various cardiac conduction disorders increased for every 1 standard deviation increase in log (hsCRP). The restricted cubic spline function confirmed a linear relationship between log (hsCRP) and the risk of developing cardiac conduction disorders (All nonlinearity P > 0.05). Conclusions High hsCRP levels are an independent risk factor for cardiac conduction disorders, and hsCRP levels are dose-dependently associated with the risk of conduction disorders. Our study results may provide new strategies for preventing cardiac conduction disorders.

Abstract Background The relationship of cumulative remnant-cholesterol (Cum-RC) concentration with the risk of cardiovascular disease (CVD) in patients with hypertension remains unclear. Methods We studied data for 28,698 individuals for whom three consecutive total cholesterol, high-density lipoprotein-cholesterol (HDL-C), and triglyceride concentrations were available, and who did not have CVD (14,349 with hypertension and 14,349 without), that was collected between 2006 and 2010. Participants with hypertension were placed into four groups based on Cum-RC quartile: a Q1 group (

Abstract Objective To investigate the association between metabolic syndrome (MetS) and its components and the risk of developing urologic cancers. Methods This study included 101,510 observation subjects from May 2006 to December 2007. The subjects received questionnaires and were subjected to clinical and laboratory examinations to collect data on baseline population characteristics, waist circumference (WC), blood pressure (BP), blood glucose, blood lipids, lifestyle, and past disease history. Finally, follow-up was conducted from the date of recruitment to December 31, 2019. Cox proportional hazards modelling was applied to analyze the association between MetS and its components and the risk of developing urologic cancers. Results A total of 97,975 observation subjects met the inclusion criteria. The cumulative follow-up period included 1,209,178.65 person-years, and the median follow-up time was 13.03 years. During the follow-up period, 485 cases of urologic cancers (165 cases of kidney cancer, 134 cases of prostate cancer, 158 cases of bladder cancer, and 28 cases of other urologic cancers) were diagnosed. The log-rank test results for the cumulative incidences of urologic cancer, kidney cancer, and prostate cancer indicated significant (P

Abstract Background High triglyceride-glucose index (TyG) is a major risk factor for heart failure, but the long-term effect of high TyG index on the risk of developing heart failure remains unclear. Therefore, we aimed to determine the relationship between the cumulative exposure to TyG index and the risk of heart failure. Methods A total of 56,149 participants from the Kailuan Study, who participated in three consecutive health examinations in 2006, 2008, and 2010 and had no history of heart failure or cancer were recruited for this study. The cumulative TyG index was calculated as the weighted sum (value × time) of the mean TyG index for each time interval. The participants were placed into quartiles based on their cumulative TyG index. The study ended on December 31, 2020, and the primary outcome was new-onset heart failure during the follow-up period. In addition, a Cox proportional hazards regression model and a restricted cubic spline analysis were used to further evaluate the relationship between cumulative TyG index and the risk of heart failure. Results During a median follow-up period of 10.04 years, a total of 1,312 new heart failure events occurred. After adjustment for potential confounding factors, the Cox regression analysis showed that the hazard ratios (95% confidence intervals) for the risk of heart failure in the Q2, Q3, and Q4 groups were 1.02 (0.83,1.25), 1.29 (1.07,1.56) and 1.40 (1.15,1.71), respectively, vs. the Q1 group. The subgroup analysis showed a significant interaction between cumulative TyG index and BMI or waist circumference, but there was no interaction between age, sex and cumulative TyG index. The restricted cubic spline analysis showed a dose-response relationship between cumulative TyG index and the risk of heart failure. In addition, the sensitivity analysis generated results that were consistent with the primary results. Conclusions High cumulative TyG index is associated with a higher risk of heart failure. Thus, the TyG index may be useful for the identification of individuals at high risk of heart failure. The present findings emphasize the importance of the long-term monitoring of the TyG index in clinical practice.

Abstract Despite an alarming increase in the prevalence of hypertension among Chinese young adults, longitudinal studies investigating factors that affect the maintenance of normal blood pressure (BP) in this population are lacking. Our study aimed to address this knowledge gap. A total of 7100 participants from the Kailuan Study who had normal BP and were aged

Abstract Background There is limited evidence on the association between arterial stenosis and the risk of all‐cause mortality in cancer patients (ACMC). This study investigated whether the status of arterial function and structure measured by brachial–ankle pulse wave velocity (baPWV) is associated with ACMC. Methods A total of 43,943 Chinese adults underwent a baPWV examination. Cox proportional hazards model was used to assess the association between the baPWV values and ACMC. Results During a total follow‐up duration of 3.81 ± 2.50 years, there were 157 deaths among 553 cancer cases diagnosed during the follow‐up. Patients with baPWV ≥18 m/s showed an increased risk of ACMC compared to patients with ideal vascular function. In the multivariate‐adjusted model, we observed a significant association between arterial stiffness severity and ACMC with a hazard ratio (HR) 2.72 (95% confidence interval [CI]: 1.55–4.80; p