ObjectiveTo systematically evaluate the association between serum indirect bilirubin （IBIL） levels and the risk of stroke incidence in patients with cardiovascular-kidney-metabolic （CKM） syndrome stages 0-3. MethodsA total of 48 301 participants with CKM syndrome stages 0-3 were included， during which 2 904 stroke events were recorded. A prospective cohort study design was employed. Cox proportional hazards regression models were used to analyze the relationship between IBIL and stroke risk， and restricted cubic spline （RCS） regression was applied to examine the dose-response relationship. Threshold effect analysis was conducted to identify potential inflection points in nonlinear relationships. ResultsMultivariable Cox regression analysis showed that in the overall population， each 1 μmol/L increase in IBIL level was associated with approximately a 1.2% reduction in stroke risk （HR = 0.988， 95% CI： 0.979-0.996， P < 0.05）. A significant interaction was observed between IBIL and CKM stages in relation to stroke risk （P_interaction < 0.05）. In individuals with stages 0–2 of CKM syndrome， higher IBIL levels showed a significant inverse association with stroke risk （P_trend < 0.05）； however， no such association was observed in stage 3 patients. RCS regression and threshold effect analysis further revealed a nonlinear relationship between IBIL levels and stroke risk in stage 3 CKM patients （P_{log-likelihood ratio} < 0.05）. When serum IBIL exceeded 10.980 μmol/L， each 1 μmol/L increase was associated with approximately 5.7% increase in stroke risk （HR = 1.057， 95% CI： 1.009–1.107， P < 0.05）. ConclusionThe correlation between serum IBIL and stroke varies across different stages of CKM syndrome， showing a significant negative association in individuals at stages \0–2， while in stage 3 patients， it exhibits a threshold effect with an inflection point at 10.980 μmol/L.

Objective:To explore the association between cardiovascular health status and cardiovascular events in hypertensive patients with different ages of onset.Methods:This study was a prospective cohort study. Participants who were free of hypertension, myocardial infarction, stroke, heart failure, and other cardiovascular diseases at their first annual health examination at Kailuan Group from 2006 to 2012, but were newly diagnosed with hypertension during subsequent follow-up, were included. Clinical data was collected, and cardiovascular health status was assessed using the Life′s Essential 8 (LE8) score (categorized as low level and moderate-to-high level). Based on changes in LE8 scores from the first to the second health examination, transitions in cardiovascular health status were classified into 4 patterns: consistently low, low to moderate-to-high, moderate-to-high to low, and consistently moderate-to-high. Newly diagnosed hypertensive patients were stratified by age at diagnosis into 3 groups:<45 years, 45-<60 years, and ≥60 years. Participants were followed up, with the primary outcome being cardiovascular events, including myocardial infarction and stroke. Multivariable Cox regression models with age as the time scale were used to analyze the association between cardiovascular health status, its transitions, and cardiovascular events across different ages of hypertension onset. Restricted cubic spline models were employed to examine the patterns of association between LE8 scores, their changes, and cardiovascular events.Results:A total of 22 217 newly diagnosed hypertensive patients were included, with a mean age of (53.68±11.45) years and 18 260 males (75.13%). The median follow-up time was 9.62 years. Across all three age strata, compared with participants with low cardiovascular health status, those with moderate-to-high cardiovascular health status had a lower risk of cardiovascular events: HR=0.53 (95% CI: 0.36-0.79) for onset age <45 years; HR=0.64 (95% CI: 0.58-0.82) for onset age 45-60 years; and HR=0.71 (95% CI: 0.54-0.93) for onset age ≥60 years. Among newly diagnosed hypertensive patients with onset age <45 years and 45-<60 years, those with consistently moderate-to-high cardiovascular health status had a reduced risk of cardiovascular events compared to those with consistently low status (all P<0.05); however, the difference was not statistically significant in patients with onset age ≥60 years ( P>0.05). The protective effect of consistently moderate-to-high cardiovascular health status was strongest in patients with onset age <45 years ( HR=0.47, 95% CI: 0.25-0.88). Across all age strata, the risk of cardiovascular events decreased with increasing LE8 score ( P<0.05), with the most pronounced reduction observed in patients with onset age <45 years. For every 10-point increase in LE8 score, the risk of cardiovascular events decreased by 29% in this group ( HR=0.71, 95% CI: 0.56-0.89). Restricted cubic spline analysis indicated a linear dose-response relationship between LE8 scores, their changes, and the risk of cardiovascular events ( P<0.05). Conclusions:Hypertensive patients with moderate-to-high cardiovascular health status across different ages of onset have a lower risk of cardiovascular events, with the strongest protective effect observed among younger individuals. Moreover, different patterns of change in cardiovascular health status have distinct impacts on cardiovascular events. Improvement in cardiovascular health status can reduce the risk of cardiovascular events in newly diagnosed hypertensive patients, and this protective effect is more pronounced in younger adults.

Objective To investigate the correlation of the cumulative exposure of body mass index(BMI)with epicardial adipose tissue(EAT)volume.Methods Based on the Kailuan study cohort,subjects were divided into Q1,Q2 and Q3 according to the cumula-tive BMI exposure level.The generalized linear regression model was used to analyze the correlation between different cumulative BMI exposure levels and EAT volume.According to the median of EAT volume(115.83 cm3),EAT volume was defined as increased EAT volume when EAT volume was higher than or equal to the median EAT volume.Logistic regression model was used to analyze the correlation between different cumulative BMI exposure levels and increased EAT volume.Results With the increased of cumu-lative BMI exposure level.The EAT volume increased gradually and the risk of increased EAT volume was significantly increased.Conclusion The level of cumulative BMI exposure is significantly correlated with EAT volume.High levels of cumulative BMI exposure lead to an increased risk of increased EAT volume.

Objective To investigate the association of Chinese visceral adiposity index(CVAI)and high-sensitivity C-reactive protein(hs-CRP)with the risk of digestive malignancies in the Kailuan study population,and to provide a basis for the prevention and control of digestive malignancies in the population.Methods A prospective cohort study was conducted,and a total of 94 377 Kailuan workers who participated in the 2006 health examination,had no history of cancer,and had complete data on CVAI,CRP,and related covariates were selected as the observation cohort.According to the levels of CVAI and CRP,the subjects were divided into low CVAI+CRP≤3 mg/L group[CVAI(-)CRP(-)group],low CVAI+CRP>3 mg/L group[CVAI(-)CRP(+)group],high CVAI+CRP≤3 mg/L group[CVAI(+)CRP(-)group],and high CVAI+CRP>3 mg/L group[CVAI(+)CRP(+)group].An analysis of variance was used for comparison of normally distributed continuous data between groups,and the non-parametric Kruskal-Wallis H test was used for comparison of continuous data with skewed distribution between groups;the chi-square test was used for comparison of categorical data between groups.The Cox proportional-hazards regression model was used to assess the impact of CVAI and CRP alone or in combination on the risk of digestive malignancies.Results There were significant differences between the four groups in age,male/female ratio,total cholesterol,triglycerides,high-density lipoprotein cholesterol,systolic blood pressure,diastolic blood pressure,fasting blood glucose,high-sensitivity C-reactive protein,waist circumference,body mass index,marital status,alcohol consumption,smoking,reported income,and physical exercise(all P<0.05).During a mean follow-up time of 14.08±2.76 years,2 043 new-onset cases of digestive malignancies were identified by the end of follow-up on December 31,2021.The Cox proportional-hazards regression model showed that after adjustment for CRP and other factors,compared with the low CVAI group,the high CVAI group had a hazard ratio(HR)of 1.34(95%confidence interval[CI]:1.23-1.47)for the risk of digestive malignancies.After adjustment for CVAI and other factors,compared with the CRP≤3 mg/L group,the CRP>3 mg/L group had an HR of 1.14(95%CI:1.02-1.28)for the risk of digestive malignancies.Compared with the CVAI(-)CRP(-)group(n=40 978),the CVAI(-)CRP(+)group(n=6 210),the CVAI(+)CRP(-)group(n=36 502),and the CVAI(+)CRP(+)group(n=10 687)had an HR of 1.05(95%CI:1.01-1.09,P<0.05),1.32(95%CI:1.20-1.45,P<0.05),and 1.48(95%CI:1.28-1.70,P<0.05),respectively,for the risk of digestive malignancies.As for digestive malignancies at specific locations,the CVAI(+)CRP(+)group had an increased risk of liver cancer,gastric cancer,pancreatic cancer,colorectal cancer,and small intestinal cancer with an HR of 1.35(95%CI:1.05-1.81,P<0.05),1.48(95%CI:1.09-2.00,P<0.05),1.60(95%CI:1.07-2.41,P<0.05),1.76(1.40-2.21,P<0.05),and 3.85(95%CI:1.43-10.33,P<0.05),respectively.Conclusion A high level of CVAI,a high level of CRP,and high levels of CVAI and CRP in combination can all increase the risk of digestive malignancies,among which the high levels of CVAI and CRP in combination may lead to a higher risk.

ObjectiveTo investigate the association between cumulative atherogenic index of plasma （cumAIP） and the risk of new-onset nonalcoholic fatty liver disease （NAFLD） in young and middle-aged individuals. MethodsA prospective cohort study was conducted among the young and middle-aged individuals （aged 18 to <60 years） in the Kailuan study cohort who underwent physical examination in Kailuan General Hospital and its 10 affiliated hospitals in June 2006 to October 2010， and after screening based on the inclusion and exclusion criteria， 33 987 individuals were included in the observation cohort. The individuals were divided into Q1， Q2， Q3， and Q4 groups based on the quantiles of cumAIP. The Kaplan-Meier method was used to calculate the cumulative incidence rate of new-onset NAFLD in the four groups， while the log-rank test was used for comparison between groups. A multivariate Cox regression analysis was used to obtain the hazard ratio （HR） and 95% confidence interval （CI） of the risk of new-onset NAFLD in the four groups. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups， and the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups； the chi-square test was used for comparison of categorical variables between groups. ResultsThe mean follow-up was 10.89±2.54 years， and there were 6 011 cases of new-onset NAFLD， including 995 cases in the Q1 group， 1 366 in the Q2 group， 1661 in the Q3 group， and 1 989 in the Q4 group， with an incidence density of 11.37， 16.02， 19.97， and 24.91 per thousand person-years. The log-rank test showed that there was a significant difference in cumulative incidence rate between the four groups （P<0.001）. With the presence or absence of NAFLD as the dependent variable and the quantiles of different exposure levels to cumAIP as the independent variable， the multivariate Cox regression model analysis showed that compared with the Q1 group， the Q2， Q3， and Q4 groups had an HR of 1.30 （95%CI： 1.20 — 1.41）， 1.52 （95%CI： 1.41 — 1.65）， and 1.79 （95%CI： 1.64 — 1.95）， respectively， for new-onset NAFLD， with a P_trend value of <0.001. With the presence or absence of new-onset NAFLD as the dependent variable and the cumulative exposure to AIP for 0， 2， 4， and 6 years as the independent variable， the Cox regression analysis showed that compared with cumulative exposure to AIP for 0 years， cumulative exposure to AIP for 2， 4， and 6 years had an HR of 1.24 （95%CI： 1.15 — 1.35）， 1.51 （95%CI： 1.40 — 1.64）， and 1.70 （95%CI： 1.56 — 1.84）， respectively， with a P_trend value of <0.001. A sensitivity analysis was performed after exclusion of the individuals with new-onset NAFLD within 2 years， the individuals who experienced atherosclerotic cardiovascular disease events during follow-up， and the individuals taking antihypertensive， hypoglycemic， and lipid-lowering drugs， and the results were similar to those of the main analysis. Considering the competitive relationship between all-cause death and outcome events， a competing risk analysis of death was performed， which showed that the results of risk analysis were similar to those of the main analysis. ConclusionA high level of cumAIP exposure can increase the risk of new-onset NAFLD in young and middle-aged individuals.

Objective To investigate the association between the variability of remnant cholesterol inflammatory index(RCII),a novel composite biomarker,and the risk of stroke,in order to provide a theoretical basis for stroke prevention.Methods A prospective cohort study was conducted on 38 659 Kailuan individuals who took annual physical examinations in 2006,2008,and 2010.These subjects were grouped based on the quartiles of RCII variability,which was represented by standard deviation(SD)and average real variability(ARV),and were followed up every 2 years,with the occurrence of stroke(including ischemic and hemorrhagic strokes),death,or the end of follow-up on December 31,2022 as the endpoints.Kaplan-Meier method was used to calculate the cumulative incidence rate of endpoint events across different groups,and log-rank test was used to compare the difference of cumulative incidence of endpoint events in each group.Multivariate Cox proportional hazards regression model was adopted to analyze the association between RCII variability and risk of stroke.Results Among the 38 659 participants,a total of 2 539 strokes occurred during a mean follow-up period of 11.22±2.26 years.After adjusting confounding factors,when the participants were grouped by the quartiles of RCII-SD,the hazard ratio(HR)for stroke was 1.034(95%CI:0.917～1.167,P=0.584),1.146(95%CI:1.018～1.290,P=0.025),and 1.209(95%CI:1.066～1.370,P=0.003),respectively in the Q2,Q3,and Q4 groups,when compared with the Q1 group(Ptrend<0.05).When they were grouped by the quartiles of RCII-ARV,the HR for stroke was 1.008(95%CI:0.894～1.136,P=0.901),1.109(95%CI:0.986～1.248,P=0.085),and 1.152(95%CI:1.018～1.303,P=0.025),respectively,in the Q2,Q3,and Q4 groups,when compared with the Q1 group.Furthermore,both sensitivity and stratified analyses yielded similar results.Conclusion RCII variability is significantly associated with stroke,and the risk of stroke is gradually increasing with increment of the variability.Countermeasures Relevant authorities can focus on reducing RCII variability as a central objective by establishing regular monitoring mechanism,strengthening lifestyle interventions,and standardizing dietary,exercise,and weight management in order to suppress the index fluctuations.The principle of stable lipid-lowering in medication and optimization of therapeutic regimens with stable efficacy should be emphasized to prevent the risk of additional vascular damage.

Aim To investigate the effect of cumulative non-high density lipoprotein cholesterol/high density lip-oprotein cholesterol(non-HDLC/HDLC)exposure on atherosclerotic cardiovascular disease(ASCVD).Methods A prospective cohort study was conducted.A total of 50 777 employees of Kailuan Group who participated in three physical examinations in 2006-2007,2008-2009 and 2010-2011 were selected as the study subjects.Groups were divided into Q1,Q2,Q3 and Q4 according to the cumulative non-HDLC/HDLC exposure quartiles.Kaplan-Meier curve was used to calculate the cumulative incidence of ASCVD in different cumulative non-HDLC/HDLC groups,and Log-rank test was used to compare the differences among groups.Cox proportional risk model was used to analyze the effect of cumulative non-HDLC/HDLC exposure on ASCVD.Results The average follow-up was(10.19±2.21)years,and 5 003 new cases of ASCVD occurred.The cumulative incidence of ASCVD in groups Q1 to Q4 was 6.49％,8.71％,10.86％and 14.85％,respectively(Log-rank P＜0.01).Multivariate Cox regression analysis showed that compared with group Q1,the HR(95％CI)of ASCVD in groups Q2,Q3 and Q4 were 1.13(1.03～1.24),1.18(1.07～1.29),1.22(1.12～1.34),respectively;the HR(95％CI)of myocardial infarction were 1.15(0.87～1.53),1.44(1.10～1.88),1.67(1.29～2.17),respectively;the HR(95％CI)of revascularization were 1.21(0.99～1.49),1.31(1.07～1.60)and 1.49(1.22～1.81),respectively;the HR(95％CI)of ischemic stroke were 1.17(1.03～1.32),1.17(1.04～1.33)and 1.21(1.06～1.37),respectively;but the above association was not found when heart failure and atrial fibrillation were used as the outcome events.The restricted cubic spline showed that cumulative non-HDLC/HDLC values were line-arly associated with the risk of ASCVD.Conclusion Cumulative non-HDLC/HDLC exposure was positively associated with the risk of ASCVD.

Objectives:To investigate the correlation between resting heart rate(RHR)and atherosclerotic cardiovascular disease(ASCVD)and all-cause death in young and middle-aged people.Methods:A prospective cohort study was conducted enrolling 72 642 young and middle-aged participants(aged<60 years),who participated in the medical examination of the Kailuan Study from June 2006 to October 2007.According to the quartile of the RHR level,the participants were divided into Q1 group(<67 beats/min,n=14 381),Q2 group(67-70 beats/min,n=15 815),Q3 group(71-75 beats/min,n=15 876),Q4 group(76-80 beats/min,n=13 933)and Q5 group(>80 beats/min,n=12 637).Cox proportional hazard regression model was used to analyze the effect of RHR on ASCVD and all-cause death.The dose-response relationship between RHR and the risk of ASCVD and all-cause death was investigated using a restricted cubic spline regression model.Results:During a mean follow-up of(10.0±4.85)years,2 898 patients(3.99%)developed ASCVD.Multivariate Cox regression analysis showed that after adjusting for confounding factors,the risk of RHR and ASCVD in group Q5 increased by 20%compared with group Q1(HR=1.20,95%CI:1.06-1.35,P<0.05).There was no significant risk in groups Q2 to Q4 compared to Q1 group(all P>0.05).In addition,the risk of ASCVD increased by 4%for every 10 beats/min increase in RHR(HR=1.04,95%CI:1.01-1.07,P=0.009).During the follow-up period of(10.2±4.82)years,all-cause death occurred in 2 175 participants(2.99%).The results showed that compared with Q1 group,the risk of all-cause death in Q3 to Q5 groups increased by 33%(HR=1.33,95%CI:1.15-1.54,P<0.001),33%(HR=1.33,95%CI:1.14-1.54,P<0.001),and 78%(HR=1.78,95%CI:1.54-2.05,P<0.001)respectively,and there was no statistical significance between group Q2 and group Q1.The risk of all-cause death increased by 15%for every 10 beats/min increase in RHR(HR=1.15,95%CI:1.11-1.19,P<0.001).Restricted cubic spline analysis showed that RHR was linearly correlated with risk of ASCVD(Poverall=0.022,Pnon-linear=0.617),and the risk of ASCVD increased significantly with RHR>72 beats/min.RHR was linearly associated with the risk of all-cause death(Poverall<0.001,Pnon-linear=0.212),and the risk of all-cause death was significantly increased with RHR>72 betas/min.Conclusions:Higher RHR is associated with an increased risk of ASCVD and all-cause mortality in young and middle-aged individuals.

Objective:To explore the impact of metabolic syndrome in conjunction with hyperuricemia on the risk of new-onset cardiovascular disease.Methods:This study was a prospective cohort study. From June 2006 to October 2007, employees of Kailuan Group in Tangshan City, Hebei Province were selected as the research subjects. Participants were divided into four groups based on the presence or absence of metabolic syndrome and hyperuricemia. The groups include the normal group, pure hyperuricemia group, pure metabolic syndrome group, and the metabolic syndrome combined with hyperuricemia group. Four groups of participants were followed up, the primary endpoint was the occurrence of a first-ever cardiovascular disease event, including stroke and myocardial infarction. The cumulative incidence rates of cardiovascular disease in different groups during the continuous follow-up period were calculated using the Kaplan-Meier method, and the differences in cumulative incidence rates among groups were compared using the log-rank test. Multivariate Cox regression analysis was used to analyze the effect of hyperuricemia combined with metabolic syndrome on the risk of cardiovascular disease. The likelihood ratio test was used to analyze whether there was a multiplicative interaction and additive interaction between hyperuricemia and metabolic syndrome.Results:A total of 82 780 individuals were included, aged (51.5±12.6) years, and 68 622 (82.90%) were males, with a median follow-up of 14.97 years. Kaplan-Meier survival curve analysis showed that the cumulative incidence of cardiovascular disease was the highest in the metabolic syndrome combined with hyperuricemia group (log-rank P<0.001). Multivariate Cox regression analysis indicated that after adjusting for various confounding factors, the HR value and 95% CI of cardiovascular disease in the metabolic syndrome combined with hyperuricemia group were 1.24 (1.12-1.38) compared with the normal group, which were higher than those in the pure hyperuricemia group and the pure metabolic syndrome group alone. The effect of metabolic syndrome combined with hyperuricemia on the risk of cardiovascular disease demonstrated an additive effect (relative excess risk of interaction: 0.18(0.11-0.25), attributable proportion due to interaction: 0.14(0.09-0.19)). Conclusions:The combination of hyperuricemia and metabolic syndrome is an independent risk factor for cardiovascular disease. Compared to pure metabolic syndrome or hyperuricemia alone, the impact of metabolic syndrome combined with hyperuricemia on cardiovascular disease is more significant.