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.

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.

ObjectiveTo investigate the association between cumulative triglyceride （cumTG） exposure and the risk of acute pancreatitis （AP）. MethodsA prospective study was conducted for a cohort of 56 883 workers from Kailuan Group who participated in annual physical examination for three consecutive times in 2006-2010 （2006， 2008， and 2010） and had complete TG data without the medical history of AP. According to the quartiles of cumTG calculated， the subjects were divided into four groups （Q1， Q2， Q3， and Q4 groups）， and general information was compared between the two 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 continuous data with skewed distribution between multiple groups； the chi-square test was used for comparison of categorical data between groups. The Kaplan-Meier method was used to plot the survival curve and calculate the cumulative incidence rate of AP， and the Log-rank test was used for comparison between groups； the Cox regression model was used to analyze the effect of different cumTG levels on new-onset AP events. ResultsAfter follow-up for 10.51±1.76 years， there were 158 AP events in total， with a total incidence density of 2.64 per 10 000 person-years， and the number of cases and incidence density in the Q1， Q2， Q3， and Q4 groups were 29 cases （1.93 per 10 000 person-years）， 34 cases （2.27 per 10 000 person-years）， 30 cases （2.01 per 10 000 person-years）， and 65 cases （4.37 per 10 000 person-years）. The Log-rank test showed that there was a significant difference in cumulative incidence rate between groups （χ²=22.41， P<0.001）. The multivariate Cox regression analysis showed that compared with the Q1 group， the Q4 group had a significantly higher risk of AP （hazard ratio ［HR］=1.94， 95% confidence interval ［CI］： 1.20‍ ‍—‍ 3.13， P=0.01）. Compared with cumulative triglyceride exposure for 0 year， cumulative triglyceride exposure for 4 and 6 years significantly increased the risk of AP， with an HR value of 2.04 （95%CI： 1.26‍ ‍—‍ 3.30， P<0.01） and 3.20 （95%CI： 1.98‍ ‍—‍ 5.17， P<0.01）， respectively. After exclusion of the AP cases that occurred during the 2-year follow-up， the repeated multivariate Cox regression analysis showed that the Q4 group had an HR value of 1.96 （95%CI： 1.23‍ ‍—‍ 3.12， P<0.01） for the onset of AP， and after exclusion of the death cases during follow-up， the repeated multivariate Cox regression analysis showed that the Q4 group had an HR value of 1.85 （95%CI： 1.10‍ ‍—‍ 3.14， P<0.05） for the onset of AP. ConclusionThe incidence rate and risk of AP tend to increase with the increase in cumTG exposure.

Objective:To investigate the impact of non-high-density lipoprotein cholesterol (non-HDL-C) level on major adverse cardiovascular and cerebrovascular events (MACCE) and all-cause mortality in the Kailuan Study cohort undergoing revascularization.Methods:This is a prospective cohort study, with participants from the Kailuan Study cohort who participated in physical examinations from 2006 to 2020 and received revascularization therapy for the first time. According to the level of non-HDL-C, the study subjects were divided into 3 groups:<2.6 mmol/L group, 2.6-<3.4 mmol/L group, and≥3.4 mmol/L group. Annual follow-up was performed, and the endpoint events were MACCE and all-cause mortality. Cox proportional regression model was implemented to estimate the impact on MACCE and all-cause mortality associated with the different non-HDL-C groups. The partial distributed risk model was used to analyze the impact of different non-HDL-C levels on MACCE event subtypes, and death was regarded as a competitive event. The restricted cubic spline regression model was used to explore the dose-response relationship between non-HDL-C level and all-cause mortality, MACCE and its subtypes.Results:A total of 2 252 subjects were enrolled in the study, including 2 019 males (89.65%), aged (62.8±8.3) years, the follow-up time was 5.72 (3.18, 8.46) years. There were 384 cases(17.05%) of MACCE and 157 cases(6.97%) of all-cause mortality. Compared with patients with non-HDL-C≥3.4 mmol/L, patients with non-HDL-C<2.6 mmol/L were associated with a 38% reduced risk of MACCE after revascularization [ HR=0.62(95% CI: 0.48-0.80)]. Every 1 mmol/L decrease in non-HDL-C was associated with a 20% reduction in the risk of MACCE [ HR=0.80(95% CI: 0.73-0.88)]. The results of restricted cubic spline also showed that non-HDL-C levels after revascularization therapy were positively correlated with MACCE events (overall association P<0.001, non-linear association P=0.808). For all-cause mortality, compared to the non-HDL-C≥3.4 mmol/L group, the HR for all-cause mortality after revascularization in non-HDL-C<2.6 mmol/L group was 0.67(95% CI: 0.46-1.01). Every 1 mmol/L decrease in non-HDL-C was associated with a 15% reduction in the risk of all-cause mortality [ HR=0.85(95% CI: 0.73-0.99)]. The restricted cubic spline results showed a linear association between non-HDL-C levels after revascularization therapy and the risk of all-cause mortality (overall association P=0.039, non-linear association P=0.174). Conclusion:The decrease in non-HDL-C levels after revascularization were significantly associated with a reduced risk of MACCE and all-cause mortality.

Objectives:To investigate the association of trajectories of atherogenic index of plasma(AIP)with the risk of atherosclerotic cardiovascular disease(ASCVD). Methods:A total of 51 831 employees and retirees who participated in Kailuan Group health examination for three consecutive times from 2006 to 2010 were included in this study.AIP was calculated using the log(triglycerides[TG]/high-density lipoprotein-cholesterol[HDL-C])formula.AIP trajectory models were fitted by the SAS Proc Traj program,and according to AIP trajectory,the subjects were divided into low stability group(n=11 114),low to moderate stability group(n=21 647),medium to high stability group(n=13 659),and high stability group(n=5 411).Kaplan-Meier method was used to calculate the cumulative incidence of ASCVD in different groups and compared by log-rank test.Cox proportional risk regression model was used to analyze the effects of different AIP trajectories on ASCVD risk. Results:Finally,51 831 patients were included in the analysis.During a mean follow-up of(10.19±2.22)years,5 142(9.92%)subjects developed ASCVD,4 013(7.74%)subjects died.Cox regression analysis after adjusting for confounding factors showed:compared with the low stability group,the risk of ASCVD increased by 13%(HR=1.13,95%CI:1.04-1.23,P=0.003)and 20%(HR=1.20,95%CI:1.10-1.31,P＜0.001)and 41%(HR=1.41,95%CI:1.27-1.57,P＜0.001)in the low to moderate stability group,moderate to high stability group and high stability group,respectively,and the risk increased gradually(Ptrend＜0.001).Stratified analysis showed that the risk of ASCVD in people aged＜65 years and low-density lipoprotein cholesterol(LDL-C)＜3.4 mmol/L with long-term high levels of AIP was higher than that in people aged≥65 years and LDL-C≥3.4 mmol/L(both Pinteraction＜0.01). Conclusions:In Kailuan Study cohort,those with long-term high levels of AIP had a higher risk of ASCVD,and the risk gradually increased.In addition,we found that the risk of ASCVD in people with long-term high levels of AIP was higher in＜65 years old than in≥65 years old,and the risk of ASCVD in people with LDL-C＜3.4 mmol/L was higher than that in people with LDL-C≥3.4 mmol/L.

Objectives:To evaluate the association between estimated pulse wave velocity(ePWV)and risk of new-onset diabetes. Methods:A total of 82 440 employees without prior diabetes who participated in the health examination from July 2006 to October 2007 were selected as the observation cohort,participants were followed-up for a mean of(13.19±3.73)years.The study population was divided into four groups according to the ePWV quartiles:group Q1(ePWV<12.35 m/s,n=20 610),group Q2(12.35 m/s≤ePWV<13.74 m/s,n=20 610),group Q3(13.74 m/s≤ePWV<15.16 m/s,n=20 611),and group Q4(ePWV≥15.16 m/s,n=20 609).ROC curve was used to analyze the predictive value of ePWV for new-onset diabetes.The incidence density of diabetes in each group was calculated.After adjustment for the traditional cardiovascular risk factors(including sex,smoking,drinking,exercise,education level,family history of cardiovascular disease,history of myocardial infarction,history of stroke,body mass index,total cholesterol,fasting blood glucose,uric acid and high-sensitivity C-reactive protein),multivariate Cox regression models were used to evaluate the association between ePWV and risk of new-onset diabetes. Results:The area under the ROC curve of ePWV was 0.60 in the prediction of new-onset diabetes,and the optimal cut-offvalue was 12.78 m/s.With the increase of ePWV quartile,the incidence density of diabetes showed an increasing trend,which was 5.84/1 000 person years,12.04/1 000 person years,15.70/1 000 person years and 16.87/1 000 person years,respectively.After adjusting for the traditional cardiovascular risk factors,the risk of new onset diabetes increased by 9%(HR=1.09,95%CI:1.08-1.11,P<0.01)for each 1 m/s increase in ePWV.Subgroup analysis showed that higher ePWV was significantly associated with increased risk of new-onset diabetes regardless of presence or absence of cardiovascular risk factors,male or female,and age<51 years or age≥51 years,with the HR(95%CI)values of 1.07(1.05-1.08)and 1.21(1.08-1.36),1.07(1.06-1.09)and 1.17(1.15-1.20),1.22(1.19-1.24)and 1.06(1.04-1.07). Conclusions:ePWV has a certain predictive value for new-onset diabetes and is an independent risk factor for new-onset diabetes.

Objectives:To investigate the association between normal-weight central obesity with new-onset cardiovascular disease and all-cause mortality risk. Methods:A prospective cohort study was conducted,selecting a total of 93885 participants from the Kailuan Study who had their first physical examination in 2006-2007.According to waist circumference (central obesity:male waist circumference ≥90 cm,female waist circumference ≥85 cm;no central obesity:male waist circumference<90 cm,female waist circumference<85 cm) and body mass index (BMI,normal weight:18.5 kg/m2≤BMI<24.0 kg/m2;overweight/obesity:BMI ≥24.0 kg/m2),the participants were divided into 4 groups:normal weight no central obesity group (G1 group),normal weight central obesity group (G2 group),overweight/obesity no central obesity group (G3 group) and overweight/central obesity group (G4 group);Using the Kaplan-Meier method,the cumulative incidence of new-onset cardiovascular diseases (including hemorrhagic stroke,ischemic stroke and myocardial infarction) and all-cause mortality in different groups was calculated,and the Log-rank test was used for intergroup comparisons.Furthermore,the associations between the different groups and the risk of new-onset cardiovascular diseases and all-cause mortality were analyzed using the multivariate Cox proportional hazard regression model. Results:After a median follow-up of 14.97 (14.55,15.17) years,the cumulative incidence of new-onset cardiovascular diseases in G1 group,G2 group,G3 group and G4 group was 7.62％,10.84％,8.67％,12.91％ respectively (log-rank P<0.05) and the cumulative incidence of all-cause mortality was 12.83％,19.72％,10.65％,16.33％ respectively (log-rank P<0.01).After adjusting for confounding factors,Cox regression analysis showed that the HR (95％CI) of new-onset cardiovascular diseases in G2 group,G3 group and G4 group were 1.14 (1.04-1.25),1.07 (1.01-1.14),1.27 (1.21-1.34),respectively compared with G1 group (all P<0.05).The HR (95％CI) of all-cause mortality were 1.06 (1.00-1.14),0.90 (0.85-0.95),0.97 (0.93-1.01) compared with G1 group,and P values were 0.07,<0.01,0.15,respectively.The results of sensitivity analysis were consistent with the above major studies after excluding overweight/obesity and cancer participants during follow-up. Conclusions:Normal-weight central obesity increases the risk of new-onset cardiovascular diseases and all-cause mortality.

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 <130 mmHg (intensive treatment) or 130 mmHg to <150 mmHg (standard treatment). Patients underwent repeated examinations of the brachial-ankle pulse wave velocity (baPWV) and ankle-brachial index (ABI) at baseline, and the arterial stiffness was evaluated at the 3-year follow-up. A total of 5339 patients who had twice repeated measurements were included in this study. Changes in arterial stiffness between the intensive and standard treatment groups were analyzed using a multivariate linear regression model. The Cox proportional hazard regression model was used to evaluate the effect of intensive treatment on primary CVD outcomes.Results::The changes in baPWV were 61.5 cm/s (95% confidence interval [CI]: 49.8–73.2 cm/s) in the intensive treatment group and 98.4 cm/s (95% CI: 86.7–110.1 cm/s) in the standard treatment group ( P <0.001). Intensive treatment significantly delayed the progression of arterial stiffness, with an annual change of 23.1 cm·s –1·year –1vs. 36.7 cm·s –1·year -1 of baPWV in the intensive and standard treatment groups, respectively. During a median follow-up period of 3.36 years, primary CVD outcomes occurred in 77 (2.9%) patients in the intensive treatment group compared with 93 (3.5%) in the standard treatment group. Intensive treatment resulted in a significantly lower CVD risk in patients aged 70–80 years or with SBP <140 mmHg. Conclusion::Intensive blood pressure control with an SBP target of 110 mmHg to <130 mmHg could delay the progression of arterial stiffness and reduce the risk of CVD in older patients with hypertension.Clinical trial registration::http://www.clinicaltrials.gov; No. NCT03015311.

Objective To investigate the correlation between exposure of uric acid accumulation and the risks of acute pancreatitis(AP)in the population in Kailuan Group.Methods A prospective study was performed based on thesubjects receiving annual physical examination during 2006 to 2010 in Kailuan Group.All of them had no AP history but had complete data on UA.The starting point of follow-up was when the subjects completed the health examination in 2010,and the end point was new AP events,deaths or the end of follow-up(2021-12-31).Exposure of uric acid accumulation(cumUA)was calculated according to the average values of uric acid measured in each two consecutive physical examinations and the intervalbetween these two consecutive physical examinations.The cumulative incidences of AP indifferent subgroups(determined by the quartile of cumUA)were described using Kaplan-Meier product limit-method and compared by log-rank test.Multivariate Cox proportional hazards regression model was used to analyze the impacts of different cumUA subgroups on new occurrence of AP events.Results A total of 55,799 subjects were included in this study.The subjects were divided into four groups according to the quartile of cumUA.Sex ratio,average age,BMI,systolic blood pressure(SBP),diastolic blood pressure(DBP),FPG,TC,TG,LDL-C,HDL-C,smoking,alcohol consumption,education≥9 years,physical exercise,history of hypertension,and history of cholelithiasis differed significantly among the groups(P<0.05),there was no difference in diabetes history among the 4 groups(P=0.30).153 patients developed AP during an average follow-up of(10.52±1.75)years,the incidence rates were 1.65,2.76,2.13 and 3.96 per 10 000 person-year in the Q1,Q2,Q3and Q4,respectively(P<0.01).After adjusting sex,age,TC,TG,eGFR,smoking,alcohol consumption,education,physical activity,and history of hypertension,diabetes,or cholelithiasis,Multivariate analysis showed a significantly increased risk in Q4(HR=1.77,95%CI:1.07～2.92)as comparing with Q1.After excluding deaths during the follow-up period,Multivariate Cox regression analysis was performed again in Q4 HR=1.75(95%CI:1.04～2.95).Conclusions With the increase of cumUA exposure,both morbidity and risk of AP occur-rence have the tendency of rising.