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 association between dipstick hematuria and chronic kidney disease(CKD)in patients with diabetes mellitus(DM).Methods DM patients who underwent the first health examination among the working and retired employees of Kailuan General Hospital and 11 affiliated hospitals in Tangshan City,Hebei Province from 2006 to 2007 were included as the study objects.Test dipstick hematuria is defined by the level of urine occult blood on the test paper:negative dipstick hematuria(NH)<10 erythrocytes/μl,moderate dipstick hematuria(MH)trace～1+(10～49 erythrocytes/μl),severe dipstick hematuria(SH)2+～3+(≥50 erythrocytes/μl).CKD is diagnosed based on eGFR and urinary protein levels.Logistic regression model was used to analyze the association between paper hematuria and CKD in DM patients.Results A total of 8958 DM patients were included,including 2390 patients(26.68%)in the CKD group and 6568 patients(73.32%)in the DM group.The detection rates of moderate dipstick hematuria and severe dipstick hematuria in CKD group were 9.00%and 4.64%,respectively,higher than those in DM group(7.20%and 2.33%).The risk of CKD in MH and SH patients was 1.560(95%CI 1.260～1.940)and 3.080(95%CI 2.220～4.270)times that in NH patients,respectively.The odds ratios were 1.960(95%CI 1.530～2.510)and 3.430(95%CI 2.270～5.200)in males and 0.910(95%CI 0.580～1.430)and 2.760(95%CI 1.570～4.880)in females.The odds ratios were 1.650(95%CI 1.150～2.350)and 4.070(95%CI 2.240～7.400)in patients aged≥60 years,and 1.550(95%CI 1.170～2.040)and 2.860(95%CI 1.920～4.240)in patients aged<60 years.Conclusions Dipstick hematuria is a risk factor for CKD in DM patients.The association between dipstick hematuria and CKD in DM patients is not only independent of traditional risk factors,but also affected by age and gender.

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.

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.

Objectives:To investigate the impact of baseline non-high-density lipoprotein cholesterol(non-HDL-C)levels on new-onset cardiovascular disease(CVD)in postmenopausal women. Methods:This prospective cohort study selected 8 893 postmenopausal women who participated from 2006 to 2018 employee health examination of Kailuan Group and had complete total cholesterol(TC)and HDL-C data and no history of CVD.Participants were followed up to 31 December,2021.The primary endpoint was the occurrence of CVD or death.According to the Chinese Lipid Management Guidelines(2023),the participants were divided into non-HDL-C<4.1 mmol/L group(n=6 079),4.1 mmol/L≤non-HDL-C<4.9 mmol/L group(n=1 824)and non-HDL-C≥4.9 mmol/L group(n=990).The cumulative incidence of CVD in different groups of non-HDL-C levels was calculated using the Kaplan-Meier method and tested by log-rank analysis.Multivariate Cox regression model was used to analyze the effects of different non-HDL-C levels on CVD. Results:The mean follow-up time was(10.78±4.48)years,the cumulative incidence of CVD in different non-HDL-C level groups was 1.82%,3.24%and 2.89%,respectively.Kaplan-Meier survival curve showed a statistically significant difference in cumulative incidence among the three groups(log-rank P<0.0001).The results of Cox regression analysis showed that after adjusting for confounding factors such as age and sex,the HR(95%CI)values for CVD in the 4.1≤non-HDL-C<4.9 mmol/L group and the non-HDL-C≥4.9 mmol/L group were 1.40(1.13-1.74)and 1.35(1.03-1.78),respectively. Conclusions:High non-HDL-C levels are an independent risk factor for new-onset CVD in postmenopausal women.

Objectives:To investigate the impact of resting heart rate on the risk of all-cause mortality in ultra-high risk atherosclerotic cardiovascular disease(ASCVD)patients. Methods:A total of 3 645 patients with ultra-high risk ASCVD(as defined in the 2023 Chinese Lipid Management Guidelines)were screened from the 2006 to 2020 Kailuan Study cohort,and after excluding 602 patients with missing resting heart rate,3 043 patients were included in the final analysis.Patients were divided into＜68 beats/min group(n=744),68-74 beats/min group(n=786),75-80 beats/min group(n=760),and≥81 beats/min group(n=753)according to the resting heart rate.Cox proportional regression model was used to estimate the hazard ratios(HRs)and 95%CI for all-cause mortality associated with the different resting heart rate groups and every 10 beats/min increase of resting heart rate.The dose-effect relationship of resting heart rate level and all-cause mortality was assessed by a restricted cubic spline regression model.The Kaplan-Meier method was applied to calculate the cumulative all-cause mortality in different groups,and the differences were compared using log-rank test. Results:The median follow-up time was 5.81(3.46,9.64)years,there were 772(25.37%)all-cause deaths during follow up.After adjusting major confounding factors,the results showed that compared with＜68 beats/min group,the risk of all-cause mortality in 75-80 beats/min group and≥81 beats/min group increased by 24%(HR=1.24,95%CI:1.01-1.52,P=0.047)and 47%(HR=1.47,95%CI:1.20-1.81,P＜0.001),respectively;the risk of all-cause mortality in 68-74 beats/min group was similar(HR=1.06,95%CI:0.86-1.31,P=0.625).In addition,an increase of 10 beats/min in resting heart rate was associated with a 13%increase in the risk of all-cause mortality(HR=1.13,95%CI:1.07-1.19,P＜0.001).In stratified analyses,it was found that for every 10 beats/min increase in resting heart rate,women faced a higher risk of all-cause mortality than men,and patients＜65 years old faced a higher risk of all-cause mortality than patients≥65 years old.The restricted cubic spline analysis also showed that resting heart rate was linearly associated with the risk of all-cause mortality(Poverall＜0.001,Pnon-linear=0.933),and the risk increased significantly with resting heart rate＞70 beats/min. Conclusions:Increased resting heart rate is linearly associated with increased risk of all-cause mortality in patients with ultra-high risk ASCVD.The appropriate intervention cut-off point of resting heart rate for ultra-high risk ASCVD patients may be＞75 beats/min.

Objectives:To explore the influencing factors of inter-arm systolic blood pressure difference(sIAD)in young hypertensive population. Methods:A total of 12 895 young Kailuan employees aged≤40 years,who participated in the physical examination from 2010 to 2020,were enrolled in this study.All of them underwent blood pressure measurements of four limbs in supine position.Young hypertensive group(n=3 584)and young non-hypertensive group(n=3 584)were 1∶1 matched by sex and age(±1 year),and participants were further divided into sIAD＜10 mmHg(1 mmHg=0.133 kPa)and sIAD≥10 mmHg subgroups.A stepwise multivariate logistic regression model was established to analyze the determinants of sIAD≥10 mmHg. Results:The detection rate of sIAD≥10 mmHg was significantly higher in the young hypertensive group than in the young non-hypertensive group(31.72%vs.27.76%,P＜0.001).Stepwise multivariate logistic regression analysis showed that in young hypertensive population,ankle-brachial index(ABI)＜0.9,male,obesity,overweight,elevated low density lipoprotein cholesterol(LDL-C)level,and systolic blood pressure were positively associated with sIAD≥10 mmHg,while college education or above,physical exercise were negatively correlated with sIAD≥10 mmHg(all P＜0.05).In the young non-hypertensive population,ABI＜0.9,systolic blood pressure were positively correlated with sIAD≥10 mmHg,while age was negatively associated with sIAD≥10 mmHg(all P＜0.05). Conclusions:The detection rate of sIAD≥10 mmHg is higher in young hypertensive population than in young non-hypertensive population.Decreased ABI,male sex,obesity,overweight,increased LDL-C level,systolic blood pressure,college education and above,and physical exercise are the influencing factors of sIAD≥10 mmHg in young hypertensive population.

Objective:To analyze the changes of fasting plasma glucose(FPG)level before and after menopause.Methods:Kailuan health checkup cohort was used to extract data of women aged≥18 years who participated in the first physical examination of Kailuan physical examination cohort and had menopausal age at the end of the seventh physical examination. A total of 3 749 women with 22 057 physical examination records were included in the analysis. Natural logarithmic transformation was applied to FPG, and a segmented linear mixed-effects model was used to analyze the changes in ln-transformed FPG before and after menopause. Additionally, an interaction analysis was performed to assess the multiplicative effect of baseline age and baseline body mass index(BMI)on ln-transformed FPG concerning pre- and post-menopausal periods.Results:The average age of the first physical examination for women in this study was (45.63±4.52)years, the median menopausal age was 51(50~53)years, and the median number of physical examinations was 6(5~7)times. The results of the piecewise linear mixed effect model showed that lnFPG increased from 1 year before menopause, with an average annual increase of 0.021 mmol/L, and continued to increase from menopause to 5 years after menopause, with an average annual increase of 0.007 mmol/L. LnFPG tended to be stable after 5 years of menopause. Baseline age could affect the changes of lnFPG before and after menopause, and there was a negative multiplicative interaction between baseline age ≥45 years and the time period from 6 years to 1 year before menopause( P=0.032). Women with baseline age ≥45 years had a higher average annual increase in lnFPG from 1 year before menopause to 5 years after menopause than women with baseline age <45 years( P<0.05). On lnFPG, there was a positive multiplicative interaction between baseline BMI and time segments around menopause. Compared to women with BMI <24.0 kg/m 2, obese women displayed more annual increase in lnFPG from 6 years to 1 year before menopause as well as from menopause to 5 years after menopause( P<0.05). Conclusions:Menopause has an adverse impact on FPG, with the most significant changes occurring within the period of one year before menopause and up to five years after menopause. Age and BMI significantly influence the changes in FPG before and after menopause.