摘要目的 探讨不同血尿酸水平对新发胆石症的预测价值.方法 采用回顾性队列研究方法.收集2006年6月至2015年12月华北理工大学附属开滦总医院、开滦林西医院、开滦赵各庄医院、开滦唐家庄医院、开滦范各庄医院、开滦吕家坨医院、开滦荆各庄医院、开滦林南仓医院、开滦钱家营医院、开滦马家沟医院、开滦医院分院行健康体检的97 469例受试者的体检资料,分别收集流行病学调查内容、人体测量学指标、生化指标.受试者按照血尿酸四分位数水平分为4组:2 4140例受试者血尿酸＜232μmol/L设为Q1组(对照组)、24 473例受试者232 μmol/L≤血尿酸＜282 μmol/L设为Q2组、24 382例受试者282 μmol/L≤血尿酸＜338 μmol/L设为Q3组、24 474例受试者血尿酸≥338 μmol/L设为Q4组.观察指标:(1)4组受试者临床特征比较.(2)受试者胆石症的发病情况.(3)血尿酸水平对新发胆石症发病的影响:①血尿酸水平与胆石症发病风险的剂量-反应关系;②血尿酸对胆石症模型拟合优度的比较;③按性别分层后不同血尿酸水平对胆石症发病的影响;④箱线图示不同性别的血尿酸情况;⑤按年龄分层后不同血尿酸水平对胆石症发病的影响.正态分布的计量资料以(x)±s表示,多组间比较采用单因素方差分析.偏态分布的计量资料采用M(Q)表示,多组间比较采用Krustal-willis非参数检验.计数资料以百分比表示,组间比较采用x2检验.采用人年发病率计算不同血尿酸分组中胆石症的发病情况.使用限制性立方样条曲线(RCS)计算连续型变量与结局事件风险之间的剂量-反应关系以及95％可信区间(95％CI);进一步使用COX风险比例模型分析不同血尿酸水平对新发胆石症的风险比(HR)和95％CI;使用似然比检验和赤池信息量准则(AIC)计算血尿酸水平对新发胆石症模型的拟合情况;使用箱线图显示不同性别人群中的血尿酸情况.结果 (1)4组受试者临床特征比较:Q1组受试者性别(男性)、年龄、体质量指数(BMI)、收缩压、舒张压、空腹血糖、总胆固醇(TC)、甘油三酯(TG)、超敏C-反应蛋白、糖尿病、高血压病、吸烟、饮酒、体育锻炼人数分别为15 162例、(50±11)岁、(24±3) kg/m2、(123±21)mmHg(1 mmHg=0.133 kPa)、(82±12) mmHg、(5.6±2.0) mmol/L、(4.8±1.2) mmol/L、1.14 mmol/L(0.81～1.63 mmol/L)、0.70 mmol/L(0.23～2.23 mmol/L)、2 537例、9 415例、4 575例、2 380例、2 649例;Q2组分别为19 079例、(51±12)岁、(25±3) kg/m2、(130±21) mmHg、(83±12)mmHg、(5.5±1.7) mmol/L、(4.9±1.2) mmol/L、1.20 mmol/L(0.86～ 1.76 mmol/L)、0.71 mmol/L(0.28～1.98 mmol/L)、2 287例、10 124例、6 918例、3 649例、3 288例;Q3组分别为21 132例、(52±13)岁、(25±3)kg/m2、(132±21) mmHg、(84±12) mmHg、(5.5±1.6) mmol/L、(5.0±1.2) mmol/L、1.29 mmol/L(0.91～1.94 mmol/L)、0.80 mmol/L(0.30～2.06 mmol/L)、2 027例、10 755例、8 259例、4 730例、3 958例;Q4组分别为22 651例、(53±14)岁、(26±3) kg/m2、(134±21) mmHg、(85±12) mmHg、(5.4±1.5) mmol/L、(5.1±1.2) mmol/L、1.54 mmol/L(1.05～2.35 mmol/L)、1.02 mmol/L(0.43～2.50 mmol/L)、1 981例、12 082例、9 562例、6 209例、4 758例;4组受试者上述指标比较,差异均有统计学意义(x2=7 624.63,F=279.93,961.91,330.84,271.40,38.25,353.18,H=3 406.30,912.23,x2=108.15,590.49,2 567.07,2 209.21,760.15,P＜0.05).(2)受试者胆石症的发病情况:97 469例受试者总随访时间为592 922人年,共有新发胆石症4 270例,总发病率为7.20千人/年;Q1、Q2、Q3和Q4组受试者的人年发病率分别为:6.34千人/年(971/153 205*1 000)、6.91千人/年(1 034/149 686*1 000)、7.44千人/年(1 090/146 549*1 000)、8.19千人/年(1 175/143 482*1 000).(3)血尿酸水平对新发胆石症发病的影响:①血尿酸水平与胆石症发病风险的剂量-反应关系.RCS结果表明:以单位变化的血尿酸水平和经对数转化后的血尿酸水平与胆石症发病风险均呈直线关系(x2=11.74,8.01,P＜0.05).②血尿酸对胆石症模型拟合优度的比较:所有受试者中,校正了性别、年龄、BMI、TC、TG、糖尿病、高血压病、吸烟、饮酒和体育锻炼因素对新发胆石症的影响后,与Q1组比较,Q3、Q4组受试者新发胆石症风险均增加(HR=1.10,1.12,95％CI:1.01～ 1.20,1.03～ 1.23,P＜0.05).多因素模型-2Log L值和AIC值分别为92 532.39、92 550.39,多因素模型+血尿酸分别为92 525.35、92 549.35,加入血尿酸的多因素模型与未加入血尿酸的多因素模型比较,差异有统计学意义(x2=7.04,P＜0.05).③按性别分层后不同血尿酸水平对胆石症发病的影响:进行性别分层后,在女性受试者中,校正了年龄、BMI、TC、TG、糖尿病、高血压病、吸烟、饮酒和体育锻炼因素对新发胆石症的影响后,与Q1组比较,Q2、Q3、Q4组受试者新发胆石症风险差异均无统计学意义(HR=1.06,1.15,1.09,95％CI:0.88～1.28,0.93～1.34,0.91～ 1.31,P＞0.05);在男性受试者中,校正了其他上述相同胆石症发病危险因素后,与Q1组比较,Q2、Q3、Q4组受试者新发胆石症风险均增加(HR=1.17,1.24,1.30,95％CI:1.06～1.30,1.12～1.37,1.18～1.44,P＜0.05).④箱线图示不同性别的血尿酸情况:在女性受试者中以年龄每增加10岁分组,18～27岁组、28～37岁组、38～47岁组、48～57岁组、58～67岁组、68～77岁组、78～ 87岁组、88～97岁组受试者血尿酸水平分别为(249±61) μmol/L、(235±50) μmol/L、(231±56) μmol/L、(250±66) μmol/L、(266±75) μmol/L、(281±81) μmol/L、(298±76) μmol/L、(379±86) μmol/L;在男性受试者中,上述各年龄组血尿酸水平分别为(310±76) μmol/L、(298±75) μmol/L、(298±74) μmol/L、(294±74) μmol/L、(302±78)μmol/L、(311±80) μmol/L、(322±80) μmol/L、(330±75) μmol/L.⑤按年龄分层后不同血尿酸水平对胆石症发病的影响:在青中年受试者(年龄≤60岁)中,校正了性别、BMI、TC、TG、糖尿病、高血压病、吸烟、饮酒和体育锻炼因素对新发胆石症的影响后,与Q1组比较,Q2组和Q3组受试者新发胆石症风险均未增加(HR=1.05,1.10,95％CI:0.94～ 1.17,0.99～1.23,P＞0.05),而Q4组受试者新发胆石症风险增加(HR=1.15,95％CI:1.02～ 1.28,P＜0.05);在老年受试者(年龄＞60岁)中,校正了上述相同胆石症发病危险因素后,与Q1组比较,Q2组受试者新发胆石症风险未增加(HR=1.16,95％CI:0.99～1.36,P＞0.05),而Q3、Q4组受试者新发胆石症风险增加(HR=1.19,1.21,95％CI:1.02～ 1.40,1.04～ 1.41,P＜0.05).结论 高水平血尿酸是影响新发胆石症的独立危险因素.

abstractsObjective To explore the predictive value of serum uric acid on new-onset cholelithiasis.Methods The retrospective cohort study was conducted.The data of 97 469 subjects who participated health examination at the Kailuan General Hospital Affiliated to the North China University of Science and Technology,Kailuan Linxi Hospital,Kailuan Zhaogezhuang Hospital,Kailuan Tangjiazhuang Hospital,Kailuan Fan'gezhuang Hospital,Kailuan Lyujiatuo Hospital,Kailuan Jinggezhuang Hospital,Kailuan Linnancang Hospital,Kailuan Qianjiaying Hospital,Kailuan Majiagou Hospital and Kailuan Branch Hospital from June 2006 to December 2015 were collected.Epidemiological investigation,anthropometric parameters and biochemical indicators were collected.All the subjects were allocated into 4 groups according to squartiles of serum uric acid:24 140 with serum uric acid ＜232 μmol/L in the Q1 group,24 473 with 232 μmol/L≤ serum uric acid ＜282 μmol/L in the Q2 group,24 382 with 282 μmol/L≤ serum uric acid ＜338 μmol/L in the Q3 group and 24 474 with serum uric acid ≥ 338 μmol/L in the Q4 group.Observation indicators:(1) comparisons of clinical characteristics among the 4 groups;(2) incidence of cholelithiasis in the 4 groups;(3) effects of serum uric acid on the new-onset cholelithiasis:① the dose-response relationship between serum uric acid and the risk of cholelithiasis,② comparisons of the fitting degree of serum uric acid on the cholelithiasis model,③ effects of different serum uric acid levels on incidence of cholelithiasis after stratification by sex,④ serum uric acid of different gender on the boxplots,⑤ effects of different serum uric acid levels on the incidence of cholelithiasis after stratification by age.Measurement data with normal distribution were expressed as (x)±s,and comparisons among groups were analyzed using the one-way ANOVA.Measurement data with skewed distribution is expressed by M (Q),and comparisons among groups were analyzed using the nonparametric Krustal-willis test.Count data were represented by percentage,and comparisons among groups were analyzed using chi-square test.The incidences of cholethiasis in 4 groups of different serum uric acid were calculated by person-year incidence.Restrictive cubic spline regression was used to calculate the dose-response relation between the continuous variable and the risks of new-onset cholelithiasis and 95％ confidence interval (CI).COX regression model was used to analyze the hazard ratio (HR) and 95％ CI of different serum uric acid levels on new-onset cholelithiasis.Likelihood ratio test and akaike information criterion (AIC) were used to calculate the fitting degree of serum uric acid on new-onset cholelithiasis model.Boxplots were used to describe serum uric acid in different genders.Results (1) comparisons of clinical characteristics among the 4 groups:sex (male),age,body mass index (BMI),systolic pressure,diastolic pressure,fasting plasma glucose (FPG),total cholesterol (TC),triglyceride (TG),high sensitive C-reactive protein,diabetes,hypertension,smoking,drinking and physical exercise were 15 162,(50± 11) years,(24±3)kg/m2,(123±21)mmHg (1 mmHg=0.133 kPa),(82± 12)mmHg,(5.6±2.0) mmol/L,(4.8±1.2) mmol/L,1.14 mmol/L (range,0.81-1.63 mmol/L),0.70 mmol/L (range,0.23-2.23 mmol/L),2 537,9 415,4575,2380,2 649 in the Q1 group,19 079,(51±12) years,(25±3)kg/m2,(130±21)mmHg,(83±12) mmHg,(5.5 ± 1.7) mmol/L,(4.9 ± 1.2) mmol/L,1.20 mmol/L (range,0.86-1.76 mmol/L),0.71 mmol/L (range,0.28-1.98 mmol/L),2 287,10 124,6 918,3 649,3 288 in the Q2 group,21 132,(52±13)years,(25±3)kg/m2,(132±21)mmHg,(84±12)mmHg,(5.5±1.6)mmol/L,(5.0±1.2) mmol/L,1.29 mmol/L (range,0.91-1.94 mmol/L),0.80 mmol/L (range,0.30-2.06 mmol/L),2 027,10 755,8 259,4 730,3 958 in the Q3 group,22 651,(53± 14) years,(26± 3) kg/m2,(134± 21) mmHg,(85±12)mmHg,(5.4±1.5)mmol/L,(5.1±1.2)mmol/L,1.54 mmol/L (range,1.05-2.35 mmol/L),1.02 mmol/L (range,0.43-2.50 mmol/L),1 981,12 082,9 562,6 209,4 758 in the Q4 group,respectively,with statistically significant differences among the 4 groups (x2 =7 624.63,F=279.93,961.91,330.84,271.40,38.25,353.18,H =3 406.30,912.23,x2 =108.15,590.49,2567.07,2 209.21,760.15,P＜0.05).(2)Incidence of cholelithiasis in the 4 groups:97 469 participants were followed up for 592 922 person-year,4 270 participants had new-onset cholelithiasis,with a total person-year incidence of 7.20 thousand person / year.The person-year incidence were respectively 6.34 (971/153 205 * 1 000),6.91 (1 034/149 686 * 1 000),7.44 (1 090/146 549 * 1 000),8.19 (1 175/143 482 * 1 000) thousand person / year in Q1,Q2,Q3 and Q4 group.(3) Effects of serum uric acid on the new-onset cholelithiasis.① The dose-response relationship between serum uric acid and the risk of cholelithiasis:restricted cubic spline regression showed a linear relationship between continuous serum uric acid,logarithmic transformated serum uric acid and the risk of cholelithiasis (x2 =11.74,8.01,P＜0.05).② Comparisons of the fitting degree of serum uric acid on the cholelithiasis model:adjusted for sex,age,BMI,TC,TG,diabetes,hypertension,smoking,drinking and physical exercise,risks of new-onset cholelithiasis increased in Q3 and Q4 groups compared with Q1 group (HR=1.10,1.12,95％CI:1.01-1.20,1.03-1.23,P＜0.05).The-2Log L and AIC value of multivariate model,serum uric acid+multivariate model were 92 532.39,92 550.39 and 92 525.35,92 549.35,respectively,with a statistically significant difference (x2=7.04,P ＜ 0.05).③ Effects of different serum uric acid levels on incidence of cholelithiasis after stratification by sex:in female participants,adjusted for age,BMI,TC,TG,diabetes,hypertension,smoking,drinking and physical exercise,risk of new-onset cholelithiasis in Q1 group was not statistically significant different from that in Q2,Q3,Q4 group (HR=1.06,1.15,1.09,95％CI:0.88-1.28,0.93-1.34,0.91-1.31,P＞0.05).In male participants,adjusted for age,BMI,TC,TG,diabetes,hypertension,smoking,drinking and physical exercise,risks of new-onset cholelithiasis in Q2,Q3 and Q4 groups were increased compared with Q1 group (HR=1.17,1.24,1.30,95％CI:1.06-1.30,1.12-1.37,1.18-1.44,P＜0.05).④ Serum uric acid of different gender on the boxplots:in female participants,the level of serum uric acid was (249 ± 61) μmol/L,(235±50)μmol/L,(231±56) μmol/L,(250±66) μmol/L,(266±75) μmol/L,(281±81) μmol/L,(298±76) μmol/L,(379±86)μmol/L respectively in the group of 18-27 years old,28-37 years old,38-47 years old,48-57 years old,58-67 years old,68-77 years old,78-87 years old,88-97 years old after stratified by 10 years old.In male participants,the level of serum uric acid was respectively (310±76)μmol/L,(298 ±75) μmol/L,(298±74) μmol/L,(294±74) μmol/L,(302±78) μmol/L,(311 ±80) μmol/L,(322±80) μmol/Land (330±75)μmol/L after participants stratified by 10 years old.⑤ Effects of different serum uric acid levels on the incidence of cholelithiasis after stratification by age:in participants with age ≤ 60 years old,adjusted for sex,BMI,TC,TG,diabetes,hypertension,smoking,drinking and physical exercise,risk of new-onset cholelithiasis in the Q2 and Q3 groups were not increased compared with Q1 group (HR=1.05,1.10,95％CI:0.94-1.17,0.99-1.23,P＞0.05),however,risk of new-onset cholelithiasis was increased in the Q4 group (HR =1.15,95％CI:1.02-1.28,P＜0.05).In participants with age ＞ 60 years old,adjusted for sex,BMI,TC,TG,diabetes,hypertension,smoking,drinking and physical exercise,risk of new-onset cholelithiasis in the Q2 groups was not increased compared with Q1 group (HR=1.16,95％CI:0.99-1.36,P＞0.05),however,risks of new-onset cholelithiasis were increased in the Q3 and Q4 groups (HR =1.19,1.21,95％CI:1.02-1.40,1.04-1.41,P＜ 0.05).Conclusion Elevated serum uric acid is an independent risk factor for the new-onset cholelithiasis.