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新疆维吾尔族农村居民肝纤维化评分与心血管疾病发病关系前瞻性队列研究

Associations of liver fibrosis scores with cardiovascular disease incidence among adult rural Uyghurs in Xinjiang Uyghur Autonomous Region: a 6-year prospective follow-up study

  • 摘要:
    目的 了解新疆维吾尔族农村居民肝纤维化评分(LFS)与心血管疾病(CVD)发病的关系,为CVD的早期识别和预防提供参考依据。
    方法 采用前瞻性队列研究方法,于2016年8—9月采用典型抽样方法在新疆生产建设兵团第三师51团招募13 464名≥18岁维吾尔族农村居民进行基线调查,分别于2019年7月、2020年7月、2021年8月、2022年6月和2023年6月对11 863名基本信息完整且基线调查无CVD的非孕妇和频繁流动居民进行了5次随访调查;采用Kaplan-Meier法估计纤维化4项评分(FIB-4评分)、巴德评分(BARD评分)和福恩斯指数(Forns指数)3种LFS分组的CVD累积发生率,应用Cox比例风险回归模型评估3种LFS与CVD发病的关系,并采用弗雷明汉CVD风险评分模型(Framingham模型)评价LFS对CVD发病风险的预测价值。
    结果 截至2023年6月,11 863名新疆维吾尔族农村居民中失访423人,失访率为3.57%;最终纳入分析的11 440名维吾尔族农村居民共随访72 662.30人年,平均随访(6.35±1.28)人年,随访期间CVD共发病1 280例,发病密度为17.62/1 000人年,CVD累积发病率为11.19%;FIB-4评分低(<1.30分)、中(1.30~2.67分)和高(>2.67分)3组农村居民的CVD累积发病率分别为9.10%、19.28%和27.71%,BARD评分低(<2分)、中(2~3分)和高(>3分)3组农村居民的CVD累积发病率分别为7.19%、16.45%和33.81%,Forns指数低(<4.2)、中(4.2~6.9)和高(>6.9)3组农村居民的CVD累积发病率分别为1.42%、9.89%和26.88%,3种评分不同组别新疆维吾尔族农村居民CVD累积发病率差异均有统计学意义(均P<0.001);在调整了性别、年龄、吸烟情况、饮酒情况、是否高血压、是否糖尿病、是否肥胖、腰围、高密度脂蛋白胆固醇(HDL-C)和估计肾小球滤过率(eGFR)等混杂因素后,多因素Cox比例风险回归模型分析结果显示,FIB-4中和高评分组维吾尔族农村居民CVD发病风险分别为FIB-4低评分组维吾尔族农村居民的1.26倍(HR=1.26,95%CI=1.09~1.45)和1.91倍(HR=1.91,95%CI=1.59~2.30),BARD中和高评分组维吾尔族农村居民CVD发病风险分别为BARD低评分组维吾尔族农村居民的1.57倍(HR=1.57,95%CI=1.24~1.97)和2.47倍(HR=2.47,95%CI=1.51~4.04),Forns中和高指数组维吾尔族农村居民CVD发病风险分别为Forns低指数组维吾尔族农村居民的3.00倍(HR=3.00,95%CI=2.12~4.24)和4.95倍(HR=4.95,95%CI=3.44~7.11);Framingham模型的C指数(95%CI)为0.805(0.794~0.815),加入FIB-4评分、BARD评分和Forns指数后的C指数(95%CI)分别为0.809(0.799~0.820)、0.810(0.800~0.821)和0.810(0.799~0.820)(均P<0.001),加入BARD评分和Forns指数后的净重新分类指数(95%CI)分别为0.239(0.206~0.269)和0.105(0.070~0.137)(均P<0.001)、综合判别改善指数(95%CI)分别为0.007(0.003~0.011)和0.005(0.002~0.010)(均P<0.001),3种LFS的加入可改善Framingham模型对CVD发病风险的预测能力。
    结论 LFS水平的升高可增加新疆维吾尔族农村居民CVD的发病风险,加入LFS可提高Framingham模型对CVD发病风险的预测能力。

     

    Abstract:
    Objective To investigate the relationship between liver fibrosis score (LFS) and the incidence of cardiovascular disease (CVD) in rural Uyghur residents in Uyghur Autonomous Region (Xinjiang), and to provide a reference for the early detection and prevention of CVD.
    Methods Using a typical sampling, we recruited 13 464 rural Uyghur residents aged ≥18 years in the 51st Regiment of the Third Division of the Xinjiang Production and Construction Corps and conducted a baseline survey in August-September 2016. Five follow-up surveys were conducted in July 2019, July 2020, August 2021, June 2022, and June 2023 among 11 863 non-pregnant and non-frequent migrant participants with complete information and no CVD at baseline. The Kaplan-Meier method was used to estimate the cumulative incidence of CVD in three groups with different grades of LFS, including fibrosis-4 score (FIB-4 score), body mass index (BMI)-aspartate aminotransferase/alanine aminotransferase(AST/ALT) ratio-diabetes score (BARD score) , and Forns index. The Cox proportional hazards regression model was used to assess the relationship between the three LFSs and CVD incidence. The Framingham CVD risk score model (Framingham model) was used to assess the predictive value of LFS for CVD risk.
    Results At the end of the surveys, 423 (3.57%) of the 11 863 participants were lost to follow-up and 1 280 CVD events were identified in the 11 440 participants finally included in the analysis, with an incidence density of 17.62/1 000 person-years and a cumulative incidence of 11.19% for the total follow-up of 72 662.30 person-years and an average of 6.35±1.28 person-years for per participant. The cumulative incidences of CVD were 9.10%, 19.28%, and 27.71% for the low (<1.30), moderate (1.30–2.67), and high (>2.67) FIB-4 score groups; 7.19%, 16.45%, and 33.81% for the low (<2), moderate (2–3), and high (>3) BARD score groups; and 1.42%, 9.89%, and 26.88% for the low (<4.2), moderate (4.2–6.9), and high (>6.9) Forns index groups, respectively, with statistically significant differences in the cumulative CVD incidence among groups with different LFS of three types (all P<0.001). After adjustment for sex, age, smoking status, alcohol consumption, hypertension, diabetes, obesity, waist circumference, high-density lipoprotein cholesterol (HDL-C), and estimated glomerular filtration rate (eGFR), the multifactorial Cox proportional hazards regression model showed that the risk of CVD was higher in the moderate and high FIB-4 score groups (hazard risk HR=1.26, 95% confidence interval 95%CI: 1.09–1.45 and HR=1.91, 95%CI: 1.59–2.30) than those in the low score group; the risk of CVD was also higher in the moderate and high BARD score groups (HR=1.57, 95%CI: 1.24–1.97) and HR=2.47, 95%CI: 1.51–4.04) and Forns index groups (HR=3.00, 95%CI: 2.12–4.24 and HR=4.95, 95%CI: 3.44–7.11) than those in the low BARD score and Forns index groups, respectively. The concordance index (C-index) (95%CI) of the Framingham model analysis was 0.805 (0.794–0.815). The C-index (95%CI) after adding the FIB-4 score, BARD score, and Forns index was 0.809 (0.799–0.820), 0.810 (0.800–0.821), and 0.810 (0.799–0.820), respectively (all P<0.001). The net reclassification index (95%CI) after adding the BARD score and the Forns index was 0.239 (0.206–0.269) and 0.105 (0.070–0.137), respectively (all P<0.001). The integrated discrimination improvement index (95%CI) was 0.007 (0.003–0.011) and 0.005 (0.002–0.010), respectively (all P<0.001). The addition of the three LFSs may improve the predictive ability of the Framingham model for CVD risk.
    Conclusions Elevated LFS levels may increase the risk of CVD in rural Uyghur residents in Xinjiang. The addition of LFS may improve the predictive ability of the Framingham model for CVD risk.

     

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