Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the People's Republic of China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Metabolism. 2021 Nov;124:154874. doi: 10.1016/j.metabol.2021.154874. Epub 2021 Sep 10.
AIMS/HYPOTHESIS: We aimed to evaluate the effect of NAFLD on the risk of incident cardiovascular disease (CVD) and estimated glomerular filtration rate (eGFR)-based chronic kidney disease (CKD), and further test the joint effects and interactions between NAFLD status and individual metabolic element, as well as the total 'ABCs' metabolic goal achievement, on the CVD and CKD risk among 101,296 patients with prediabetes or diabetes from a prospective cohort study.
We conducted the study based on the China Cardiometabolic Disease and Cancer Cohort (4C) study, a large-scale, population-based prospective cohort. After excluding alcohol abuse and other cause of hepatic diseases, we used fatty liver index (FLI) ≥ 60 as a proxy of NAFLD and stratified the probability of fibrosis by aspartate transaminase/alanine transaminase ratio (AAR) with cut-offs of 0.8 and 1.4. 'ABCs' metabolic goal was defined as subjects who had HbA1c < 6.5% (A), SBP/DBP < 130/80 mmHg (B), and LDL-C < 100 mg/dL (C). During 3.8 years follow-up, we validated 2340 CVD events based on medical records and identified 1943 participants developed CKD based on centrally tested eGFR.
The multivariable adjusted hazard ratios (HRs) were 1.15 (95% confidence interval (CI), 1.05-1.27) for CVD events and 1.33 (95% CI, 1.20-1.48) for CKD among NAFLD patients, compared with participants without NAFLD. Of NAFLD patients, relative to individuals with low AAR (<0.8), those with high AAR (≥1.4) were more likely to experience CVD events [1.62 (1.21-2.18)] and CKD [1.63 (1.17-2.28)]. Participants with NAFLD and comorbid poorly controlled metabolic risk factors had higher risk of CVD events or CKD than having either alone, with a significant interaction between poor glycemic control and NAFLD on the risk of vascular complications.
NAFLD was associated with incident CVD and CKD among patients with prediabetes or diabetes. Such associations were substantially modified by the comprehensive achievement of metabolic goal.
目的/假设：我们旨在评估非酒精性脂肪性肝病（NAFLD）对心血管疾病（CVD）和估计肾小球滤过率（eGFR）为基础的慢性肾脏病（CKD）事件风险的影响，并进一步检验 NAFLD 状态与个体代谢元素之间的联合作用和相互作用，以及总“ABCs”代谢目标的实现，对来自前瞻性队列研究的 101296 例糖尿病前期或糖尿病患者的 CVD 和 CKD 风险的影响。
我们在中国心血管代谢疾病和癌症队列（4C）研究的基础上进行了这项研究，这是一项大规模的、基于人群的前瞻性队列研究。在排除酗酒和其他肝脏疾病原因后，我们使用脂肪肝指数（FLI）≥60 作为 NAFLD 的替代指标，并根据天门冬氨酸转氨酶/丙氨酸转氨酶比值（AAR）的截断值 0.8 和 1.4 将纤维化的可能性分层。“ABCs”代谢目标定义为糖化血红蛋白（HbA1c）<6.5%（A）、收缩压/舒张压（SBP/DBP）<130/80mmHg（B）和低密度脂蛋白胆固醇（LDL-C）<100mg/dL（C）的患者。在 3.8 年的随访中，我们根据病历验证了 2340 例 CVD 事件，并根据中心检测的 eGFR 确定了 1943 名参与者发生 CKD。
与无 NAFLD 的患者相比，NAFLD 患者的 CVD 事件多变量调整后的危险比（HR）为 1.15（95%置信区间（CI），1.05-1.27），CKD 事件的 HR 为 1.33（95%CI，1.20-1.48）。在 NAFLD 患者中，与低 AAR（<0.8）者相比，高 AAR（≥1.4）者发生 CVD 事件的可能性更高[1.62（1.21-2.18）]和 CKD [1.63（1.17-2.28）]。同时患有代谢风险因素控制不佳的 NAFLD 患者比单独患有代谢风险因素控制不佳的患者发生 CVD 事件或 CKD 的风险更高，且血糖控制不佳和 NAFLD 之间存在显著的交互作用，对血管并发症的风险有影响。
NAFLD 与糖尿病前期或糖尿病患者的 CVD 和 CKD 事件有关。这种关联受到代谢目标综合实现的显著影响。
