Abstract：
OBJECTIVE: Optimizing glycemic control may prevent liver-related events and major adverse cardiovascular events (MACE) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). However, the optimal hemoglobin A1c (HbA1c) threshold associated with a lower risk of complications, particularly liver-related events as well as MACE is unknown.
METHODS: We investigated a nationwide population-based cohort and identified 633 279 patients with MASLD, with a mean follow-up of 4.2 years. Hemoglobin A1c levels were measured annually. The primary endpoint was the risk of liver-related events and MACE and to determine the optimal HbA1c level associated with the risk of complications.
RESULTS: Mean HbA1c (per 1%) was associated with liver-related events (subdistribution hazard ratio [sHR] 1.26; 95% confidence interval [CI], 1.12-1.42) as well as MACE (sHR 1.36; 95% CI, 1.32-1.41) after adjustment for confounders. Multivariable sHR (95% CI) for HbA1c of <5.0%, 6.0%-6.9%, 7.0%-7.9%, 8.0%-8.9%, and ≥9.0% (reference, 5.0%-5.9%) were 14 (9.1-22), 1.70 (1.2-2.3), 3.32 (2.3-4.8), 3.81 (2.1-6.8), and 4.83 (2.4-9.6) for liver-related events, and 1.24 (0.8-1.8), 1.27 (1.2-1.4), 1.70 (1.5-2.0), 2.36 (1.9-2.9), and 4.17 (3.5-5.0) for MACE. An HbA1c level of 7% was selected as the optimal threshold for predicting complications (sHR 2.40 [1.8-3.2] for liver-related events and 1.98 [1.8-2.2] for MACE).
CONCLUSIONS: The risk of liver-related events as well as MACE increased in a dose-dependent fashion with an increase in HbA1c levels, except for patients with HbA1c <5.0% for liver-related events. An HbA1c level of 7% was the optimal threshold associated with a lower risk of complications and may be utilized as a target for glycemic control in patients with MASLD.
METHODS: We investigated a nationwide population-based cohort and identified 633 279 patients with MASLD, with a mean follow-up of 4.2 years. Hemoglobin A1c levels were measured annually. The primary endpoint was the risk of liver-related events and MACE and to determine the optimal HbA1c level associated with the risk of complications.
RESULTS: Mean HbA1c (per 1%) was associated with liver-related events (subdistribution hazard ratio [sHR] 1.26; 95% confidence interval [CI], 1.12-1.42) as well as MACE (sHR 1.36; 95% CI, 1.32-1.41) after adjustment for confounders. Multivariable sHR (95% CI) for HbA1c of <5.0%, 6.0%-6.9%, 7.0%-7.9%, 8.0%-8.9%, and ≥9.0% (reference, 5.0%-5.9%) were 14 (9.1-22), 1.70 (1.2-2.3), 3.32 (2.3-4.8), 3.81 (2.1-6.8), and 4.83 (2.4-9.6) for liver-related events, and 1.24 (0.8-1.8), 1.27 (1.2-1.4), 1.70 (1.5-2.0), 2.36 (1.9-2.9), and 4.17 (3.5-5.0) for MACE. An HbA1c level of 7% was selected as the optimal threshold for predicting complications (sHR 2.40 [1.8-3.2] for liver-related events and 1.98 [1.8-2.2] for MACE).
CONCLUSIONS: The risk of liver-related events as well as MACE increased in a dose-dependent fashion with an increase in HbA1c levels, except for patients with HbA1c <5.0% for liver-related events. An HbA1c level of 7% was the optimal threshold associated with a lower risk of complications and may be utilized as a target for glycemic control in patients with MASLD.
摘要：
目的：优化血糖控制可以预防代谢功能障碍相关脂肪变性肝病（MASLD）患者的肝脏相关事件和主要不良心血管事件（MACE）。然而,最佳血红蛋白A1c（HbA1c）阈值与较低的并发症风险相关，特别是肝脏相关事件以及MACE未知.
方法：我们调查了一个全国人群队列，确定了633.279名MASLD患者，平均随访4.2年。每年测量血红蛋白A1c水平。主要终点是肝脏相关事件和MACE的风险，并确定与并发症风险相关的最佳HbA1c水平。
结果：平均HbA1c（每1％）与肝脏相关事件相关（亚分布风险比[sHR]1.26；95％置信区间[CI]，1.12-1.42）以及校正混杂因素后的MACE（sHR1.36；95%CI，1.32-1.41）。HbA1c的多变量sHR（95%CI）<5.0%，6.0%-6.9%，7.0%-7.9%，8.0%-8.9%，且≥9.0%(参考，5.0%-5.9%)为14(9.1-22)，1.70(1.2-2.3),3.32(2.3-4.8),3.81(2.1-6.8),和4.83（2.4-9.6）肝脏相关事件，和1.24（0.8-1.8），1.27(1.2-1.4),1.70（1.5-2.0），2.36（1.9-2.9），和4.17（3.5-5.0）的MACE。选择7%的HbA1c水平作为预测并发症的最佳阈值（肝脏相关事件的sHR为2.40[1.8-3.2]，MACE的sHR为1.98[1.8-2.2]）。
结论：随着HbA1c水平的升高，肝脏相关事件和MACE的风险呈剂量依赖性增加，除了HbA1c<5.0％的患者与肝脏相关的事件。7%的HbA1c水平是与并发症风险较低相关的最佳阈值,并且可以用作MASLD患者的血糖控制的目标。
方法：我们调查了一个全国人群队列，确定了633.279名MASLD患者，平均随访4.2年。每年测量血红蛋白A1c水平。主要终点是肝脏相关事件和MACE的风险，并确定与并发症风险相关的最佳HbA1c水平。
结果：平均HbA1c（每1％）与肝脏相关事件相关（亚分布风险比[sHR]1.26；95％置信区间[CI]，1.12-1.42）以及校正混杂因素后的MACE（sHR1.36；95%CI，1.32-1.41）。HbA1c的多变量sHR（95%CI）<5.0%，6.0%-6.9%，7.0%-7.9%，8.0%-8.9%，且≥9.0%(参考，5.0%-5.9%)为14(9.1-22)，1.70(1.2-2.3),3.32(2.3-4.8),3.81(2.1-6.8),和4.83（2.4-9.6）肝脏相关事件，和1.24（0.8-1.8），1.27(1.2-1.4),1.70（1.5-2.0），2.36（1.9-2.9），和4.17（3.5-5.0）的MACE。选择7%的HbA1c水平作为预测并发症的最佳阈值（肝脏相关事件的sHR为2.40[1.8-3.2]，MACE的sHR为1.98[1.8-2.2]）。
结论：随着HbA1c水平的升高，肝脏相关事件和MACE的风险呈剂量依赖性增加，除了HbA1c<5.0％的患者与肝脏相关的事件。7%的HbA1c水平是与并发症风险较低相关的最佳阈值,并且可以用作MASLD患者的血糖控制的目标。
