Cho Eun Ju, Han Kyungdo, Lee Seung-Pyo, Shin Dong Wook, Yu Su Jong
Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
Department of Biostatistics, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Liver Int. 2020 Jun;40(6):1292-1302. doi: 10.1111/liv.14432. Epub 2020 Mar 18.
BACKGROUND & AIMS: Liver enzymes, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ-glutamyltransferase (GGT), have been suggested as surrogate markers of various cardiovascular diseases. However, previous studies assessed liver enzymes only once at baseline. We investigated the association between liver enzyme variability and the risk of mortality and cardiovascular outcomes in general population.
A total of 6 496 271 subjects participating in ≥3 health examinations within the previous 5 years including the index year (2009-2010) were included. Variability was measured using variability independent of the mean. Cox proportional hazard models adjusting demographic factors, comorbidities, blood pressure, total cholesterol, glomerular filtration rate and baseline liver enzyme level were used.
During a median follow-up of 6 years, there were 106 413 deaths (1.6%), 53 385 myocardial infarctions (MI, 0.8%), 65 143 atrial fibrillations (AF, 1.0%) and 50 139 congestive heart failures (CHF, 0.7%). High variability in AST, ALT and GGT was associated with a higher risk for all-cause mortality, MI, AF and CHF. The degree of association was largest for GGT variability. For the highest quartile of GGT variability relative to the lowest quartile, the hazard ratios (95% confidence intervals) were 1.32 (1.28-1.35) for all-cause mortality, 1.16 (1.11-1.20) for MI, 1.28 (1.18-1.38) for AF and 1.25 (1.20-1.30) for CHF. These findings were consistent regardless of alcohol consumption, body mass index and degree of fatty liver. Sensitivity analysis also revealed similar results.
Higher visit-to-visit variability of liver enzymes was an independent predictor of all-cause mortality and cardiovascular events.
丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）和γ-谷氨酰转移酶（GGT）等肝脏酶类已被视为各种心血管疾病的替代标志物。然而，既往研究仅在基线时对肝脏酶类进行过一次评估。我们调查了肝脏酶类变异性与普通人群死亡率及心血管结局风险之间的关联。
纳入了在包括索引年份（2009 - 2010年）在内的过去5年中参加过≥3次健康检查的6496271名受试者。使用独立于均值的变异性来衡量变异性。采用Cox比例风险模型，对人口统计学因素、合并症、血压、总胆固醇、肾小球滤过率和基线肝脏酶水平进行了校正。
在中位随访6年期间，共有106413人死亡（1.6%），53385人发生心肌梗死（MI，0.8%），65143人发生心房颤动（AF，1.0%），50139人发生充血性心力衰竭（CHF，0.7%）。AST、ALT和GGT的高变异性与全因死亡率、MI、AF和CHF的较高风险相关。GGT变异性的关联程度最大。相对于最低四分位数，GGT变异性最高四分位数的风险比（95%置信区间）为：全因死亡率1.32（1.28 - 1.35），MI为1.16（1.11 - 1.20），AF为1.28（1.18 - 1.38），CHF为1.25（1.20 - 1.30）。无论饮酒情况、体重指数和脂肪肝程度如何，这些发现都是一致的。敏感性分析也得出了类似结果。
肝脏酶类每次检查之间的变异性较高是全因死亡率和心血管事件的独立预测因素。
