Eun Ju Cho1, Kyungdo Han2, Seung-Pyo Lee3,4, Dong Wook Shin5,6, Su Jong Yu1. 1. Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea. 2. Department of Biostatistics, College of Medicine, The Catholic University of Korea, Seoul, Korea. 3. Cardiovascular Center, Seoul National University Hospital, Seoul, Korea. 4. Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea. 5. Department of Family Medicine, Samsung Medical Center Supportive Care Center, Samsung Comprehensive Cancer Center, Seoul, Korea. 6. Department of Digital Health, SAIHST, Sungkyunkwan University, Seoul, Korea.
Abstract
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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Higher visit-to-visit variability of liver enzymes was an independent predictor of all-cause mortality and cardiovascular events.
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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Higher visit-to-visit variability of liver enzymes was an independent predictor of all-cause mortality and cardiovascular events.
Authors: Xinyu Wang; Si Cheng; Jun Lv; Canqing Yu; Yu Guo; Pei Pei; Ling Yang; Iona Y Millwood; Robin Walters; Yiping Chen; Huaidong Du; Haiping Duan; Simon Gilbert; Daniel Avery; Junshi Chen; Yuanjie Pang; Zhengming Chen; Liming Li Journal: Front Cardiovasc Med Date: 2022-08-11