Low ALT blood levels predict long-term all-cause mortality among adults. A historical prospective cohort study

Ramaty, Erez; Maor, Elad; Peltz-Sinvani, Naama; Brom, A.G.; Grinfeld, A; Kivity, Shaye; Segev, Shlomo; Sidi, Yechezkel; Keßler, Tobias; Sela, Ben Ami; Segal, Gad

doi:10.1016/j.ejim.2014.10.019

Cited by 59 publications

(60 citation statements)

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“…This exclusion may also at least partly explain the paradoxical associations between ALT and GGT and mortality observed. Despite this, our data set is consistent with multiple equivalent publications where higher ALT has been excluded in order to avoid the inclusion of individuals with significant liver disease [5,51,52]. Other weaknesses of our analysis include the lack of data for alcohol consumption in grams per week, although this is a notoriously difficult measure to quantify accurately [53], and also the possible inadequate period of follow-up to see the effects of an adverse metabolic profile that may be seen at higher levels of ALT.…”

Section: Accepted M Manuscriptsupporting

confidence: 72%

“…However, links with frailty were neither supported nor conclusively refuted by our analysis and other factors are also likely to be important in those with type 2 diabetes [5,7,23]. Research into the causes, liver-related or otherwise, behind the association between low ALT and mortality is needed.…”

Section: Accepted M Manuscriptmentioning

confidence: 87%

“…Several recent publications report an inverse association between ALT and mortality [5,6]. While this would seem counterintuitive if lower ALT is to be considered a marker of liver health, this observation has been repeatedly noted in different populations, including in the elderly, the middle-aged and those with HIV infection [5][6][7][8][9].…”

Section: Introductionmentioning

confidence: 96%

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Opposite associations between alanine aminotransferase and γ-glutamyl transferase levels and all-cause mortality in type 2 diabetes: Analysis of the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study

et al. 2016

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Opposite associations between alanine aminotransferase and γ-glutamyl transferase levels and all-cause mortality in type 2 diabetes: analysis of the fenofibrate intervention and event lowering in diabetes (FIELD) study Kathryn H. Williams, David R. Sullivan, Geoffrey C. Nicholson, Jacob George, Alicia J. Jenkins, Andrzej S. Januszewski, Val J. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. (2) 9562 5304; E-mail: fieldtrial@ctc.usyd.edu.au. A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT3 Abstract AimsReported associations between liver enzymes and mortality may not hold true in type 2 diabetes, owing to a high prevalence of non-alcoholic fatty liver disease, which has been linked to cardiovascular disease and mortality in its own right. Our study aimed to determine whether alanine aminotransferase (ALT) or γ-glutamyl transferase (GGT) levels predict mortality in type 2 diabetes, and to examine possible mechanisms. MethodsData from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study were analysed to examine the relationship between liver enzymes and all-cause and cause-specific mortality over 5 years. ResultsOver 5 years, 679 (6.9%) individuals died. After adjustment, for every standard deviation increase in ALT (13.2U/L), the HR for death on study was 0.85 (95% CI 0.78-0.93), p<0.001.Conversely, GGT >70 U/L, compared with GGT ≤70 U/L, had HR 1.82 (1.48−2.24), p<0.001.For cause-specific mortality, lower ALT was associated with a higher risk of cardiovascular death only, whereas GGT >70 U/L was associated with higher risks of death due to cardiovascular disease, cancer and non-cancer/non-cardiovascular causes. The relationship for ALT persisted after adjustment for indirect measures of frailty but was attenuated by elevated hsCRP. ConclusionsAs in the general population, ALT has a negative, and GGT a positive, correlation with mortality in type 2 diabetes when ALT is less than two times the upper limit of normal. The relationship A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT4 for ALT appears specific for death due to cardiovascular disease. Links of low ALT with frailty, as a potential mechanism for relationships seen, were neither supported nor conclusively refuted by our analysis and other factors are also likely to be important in those with type 2 diabetes.

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Section: Accepted M Manuscriptsupporting

confidence: 72%

Section: Accepted M Manuscriptmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 96%

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Opposite associations between alanine aminotransferase and γ-glutamyl transferase levels and all-cause mortality in type 2 diabetes: Analysis of the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study

et al. 2016

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“…In a recent study by Ramati et al, 8 this was demonstrated in a population of healthy middle-aged adults. The fact that low ALT values and frailty lead to shortened survival is not necessarily the case for all adults, to say the least for adults suffering from chronic diseases, potentially shortening their life expectancy, at times leading to their death without a state of frailty on their path.…”

Section: Discussionmentioning

confidence: 77%

“…Among others, this association was statistically significant among middle-aged adults attending an annual preventive medicine clinic. 8 Furthermore, in our study population, ALT<17 represented the lower quartile.…”

Section: Introductionmentioning

confidence: 69%

Low ALT Levels Independently Associated with 22-Year All-Cause Mortality Among Coronary Heart Disease Patients

et al. 2015

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BACKGROUND: Low alanine aminotransferase (ALT) blood levels are known to be associated with frailty and increased risk of long-term mortality in certain populations. However, the contribution of this marker to longterm outcome has not been assessed in patients with chronic coronary heart disease. OBJECTIVE: The aim of the current study was to assess the association between low ALT values and long-term, 22.8-year, all-cause mortality in this population. PARTICIPANTS: We examined the association of low ALT (<17 IU/l) with long-term all-cause mortality in the Bezafibrate Infarction Prevention (BIP) Registry population. KEY RESULTS: Appropriate laboratory and survival data were available for 6,575 patients, without known liver pathology, included in the BIP registry, with a median follow-up period of 22.8 years. The cumulative probability of all-cause mortality was significantly higher in the low ALT group compared with patients with higher ALT levels (65.6 % vs. 58.4 %; log-rank p<0.001). Consistently, multivariate analysis, adjusted for multiple established predictors of mortality in this population, demonstrated that low ALT is independently associated with 11 % greater long-term (22.8 years) mortality risk [HR 1.11 (95 % confidence interval: 1.03-1.19; adjusted p<0.01)]. CONCLUSIONS: Low ALT levels are associated with increased long-term mortality among middle-aged patients with stable coronary heart disease. This association remained statistically significant after adjustment for other well-established risk factors for mortality in this population.

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Abdominal skeletal muscle mass as a predictor of mortality in Japanese patients undergoing left ventricular assist device implantation

et al. 2019

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Aims We assessed preoperative muscle wasting in patients undergoing left ventricular assist device (LVAD) implantations using abdominal skeletal muscle images on computed tomography (CT) and explored the associations between the preoperative muscle wasting and clinical outcomes after LVAD implantation. Methods and results We retrospectively examined the records of 111 patients who underwent continuous‐flow LVAD implantations as bridge‐to‐transplant therapy from January 2010 to December 2016 at our institution. After 33 patients were excluded, the study cohort consisted of 78 individuals. CT images used to calculate the skeletal muscle index (SMI) at the third lumbar vertebra level were obtained before the LVAD implantation procedures. Patients were classified as having muscle wasting if their SMI fell into the lowest gender‐based tertile. The median SMI for the study patients was 37.6 cm 2 /m 2 . The SMI cut‐off values for the lowest tertiles were 36.7 cm 2 /m 2 for men and 28.2 cm 2 /m 2 for women, resulting in 26 patients (33.3%) with muscle wasting in this study. During the mean follow‐up of 738 ± 379 days, there were 10 deaths (12.8% mortality). Seven of the 26 patients with muscle wasting (26.9%) died, and 3 of the 52 patients without muscle wasting (5.8%) died. The times to all‐cause mortality were significantly different between patients with and without muscle wasting ( P = 0.0094). Muscle wasting was found to be associated with mortality in univariate and multivariate Cox analyses (hazard ratio: 4.32; 95% CI: 1.19–20.2). Conclusions Preoperative muscle wasting was associated with a higher mortality in patients with LVAD. Assessment of the abdominal skeletal muscle area on CT prior to LVAD implantation can help predict mortality.

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Low ALT blood levels predict long-term all-cause mortality among adults. A historical prospective cohort study

Cited by 59 publications

References 10 publications

Opposite associations between alanine aminotransferase and γ-glutamyl transferase levels and all-cause mortality in type 2 diabetes: Analysis of the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study

Opposite associations between alanine aminotransferase and γ-glutamyl transferase levels and all-cause mortality in type 2 diabetes: Analysis of the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study

Low ALT Levels Independently Associated with 22-Year All-Cause Mortality Among Coronary Heart Disease Patients

Abdominal skeletal muscle mass as a predictor of mortality in Japanese patients undergoing left ventricular assist device implantation

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