Secondary Logo

Institutional members access full text with Ovid®

Elevated liver enzymes and cardiovascular mortality

a systematic review and dose–response meta-analysis of more than one million participants

Rahmani, Jamala; Miri, Alif; Namjoo, Imang; Zamaninour, Negarc; Maljaei, Mohammad B.d,h; Zhou, Kehuai; Cerneviciute, Ramintaj; Mousavi, Seyed M.e; Varkaneh, Hamed K.b; Salehisahlabadi, Ammarb; Zhang, Yongk

European Journal of Gastroenterology & Hepatology: May 2019 - Volume 31 - Issue 5 - p 555–562
doi: 10.1097/MEG.0000000000001353
Review Article

Gamma glutamyl transferase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) are commonly used liver function markers. We performed a dose–response meta-analysis to investigate the association between liver enzymes and cardiovascular disease (CVD) mortality in prospective cohort studies. We conducted a systematic search up to April 2018 in Medline/PubMed, Scopus, Cochrane, and Embase databases. Combined hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using a random-effects model as described by DerSimonian and Laird. Dose–response analysis was also carried out. Twenty-three studies with 1 067 922 participants reported association between GGT and CVD mortality and were included in our analysis. Pooled results showed a significant association between GGT and risk of CVD mortality (HR: 1.62; 95% CI: 1.47–1.78, P=0.001, P-heterogeneity=0.001) and it was HR: 0.87; 95% CI: 0.73–1.07; P=0.221, P-heterogeneity=0.028, for ALT. There was a direct association between baseline levels of ALP and AST/ALT ratio with CVD mortality (HR: 1.45; 95% CI: 1.11–1.89; P=0.005, P-heterogeneity=0.026, and HR: 2.20; 95% CI: 1.60–3.04; P=0.001, P-heterogeneity=0.540, respectively). Pooled results did not show any significant association between AST and the risk of CVD mortality (HR: 1.20; 95% CI: 0.83–1.73; P=0.313, P-heterogeneity=0.024). Moreover, there was a significant nonlinear association between GGT and ALP levels and the risk of CVD mortality (P=0.008 and 0.016, respectively). Our dose–response meta-analysis revealed a direct relationship between GGT and ALP levels and the risk of CVD mortality. High levels of GGT, ALP and AST/ALT were associated with an increased CVD mortality rate.

aDepartment of Community Nutrition

bDepartment of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, National Nutrition and Food Technology Research Institute, Student Research Committee, Shahid Beheshti University of Medical Sciences

cMinimally Invasive Surgery Research Center

dDepartment of Nutrition, School of Public Health, Iran University of Medical Sciences

eDepartment of Community Nutrition, School of Nutritional Sciences and Dietetics, Student Research Committee, Tehran University of Medical Sciences (TUMS), Tehran

fDepartment of Nutrition, School of Health, Zabol University of Medical Sciences, Zabol

gDepartment of Community Nutrition, School of Nutrition and Food Sciences, Food Security Research Center

hIsfahan Neuroscience Research Center, Alzahra Hospital, Isfahan University of Medical Sciences, Isfahan, Iran

iDepartment of Internal Medicine, University at Buffalo, Buffalo, New York, USA

jFaculty of Medicine, Lithuanian University of Health Sciences, Kaunas, Lithuania

kDepartment of Nutrition and Food Hygiene, School of Public Health and Health Management, Chongqing Medical University, Chongqing, China

Correspondence to Yong Zhang, MD, MS, PhD, Department of Nutrition and Food Hygiene, School of Public Health and Health Management, Chongqing Medical University, No. 1 Yixueyuan Road, Yuzhong District, Chongqing 400016, China Tel/fax: +86 236 848 5008; e-mail:

Received November 5, 2018

Accepted December 17, 2018

Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.