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Gamma-glutamyltransferase and risk of hypertension

a systematic review and dose–response meta-analysis of prospective evidence

Kunutsor, Setor K.a; Apekey, Tanefa A.b; Cheung, Bernard M.Y.c,d

doi: 10.1097/HJH.0000000000000763

The objective of this review was to obtain a reliable estimate of the magnitude of the prospective association between gamma-glutamyltransferase (GGT) and risk of hypertension, and to characterize the nature of the dose–response relationship. We conducted a systematic review and dose–response meta-analysis of published prospective studies. Relevant studies were identified in a literature search of MEDLINE, EMBASE, and Web of Science databases up to May 2015. Study-specific relative risks (RRs) were meta-analyzed using random effects models. We examined a potential nonlinear relationship using restricted cubic splines. Of the 612 titles reviewed, we included 14 cohort studies with data on 44 582 participants and 5 270 hypertension cases. In a comparison of extreme thirds of baseline levels of GGT, RR for hypertension in pooled analysis of all 14 studies was 1.32 (95% confidence interval: 1.23–1.43). There was heterogeneity among the studies (P < 0.001), which was to a large part explained by average age of participants at baseline, average duration of follow-up, and the degree of confounder adjustment. In a pooled dose–response analysis of 10 studies with relevant data, there was evidence of a linear association between GGT and hypertension risk (P for nonlinearity = 0.37). The pooled RR of hypertension per 5 U/l increment in GGT levels was 1.08 (95% confidence interval: 1.04–1.13). Baseline circulating GGT level is associated with an increased risk of hypertension in the general population, consistent with a linear dose–response relationship. Further investigation of any potential relevance of GGT in hypertension prevention is warranted.

aMusculoskeletal Research Unit, School of Clinical Sciences, University of Bristol, Southmead Hospital, Southmead

bFaculty of Health and Social Sciences, School of Health and Wellbeing, Leeds Beckett University, Leeds, UK

cDepartment of Medicine

dState Key Laboratory of Pharmaceutical Biotechnology, University of Hong Kong, Hong Kong

Correspondence to Setor K. Kunutsor, MD, PhD, Musculoskeletal Research Unit, School of Clinical Sciences, University of Bristol, Learning & Research Building (Level 1), Southmead Hospital, Southmead, BS10 5NB, United Kingdom. Tel: +44 0 7539589186; fax: +44 0 1174147924; e-mail:

Abbreviations: BP, blood pressure; CI, confidence interval; CVD, cardiovascular disease; GGT, gamma-glutamyltransferase; NOS, Newcastle–Ottawa Scale; RR, relative risk, SD; standard deviation

Received 18 May, 2015

Revised 28 August, 2015

Accepted 28 August, 2015

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