title: Gamma-glutamyltransferase, fatty liver index and hepatic insulin resistance are associated with incident hypertension in two longitudinal studies.
abstract: We hypothesized that liver markers and the fatty liver index (FLI) are predictive of incident hypertension and that hepatic insulin resistance plays a role.
  
  
  
  The association between liver markers and incident hypertension was analysed in two longitudinal studies of normotensive individuals, 2565 from the 9-year data from an epidemiological study on the insulin resistance cohort and the 321 from the 3-year 'Relationship between Insulin Sensitivity and Cardiovascular disease' cohort who had a measure of endogenous glucose production. The FLI is calculated from BMI, waist circumference, triglycerides and gamma-glutamyltransferase (GGT) and the hepatic insulin resistance index from endogenous glucose production and fasting insulin.
  
  
  
  The incidence of hypertension increased across the quartiles groups of both baseline GGT and alanine aminotransferase. After adjustment for sex, age, waist circumference, fasting glucose, smoking and alcohol intake, only GGT was significantly related with incident hypertension [standardized odds ratio: 1.21; 95% confidence interval (1.10-1.34); P = 0.0001]. The change in GGT levels over the follow-up was also related with an increased risk of hypertension, independently of changes in body weight. FLI analysed as a continuous value, or FLI at least 60 at baseline were predictive of incident hypertension in the multivariable model. In the RISC cohort, the hepatic insulin resistance index was positively related with the risk of 3-year incident hypertension [standardized odds ratio: 1.54 (1.07-2.22); P = 0.02].
  
  
  
  Baseline GGT and FLI, as well as an increase in GGT over time, were associated with the risk of incident hypertension. Enhanced hepatic insulin resistance predicted the onset of hypertension and may be a link between liver markers and hypertension.
authors.affiliation: aService Endocrinologie-Diabétologie, CHU Rennes, Université Rennes 1, Rennes bINSERM, Centre for Research in Epidemiology and Population Health (CESP), U1018 cUniversity Paris-Sud, University Versailles Saint-Quentin, UMRS 1018, Paris, France dClinical Physiology CNR, Cardiometabolic Risk Laboratory eDepartment of Internal Medicine, University of Pisa, Pisa, Italy fINSERM U1138 gAP-HP, Hôpital Bichat, Diabetology Endocrinology Nutrition, Université Paris Diderot, Paris, France hInstitute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK iIRSA, La Riche jINSERM, U991, Université de Rennes 1, Rennes, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Bonnet
authors.forename: Amalia
authors.initials: A
authors.lastname: Gastaldelli
authors.forename: Florence
authors.initials: F
authors.lastname: Pihan-Le Bars
authors.forename: Andrea
authors.initials: A
authors.lastname: Natali
authors.forename: Ronan
authors.initials: R
authors.lastname: Roussel
authors.forename: John
authors.initials: J
authors.lastname: Petrie
authors.forename: Jean
authors.initials: J
authors.lastname: Tichet
authors.forename: Michel
authors.initials: M
authors.lastname: Marre
authors.forename: Bernard
authors.initials: B
authors.lastname: Fromenty
authors.forename: Beverley
authors.initials: B
authors.lastname: Balkau
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D001786:Blood Glucose / Q000096:biosynthesis; D015992:Body Mass Index; D005215:Fasting; D005234:Fatty Liver / Q000097:blood*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000453:epidemiology*; D015994:Incidence; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D014280:Triglycerides / Q000097:blood; D055105:Waist Circumference; D005723:gamma-Glutamyltransferase / Q000097:blood*
chemical_list: D001786:Blood Glucose; D007328:Insulin; D014280:Triglycerides; D005723:gamma-Glutamyltransferase; D000410:Alanine Transaminase