title: Elevated gamma-glutamyl transferase is associated with subclinical inflammation independent of cardiometabolic risk factors in an asymptomatic population: a cross-sectional study.
abstract: BACKGROUND
  Serum Gamma-Glutamyl Transferase (GGT), a marker of oxidative stress, has been suggested to be independently associated with cardiovascular disease (CVD) events. We examined the association of serum GGT levels with the burden of subclinical inflammation across a spectrum of metabolic conditions.
  
  
  METHODS
  We evaluated 5,446 asymptomatic subjects (43 ± 10 years, 78 % males) who had an employer-sponsored physical between 2008 and 2010. Highly sensitivity C-reactive protein (hsCRP) was measured as a marker of underlying systemic inflammation. A linear regression of GGT quartiles with log transformed hsCRP and a multivariate logistic regression of GGT quartiles with elevated hsCRP (≥3 mg/L) were performed.
  
  
  RESULTS
  Median GGT was 31 IU/l (IQR: 22-45 IU/l), 1025 (19 %) had hsCRP ≥ 3 mg/L. The median hsCRP increased with GGT quartiles (Q1: 0.9 mg/L, Q2: 1.1 mg/L, Q3: 1.4 mg/L, Q4: 1.6 mg/L, p < 0.001). Linear regression models showed GGT in the fourth quartile was associated with 0.45 mg/L (95 % CI 0.35, 0.54, p < 0.001) increase in log transformed hsCRP adjusting for risk factors. The Odds Ratio (OR) for an elevated hsCRP (≥3 mg/L) also increased with higher GGT quartiles; GGT Q2 1.44 (95 % CI 1.12, 1.85), GGT Q3 1.89 (95 % CI 1.45, 2.46), GGT Q4 2.22 (95 % CI 1.67, 2.95), compared to GGT Q1. The strength of association increased in the presence of and combination of metabolic conditions.
  
  
  CONCLUSIONS
  In our cohort of asymptomatic individuals a higher serum GGT level was independently associated with increased burden of subclinical inflammation across metabolic states. These findings may explain GGT association with increased CVD risk.
authors.affiliation: Center for Healthcare Advancement and Outcomes, Baptist Health Medical Group, 1691 Michigan Avenue Suite 500, Miami, FL 33139 USA ; University of Manchester School of Medicine, Manchester, UK ; Aventura Hospital and Medical Center, Aventura, FL USA.
authors.forename: Shozab S
authors.initials: SS
authors.lastname: Ali
authors.affiliation: Center for Healthcare Advancement and Outcomes, Baptist Health Medical Group, 1691 Michigan Avenue Suite 500, Miami, FL 33139 USA ; Department of Medicine, The Brooklyn Hospital Center, affiliate of Icahn School of Medicine at Mount Sinai, Brooklyn, NY USA.
authors.forename: Ebenezer T
authors.initials: ET
authors.lastname: Oni
authors.affiliation: Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Johns Hopkins University, Baltimore, MD USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Blaha
authors.affiliation: Center for Healthcare Advancement and Outcomes, Baptist Health Medical Group, 1691 Michigan Avenue Suite 500, Miami, FL 33139 USA.
authors.forename: Emir
authors.initials: E
authors.lastname: Veledar
authors.affiliation: Aventura Hospital and Medical Center, Aventura, FL USA.
authors.forename: Hamid R
authors.initials: HR
authors.lastname: Feiz
authors.affiliation: Center for Healthcare Advancement and Outcomes, Baptist Health Medical Group, 1691 Michigan Avenue Suite 500, Miami, FL 33139 USA.
authors.forename: Theodore
authors.initials: T
authors.lastname: Feldman
authors.affiliation: Center for Healthcare Advancement and Outcomes, Baptist Health Medical Group, 1691 Michigan Avenue Suite 500, Miami, FL 33139 USA.
authors.forename: Arthur S
authors.initials: AS
authors.lastname: Agatston
authors.affiliation: Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Johns Hopkins University, Baltimore, MD USA.
authors.forename: Roger S
authors.initials: RS
authors.lastname: Blumenthal
authors.affiliation: Preventive Medicine Center, Hospital Israelita Albert Einstein, Sao Paulo, Brazil.
authors.forename: Raquel D
authors.initials: RD
authors.lastname: Conceicao
authors.affiliation: Preventive Medicine Center, Hospital Israelita Albert Einstein, Sao Paulo, Brazil.
authors.forename: Jose A M
authors.initials: JA
authors.lastname: Carvalho
authors.affiliation: Preventive Medicine Center, Hospital Israelita Albert Einstein, Sao Paulo, Brazil ; Lipid Clinic-Heart Institute (InCor), University of Sao Paulo Medical School, Sao Paulo, Brazil.
authors.forename: Raul D
authors.initials: RD
authors.lastname: Santos
authors.affiliation: Center for Healthcare Advancement and Outcomes, Baptist Health Medical Group, 1691 Michigan Avenue Suite 500, Miami, FL 33139 USA ; Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Johns Hopkins University, Baltimore, MD USA ; Robert Stempel College of Public Health, Florida International University, Miami, FL USA ; Herbert Wertheim College of Medicine, Florida International University, Miami, FL USA.
authors.forename: Khurram
authors.initials: K
authors.lastname: Nasir
keywords: C-reactive protein; Gamma-glutamyl transferase; Subclinical inflammation