title: Baseline and long-term gamma-glutamyltransferase, heart failure and cardiac arrhythmias in middle-aged Finnish men: Prospective study and pooled analysis of published evidence.
abstract: To assess the associations of baseline and long-term gamma-glutamyltransferase (GGT) activity with risk of heart failure (HF), ventricular arrhythmias (VAs) and atrial fibrillation (AF).
  
  
  
  GGT measurements were made in a prospective cohort of 1780 men free of HF and cardiac arrhythmias at baseline. Correction for within-person variability was made using data from repeat measurements taken several years apart.
  
  
  
  During an average follow-up of 22 years, 222 HF, 56 VA and 336 AF events occurred. The regression dilution ratio of loge GGT was 0.68 (95% confidence interval (CI): 0.61-0.74). Serum GGT was log-linearly associated with risk of HF, VAs and AF. In analyses adjusted for established risk factors, the hazard ratios (HRs) (95% CIs) for HF, VAs and AF per 1 SD higher baseline loge GGT values were 1.25 (1.07-1.45), 1.37 (1.04-1.80) and 1.04 (0.92-1.18), respectively. After correction for within-person variability, the corresponding HRs were 1.38 (1.11-1.73), 1.58 (1.06-2.37) and 1.06 (0.88-1.27), respectively. These findings remained consistent in analyses accounting for incident coronary heart disease and the development of impaired renal function. In a meta-analysis of five population-based studies, the fully adjusted relative risks for HF per 1 SD higher baseline and long-term GGT values were 1.28 (1.20-1.35) and 1.43 (1.31-1.56), respectively. In a pooled analysis of two studies, the corresponding risks for AF were 1.09 (1.02-1.16) and 1.14 (1.03-1.25), respectively.
  
  
  
  GGT is positively and log-linearly associated with future risk of HF, VAs and AF. Further research is needed in order to assess the causal relevance of these findings.
authors.affiliation: School of Clinical Sciences, University of Bristol, Southmead Hospital, Bristol, UK skk31@cantab.net.
authors.forename: Setor K
authors.initials: SK
authors.lastname: Kunutsor
authors.affiliation: Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Finland.
authors.forename: Jari A
authors.initials: JA
authors.lastname: Laukkanen
authors.affiliation: NIH Clinical Center, Bethesda, MD, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Bluemke
authors.affiliation: Division of Cardiology, Stony Brook University, Health Sciences Center, NY, USA.
authors.forename: Javed
authors.initials: J
authors.lastname: Butler
authors.affiliation: Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Hassan
authors.initials: H
authors.lastname: Khan
mesh_terms: D001145:Arrhythmias, Cardiac / Q000201:enzymology* / Q000453:epidemiology; D015415:Biomarkers / Q000097:blood; D005260:Female; D005387:Finland / Q000453:epidemiology; D005500:Follow-Up Studies; D005544:Forecasting; D006333:Heart Failure / Q000201:enzymology* / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D010506:Periodicals as Topic / Q000706:statistics & numerical data*; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D015415:Biomarkers; D005723:gamma-Glutamyltransferase
keywords: Gamma-glutamyltransferase; atrial fibrillation; heart failure; ventricular arrhythmias