Baseline and long-term gamma-glutamyltransferase, heart failure and cardiac arrhythmias in middle-aged Finnish men: Prospective study and pooled analysis of published evidence

Aim 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). Methods 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. Results During an average follow-up of 22 years, 222 HF, 56 VA and 336 AF events occurred. The regression dilution ratio of log_e 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 log_e 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. Conclusion 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.