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

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.