Abstract
Background: The elevated gamma-glutamyltransferase (GGT) activity is regarded as an indicator of cardiovascular disease, with males having higher values than females. The greater incidence of idiopathic pulmonary arterial hypertension (IPAH) is observed in women, whereas prognosis is poor in men. The present study aims to investigate the potential association of GGT on male patients.Methods: Serum GGT levels were measured in 338 consecutive adult IPAH patients, who underwent bone morphogenetic protein receptor type 2 (BMPR2) genetic counseling, and matched with healthy subjects by sex and age. The followed interval was 48 ± 34 months.Results: Increased serum GGT levels were more common in patients with IPAH than controls (p < 0.001). GGT values were significantly higher in male patients than those of females (p < 0.001). Compared with female patients with BMPR2 mutation, GGT level in male patients with BMPR2 mutation was further increased (p = 0.002). Higher GGT levels were associated with worse hemodynamics and Nterminal pro B-type natriuretic peptide in all patients. However, males with a GGT concentration ≥ 53 U/L had a worse survival than those of females. Contrarily, if GGT concentration <53 U/L, there was no survival difference between male and female patients. After adjustment for relevant variables of clinical features and hemodynamics, baseline higher GGT levels remained increased risks of all-cause mortality in males rather than females. During rehospitalization follow-up, male patients still had significantly higher values of GGT than females.Conclusions: Increased GGT levels were correlated with BMPR2 mutation, hemodynamic dysfunction, and poor outcomes in male patients with IPAH. Further studies are needed to explain the origin of abnormal GGT and its potential pathogenesis in men.
Highlights
Patients with pulmonary arterial hypertension (PAH) have a poor prognosis due to progressive pulmonary vascular remodeling, which leads to right ventricular (RV) overload and right heart failure without effective treatment [1]
The objectives of this study were to determine whether (a) GGT levels were further increased in male patients; (b) abnormalities of GGT activities were related to hemodynamic dysfunction and clinical characters; (c) male patients with bone morphogenetic protein receptor type 2 (BMPR2) mutation had higher GGT levels than those of females; (d) serum GGT could be a predictor for prognosis and clinical outcomes in male patients with idiopathic PAH (IPAH)
The GGT concentration in men was markedly reduced in patients with World Health Organization Function Class (WHO World Health Organization functional class (FC)) I/II (50.1 ± 39.3 U/L), compared with those with WHO FC III (63.2 ± 56.2 U/L, p = 0.04) or IV (99.9 ± 88.8 U/L, p = 0.01), respectively
Summary
Patients with pulmonary arterial hypertension (PAH) have a poor prognosis due to progressive pulmonary vascular remodeling, which leads to right ventricular (RV) overload and right heart failure without effective treatment [1]. GGT activity is determined by genes and age, there is still a remarkable sex difference that females have lower value than males in normal physiology [7, 8]. In clinical practice in China, different sex had the same reference value range of GGT (normal range ≤ 38 U/L). It was unclear whether GGT involved in the pathology of PAH. Wannamethee et al have reported that elevated serum GGT activity was a predictor of increased CVD mortality in British men, in those with age
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