Gamma-glutamyltransferase, arterial remodeling and prehypertension in a healthy population at low cardiometabolic risk

Michaela Kozakova, Amalia Gastaldelli, Carmela Morizzo, Kurt Højlund, Peter M. Nilssson, Ele Ferrannini, R. J. Heine, J. Dekker, S. de Rooij, G. Nijpels, W. Boorsma, A. Kok, A. Mitrakou, S. Tournis, K. Kyriakopoulou, P. Thomakos, N. Lalic, K. Lalic, A. Jotic, L. LukicM. Civcic, J. Nolan, T. P. Yeow, M. Murphy, C. DeLong, G. Neary, M. P. Colgan, M. Hatunic, P. Gaffney, G. Boran, T. Konrad, H. Böhles, S. Fuellert, F. Baer, H. Zuchhold, A. Golay, E. Harsch Bobbioni, V. Barthassat, V. Makoundou, T. N.O. Lehmann, T. Merminod, J. R. Petrie (now Dundee), C. Perry, F. Neary, C. MacDougall, K. Shields, L. Malcolm, M. Laakso, U. Salmenniemi, A. Aura, R. Raisanen, U. Ruotsalainen, T. Sistonen, M. Laitinen, H. Saloranta, S. W. Coppack, N. McIntosh, J. Ross, L. Pettersson, P. Khadobaksh, B. Balkau, L. Mhamdi, M. T. Guillanneuf, M. Laville, F. Bonnet, A. Brac de la Perriere, C. Louche-Pelissier, C. Maitrepierre, J. Peyrat, S. Beltran, A. Serusclat, R. Gabriel, E. M. Sánchez, R. Carraro, A. Friera, B. Novella, P. Nilssone, M. Persson, G. Östling, O. Melander, P. Burri, P. M. Piatti, L. D. Monti, E. Setola, E. Galluccio, F. Minicucci, A. Colleluori, M. Walker, I. M. Ibrahim, M. Jayapaul, D. Carman, C. Ryan, K. Short, Y. McGrady, D. Richardson, S. Patel, H. Beck-Nielsen, P. Staehr, K. Hojlundd, V. Vestergaard, C. Olsen, L. Hansen, G. B. Bolli, F. Porcellati, C. Fanelli, P. Lucidi, F. Calcinaro, A. Saturni, E. Ferranninia, A. Natali, E. Muscelli, S. Pinnola, M. Kozakovaa, S. A. Hills, L. Landucci, L. Mota, A. Gastaldelli, D. Ciociaro, A. Mari, G. Pacini, C. Cavaggion, G. Mingrone, C. Guidone, A. Favuzzi, P. Di Rocco, C. Anderwald, M. Bischof, M. Promintzer, M. Krebs, M. Mandl, A. Hofer, A. Luger, W. Waldhäusl, M. Roden, Carlo Palombo*, RISC Investigators

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Plasma gamma-glutamyltransferase (GGT) was suggested to reflect the level of systemic oxidative stress. Oxidative stress induces changes in arterial structure and function and contributes to the development of hypertension. Therefore, GGT may be associated with arterial remodeling and blood pressure (BP) increment, even in absence of disease. To test this hypothesis, we evaluated, in 825 healthy subjects at low cardiometabolic risk, the associations of plasma GGT with carotid artery intima-media thickness (IMT), luminal diameter and prehypertension; in 154 subjects was evaluated also the association with aortic stiffness (cfPWV). Associations were controlled for insulin sensitivity, C-reactive protein, and life-style habits. In the main population, BP was remeasured after 3 years. Carotid diameter and cfPWV, but not IMT, were directly and independently related to plasma GGT. Subjects with prehypertension (N = 330) had higher GGT as compared with subjects with normal BP (22 [14] vs 17 [11] IU/L; adjusted P = 0.001), and within prehypertensive subjects, those who developed hypertension during 3 years had higher GGT than those without incident hypertension (27 [16] vs 21 [14] IU/L; adjusted P < 0.05). Within subjects with arterial stiffness measurement, those with prehypertension (N = 79) had higher both GGT and arterial stiffness (25 [14] vs 16 [20] IU/L and 9.11 ± 1.24 vs 7.90 ± 0.94 m/s; adjusted P < 0.01 and <0.05). In the view of previous evidence linking plasma GGT concentration to the level of systemic oxidative stress, our findings suggest a role of oxidative stress in subclinical arterial damage and in prehypertension, even in healthy subjects free of cardiometabolic risk. Arterial organ damage may represent the link between GGT and hypertension.

Original languageEnglish
JournalJournal of Human Hypertension
DOIs
Publication statusAccepted/In press - 1 Jan 2020

Cite this

Kozakova, M., Gastaldelli, A., Morizzo, C., Højlund, K., Nilssson, P. M., Ferrannini, E., ... RISC Investigators (Accepted/In press). Gamma-glutamyltransferase, arterial remodeling and prehypertension in a healthy population at low cardiometabolic risk. Journal of Human Hypertension. https://doi.org/10.1038/s41371-020-0337-1