Cytotoxin-associated gene-A-seropositivity and Interleukin-1 polymorphisms influence adverse cardiovascular events

Noriaki Tabata; Daisuke Sueta; Yuichiro Arima; Ken Okamoto; Takashi Shono; Shinsuke Hanatani; Seiji Takashio; Kentaro Oniki; Junji Saruwatari; Kenji Sakamoto; Koichi Kaikita; Jan-Malte Sinning; Nikos Werner; Georg Nickenig; Yutaka Sasaki; Toshihiro Fukui; Kenichi Tsujita

doi:10.1016/j.ijcha.2020.100498

Cytotoxin-associated gene-A-seropositivity and Interleukin-1 polymorphisms influence adverse cardiovascular events

Int J Cardiol Heart Vasc. 2020 Mar 7:27:100498. doi: 10.1016/j.ijcha.2020.100498. eCollection 2020 Apr.

Authors

Noriaki Tabata^{1

2}, Daisuke Sueta¹, Yuichiro Arima¹, Ken Okamoto³, Takashi Shono⁴, Shinsuke Hanatani¹, Seiji Takashio¹, Kentaro Oniki⁵, Junji Saruwatari⁵, Kenji Sakamoto¹, Koichi Kaikita¹, Jan-Malte Sinning², Nikos Werner², Georg Nickenig², Yutaka Sasaki⁴, Toshihiro Fukui³, Kenichi Tsujita¹

Affiliations

¹ Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto City, Japan.
² Medizinische Klinik und Poliklinik II, Herzzentrum Bonn, Universitätsklinikum Bonn, Bonn, Germany.
³ Department of Cardiovascular Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto City, Japan.
⁴ Department of Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto City, Japan.
⁵ Division of Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto City, Japan.

Abstract

Aims: Although the bacterial virulent factor of cytotoxin-associated gene-A (CagA)-seropositivity and the host genetic factors of interleukin (IL)-1 polymorphisms have been suggested to influence Helicobacter pylori (HP) -related diseases, the underlying mechanisms of the association between HP infection and acute coronary syndrome (ACS) remain unknown.

Methods and results: Among 341 consecutive ACS patients, the clinical outcomes after ACS included composite cardiovascular events within the 2-year follow-up period.A significantly higher probability of primary outcomes was observed in HP positive patients than in HP negative patients. There were no significant differences in the rate of cardiovascular events between HP positive and HP negative patients in the absence of an IL-polymorphism, while there were significant differences in the presence of an IL-polymorphism. There were significant differences in the rate of cardiovascular events among CagA positive, CagA negative/ HP positive and CagA negative/HP negative patients. Moreover, via immunohistochemical staining, aortic CagA positive cells were confirmed in the vasa vasorum in CagA positive patients, whereas they could not be identified in CagA negative patients.

Conclusions: The bacterial virulence factor CagA and host genetic IL-1 polymorphisms influence the incidence of adverse cardiovascular events, possibly through infection of atherosclerotic lesions.Registration: University Hospital Medical Information Network (UMIN)-CTR (http://www.umin.ac.jp/ctr/).Identifier: UMIN000035696.

Keywords: CagA; Helicobacter pylori; Interleukin-1; MACE.