title: Endodontic infection and endothelial dysfunction are associated with different mechanisms in men and women.
abstract: BACKGROUND
  To investigate the potential link between apical periodontitis (AP) and cardiovascular (CV) function, inflammation markers, endothelial flow reserve (EFR), and levels of asymmetrical dimethylarginine (ADMA), the endogenous inhibitor of nitric oxide synthase (NOS), were measured in young adults with AP aged 20-40 years of both sexes.
  
  
  METHODS
  Forty men and 41 women (31 ± 5.71 years) free from periodontal disease, CV disease, and traditional CV risk factors were enrolled in the study. Twenty men and 21 women had AP; 40 healthy individuals matched for age, sex, and physical characteristics were also recruited as controls. All subjects underwent dental and complete physical examination, electrocardiography, conventional and tissue Doppler imaging echocardiography, and measurement of EFR. Interleukin (IL)-2, tumor necrosis factor alpha, reactive oxygen species (ROS), and ADMA were also assessed. Data were analyzed using the 2-tailed Student t test, the Pearson t test (or the Spearman t test for nonparametric variables), and multivariate linear regression analysis.
  
  
  RESULTS
  Echocardiography excluded any morphologic and functional cardiac alteration in all the subjects studied. Patients with AP of both sexes showed a significant reduction in EFR (P < .05) and a significant increase in IL-2 (men: P < .01, women: P < .05), whereas ROS were increased significantly only in women (P < .05). ADMA levels were unchanged in women with AP, but they were significantly increased in men (P < .05). A significant direct correlation between ADMA and IL-2 (r = 0.67, P < .001) and an inverse correlation between ADMA and EFR (r = -0.42, P < .05) in men and a significant inverse correlation between ROS and EFR (r = -0.71, P < .01) in female patients were observed.
  
  
  CONCLUSIONS
  The presence of chronic inflammation in young adults with AP may cause early endothelial dysfunction documented by the reduced EFR. AP in men may influence the metabolism of NOS, whereas in women it appears to implicate a more direct detrimental mechanism. This difference is sex dependent and may be attributable to the protective action of estrogen in women.
authors: Department of Conservative Dentistry and Endodontics, University of Cagliari, Cagliari, Italy. Electronic address: cottiend@tin.it.
authors: Elisabetta
authors: E
authors: Cotti
authors: Department of Medical Sciences, University of Cagliari, Cagliari, Italy.
authors: Angela
authors: A
authors: Zedda
authors: Department of Medical Sciences, University of Cagliari, Cagliari, Italy.
authors: Martino
authors: M
authors: Deidda
authors: Department of Medical Sciences, University of Cagliari, Cagliari, Italy.
authors: Alessandra
authors: A
authors: Piras
authors: Department of Medical Sciences, University of Cagliari, Cagliari, Italy.
authors: Giovanna
authors: G
authors: Flore
authors: Department of Conservative Dentistry and Endodontics, University of Cagliari, Cagliari, Italy.
authors: Francesca
authors: F
authors: Ideo
authors: Department of Medical Sciences, University of Cagliari, Cagliari, Italy.
authors: Clelia
authors: C
authors: Madeddu
authors: Department of Conservative Dentistry and Endodontics, University of Cagliari, Cagliari, Italy.
authors: Valentina Maria
authors: VM
authors: Pau
authors: Department of Medical Sciences, University of Cagliari, Cagliari, Italy.
authors: Giuseppe
authors: G
authors: Mercuro
mesh_terms: D000328:Adult; D001120:Arginine / Q000031:analogs & derivatives / Q000097:blood; D002319:Cardiovascular System / Q000503:physiopathology*; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000097:blood; D015150:Echocardiography, Doppler; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010485:Periapical Periodontitis / Q000000981:diagnostic imaging / Q000503:physiopathology*; D017382:Reactive Oxygen Species; D012737:Sex Factors; D055815:Young Adult
chemical_list: D016207:Cytokines; D017382:Reactive Oxygen Species; C487735:dimethylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase
keywords: Apical periodontitis; cardiovascular disease; markers of inflammation