title: Plasma levels of nitric oxide metabolites are markedly reduced in normotensive men with electrocardiographically determined left ventricular hypertrophy.
abstract: Recent studies have revealed that electrocardiographically determined left ventricular hypertrophy (ECG-LVH) is a risk factor for cardiovascular death not only in hypertensive patients but also in normotensive subjects. However, the underlying mechanisms remain to be elucidated. In this study, we tested our hypothesis that normotensive subjects with ECG-LVH have reduced nitric oxide production. A total of 840 Japanese male workers were enrolled, and 579 eligible subjects were studied. ECG-LVH was assessed according to the Sokolow-Lyon voltage criteria and the Cornell voltage-duration product. The median level of plasma NOx (nitrite plus nitrate), a marker of systemic nitric oxide production, was markedly lower in the normotensive subjects with ECG-LVH (n=73) than in those without (n=506), and the clinical characteristics were significantly different between the 2 groups (each P<0.05). Importantly, a one-to-one propensity score matching analysis showed similar markedly lower median plasma NOx level in the normotensive subjects with ECG-LVH compared with that observed in the matched normotensive subjects without ECG-LVH (P<0.05). Furthermore, the tertiles of the plasma NOx levels were inversely correlated with the prevalence and severity of ECG-LVH (both P<0.05). The lower plasma NOx levels were associated with significantly higher plasma 8-isoprostane levels, a marker of systemic lipid peroxidation (P<0.05). These results provide the first evidence that normotensive subjects with ECG-LVH exhibit defective nitric oxide production, along with increased oxidative stress. Our findings may thus explain, at least in part, a potential mechanism underlying the increased risk of cardiovascular death in normotensive individuals with ECG-LVH.
authors.affiliation: From the Department of Emergency Medicine (F.K., T.M.), Second Department of Internal Medicine (M. Takahashi, S.S., H.A., M. Takeuchi, Y.O.), and Department of Public Health (T.K., Y.F.), School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan; Department of Pharmacology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan (M. Tsutsui); and Laboratory of Clinical Pharmaceutics, Gifu Pharmaceutical University, Gifu, Japan (T.A.). kamezaki@km-clnc.jp.
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Kamezaki
authors.affiliation: From the Department of Emergency Medicine (F.K., T.M.), Second Department of Internal Medicine (M. Takahashi, S.S., H.A., M. Takeuchi, Y.O.), and Department of Public Health (T.K., Y.F.), School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan; Department of Pharmacology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan (M. Tsutsui); and Laboratory of Clinical Pharmaceutics, Gifu Pharmaceutical University, Gifu, Japan (T.A.).
authors.forename: Masato
authors.initials: M
authors.lastname: Tsutsui
authors.affiliation: From the Department of Emergency Medicine (F.K., T.M.), Second Department of Internal Medicine (M. Takahashi, S.S., H.A., M. Takeuchi, Y.O.), and Department of Public Health (T.K., Y.F.), School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan; Department of Pharmacology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan (M. Tsutsui); and Laboratory of Clinical Pharmaceutics, Gifu Pharmaceutical University, Gifu, Japan (T.A.).
authors.forename: Masao
authors.initials: M
authors.lastname: Takahashi
authors.affiliation: From the Department of Emergency Medicine (F.K., T.M.), Second Department of Internal Medicine (M. Takahashi, S.S., H.A., M. Takeuchi, Y.O.), and Department of Public Health (T.K., Y.F.), School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan; Department of Pharmacology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan (M. Tsutsui); and Laboratory of Clinical Pharmaceutics, Gifu Pharmaceutical University, Gifu, Japan (T.A.).
authors.forename: Shinjo
authors.initials: S
authors.lastname: Sonoda
authors.affiliation: From the Department of Emergency Medicine (F.K., T.M.), Second Department of Internal Medicine (M. Takahashi, S.S., H.A., M. Takeuchi, Y.O.), and Department of Public Health (T.K., Y.F.), School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan; Department of Pharmacology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan (M. Tsutsui); and Laboratory of Clinical Pharmaceutics, Gifu Pharmaceutical University, Gifu, Japan (T.A.).
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Kubo
authors.affiliation: From the Department of Emergency Medicine (F.K., T.M.), Second Department of Internal Medicine (M. Takahashi, S.S., H.A., M. Takeuchi, Y.O.), and Department of Public Health (T.K., Y.F.), School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan; Department of Pharmacology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan (M. Tsutsui); and Laboratory of Clinical Pharmaceutics, Gifu Pharmaceutical University, Gifu, Japan (T.A.).
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Fujino
authors.affiliation: From the Department of Emergency Medicine (F.K., T.M.), Second Department of Internal Medicine (M. Takahashi, S.S., H.A., M. Takeuchi, Y.O.), and Department of Public Health (T.K., Y.F.), School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan; Department of Pharmacology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan (M. Tsutsui); and Laboratory of Clinical Pharmaceutics, Gifu Pharmaceutical University, Gifu, Japan (T.A.).
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Adachi
authors.affiliation: From the Department of Emergency Medicine (F.K., T.M.), Second Department of Internal Medicine (M. Takahashi, S.S., H.A., M. Takeuchi, Y.O.), and Department of Public Health (T.K., Y.F.), School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan; Department of Pharmacology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan (M. Tsutsui); and Laboratory of Clinical Pharmaceutics, Gifu Pharmaceutical University, Gifu, Japan (T.A.).
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Abe
authors.affiliation: From the Department of Emergency Medicine (F.K., T.M.), Second Department of Internal Medicine (M. Takahashi, S.S., H.A., M. Takeuchi, Y.O.), and Department of Public Health (T.K., Y.F.), School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan; Department of Pharmacology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan (M. Tsutsui); and Laboratory of Clinical Pharmaceutics, Gifu Pharmaceutical University, Gifu, Japan (T.A.).
authors.forename: Masaaki
authors.initials: M
authors.lastname: Takeuchi
authors.affiliation: From the Department of Emergency Medicine (F.K., T.M.), Second Department of Internal Medicine (M. Takahashi, S.S., H.A., M. Takeuchi, Y.O.), and Department of Public Health (T.K., Y.F.), School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan; Department of Pharmacology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan (M. Tsutsui); and Laboratory of Clinical Pharmaceutics, Gifu Pharmaceutical University, Gifu, Japan (T.A.).
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Mayumi
authors.affiliation: From the Department of Emergency Medicine (F.K., T.M.), Second Department of Internal Medicine (M. Takahashi, S.S., H.A., M. Takeuchi, Y.O.), and Department of Public Health (T.K., Y.F.), School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan; Department of Pharmacology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan (M. Tsutsui); and Laboratory of Clinical Pharmaceutics, Gifu Pharmaceutical University, Gifu, Japan (T.A.).
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Otsuji
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000502:physiology*; D015237:Dinoprost / Q000031:analogs & derivatives / Q000097:blood; D004562:Electrocardiography; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000097:blood* / Q000503:physiopathology; D007564:Japan; D015227:Lipid Peroxidation / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000097:blood*; D009573:Nitrites / Q000097:blood; D018384:Oxidative Stress / Q000502:physiology; D015995:Prevalence; D012307:Risk Factors; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; D009566:Nitrates; D009573:Nitrites; C075750:8-epi-prostaglandin F2alpha; D009569:Nitric Oxide; D015237:Dinoprost
keywords: electrocardiography; hypertrophy, left ventricular; nitric oxide; oxidative stress