TY - JOUR
T1 - Serum Lipopolysaccharide-Binding Protein Levels and the Incidence of Cardiovascular Disease in a General Japanese Population
T2 - The Hisayama Study
AU - Asada, Masako
AU - Oishi, Emi
AU - Sakata, Satoko
AU - Hata, Jun
AU - Yoshida, Daigo
AU - Honda, Takanori
AU - Furuta, Yoshihiko
AU - Shibata, Mao
AU - Suzuki, Kosuke
AU - Watanabe, Hiroshi
AU - Murayama, Norihito
AU - Kitazono, Takanari
AU - Yamaura, Ken
AU - Ninomiya, Toshiharu
N1 - Funding Information:
The authors thank the residents of the town of Hisayama for their participation in the survey and the staff of the Division of Health and Welfare of Hisayama for their cooperation with this study. Professor Yoshinao Oda, Professor Toru Iwaki, and their colleagues in the Department of Anatomic Pathology and Department of Neuropathology, Graduate School of Medical Sciences, Kyushu University greatly assisted our research by providing insight and expertise on the autopsy findings; we are grateful for their help. Statistical analyses were performed using the computer resources offered under the category of General Projects by the Research Institute for Information Technology, Kyushu University.
Funding Information:
This study was supported in part by Grants‐in‐Aid for Scientific Research (A) (JP16H02692) and (B) (JP16H05850, JP17H04126, and JP18H02737) and (C) (JP17K09114, JP17K09113, JP17K01853, JP18K07565, JP18K09412, and JP19K07890) and (Early‐Career Scientists) (JP18K17925, and JP18K17382) from the Ministry of Education, Culture, Sports, Science and Technology of Japan; by Health and Labour Sciences Research Grants of the Ministry of Health, Labour and Welfare of Japan (H29‐Junkankitou‐Ippan‐003, and H30‐Shokuhin‐[Sitei]‐005); and by the Japan Agency for Medical Research and Development (JP19dk0207025, JP19ek0210082, JP19ek0210083, JP19km0405202, JP19ek0210080, and JP19fk0108075). This study was also supported by the Suntory Global Innovation Center Limited (Kyoto, Japan).
Funding Information:
Ninomiya obtained funding support from the Suntory Global Innovation Center (Kyoto, Japan). Suzuki, Watanabe, and Murayama are employed by the Suntory Global Innovation Center Limited (Kyoto, Japan). The remaining authors have no disclosures to report.
Publisher Copyright:
© 2019 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.
PY - 2019/11/5
Y1 - 2019/11/5
N2 - Background: Epidemiological studies have reported a link between serum LBP (lipopolysaccharide-binding protein) levels and lifestyle-related diseases. However, there have been no longitudinal studies investigating the association of serum LBP levels and the incidence of cardiovascular disease (CVD) in general populations. Methods and Results: A total of 2568 community-dwelling Japanese individuals 40 years and older without prior CVD were followed for 10 years (2002–2012). Serum LBP levels were divided into quartiles (quartile 1: 2.20–9.68 μg/mL; quartile 2: 9.69–10.93 μg/mL; quartile 3: 10.94–12.40 μg/mL; quartile 4: 12.41–24.34 μg/mL). The hazard ratios (HRs) and their 95% CIs for the incidence of CVD were computed using a Cox proportional hazards model. During the follow-up period, 180 individuals developed CVD. The age- and sex-adjusted cumulative incidence of CVD increased significantly with higher serum LBP levels (P for trend=0.005). Individuals with higher serum LBP levels had a significantly greater risk of the development of CVD after adjusting for conventional cardiovascular risk factors (quartile 1: HR, 1.00 [reference]; quartile 2: HR, 1.04 [95% CI, 0.60–1.78]; quartile 3: HR, 1.52 [95% CI, 0.92–2.51]; and quartile 4: HR, 1.90 [95% CI, 1.17–3.09]; P for trend=0.01). This association remained significant after additional adjustment for homeostasis model assessment of insulin resistance (P for trend=0.01). However, when additional adjustment was made for high-sensitivity C-reactive protein, the association was attenuated to the nonsignificant level (P for trend=0.08). Conclusions: The present findings suggest that higher serum LBP levels are associated with increased risk of the development of CVD in the general Japanese population. Low-grade endotoxemia may contribute to the pathogenesis of CVD through chronic systemic inflammation.
AB - Background: Epidemiological studies have reported a link between serum LBP (lipopolysaccharide-binding protein) levels and lifestyle-related diseases. However, there have been no longitudinal studies investigating the association of serum LBP levels and the incidence of cardiovascular disease (CVD) in general populations. Methods and Results: A total of 2568 community-dwelling Japanese individuals 40 years and older without prior CVD were followed for 10 years (2002–2012). Serum LBP levels were divided into quartiles (quartile 1: 2.20–9.68 μg/mL; quartile 2: 9.69–10.93 μg/mL; quartile 3: 10.94–12.40 μg/mL; quartile 4: 12.41–24.34 μg/mL). The hazard ratios (HRs) and their 95% CIs for the incidence of CVD were computed using a Cox proportional hazards model. During the follow-up period, 180 individuals developed CVD. The age- and sex-adjusted cumulative incidence of CVD increased significantly with higher serum LBP levels (P for trend=0.005). Individuals with higher serum LBP levels had a significantly greater risk of the development of CVD after adjusting for conventional cardiovascular risk factors (quartile 1: HR, 1.00 [reference]; quartile 2: HR, 1.04 [95% CI, 0.60–1.78]; quartile 3: HR, 1.52 [95% CI, 0.92–2.51]; and quartile 4: HR, 1.90 [95% CI, 1.17–3.09]; P for trend=0.01). This association remained significant after additional adjustment for homeostasis model assessment of insulin resistance (P for trend=0.01). However, when additional adjustment was made for high-sensitivity C-reactive protein, the association was attenuated to the nonsignificant level (P for trend=0.08). Conclusions: The present findings suggest that higher serum LBP levels are associated with increased risk of the development of CVD in the general Japanese population. Low-grade endotoxemia may contribute to the pathogenesis of CVD through chronic systemic inflammation.
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U2 - 10.1161/JAHA.119.013628
DO - 10.1161/JAHA.119.013628
M3 - Article
C2 - 31657258
AN - SCOPUS:85074131974
SN - 2047-9980
VL - 8
JO - Journal of the American Heart Association
JF - Journal of the American Heart Association
IS - 21
M1 - e013628
ER -