Hirotaka Fukami1, Jun Morinaga2, Yusuke Okadome3, Yoshihiko Nishiguchi4, Yasunobu Iwata4, Tomoko Kanki4, Terumasa Nakagawa4, Yuichiro Izumi4, Yutaka Kakizoe4, Takashige Kuwabara4, Haruki Horiguchi3, Michio Sato3, Tsuyoshi Kadomatsu3, Keishi Miyata3, Tetsuya Tajiri5, Yuichi Oike6, Masashi Mukoyama7. 1. Department of Nephrology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, Kumamoto, 860-8556, Japan; Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, Kumamoto, 860-8556, Japan. 2. Department of Nephrology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, Kumamoto, 860-8556, Japan; Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, Kumamoto, 860-8556, Japan; Department of Clinical Investigation, Kumamoto University Hospital, 1-1-1 Honjo, Chuo-ku, Kumamoto, Kumamoto, 860-8556, Japan. Electronic address: morijun@kumamoto-u.ac.jp. 3. Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, Kumamoto, 860-8556, Japan. 4. Department of Nephrology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, Kumamoto, 860-8556, Japan. 5. Medical Corporation, Jinseikai, 2-3-10 Toshima-nishi Higashi-ku, Kumamoto, Kumamoto, 861-8043, Japan. 6. Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, Kumamoto, 860-8556, Japan. Electronic address: oike@gpo.kumamoto-u.ac.jp. 7. Department of Nephrology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, Kumamoto, 860-8556, Japan. Electronic address: mmuko@kumamoto-u.ac.jp.
Abstract
BACKGROUND AND AIMS: Chronic low-grade inflammation is receiving much attention as a critical pathology that induces various aging phenotypes, a concept known as "inflammaging". Uremic patients undergoing hemodialysis therapy show vascular aging phenotypes characterized by greater arterial stiffness and calcification compared to healthy controls of the same generation. In the current study, we investigated whether levels of inflammaging markers in the circulation were associated with vascular aging phenotypes in hemodialysis patients, as estimated by the cardio-ankle vascular index (CAVI). METHODS: We conducted a multicenter cross-sectional study of 412 patients receiving hemodialysis and evaluated the relationship between circulating hs-CRP or ANGPTL2 levels, as markers of inflammaging, and CAVI. RESULTS: Of 412 patients, 376 were analyzed statistically. While circulating hs-CRP levels had no significant association with CAVI, generalized linear models revealed that high circulating ANGPTL2 levels were significantly associated with increasing CAVI after adjustment for classical metabolic factors and hemodialysis-related parameters [β 0.63 (95%CI 0.07-1.18)]. Exploratory analysis revealed that high circulating ANGPTL2 levels were also strongly associated with increased CAVI, particularly in patients with conditions of increased vascular mechanical stress, such elevated blood pressure [β 1.00 (95%CI 0.23-1.76)], elevated pulse pressure [β 0.75 (95%CI 0.52-0.98)], or excess body fluid [β 1.25 (95%CI 0.65-1.84)]. CONCLUSIONS: We conclude that circulating levels of ANGPTL2 rather than hs-CRP are positively associated with CAVI in the uremic population and that ANGPTL2 could be a unique marker of progression of vascular aging in patients receiving hemodialysis.
BACKGROUND AND AIMS: Chronic low-grade inflammation is receiving much attention as a critical pathology that induces various aging phenotypes, a concept known as "inflammaging". Uremic patients undergoing hemodialysis therapy show vascular aging phenotypes characterized by greater arterial stiffness and calcification compared to healthy controls of the same generation. In the current study, we investigated whether levels of inflammaging markers in the circulation were associated with vascular aging phenotypes in hemodialysis patients, as estimated by the cardio-ankle vascular index (CAVI). METHODS: We conducted a multicenter cross-sectional study of 412 patients receiving hemodialysis and evaluated the relationship between circulating hs-CRP or ANGPTL2 levels, as markers of inflammaging, and CAVI. RESULTS: Of 412 patients, 376 were analyzed statistically. While circulating hs-CRP levels had no significant association with CAVI, generalized linear models revealed that high circulating ANGPTL2 levels were significantly associated with increasing CAVI after adjustment for classical metabolic factors and hemodialysis-related parameters [β 0.63 (95%CI 0.07-1.18)]. Exploratory analysis revealed that high circulating ANGPTL2 levels were also strongly associated with increased CAVI, particularly in patients with conditions of increased vascular mechanical stress, such elevated blood pressure [β 1.00 (95%CI 0.23-1.76)], elevated pulse pressure [β 0.75 (95%CI 0.52-0.98)], or excess body fluid [β 1.25 (95%CI 0.65-1.84)]. CONCLUSIONS: We conclude that circulating levels of ANGPTL2 rather than hs-CRP are positively associated with CAVI in the uremic population and that ANGPTL2 could be a unique marker of progression of vascular aging in patients receiving hemodialysis.