Bernt Johan von Scholten1, Henrik Reinhard2, Tine Willum Hansen2, Casper G Schalkwijk3, Coen Stehouwer3, Hans-Henrik Parving4, Peter Karl Jacobsen5, Peter Rossing6. 1. Steno Diabetes Center, Gentofte, Denmark. Electronic address: bjos@steno.dk. 2. Steno Diabetes Center, Gentofte, Denmark. 3. Department of Internal Medicine and Cardiovascular Research Institute (CARIM), Maastricht University Medical Centre, Maastricht, the Netherlands. 4. Rigshospitalet, Copenhagen, Denmark; University of Copenhagen, Copenhagen, Denmark. 5. The Heart Center, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 6. Steno Diabetes Center, Gentofte, Denmark; University of Copenhagen, Copenhagen, Denmark; Aarhus University, Aarhus, Denmark.
Abstract
BACKGROUND: We evaluated markers of inflammation and endothelial dysfunction and their associations with incident cardiovascular disease (CVD), all-cause mortality and progression of coronary artery calcium (CAC) in patients with type 2 diabetes (T2D) and microalbuminuria but without known coronary artery disease (CAD). METHODS: Prospective study including 200 patients receiving multifactorial treatment. Markers of inflammation (TNF-ɑ, sICAM-1, sICAM-3, hsCRP, SAA, IL-1β, IL-6, IL-8) and endothelial dysfunction (thrombomodulin, sVCAM-1, sICAM-1, sICAM-3, sE-selectin, sP-selectin) were measured at baseline. Adjustment included traditional CVD risk factors, and full adjustment additionally NT-proBNP and CAC. The "SQRT method" assessed CAC progression after 5.8years, and cut-point was an annualised difference >2.5. RESULTS: Occurrence of CVD (n=40) and all-cause mortality (n=26) was traced after 6.1years. In adjusted and fully adjusted Cox models, TNF-ɑ was a determinant of CVD and all-cause mortality (p≤0.007). Further, in adjusted and fully adjusted logistic regression, TNF-ɑ was related to CAC progression (p≤0.042). Of the other biomarkers, sICAM-3 and thrombomodulin were also associated with both endpoints (p≤0.046), IL-1β with CVD endpoints (p=0.021), and sVCAM-1 and sICAM-1 with all-cause mortality (p≤0.005). Higher composite z-scores including all markers of inflammation and endothelial dysfunction were associated with CVD and all-cause mortality (p≤0.008). CONCLUSIONS: In patients with T2D and microalbuminuria without known CAD and receiving multifactorial treatment, biomarkers of inflammation and endothelial dysfunction were independently associated with CVD, all-cause mortality and CAC progression. Especially TNF-ɑ was a robust determinant, even after adjusting for NT-proBNP and CAC.
BACKGROUND: We evaluated markers of inflammation and endothelial dysfunction and their associations with incident cardiovascular disease (CVD), all-cause mortality and progression of coronary artery calcium (CAC) in patients with type 2 diabetes (T2D) and microalbuminuria but without known coronary artery disease (CAD). METHODS: Prospective study including 200 patients receiving multifactorial treatment. Markers of inflammation (TNF-ɑ, sICAM-1, sICAM-3, hsCRP, SAA, IL-1β, IL-6, IL-8) and endothelial dysfunction (thrombomodulin, sVCAM-1, sICAM-1, sICAM-3, sE-selectin, sP-selectin) were measured at baseline. Adjustment included traditional CVD risk factors, and full adjustment additionally NT-proBNP and CAC. The "SQRT method" assessed CAC progression after 5.8years, and cut-point was an annualised difference >2.5. RESULTS: Occurrence of CVD (n=40) and all-cause mortality (n=26) was traced after 6.1years. In adjusted and fully adjusted Cox models, TNF-ɑ was a determinant of CVD and all-cause mortality (p≤0.007). Further, in adjusted and fully adjusted logistic regression, TNF-ɑ was related to CAC progression (p≤0.042). Of the other biomarkers, sICAM-3 and thrombomodulin were also associated with both endpoints (p≤0.046), IL-1β with CVD endpoints (p=0.021), and sVCAM-1 and sICAM-1 with all-cause mortality (p≤0.005). Higher composite z-scores including all markers of inflammation and endothelial dysfunction were associated with CVD and all-cause mortality (p≤0.008). CONCLUSIONS: In patients with T2D and microalbuminuria without known CAD and receiving multifactorial treatment, biomarkers of inflammation and endothelial dysfunction were independently associated with CVD, all-cause mortality and CAC progression. Especially TNF-ɑ was a robust determinant, even after adjusting for NT-proBNP and CAC.
Authors: Marliese Dion Nist; Rita H Pickler; Tondi M Harrison; Deborah K Steward; Abigail B Shoben Journal: Early Hum Dev Date: 2020-05-22 Impact factor: 2.079
Authors: Rodrigo M C Pestana; Caroline P Domingueti; Rita C F Duarte; Rodrigo B Fóscolo; Janice S Reis; Ana Maria S Rodrigues; Laís B Martins; Lirlândia P Sousa; Daniela P Lage; Cláudia N Ferreira; Adaliene V M Ferreira; Ana P Fernandes; Karina B Gomes Journal: Immunol Res Date: 2016-08 Impact factor: 2.829
Authors: Bandana Shrestha; Priya K Prasai; Amir M Kaskas; Ankur Khanna; Vijay Letchuman; Sunjay Letchuman; Jonathan Steven Alexander; A Wayne Orr; Matthew D Woolard; Christopher B Pattillo Journal: Microcirculation Date: 2018-07-23 Impact factor: 2.628
Authors: Joshua D Bundy; Jing Chen; Wei Yang; Matthew Budoff; Alan S Go; Juan E Grunwald; Radhakrishna R Kallem; Wendy S Post; Muredach P Reilly; Ana C Ricardo; Sylvia E Rosas; Xiaoming Zhang; Jiang He Journal: Atherosclerosis Date: 2018-02-10 Impact factor: 5.162
Authors: Teresa Infante; Ernesto Forte; Marco Aiello; Marco Salvatore; Carlo Cavaliere Journal: Front Endocrinol (Lausanne) Date: 2017-08-21 Impact factor: 5.555
Authors: Anna Santarsiero; Paolo Convertini; Antonio Vassallo; Valentina Santoro; Simona Todisco; Dominga Iacobazzi; Yvonne Fondufe-Mittendorf; Giuseppe Martelli; Marcos R de Oliveira; Rosangela Montanaro; Vincenzo Brancaleone; Johannes Stöckl; Vittoria Infantino Journal: Oxid Med Cell Longev Date: 2021-05-25 Impact factor: 6.543