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Markers of inflammation and endothelial dysfunction are associated with incident cardiovascular disease, all-cause mortality, and progression of coronary calcification in type 2 diabetic patients with microalbuminuria

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Bernt Johan von Scholten
  • Henrik Reinhard
  • Tine Willum Hansen
  • Casper G Schalkwijk
  • Coen Stehouwer
  • Hans-Henrik Parving
  • Peter K Jacobsen
  • Rossing, Peter

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.

OriginalsprogEngelsk
TidsskriftJournal of Diabetes and its Complications
Vol/bind30
Udgave nummer2
Sider (fra-til)248-55
Antal sider8
ISSN1056-8727
DOI
StatusUdgivet - mar. 2016

ID: 172821759