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

作者：von Scholten Bernt Johan^*; Reinhard Henrik; Hansen Tine Willum; Schalkwijk Casper G; Stehouwer Coen; Parving Hans Henrik; Jacobsen Peter Karl; Rossing Peter

来源：Journal of Diabetes and Its Complications, 2016, 30(2): 248-255.

DOI：10.1016/j.jdiacomp.2015.11.005

• Markers of inflammation
• TNF-alpha
• Coronary artery calcium score
• Cardiovascular disease
• Type 2 diabetes
• Microalbuminuria

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-a, sICAM-1, sICAM-3, hsCRP, SAA, IL-1 beta, IL-6, IL-8) and endothelial dysthrombomodulin, 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 5.8 years, and cut-point was an annualised difference >2.5.
Results: Occurrence of CVD (n = 40) and all-cause mortality (n = 26) was traced after 6.1 years.
In adjusted and fully adjusted Cox models, TNF-a was a determinant of CVD and all-cause mortality (p <= 0.007). Further, in adjusted and fully adjusted logistic regression, TNF-a 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-1 beta 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-a was a robust determinant, even after adjusting for NT-proBNP and CAC.

• 出版日期2016-3