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

详细信息    查看全文

• 作者：Bernt Johan von Scholten^a ; ^{bjos@steno.dk" class="auth_mail" title="E-mail the corresponding author} ; ^{berntjohan@vonscholtenillum.dk" class="auth_mail" title="E-mail the corresponding author} ; Henrik Reinhard^a ; Tine Willum Hansen^a ; Casper G. Schalkwijk^b ; Coen Stehouwer^b ; Hans-Henrik Parving^c ; ^d ; Peter Karl Jacobsen^e ; Peter Rossing^a ; ^d ; ^f
• 关键词：Markers of inflammation ; TNF-alpha ; Coronary artery calcium score ; Cardiovascular disease ; Type 2 diabetes ; Microalbuminuria
• 刊名：Journal of Diabetes and its Complications
• 出版年：2016
• 出版时间：March 2016
• 年：2016
• 卷：30
• 期：2
• 页码：248-255
• 全文大小：299 K

文摘

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

10">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 5.8 years, and cut-point was an annualised difference > 2.5.

Results

15">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-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.