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

TY - JOUR

T1 - 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

AU - von Scholten, Bernt Johan

AU - Reinhard, Henrik

AU - Hansen, Tine Willum

AU - Schalkwijk, Casper G

AU - Stehouwer, Coen

AU - Parving, Hans-Henrik

AU - Jacobsen, Peter K

AU - Rossing, Peter

N1 - Copyright © 2016 Elsevier Inc. All rights reserved.

PY - 2016/3/1

Y1 - 2016/3/1

N2 - 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-α, 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 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-α was a determinant of CVD and all-cause mortality (p ≤ 0.007). Further, in adjusted and fully adjusted logistic regression, TNF-α 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-α was a robust determinant, even after adjusting for NT-proBNP and CAC.

AB - 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-α, 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 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-α was a determinant of CVD and all-cause mortality (p ≤ 0.007). Further, in adjusted and fully adjusted logistic regression, TNF-α 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-α was a robust determinant, even after adjusting for NT-proBNP and CAC.

KW - Aged

KW - Albuminuria

KW - Biomarkers

KW - Cardiovascular Diseases

KW - Cause of Death

KW - Coronary Disease

KW - Diabetes Mellitus, Type 2

KW - Diabetic Angiopathies

KW - Diabetic Nephropathies

KW - Disease Progression

KW - Endothelium, Vascular

KW - Female

KW - Humans

KW - Incidence

KW - Inflammation

KW - Male

KW - Middle Aged

KW - Vascular Calcification

U2 - 10.1016/j.jdiacomp.2015.11.005

DO - 10.1016/j.jdiacomp.2015.11.005

M3 - Journal article

C2 - 26651261

SN - 1056-8727

VL - 30

SP - 248

EP - 255

JO - Journal of Diabetes and its Complications

JF - Journal of Diabetes and its Complications

IS - 2

ER -