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

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

doi:10.1016/j.jdiacomp.2015.11.005

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

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

Department of Clinical Medicine

33 Citations (Scopus)

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-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.

Original language	English
Journal	Journal of Diabetes and its Complications
Volume	30
Issue number	2
Pages (from-to)	248-55
Number of pages	8
ISSN	1056-8727
DOIs	https://doi.org/10.1016/j.jdiacomp.2015.11.005
Publication status	Published - 1 Mar 2016

Keywords

Aged
Albuminuria
Biomarkers
Cardiovascular Diseases
Cause of Death
Coronary Disease
Diabetes Mellitus, Type 2
Diabetic Angiopathies
Diabetic Nephropathies
Disease Progression
Endothelium, Vascular
Female
Humans
Incidence
Inflammation
Male
Middle Aged
Vascular Calcification

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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von Scholten, B. J., Reinhard, H., Hansen, T. W., Schalkwijk, C. G., Stehouwer, C., Parving, H-H., Jacobsen, P. K., & Rossing, P. (2016). 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. Journal of Diabetes and its Complications, 30(2), 248-55. https://doi.org/10.1016/j.jdiacomp.2015.11.005

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. / von Scholten, Bernt Johan; Reinhard, Henrik; Hansen, Tine Willum et al.

In: Journal of Diabetes and its Complications, Vol. 30, No. 2, 01.03.2016, p. 248-55.

Research output: Contribution to journal › Journal article › Research › peer-review

von Scholten, BJ, Reinhard, H, Hansen, TW, Schalkwijk, CG, Stehouwer, C, Parving, H-H, Jacobsen, PK & Rossing, P 2016, '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', Journal of Diabetes and its Complications, vol. 30, no. 2, pp. 248-55. https://doi.org/10.1016/j.jdiacomp.2015.11.005

von Scholten BJ, Reinhard H, Hansen TW, Schalkwijk CG, Stehouwer C, Parving H-H et al. 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. Journal of Diabetes and its Complications. 2016 Mar 1;30(2):248-55. doi: 10.1016/j.jdiacomp.2015.11.005

von Scholten, Bernt Johan ; Reinhard, Henrik ; Hansen, Tine Willum et al. / 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. In: Journal of Diabetes and its Complications. 2016 ; Vol. 30, No. 2. pp. 248-55.

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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-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.",

keywords = "Aged, Albuminuria, Biomarkers, Cardiovascular Diseases, Cause of Death, Coronary Disease, Diabetes Mellitus, Type 2, Diabetic Angiopathies, Diabetic Nephropathies, Disease Progression, Endothelium, Vascular, Female, Humans, Incidence, Inflammation, Male, Middle Aged, Vascular Calcification",

author = "{von Scholten}, {Bernt Johan} and Henrik Reinhard and Hansen, {Tine Willum} and Schalkwijk, {Casper G} and Coen Stehouwer and Hans-Henrik Parving and Jacobsen, {Peter K} and Peter Rossing",

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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

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 -