Cited by 164Diabetes, Cardiovascular Risks, and LipoproteinsNitric Oxide and Endothelin EffectsAdipokines, Inflammation, and Metabolic Diseases

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Endothelial Dysfunction and Low-Grade Inflammation Explain Much of the Excess Cardiovascular Mortality in Individuals With Type 2 Diabetes: The Hoorn Study

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de Jager, Jolien, Dekker, Jacqueline M., Kooy, Adriaan, Kostense, Piet J., Nijpels, Giel, Heine, Rob J., Bouter, Lex M., Stehouwer, Coen D.A.·2006·Arteriosclerosis, Thrombosis, and Vascular Biology

DOI 10.1161/01.atv.0000215951.36219.a4

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Abstract

Objective— The mechanisms responsible for the increased cardiovascular disease risk that accompanies type 2 diabetes (T2D) remain poorly understood. It is commonly held that endothelial dysfunction and low-grade inflammation can explain, at least in part, why deteriorating glucose tolerance is associated with cardiovascular disease. However, there is no direct evidence for this contention. Methods and Results— In this population-based study (n=631), T2D was cross-sectionally associated with both endothelial dysfunction and low-grade inflammation, whereas impaired glucose metabolism (IGM) was associated only with low-grade inflammation. These findings were independent of other risk factors that accompany T2D or IGM. During a follow-up of 11.7 years (median; range 0.5 to 13.2 years), low-grade inflammation was associated with a greater risk of cardiovascular mortality (hazard ratio, 1.43 [95% CI, 1.17 to 1.77] per 1 SD difference). For endothelial dysfunction, the association with cardiovascular mortality was stronger in diabetic (hazard ratio, 1.87 [95% CI, 1.43 to 2.45]) than in nondiabetic individuals (hazard ratio, 1.23 [95% CI, 0.86 to 1.75]; P interaction=0.06). Finally, T2D-associated endothelial dysfunction and low-grade inflammation explained ≈43% of the increase in cardiovascular mortality risk conferred by T2D. Conclusions— These data emphasize the necessity of randomized controlled trials of strategies that aim to decrease cardiovascular disease risk by improving endothelial function and decreasing low-grade inflammation, especially for T2D patients.

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Authors: de Jager, J., Dekker, J. M., Kooy, A., Kostense, P. J., Nijpels, G., Heine, R. J., Bouter, L. M., & Stehouwer, C. D. A.
Affiliations: From the Department of Internal Medicine, Bethesda General Hospital, Hoogeveen, the Netherlands (J.d.J., A.K); the Institute for Research in Extramural Medicine (J.M.D., P.J.K., G.N., R.J.H., L.M.B., C.D.A.S.), VU University Medical Center, Amsterdam, The Netherlands; and the Department of Internal Medicine, University Hospital Maastricht, The Netherlands (C.D.A.S.).
Maastricht University Medical Centre (NL)
ORCID: Kooy, Adriaan
Nijpels, Giel
Bouter, Lex M.
Stehouwer, Coen D.A.
Venue: Arteriosclerosis, Thrombosis, and Vascular Biology
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2006-05
Volume: 26
Issue: 5
Pages: 1086-1093
ISSN: 1079-5642 (ISSN-L)
1524-4636
DOI: 10.1161/01.atv.0000215951.36219.a4
OpenAlex: W2096259240
Cited by: 163
References: 50
Citations by year: 2026: 5 · 2025: 8 · 2024: 5 · 2023: 7 · 2022: 8 · 2021: 8 · 2020: 7 · 2019: 5 · 2018: 3 · 2017: 7 · 2016: 9 · 2015: 13 · 2014: 8 · 2013: 8 · 2012: 10
FWCI: 7.25
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
PubMed (publishedVersion)
VU Research Portal (publishedVersion, other-oa)
Digital Academic REpository of VU University Amsterdam (Vrije Universiteit Amsterdam) (submittedVersion)
Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
Keywords: type 2 diabetes, endothelial dysfunction, low-grade inflammation, cardiovascular mortality, impaired glucose metabolism, cardiovascular risk, mediation analysis, endothelial function
MeSH terms: Aged, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Diabetic Angiopathies, Endothelium, Vascular, Glucose, Glucose Tolerance Test, Humans, Inflammation, Male, Middle Aged, Prospective Studies, Cohort Studies

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Endothelial Dysfunction and Low-Grade Inflammation Explain Much of the Excess Cardiovascular Mortality in Individuals With Type 2 Diabetes: The Hoorn Study

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