4.5 Article

Microvascular endothelial dysfunction is associated with albuminuria: the Maastricht Study

Journal

JOURNAL OF HYPERTENSION
Volume 36, Issue 5, Pages 1178-1187

Publisher

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/HJH.0000000000001674

Keywords

albuminuria; cardiovascular disease; diabetes mellitus; endothelial dysfunction; endothelium; microalbuminuria; microcirculation

Funding

  1. European Regional Development Fund via OP-Zuid
  2. Province of Limburg
  3. Dutch Ministry of Economic Affairs [31O.041]
  4. Stichting De Weijerhorst (Maastricht, the Netherlands)
  5. Pearl String Initiative Diabetes (Amsterdam, the Netherlands)
  6. Cardiovascular Center (CVC, Maastricht, the Netherlands)
  7. CARIM School for Cardiovascular Diseases (Maastricht, the Netherlands)
  8. CAPHRI School for Public Health and Primary Care (Maastricht, the Netherlands)
  9. NUTRIM School for Nutrition and Translational Research in Metabolism (Maastricht, the Netherlands)
  10. Stichting Annadal (Maastricht, the Netherlands)
  11. Health Foundation Limburg (Maastricht, the Netherlands)
  12. Janssen-Cilag B.V. (Tilburg, the Netherlands)
  13. Novo Nordisk Farma B.V. (Alphen aan den Rijn, the Netherlands)
  14. Sanofi-Aventis Netherlands B.V. (Gouda, the Netherlands)
  15. Fresenius Medical Care (Bad Homburg, Germany)

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Objective:Albuminuria is thought to be a biomarker of microvascular and macrovascular endothelial dysfunction. However, direct evidence for an association of microvascular endothelial dysfunction with albuminuria is limited. In addition, experimental data suggest a stronger association of microvascular endothelial dysfunction with albuminuria in individuals with than in those without diabetes.Methods:We examined cross-sectional associations of flicker light-induced retinal arteriolar dilation (n=2095) and heat-induced skin hyperemia (n=1508) with 24-h albuminuria in the population-based, diabetes-enriched Maastricht Study. We used linear regression analyses to adjust for age, sex, type 2 diabetes, and cardiovascular disease risk factors. In addition, we tested for statistical interaction with type 2 diabetes.Results:Median [interquartile range] albuminuria was 6.5 [3.9-11.6] mg/24h and 8.2% had albuminuria at least 30mg/24h. After adjustment, albuminuria was 1.168 (95% confidence interval, 1.046-1.303) times greater in participants in the quartile with the smallest flicker light-induced retinal arteriolar dilation relative to those with the greatest dilation, and this association was stronger in participants with type 2 diabetes (P-interaction<0.10). Further, each 100 percentage points lower heat-induced skin hyperemia was associated with a 1.022 (1.010-1.035) times greater albuminuria in participants with type 2 diabetes, whereas it was not associated with albuminuria in nondiabetic participants (P-interaction<0.10).Conclusion:This is the first population-based study that provides direct evidence that microvascular endothelial dysfunction is associated with albuminuria, and that this association is stronger in individuals with than in those without type 2 diabetes.

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