Background: Data from longitudinal studies suggest that biomarkers of inflammation and endothelial dysfunction are associated with development of hypertension. None of these studies have examined the association of these markers with hypertension risk in persons with diabetes. We examined the associations of inflammatory and endothelial dysfunction markers with long-term hypertension incidence in persons with type 1 diabetes mellitus. Methods: The 15-year cumulative incidence of hypertension was measured in Wisconsin Epidemiologic Study of Diabetic Retinopathy participants (n = 795). Hypertension was defined as a systolic blood pressure ≥140 mm Hg and/or a diastolic blood pressure ≥90 mm Hg and/or history of current antihypertensive treatment. We measured serum high-sensitivity C-reactive protein, interleukin-6, tumor necrosis factor-α, soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1, and serum total homocysteine as "novel" markers of hypertension development. The relation of risk factors to hypertension incidence was determined using a proportional hazards approach with discrete linear logistic regression modeling. Results: After controlling for age, gender, diabetes duration, body mass index, glycosylated hemoglobin, baseline systolic and diastolic blood pressure, proteinuria, and chronic kidney disease status, sVCAM-1 was significantly related to higher odds of developing incident hypertension (odds ratio per log sVCAM-1 1.95, 95% CI 1.01-3.74). None of the other markers of inflammation and endothelial dysfunction were related to incident hypertension in the cohort. Conclusions: Our data showed that sVCAM-1 as a marker of endothelial dysfunction was the strongest predictor of hypertension risk in individuals with type 1 diabetes. This association was independent of the presence of diabetic nephropathy.
Bibliographical noteFunding Information:
This research was supported by National Institutes of Health grants EY016379 (R. Klein, B. Klein) and DK073217 (R. Klein) and by a Mentor-Based Postdoctoral Fellowship Award from the American Diabetes Association, Alexandria, VA. The authors are solely responsible for the design and conduct of this study, all study analyses, the drafting and editing of the paper, and its final contents.