Endothelial Dysfunction Contributes to Renal Function–Associated Cardiovascular Mortality in a Population with Mild Renal Insufficiency

Abstract

Mildly impaired renal function is associated with cardiovascular morbidity and mortality. There are indications that endothelial dysfunction and/or chronic inflammation, which play an important role in atherothrombosis, are present in early stages of renal insufficiency. This study investigated whether and to which extent endothelial dysfunction and inflammation were related to renal function and contributed to renal function-associated cardiovascular mortality in a population-based cohort (n ‫؍‬ 613), aged 50 to 75 yr, that was followed with a median duration of 12.5 yr. During follow-up, 192 individuals died (67 of cardiovascular causes). At baseline, renal function was estimated with serum creatinine, the Cockcroft-Gault formula, and the Modification of Diet in Renal Disease equation of GFR (eGFR). Endothelial function was estimated by plasma von Willebrand factor, soluble vascular cell adhesion molecule-1, and the urinary albumin-creatinine ratio. Inflammatory activity was estimated by plasma C-reactive protein and soluble intercellular adhesion molecule-1. Renal function was mildly impaired (mean eGFR 68 ؎ 12 ml/min per 1.73 m 2 ) and independently associated with von Willebrand factor (standardized ␤ ؊0.09; 95% confidence interval [CI] ؊0.18 to ؊0.002; P < 0.05), soluble vascular cell adhesion molecule-1 (standardized ␤ ؊0.14; 95% CI ؊0.22 to ؊0.05; P < 0.01), and albumin-creatinine ratio (standardized ␤ ؊0.15; 95% CI ؊0.23 to ؊0.08; P < 0.001) but not with markers of inflammatory activity. Renal function was inversely associated with cardiovascular and all-cause mortality. The relative risk for cardiovascular mortality but not all-cause mortality associated with renal function decreased from 1.22 to 1.12 per 5 ml/min per 1.73 m 2 decrease of eGFR after adjustment for markers of endothelial dysfunction. In conclusion, endothelial dysfunction was related to renal function and contributed to the excess in cardiovascular mortality in this population-based cohort with mild renal insufficiency.

Asymmetric Dimethylarginine and Clinical Outcomes in Chronic Kidney Disease

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Oral adsorbent AST-120 ameliorates endothelial dysfunction independent of renal function in rats with subtotal nephrectomy

“…Intriguingly, endothelial dysfunction is seen in patients with CKD and is most likely linked to cardiovascular complications. 16 However, it remains to be determined whether AST-120 improves endothelial dysfunction associated with CKD.…”

Predictive value of von Willebrand factor for adverse clinical outcome in hypertensive patients with mild-to-moderate aortic regurgitation

“…Stam et al 3 revealed that renal function was mildly impaired and inversely correlated with vWF in an elderly general population. They also revealed that mild impairment of renal function was associated with cardiovascular morbidity, and, therefore, suggested that endothelial dysfunction may be an important mechanism linking mildly impaired renal function to cardiovascular diseases.…”

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