Endothelial dysfunction and C-reactive protein predict the incidence of heart failure in hypertensive patients

Endothelial dysfunction and heart failure are associated, but no prospective studies demonstrated that impaired endothelium-dependent vasodilation predicts incident heart failure. We designed this study to test whether endothelial dysfunction is associated with incident heart failure in a group of hypertensives.

We enrolled 735 White never-treated hypertensive outpatients free from heart failure, diabetes, chronic kidney disease, and previous cardiovascular events. Endothelium-dependent vasodilation was investigated by intra-arterial infusion of acetylcholine, and laboratory determinations were obtained by standard procedures. During the follow-up [median 114 months (range 26-206)], there were 208 new cases of heart failure (3.1 events/100 patient-years). Dividing the study population in progressors and non-progressors, we observed that progressors were older, showed a higher prevalence of being female, and had a higher baseline heart rate, glucose, insulin, Homeostatic Model Assessment (HOMA), creatinine, and high-sensitivity C-reactive protein (hs-CRP) mean values, while estimated glomerular filtration rate and maximal acetylcholine-stimulated forearm blood flow were lower. In the multiple Cox regression analysis, female gender [hazard ratio (HR) = 1.454, 95% CI = 1.067-1.981], fasting glucose (HR = 1.186, 95% CI = 1.038-1.357), hs-CRP (HR = 1.162, 95% CI = 1.072-1.259), HOMA (HR = 1.124, 95% CI = 1.037-1.219), acetylcholine-stimulated forearm blood flow (HR = 0.779, 95% CI = 0.695-0.874), and estimated glomerular filtration rate (HR = 0.767, 95% CI = 0.693-0.849) maintained an independent association with the outcome. Successively, testing the interaction between forearm blood flow and hs-CRP, we observed that patients who have hs-CRP values above the median and forearm blood flow under the median show a higher risk of developing heart failure (HR = 7.699, 95% CI = 4.407-13.451).

The present data demonstrate that an impaired endothelium-dependent vasodilation and hs-CRP predict development of incident heart failure in hypertensives.