Pulse pressure and endothelial dysfunction in never-treated hypertensive patients

OBJECTIVES: This study sought to investigate whether pulse pressure (PP) is associated with endothelium-dependent vasodilation in a group of never-treated hypertensives. BACKGROUND: Pulse pressure represents a well-established independent predictor for cardiovascular morbidity and mortality. Forearm endothelial dysfunction, defined as impaired vasodilating response to acetylcholine (ACh), may be associated with several cardiovascular risk factors. Recently, the prognostic value of coronary and forearm endothelial dysfunction has been demonstrated. METHODS: All patients underwent measurement of blood pressure (BP) both clinically and in an ambulatory setting. Endothelium-dependent and -independent vasodilation was investigated by strain-gauge plethysmography in 262 hypertensive patients (age 30 to 55 years) during intra-arterial infusion of increasing doses of ACh and sodium nitroprusside. RESULTS: We observed that systolic BP rather than diastolic BP significantly induces the PP increase. Linear regression analysis revealed a significant inverse correlation between ACh-stimulated forearm blood flow (FBF) and age, body mass index, clinic and monitored systolic BP, and clinic and monitored PP. However, stepwise multivariate analysis showed that monitored PP was the strongest independent predictor of ACh-stimulated FBF, accounting for 33.6% of the variation. After adjustment for other covariates, ACh-stimulated FBF decreases by 8.7% for each mm Hg increment in monitored PP. CONCLUSIONS: Our data indicate that monitored PP is inversely correlated with ACh-stimulated vasodilation. It is possible to hypothesize that elevation in PP reduces FBF by increasing oxidative stress and reducing production of nitric oxide caused by reduced shear stress. In addition, the present findings demonstrate the accuracy of ambulatory BP as a prognostic predictor of hypertension-associated endothelial dysfunction.