High pulse pressure and nondipping circadian blood pressure in patients with coronary artery disease: Relationship to thrombogenesis and endothelial damage/dysfunction

BACKGROUND: Patients with high ambulatory pulse pressure (APP) or nondipping pattern of circadian BP (nondippers) are at increased risk of cardiovascular disease that may be due to abnormalities in coagulopathy and vascular function. We hypothesized that patients with high APP or nondipper status have an adverse hemostasis profile. Accordingly, we assessed hemorheology (by plasma viscosity and fibrinogen levels), endothelial damage/dysfunction (von Willebrand factor [vWf] and flow-mediated dilatation [FMD]), thrombogenesis (D-dimer), and platelet activation (soluble P-selectin). METHODS: Seventy-three patients (58 men, 59 +/- 11 years) with stable coronary artery disease completed 24-h ambulatory BP monitoring. Plasma viscosity was assessed on a Coulter viscometer, fibrinogen by Clauss, vWf, D-dimer and soluble P selectin by ELISA, and FMD by reactive hyperemia. RESULTS: High APP (median APP >/=51 mm Hg) and nondipping was associated with significantly higher levels of vWf, D-dimer, fibrinogen, and soluble P-selectin compared to patients with low APP and dippers, respectively (all P <.05), even after adjustment for ages, 24-h mean systolic, mean diastolic, and mean arterial BPs. After the same adjustments, as well as for dipping status, white coat effects, and left ventricular mass, patients with high APP also had more impaired FMD and still significantly higher levels of vWf and D-dimer, compared to patients with low APP (all P <.05). However, the highest levels of vWf, fibrinogen, and soluble P-selectin and the most impaired FMD were found in those nondipper patients with concurrent high APP. CONCLUSIONS: High ambulatory pulse pressure or nondipping pattern of circadian BP per se are important pathophysiologic factors that may influence cardiovascular risk by altering hemostasis or endothelial function.