Arterial Stiffness Mechanisms and Orthostatic Hypotension in SPRINT

BACKGROUND: Hypertension is a leading cardiovascular disease risk factor. Intensive blood pressure (BP) control reduces cardiovascular disease events but may be limited by treatment-related serious adverse events (SAEs). OBJECTIVES: The purpose of this study was to determine if baseline carotid to femoral pulse wave velocity (PWV)-including the component of structural stiffening, due to remodeling of the vessel wall, and load-dependent stiffening, due to the BP load on the arterial wall-is independently associated with orthostatic hypotension (OH) and SAEs in the SPRINT (Systolic Blood Pressure Intervention Trial). METHODS: SPRINT compared intensive (<120 mm Hg) vs standard (<140 mm Hg) systolic BP goals. Carotid-femoral PWV was measured in 642 participants at baseline. Structural stiffening and load-dependent stiffening were calculated by adjusting PWV to a 120/80 mm Hg reference BP with participant-specific models. The association of PWV with OH and with other SAEs was assessed using negative binomial regression. RESULTS: Over a 3.0-year median follow-up, the cumulative SAE incidence was 38.7% in the intensive group and 35.1% in the standard group. OH was the most frequent event (27.0% standard; 24.4% intensive). Higher load-dependent PWV was associated with greater numbers of OH events (P = 0.005) regardless of treatment group. Higher total PWV was associated with greater rates of SAEs (P = 0.001) and this was largely driven by the association with load-dependent PWV (P < 0.001). CONCLUSIONS: Load-dependent stiffness is associated with SAEs, including OH, regardless of BP treatment intensity. Load-dependent PWV may serve as a valuable clinical tool to identify patients who require enhanced surveillance before initiating intensive BP treatment. (Systolic Blood Pressure Intervention Trial SPRINT]; NCT01206062).