Abstract Body (Do not enter title and authors here): Hypothesis and Purpose: Hypertension is a major cardiovascular disease (CVD) risk factor. Controlling blood pressure (BP) levels reduces CVD risk among adults with hypertension, but BP treatment may be limited by concerns for orthostatic hypotension (OH) and serious adverse events (SAEs). We hypothesized that arterial stiffness mechanisms would be associated with OH in The Systolic BP Intervention Trial (SPRINT) Trial.
Methods: SPRINT compared “intensive” SBP goal (<120 mmHg) to a “standard” goal (<140 mmHg) in adults with hypertension. Carotid-femoral pulse wave velocity (PWV) was measured in a subset of participants (n=642) at baseline. Participants enrolled in the SPRINT-PWV ancillary study were recruited from 11 of its 102 clinical sites. Structural stiffening due to remodeling of the vessel wall and load-dependent stiffening, from changes in BP, were calculated by adjusting PWV to a 120/80 mmHg reference BP with participant-specific models. The primary endpoints were adjudicated OH and SAEs. SAEs were defined as fatal or life-threatening events that resulted in clinically significant or persistent disability that required or prolonged hospitalization, or that was judged by the investigator to represent a clinically significant hazard or harm to the participant that might require medical or surgical intervention to prevent one of the other events listed above. The association of PWV mechanisms with OH and with other SAEs were assessed using negative binomial regression.
Results: Baseline characteristics are shown in Table 1. Over a median follow-up of 3.0 [2.7, 3.4] years, the cumulative incidence of at least one SAE was 38.7% in the intensive group and 35.1% in the standard group and most events were due to OH (standard treatment 27.0% vs intensive treatment 24.4%). Higher load dependent PWV was associated with greater numbers of OH events (p=0.005) regardless of treatment group (Figure 2). Higher total PWV was also associated with greater rates of SAEs (p=0.004) and this was largely driven by the association with load dependent PWV (p<0.001, Figure 3). Finally, higher, not lower, baseline mean arterial BP was associated with SAEs (p=0.001, Figure 2).
Conclusion: Greater load-dependent stiffness is associated with SAEs including OH. Hypertension management that incorporates load-dependent stiffness into clinical decision-making has the potential to refine risk stratification and improve the safety metrics with blood pressure treatment.