Indexed Exercise Blood Pressure and Its Relationship with Adverse Vascular and Ventricular Remodeling

About This Grant

PROJECT SUMMARY / ABSTRACT Increased arterial stiffness is a risk factor for heart failure with preserved ejection fraction (HFpEF), a disease that accounts for half of all heart failure, is twice in common in females, and once established has limited therapeutic options. Identifying individuals at risk for HFpEF before its development is therefore crucial. Arterial stiffening accelerates around menopause, which may represent an optimal time for intervention. While arterial stiffness is not commonly measured, exercise systolic blood pressure (SBP) may provide an opportunity to evaluate arterial stiffness and is assessed on every clinical exercise test. An exaggerated rise in peak exercise SBP above established cut-points is common (10-15%), but its presence does not drive clinical decisions due to conflicting data on its predictive ability for cardiovascular outcomes. This reflects fact that while exaggerated rise in peak SBP may be due to higher arterial stiffness, conversely it may also be a sign of health and reflect robust augmentation in oxygen consumption (VO2) during exercise. As the implications of an exaggerated rise in peak exercise SBP are unclear, our group and others have begun to examine how indexing peak exercise SBP to VO2 may better reflect vascular health. While it is well- established that females have lower exercise SBPs, we and others have shown that indexing change in SBP (peak-rest) to change in VO2 (peak-rest) unmasks higher SBP/VO2 in females versus males. No prior work has defined whether SBP/VO2, like arterial stiffness, accelerates around menopause and is associated with changes in cardiac structure and function that predispose to HFpEF. Because exercise SBP is collected on every exercise test but is not used in management, our goal is to define whether SBP/VO2 identifies those with high vascular stiffness at risk for HFpEF. To address this goal, we will combine 1) analysis of a large cardiopulmonary exercise test (CPET) registry (FRIEND) and 2) a prospective study using novel exercise cardiac magnetic resonance (CMR) techniques. In Aim #1, we hypothesize that indexing SBP to VO2 will unmask higher values in females than in males that will further diverge with age, specifically infecting upward at peri-menopause. We will establish how indexed SBP varies based on sex & age in FRIEND (n=10,000) and, in our prospective study (n=150) we will define how SBP/VO2 is impacted by reproductive vs. chronologic age, including longitudinal follow-up in females. In Aim #2, we hypothesize that in females more so than males, higher SBP/VO2, as assessed in our prospective cohort, will be associated with increased arterial stiffness, unfavorable CMR parameters, and biomarker profiles that are known to predict incident hypertension and HFpEF. We also hypothesize that higher SBP/VO2 will be associated with adverse cardiovascular outcomes as assessed in a cohort of heart failure patients in FRIEND (n=4,000). We anticipate that this work will facilitate use of SBP / VO2 to target future interventions to improve the disproportionate impact of HFpEF on females.