Improvement in functional capacity with spironolactone masks the treatment effect on exercise blood pressure

Objectives: A hypertensive response to submaximal exercise is associated with cardiovascular disease but this relationship is influenced by functional capacity. Spironolactone improves functional capacity, which could mask treatment effects on exercise blood pressure. This study sought to examine this hypothesis.

Design: Retrospective analysis of a randomized clinical trial.

Methods: 102 participants (54 +- 9 years; 52% male) with a hypertensive response to maximal exercise (systolic BP >=210 mm Hg men; >=190 mm Hg women) were randomized to 3-month spironolactone 25 mg daily (n = 53) or placebo (n = 49). Submaximal exercise blood pressure was measured during low-intensity cycling (50, 60 or 70% age-predicted maximal heart rate). Functional capacity was measured as maximal oxygen capacity obtained during a maximal treadmill exercise test, and (resting) aortic stiffness by carotid-to-femoral pulse wave velocity.

Results: Spironolactone improved submaximal exercise systolic blood pressure vs. placebo (-4 +- 16 vs. 2 +- 15 mm Hg, p = 0.045, Cohen's d = 0.42), and had a small (but non-statistically significant) improvement in functional capacity (0.64 +- 5.10 vs. -1.43 +- 5.04 ml/kg/min, p = 0.06, Cohen's d = 0.4). When treatment effects were expressed as the change in submaximal exercise systolic blood pressure relative to the change in functional capacity, a larger effect size was observed (-0.3 +- 1.1 vs. 0.3 +- 1.1 mm Hg/ml kg min^-1, p = 0.01, Cohen's d = 0.58), but was not explained by improved aortic stiffness.

Conclusions: Spironolactone reduces submaximal exercise blood pressure, but this treatment effect may be hidden by improved functional capacity and a non-fixed workload. This highlights the most clinically relevant exercise blood pressure is at a low intensity and fixed workload where the influence of fitness on exercise blood pressure is removed, and the effects of therapy can be appreciated.