Abstract
BACKGROUND AND AIMS: A hypertensive response to exercise is independently associated with cardiovascular disease (CVD), but clinical interpretation may be confounded by aerobic capacity (fitness). The aim of this study was to determine the relationship between exercise blood pressure (BP) relative to fitness and CVD events. METHODS: Clinical exercise test records were analysed from 12 743 people (aged 53 ± 13 years, 60% male) who completed a standard exercise stress test (Bruce treadmill protocol, stages 1-4) at six Australian hospitals. Records were linked to administrative datasets (hospital and emergency admissions, death register) to define clinical characteristics and the primary outcome of fatal/non-fatal CVD events. Exercise systolic BP relative to fitness was calculated from the quotient of systolic BP and peak METs (SBP/METPeak). Competing risks regression was undertaken to compare events across quartiles, at the 90th percentile, and at various thresholds of SBP/METPeak. RESULTS: Over a median follow-up of 51 months (interquartile range: 32-75 months), 1349 events occurred. Exercise systolic BP without consideration of fitness was not associated with cardiovascular events (P > .05). In models adjusted for age, sex, and pre-exercise systolic BP, there was a stepwise increase in cardiovascular events across SBP/METPeak quartiles at stages 1-3 and peak (fourth quarter hazard ratios [HR]: stage 1 HR 2.54, 95% confidence interval [CI] 2.08-3.12; stage 2 HR 2.05, 95% CI 1.64-2.57; stage 3 HR 1.60, 95% CI 1.22-2.10; peak HR 2.43, 95% CI 1.99-2.98). SBP/METPeak ≥90th percentile was associated with a 55-94% increased risk of cardiovascular events vs < 90th percentile (stages 1-3 and peak, P < .001). Thresholds from 15 to 24 mmHg/METPeak were associated with cardiovascular events in both males and females (P < .001, stages 1-3 and peak). Results persisted in those without CVD, normal pre-exercise BP, and in those on BP-lowering medication. CONCLUSIONS: Exercise systolic BP relative to fitness is associated with increased risk for cardiovascular events and could provide a clinically actionable marker to prompt targeted intervention to lower hypertension-related cardiovascular risk.