Responses to active stand test predict 12-year incident cardiovascular disease and mortality

An integrated haemodynamic response during standing may serve as a marker of neuro-cardiovascular function. Individual components of both heart rate (HR) and blood pressure (BP) responses to active stand (AS) have been linked with cardiovascular disease (CVD) and mortality. We hypothesised that integrating BP/HR information from the entire haemodynamic response curve may uncover otherwise unknown associations with both CVD and mortality.

Beat-to-beat measurements of dynamic HR/BP responses to AS were conducted in 4336 individuals (61.5 ± 8.2 years; 53.7% female). We assessed longitudinal associations between entire HR/BP response curves during AS, incident CVD and mortality over 12 years, and cross-sectional association with CVD on an independent clinical cohort. Functional Principal Components Analysis was applied to response curves, and their association with CVD and mortality was assessed.

In multivariable models, components with higher systolic BP (SBP) before AS and blunted recovery of SBP during AS are associated with all-cause mortality over 12-years (Hazard Ratio [HR]: 1.14; 1.04, 1.26; p = 0.007). Components with higher baseline/peak HR and lower HR from 30 seconds post stand are associated with lower Hazard of cardiovascular deaths (HR: 0.78; 0.64, 0.95; p = 0.013). Impaired recovery of DBP from 35 seconds onward is associated with CVD in a validation cohort (Odds Ratio: 0.65; 0.17, 0.88).

We observe distinct relationships between HR/BP responses to AS and 12-year incident CVD and mortality. BP recovery and CVD are also associated in an independent clinical validation cohort. Integrating the entire haemodynamic response may reveal more nuanced relationships between HR/BP responses to AS, CVD and mortality - serving as an integrative marker of neuro-cardiovascular health in midlife and beyond.