Heart rate response and recovery during exercise predict future delirium risk-A prospective cohort study in middle- to older-aged adults

Background: Delirium is a neurocognitive disorder characterized by an abrupt decline in attention, awareness, and cognition after surgical/ illness-induced stressors on the brain. There is now an increasing focus on how cardiovascular health interacts with neurocognitive disorders given their overlapping risk factors and links to subsequent dementia and mortality. One common indicator for cardiovascular health is the heart rate response/recovery (HRR) to exercise, but how this relates to future delirium is unknown.Methods: Electrocardiogram data were examined in 38,740 middle-to older-aged UK Biobank participants (mean age = 58.1 years, range: 40-72 years; 47.3% males) who completed a standardized submaximal exercise stress test (15-s baseline, 6-min exercise, and 1-min recovery) and required hospitalization during follow-up. An HRR index was derived as the product of the heart rate (HR) responses during exercise (peak/ resting HRs) and recovery (peak/recovery HRs) and categorized into low/average/high groups as the bottom quartile/middle 2 quartiles/top quar-tile, respectively. Associations between 3 HRR groups and new-onset delirium were investigated using Cox proportional hazards models and a 2-year landmark analysis to minimize reverse causation. Sociodemographic factors, lifestyle factors/physical activity, cardiovascular risk, comorbidities, cognition, and maximal workload achieved were included as covariates.Results: During a median follow-up period of 11 years, 348 participants (9/1000) newly developed delirium. Compared with the high HRR group (16/1000), the risk for delirium was almost doubled in those with low HRR (hazard ratio = 1.90, 95% confidence interval (95%CI): 1.30-2.79, p = 0.001) and average HRR (hazard ratio = 1.54, 95%CI: 1.07-2.22, p = 0.020)). Low HRR was equivalent to being 6 years older, a current smoker, or >3 additional cardiovascular disease risks. Results were robust in sensitivity analysis, but the risk appeared larger in those with better cognition and when only postoperative delirium was considered (n = 147; hazard ratio = 2.66, 95%CI: 1.46-4.85, p = 0.001).Conclusion: HRR during submaximal exercise is associated with future risk for delirium. Given that HRR is potentially modifiable, it may prove useful for neurological risk stratification alongside traditional cardiovascular risk factors.