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

Highlights

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  Heart rate response/recovery (HRR) to submaximal exercise predicted future delirium risk during hospitalization.

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  Lowest quartile for a HRR index was equivalent to being 6 years older, a current smoker, or having 3 or more additional cardiovascular risks compared to those in the highest quartile.

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  Findings were robust in subsets by age, sex, physical activity level, rate-control medications, but the risk from low HRR appeared greater in those with better baseline cognition.

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  Results were also consistent when only postoperative delirium was considered, and when dementia related cases were excluded.

Abstract

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 quartile, 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.

Graphical abstract