The relationship between heart rate variability and frailty in older adults: Systematic review and three-level meta-analysis

Background: Heart rate variability (HRV) is a potential biomarker for frailty, which is burdensome in older adults. However, existing studies report inconsistent findings regarding their relationship, and no meta-analysis has been conducted. This systematic review and meta-analysis aim to examine the association between HRV and frailty, as well as the boundary conditions that influence this relationship. Methods: We systematically searched eight databases for studies examining three domains of HRV parameters – time-, frequency-, and nonlinear-domain – and their associations with frailty. Using a three-level random-effects meta-analytic model, we investigated the pooled effect sizes (Hedges’ g) for short-term (≤ 5 minutes) and long-term (24-hour) HRV, and potential variables moderating the relationship between HRV and frailty. Results: We included 16 studies (n = 2365) in the review from 1132 records, and 13 of them were meta-analyzed (n = 1677) contributing 90 effect sizes. Both short-term (7 studies, 47 effect sizes) and long-term (6 studies, 43 effect sizes) models indicated lower HRV in (pre)frail individuals compared to their non-frail counterparts, while the effects were not statistically significant. For long-term HRV, the relationship was moderated by HRV domain: time-domain parameters exhibited a larger effect size (g = 2.097) than frequency-domain parameters (g = 1.698). Conclusions: Our meta-analyses revealed a trend towards lower HRV in (pre)frail individuals; however, the effects in both models were not statistically significant. Although HRV may be a potential biomarker of frailty, the current evidence remains inconclusive. Further prospective studies are necessary, considering the heterogeneity and potential publication bias observed.