# Exploring heart rate variability as a biomarker for frailty: A narrative review

**Authors:** Luca Tagliafico, Silvia Ottaviani, Riccardo Balzano, Stefania Peruzzo, Alessio Nencioni, Fiammetta Monacelli

PMC · DOI: 10.1111/eci.70194 · 2026-03-27

## TL;DR

This review explores heart rate variability (HRV) as a potential biomarker for frailty, highlighting its role in reflecting autonomic nervous system function and its associations with health outcomes.

## Contribution

The paper systematically reviews HRV's potential as a biomarker for frailty, emphasizing its physiological relevance and associations with clinical outcomes.

## Key findings

- Reduced HRV is linked to frailty status and adverse health outcomes.
- HRV shows stronger associations with frailty when measured during physiological challenges rather than at rest.
- HRV is a non-invasive and accessible marker for multimodal frailty assessment.

## Abstract

Frailty is defined as a state of increased vulnerability to stressors resulting from reduced physiological homeostasis. The need to identify biomarkers capable of offering insight into the biological underpinnings of frailty and supporting early detection, diagnosis, and prognostic evaluation has grown in recent years. Heart rate variability (HRV), defined as the temporal variability between consecutive R waves of the electrocardiogram (R‐R intervals), has emerged as a promising physiological biomarker in this context.

We conducted a narrative review of studies to synthesize evidence on HRV and frailty, examining analytical domains of HRV and situating findings within the current biomarker framework. Relevant literature was assessed across time‐domain, frequency‐domain, geometric and non‐linear measures of HRV, together with reported associations involving clinical, functional and cognitive outcomes.

Within the landscape of frailty biomarkers, HRV provides a non‐invasive index of autonomic nervous system function. Reduced HRV has been associated with frailty status, diminished physiological reserve, adverse clinical outcomes, and cognitive decline, with particularly notable findings when assessed during physiological challenges rather than at rest. It should be noted, however, that the literature is heterogeneous and methodologically inconsistent, especially regarding recording duration and the specific HRV parameters analysed.

HRV is a highly promising physiological biomarker in the context of frailty, but further research is needed to clarify several aspects of its role. Its potential integration with other biomarkers may help confirm its validity and could contribute to identifying biomarker clusters relevant to personalized approaches.

Frailty arises from progressive multisystem dysregulation, prompting interest in biomarkers that capture declining physiological reserve. This review positions heart rate variability (HRV) within this evolving biomarker landscape, outlining its physiological basis, analytical domains and relevance to clinical research. Evidence indicates that reduced HRV reflects impaired autonomic–cardiovascular regulation and is associated with frailty, cognitive impairment and adverse health outcomes. HRV thus emerges as an accessible, integrative marker to support multimodal frailty assessment. Created in https://BioRender.com.

## Full-text entities

- **Genes:** MAPT (microtubule associated protein tau) [NCBI Gene 4137] {aka DDPAC, FTD1, FTDP-17, MAPTL, MSTD, MTBT1}, REN (renin) [NCBI Gene 5972] {aka ADTKD4, HNFJ2, RTD}
- **Diseases:** dementia (MESH:D003704), rheumatologic conditions (MESH:D020763), myocardial infarction (MESH:D009203), cerebrovascular conditions (MESH:D002561), atrial fibrillation (MESH:D001281), gastrointestinal, orthostatic and sudomotor symptoms (MESH:D012817), cancer (MESH:D009369), weight loss (MESH:D015431), cirrhosis (MESH:D005355), coronary disease (MESH:D003327), sepsis (MESH:D018805), brain atrophy (MESH:C566985), neurovascular dysregulation (MESH:D013901), pressure ulcers (MESH:D003668), chronic diseases (MESH:D002908), brain damage (MESH:D001925), AD (MESH:D000544), fatigue (MESH:D005221), autonomic (MESH:D001342), LBD (MESH:D020961), bradycardia (MESH:D001919), hypertension (MESH:D006973), heart failure (MESH:D006333), Neurotransmitter deficits (MESH:D009461), chronic inflammation (MESH:D007249), renal failure (MESH:D051437), arrhythmias (MESH:D001145), geriatric syndrome (MESH:D013577), VaD (MESH:D015140), liver cirrhosis (MESH:D008103), COVID-19 (MESH:D000086382), chronic kidney disease (MESH:D051436), traumatic brain injury (MESH:D000070642), anxiety (MESH:D001007), infection (MESH:D007239), haemorrhage (MESH:D006470), transient ischemic attacks (MESH:D002546), respiratory infections (MESH:D012141), affective dysregulation (MESH:D021081), acetylcholine (MESH:C536090), stroke (MESH:D020521), type 2 diabetes (MESH:D003924), obesity (MESH:D009765), depression (MESH:D003866), falls (MESH:C537863), Malnutrition (MESH:D044342), HRV (MESH:D006331), age (MESH:D019588), delirium (MESH:D003693), sarcopenia (MESH:D055948), loss of independence (MESH:D064129), Psychiatric comorbidity (MESH:D001523), cognitive decline (MESH:D003072), psycho-affective disorders (MESH:D019964), PD (MESH:D010300), diabetic neuropathy (MESH:D003929), systemic (MESH:D015619), fibromyalgia (MESH:D005356), Cardiovascular disease (MESH:D002318), weakness (MESH:D018908)
- **Chemicals:** Acetylcholine (MESH:D000109), aldosterone (MESH:D000450), Ca2+ (-), calcium (MESH:D002118), oxygen (MESH:D010100), Noradrenaline (MESH:D009638)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]

## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13031885/full.md

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Source: https://tomesphere.com/paper/PMC13031885