# Frailty and Cardiometabolic Outcomes: A Narrative Review

**Authors:** Saam Foroshani, Kevin S. Tang, Nathan D. Wong

PMC · DOI: 10.3390/jcm15041348 · 2026-02-09

## TL;DR

Frailty is linked to worse outcomes in heart disease, and understanding this connection can improve patient care and treatment decisions.

## Contribution

This review synthesizes current evidence on how frailty interacts with cardiovascular disease and its impact on outcomes.

## Key findings

- Frailty independently predicts higher risks of mortality and cardiovascular events.
- Biological mechanisms like inflammation and sarcopenia link frailty with cardiovascular disease.
- Frailty's prognostic value exceeds traditional risk factors and can be reversed with proper care.

## Abstract

Frailty is a multidimensional state of reduced physiological reserve that is increasingly recognized as a major determinant of outcomes in cardiovascular diseases (CVDs). As populations age and cardiometabolic multimorbidity becomes more prevalent, understanding how frailty interacts with CVD pathology has important implications for risk stratification, clinical decision-making, and patient-centered care. Across diverse cardiovascular conditions and interventions, frailty independently predicts higher risks of mortality, major adverse cardiovascular events (MACE), rehospitalization, procedural complications, functional decline, and reduced quality of life. Shared biological mechanisms—including chronic inflammation, sarcopenia, endothelial dysfunction, and the effects of multimorbidity and polypharmacy—help explain the strong and often bidirectional relationship between frailty and CVD, one that is reported by recent data to be multiplicative as well as additive. Importantly, frailty demonstrates prognostic value beyond traditional risk factors and varies in predictive performance depending on the assessment tool used. Finally, frailty should not be viewed as immutable; evidence shows that appropriate conditioning may slow the decline or even reverse frail or prefrail states. This narrative review aims to synthesize contemporary evidence on frailty definitions and assessment, epidemiology, mechanistic pathways linking frailty with CVD, associated outcomes, prognostic value, and emerging interventions relevant to CVD prevention and management.

## Full-text entities

- **Genes:** TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, GLP1R (glucagon like peptide 1 receptor) [NCBI Gene 2740] {aka GLP-1, GLP-1-R, GLP-1R}
- **Diseases:** stroke (MESH:D020521), coronary artery disease (MESH:D003324), Chronic low (MESH:D009800), acute kidney injury (MESH:D058186), protein-energy malnutrition (MESH:D011502), cardiac conditions (MESH:D006331), functional (MESH:D003291), heart failure (MESH:D006333), ST elevation MI (MESH:D000072657), advanced cardiovascular-kidney-metabolic (CKM) syndrome (MESH:D007674), falls (MESH:C537863), obesity (MESH:D009765), bleeding (MESH:D006470), excess adiposity (MESH:D018205), type 2 diabetes (MESH:D003924), chronic diseases (MESH:D002908), non (MESH:C580335), nutritional deficits (MESH:D009748), Frailty (MESH:D000073496), bone fragility (MESH:C536063), cognitive decline (MESH:D003072), disability (MESH:D009069), loss of skeletal muscle mass and function (MESH:C536030), metabolic dysregulation (MESH:D021081), health deficits (MESH:D009461), immune dysregulation (OMIM:614878), impaired stress tolerance (MESH:D018149), metabolic dysfunction (MESH:D008659), acute coronary syndromes (MESH:D054058), geriatric syndrome (MESH:D013577), atherosclerosis (MESH:D050197), mitochondrial and endothelial dysfunction (MESH:D028361), hypertension (MESH:D006973), malnutrition (MESH:D044342), death (MESH:D003643), peripheral vascular disease (MESH:D016491), CMDs (MESH:D024821), injury to (MESH:D014947), chronic inflammation (MESH:D007249), Sarcopenia (MESH:D055948), NSTEMI (MESH:D000072658), insulin resistance (MESH:D007333), vascular dysfunction (MESH:D002561), vascular injury (MESH:D057772), weight loss (MESH:D015431), Vascular endothelial dysfunction (MESH:D014652), weakness (MESH:D018908), impaired immune function (MESH:D007154), valvular disease (MESH:D006349), ischemic heart disease (MESH:D017202), diabetes (MESH:D003920), functional decline (MESH:D060825), MI (MESH:D009203), CVD (MESH:D002318)
- **Chemicals:** lipid (MESH:D008055), glycemia (MESH:D001786), calcium (MESH:D002118), glucose (MESH:D005947), vitamin D (MESH:D014807), Tai (-)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12942295/full.md

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Source: https://tomesphere.com/paper/PMC12942295