Frailty and Cardiovascular Disease: A Bidirectional Relationship with Clinical Implications

Neil Johnson¹Junru Qu¹Kenji Wagatsuma²Yingying Su³Beibei Du^1*Yuquan He¹Ping Yang¹

• ¹China-Japan Union Hospital, Jilin University, Changchun, China
• ²Tsukuba Heart Center, Tsukuba Memorial Hospital, Tsukuba, Ibaraki, Japan
• ³Changchun University of Chinese Medicine, Changchun, China

Background: Frailty and cardiovascular disease (CVD) are increasingly recognized as interconnected conditions that significantly impact aging populations. This review synthesizes evidence from studies published between 2000 and 2025, identified through Google Scholar and PubMed using keywords such as “frailty”, “CVD”, “frailty assessment”, and “multicomponent interventions”. Frailty, characterized by reduced physiological resilience and increased vulnerability to stressors, affects 10-15% of community-dwelling older adults and is associated with adverse CVD outcomes. Main Body: Our analysis demonstrates that frailty and CVD share common pathophysiological mechanisms, including chronic inflammation ("inflammaging"), mitochondrial dysfunction, and endothelial impairment. The reviewed literature reveals frailty prevalence varies substantially by CVD subtype, ranging from 30% in patients with coronary artery disease (CAD) to 80% in those with heart failure (HF). Frailty independently predicts adverse outcomes, conferring a 2.5-3.5-fold higher mortality risk. While multiple assessment tools exist (e.g., Fried Phenotype, Clinical Frailty Scale), this review highlights the absence of a gold standard assessment tool for cardiovascular populations. A critical challenge is that traditional cardiovascular risk scores often fail to account for frailty, leading to significant treatment disparities. Effective management requires a paradigm shift towards multimodal interventions. Evidence supports combined exercise and nutritional programs (e.g., VIVIFRAIL, SPRINT-T), which improve physical function and frailty severity. Recent guidelines now recommend such rehabilitation. Emerging therapeutic strategies—including senolytics (e.g., dasatinib plus quercetin), stem cell mobilization, and angiogenic gene therapy—show promise for targeting shared biological pathways of vascular decline. Conclusion: The synthesis of recent evidence underscores the necessity of routine frailty assessment in cardiovascular care. Integrating validated frailty measures can improve risk stratification and enable personalized treatment. Future research should focus on standardizing assessment in cardiology and developing targeted interventions for shared pathways. Addressing frailty as a modifiable risk factor could significantly improve outcomes for older adults with CVD.