Endothelial Dysfunction as a Key Link between Cardiovascular Disease and Frailty: A Systematic Review

Background: Frailty is increasingly recognized as a significant health concern, particularly due to its association with cardiovascular pathologies. This study aims to examine how vascular endothelial dysfunction, a known premorbid stage in the pathophysiology of cardiovascular diseases, contributes to the link between cardiovascular illness and frailty. Methods: The inclusion criteria allowed us to focus on original clinical research articles published in English between January 2014 and January 2024, which reported quantitative assessments of the relationship between frailty and vascular endothelial dysfunction. Excluded from the study were systematic literature reviews, meta-analyses, editorials, conference articles, theses, methodological articles, and studies using animal or cell culture models. Searches were conducted of electronic databases, including Scopus, ScienceDirect, and Medline, up to 22 January 2024. The risk of bias was assessed using the Joanna Briggs Institute's critical appraisal tools. The methods used to present and synthesize the results involved data extraction and categorization based on biomolecular and clinical findings of endothelial dysfunction. Results: Following the application of the inclusion and exclusion criteria, a total of 29 studies were identified. Vascular endothelial dysfunction was associated with increased frailty phenotypes, and we also identified SGLT-2 inhibitors' potential role as an anti-fragility treatment that affects endothelial dysfunction. This study found that the physical and biomolecular markers of endothelial dysfunction are associated with frailty measures and have predictive value for incident frailty. Furthermore, some studies have shown inflammation to have an impact on endothelial dysfunction and frailty, and an innovative age-related chronic inflammation measure has been proven to predict frailty scores. Conclusions: The current evidence suggests an association between endothelial dysfunction and frailty, highlighting the need for further research to elucidate the underlying mechanisms.