Why frailty and heart health may be more closely connected than we thought

By Dr. Sanchari Sinha Dutta, Ph.D.Reviewed by Lauren HardakerSep 15 2026

From arterial stiffness and shifting blood pressure to chronic inflammation, researchers examine the interconnected processes that may link cardiovascular aging with frailty.

Review: Cardiovascular frailty – an emerging frailty phenotype. Image Credit: New Africa / Shutterstock

A narrative review article published in the Journal of Human Hypertension examines cardiovascular frailty, a proposed frailty phenotype intended to capture the bidirectional relationship between frailty and the cardiovascular system.

Background

Advances in healthcare systems and improvements in life expectancy have led to a corresponding increase in older populations worldwide, accompanied by a rise in the prevalence of frailty.

Frailty is an age-related clinical condition characterized by reduced physiological reserves and increased vulnerability, which make older adults more susceptible to health decline even in response to minor stressors.

The most commonly used frailty assessment models are the Rockwood Clinical Frailty Scale for cumulative deficits and Fried’s phenotype for physical frailty. But these models neither fully capture the biological basis of frailty nor comprehensively explore the cardiovascular, cognitive, and psychosocial factors related to frailty.

In recent times, new models have been developed to assess new frailty domains or phenotypes, such as vascular, cognitive, and social frailty. But cardiovascular frailty remains an unexplored area.

It is well established that a bidirectional relationship exists between frailty and cardiovascular morbidity and mortality. Pre-frailty and frailty have been associated with an overall 70% higher risk of cardiovascular disease, while frailty has been associated with a nearly three-fold higher risk of cardiovascular death.

It has been hypothesized that the relationship between frailty and cardiovascular morbidity and mortality may be driven by oxidative stress, inflammation, DNA damage, cardiac alterations, endocrine dysregulation, cellular senescence, and epigenetic modifications.

The existence of this bidirectional relationship highlights the need to identify biological mechanisms and vascular changes associated with cardiovascular frailty.

The authors of the current review article hypothesized that developing a cardiovascular frailty index to define the role of frailty in cardiovascular aging could aid in prognostication and personalized management of cardiovascular frailty in older adults.

Impact of oxi-inflammaging on frailty

Older adults with frailty exhibit higher levels of oxidative stress and inflammation than those without frailty. The term ‘oxi-inflammaging’ has been coined to describe the association between oxidative stress and inflammation that occurs during aging. Factors including poor nutrition, a sedentary lifestyle, genetic susceptibility, and age-related comorbidities have been associated with free radical production and oxidative tissue damage that may contribute to this process.

Several studies have identified inflammatory and oxidative stress biomarkers that are associated with increased frailty risk. Lower antioxidant levels have also been observed alongside higher oxidative stress biomarkers in people with frailty. Much of this evidence is cross-sectional, so directionality and causation remain uncertain. These observations suggest that oxi-inflammaging may contribute to the pathophysiology of frailty.

Oxi-inflammaging has also been linked to the pathogenesis of cardiovascular disease. Cardiovascular disease and frailty are strongly associated in both directions, while lifestyle factors associated with cardiovascular disease risk have been implicated in the etiology of oxi-inflammaging.

Because frailty and cardiovascular disease are bidirectionally associated, addressing cardiovascular frailty through strategies targeting shared risk factors could help improve overall health.

Impact of vascular aging on frailty

Vascular aging, characterized by structural and functional changes in blood vessels over time, is strongly associated with chronological aging and may be a better predictor of frailty than age alone. These changes collectively lead to vascular stiffening, which in turn alters blood flow and affects the cardiovascular system.

Arterial stiffness is independently associated with isolated systolic hypertension in older adults. It has also been consistently linked to frailty and disability, including incident frailty in longitudinal studies.

These observations support the possibility that interventions aimed at reducing arterial stiffness or vascular aging may reduce hypertension and cardiovascular risk, with potential implications for frailty.

Impact of blood pressure regulation on frailty

Impaired blood pressure regulation can manifest as hypertension, isolated systolic hypertension, orthostatic hypotension, and white coat hypertension in older adults, especially those with frailty. The complex interplay among hypertension, orthostatic hypotension, and frailty is primarily driven by blood pressure variability, autonomic dysregulation, endothelial dysfunction, and vascular stiffness.

Risk factors commonly associated with these conditions, including diabetes, atrial fibrillation, chronic kidney disease, stroke, and heart failure, can also explain this complex interplay.

Vascular oxi-inflammaging may contribute to endothelial damage, which in turn impairs vascular expansion and baroreceptor function. Vascular stiffness is also known to reduce baroreceptor sensitivity, contributing to orthostatic hypotension. These mechanisms are interconnected and compounded by both the aging process and frailty.

Frailty and hypertension commonly coexist in older adults, but therapeutic management of hypertension in frailty remains inconclusive. An analysis of the HYVET trial found that frailty did not appear to modify the benefits of antihypertensive treatment in adults aged over 80 years.

Observational evidence has associated lower blood pressure with excess mortality in frail older adults, while hypertension is generally not associated with higher mortality in older adults aged 85 years or older, irrespective of frailty status.

International hypertension guidelines, including those from the European Society of Hypertension and the National Institute for Health and Care Excellence, recommend focusing on clinical judgment and risk-benefit assessment in older adults with frailty and multimorbidity. This reflects the scarcity of evidence in this patient population because frail older adults, particularly those with more severe frailty, have historically been excluded from or underrepresented in clinical trials focusing on hypertension management.

Take-home message

This review highlights the need to investigate a cardiovascular frailty phenotype and index that incorporates the important roles of blood pressure regulation, vascular aging, oxi-inflammaging biomarkers, and self-reported clinical frailty deficits and could provide an objective tool for early detection and personalized clinical management. Longitudinal studies are needed to confirm the proposed associations and validate the index before clinical use.