With improvements in medicine and technology, life expectancy has increased and adults 75 years and older are the fastest-growing segment of the population. By 2050 more than 45 million Americans will be 75 years and older, with a proportional rate of increase greatest in those 85 years and older.¹ Incidence and prevalence of atherosclerotic cardiovascular disease (ASCVD) rises with age and remains the leading cause of death, reduced quality of life and increased medical costs.² However, although older adults bear the majority of the global ASCVD burden, they are infrequently included in clinical trials that provide the evidence for prevention and treatment guidelines.^3,4

The incidence of frailty and cardiovascular disease (CVD) increases as the population ages. There is a bidirectional relationship between frailty and CVD, and both conditions share several risk factors and underlying biological mechanisms. Frailty has been established as an independent prognostic marker in patients with CVD. Moreover, its presence significantly influences both primary and secondary prevention strategies for adults with CVD while also posing a barrier to the inclusion of these patients in pivotal clinical trials and advanced cardiac interventions. This review discusses the current knowledge base on the relationship between frailty and CVD, how managing CVD risk factors can modify frailty, the influence of frailty on CVD management, and future directions for frailty detection and modification in patients with CVD.

The Veterans Affairs Frailty Index (VA-FI) is an electronic frailty index developed to measure frailty using administrative claims and electronic health records data in Veterans. An update to ICD-10 coding is needed to enable contemporary measurement of frailty. International Classification of Diseases, ninth revision (ICD-9) codes from the original VA-FI were mapped to ICD-10 first using the Centers for Medicaid and Medicare Services (CMS) General Equivalence Mappings. The resulting ICD-10 codes were reviewed by 2 geriatricians. Using a national cohort of Veterans aged 65 years and older, the prevalence of deficits contributing to the VA-FI and associations between the VA-FI and mortality over years 2012–2018 were examined. The updated VA-FI-10 includes 6422 codes representing 31 health deficits. Annual cohorts defined on October 1 of each year included 2 266 191 to 2 428 115 Veterans, for which the mean age was 76 years, 97%–98% were male, 78%–79% were White, and the mean VA-FI was 0.20–0.22. The VA-FI-10 deficits showed stability before and after the transition to ICD-10 in 2015, and maintained strong associations with mortality. Patients classified as frail (VA-FI > 0.2) consistently had a hazard of death more than 2 times higher than nonfrail patients (VA-FI ≤ 0.1). Distributions of frailty and associations with mortality varied with and without linkage to CMS data and with different assessment periods for capturing deficits. The updated VA-FI-10 maintains content validity, stability, and predictive validity for mortality in a contemporary cohort of Veterans aged 65 years and older, and may be applied to ICD-9 and ICD-10 claims data to measure frailty.

Aims: Frailty is associated with an increased risk of all-cause mortality and cardiovascular (CV) events. Limited data exist from the modern era of CV prevention on the relationship between frailty and CV mortality. We hypothesized that frailty is associated with an increased risk of CV mortality. Methods and results: All US Veterans aged ≥65 years who were regular users of Veteran Affairs care from 2002 to 2017 were included. Frailty was defined using a 31-item previously validated frailty index, ranging from 0 to 1. The primary outcome was CV mortality with secondary analyses examining the relationship between frailty and CV events (myocardial infarction, stroke, revascularization). Survival analysis models were adjusted for age, sex, ethnicity, geographic region, smoking, hyperlipidaemia, statin use, and blood pressure medication use. There were 3 068 439 US Veterans included in the analysis. Mean age was 74.1 ± 5.8 years in 2002, 76.0 ± 8.3 years in 2014, 98% male, and 87.5% White. In 2002, the median (interquartile range) frailty score was 0.16 (0.10–0.23). This increased and stabilized to 0.19 (0.10–0.32) for 2006–14. The presence of frailty was associated with an increased risk of CV mortality at every stage of frailty. Frailty was associated with an increased risk of myocardial infarction and stroke, but not revascularization. Conclusion: In this population, both the presence and severity of frailty are tightly correlated with CV death, independent of underlying CV disease. This study is the largest and most contemporary evaluation of the relationship between frailty and CV mortality to date. Further work is needed to understand how this risk can be diminished. Key Question: Can an electronic frailty index identify adults aged 65 and older who are at risk of CV mortality and major CV events? Key Finding: Among 3 068 439 US Veterans aged 65 and older, frailty was associated with an increased risk of CV mortality at every level of frailty. Frailty was also associated with an increased risk of myocardial infarction and stroke, but not revascularization. Take Home Message: Both the presence and severity of frailty are associated with CV mortality and major CV events, independent of underlying CV disease.

As the older adult population expands, an increasing number of patients affected by geriatric syndromes are seen by cardiovascular clinicians. One such syndrome that has been associated with poor outcomes is cognitive frailty: the simultaneous presence of cognitive impairment, without evidence of dementia, and physical frailty, which results in decreased cognitive reserve. Driven by common pathophysiologic underpinnings (eg, inflammation and neurohormonal dysregulation), cardiovascular disease, cognitive impairment, and frailty also share the following risk factors: hypertension, diabetes, obesity, sedentary behavior, and tobacco use. Cardiovascular disease has been associated with the onset and progression of cognitive frailty, which may be reversible in early stages, making it essential for clinicians to diagnose the condition in a timely manner and prescribe appropriate interventions. Additional research is required to elucidate the mechanisms underlying the development of cognitive frailty, establish preventive and therapeutic strategies to address the needs of older patients with cardiovascular disease at risk for cognitive frailty, and ultimately facilitate targeted intervention studies.

The rapid increase of the worldwide population of aging individuals has led to increased urgency to identify potential preventive strategies for frailty. Frailty is a syndrome of decreased physiologic reserve in the face of external stressors that is associated with an increased risk of morbidity and mortality.^1-3 Although frailty is independent of age, it increases in prevalence with age, with estimates that up to half of adults aged 85 years and older are living with frailty.¹ Chronic inflammation is a primary hypothesized mechanism leading to frailty.⁴ Whether medications and supplements with anti-inflammatory properties can lower the risk of frailty remains uncertain.^1,5