Can pre-frailty and frailty predict the risk for cardiovascular events like myocardial infarction or stroke? According to new study findings, frailty in older adults is a dynamic state that often progresses to cardiovascular disease (CVD). But frailty progression might be delayed with targeted, timely intervention.

The longitudinal study, published on December 11 in the Canadian Journal of Cardiology, is reportedly one of the first to examine the transition from different states of frailty (frailty-free, pre-frailty, and frailty) to CVD events. Other studies of frailty have focused on a single time point.

“We know that there is a close bidirectional relationship between frailty and CVD,” senior study author Joanne Ryan, PhD, professor of epidemiology in the School of Public Health and Preventive Medicine at Monash University in Melbourne, Australia, told Medscape News Canada. Cardiovascular events like stroke or heart attack increase risk for frailty, and patients with frailty are at increased risk for a CVD event, she explained.

“Frailty is not a chronic condition; people can recover from it. Assessing it at a single point fails to capture its dynamic nature and how it influences CVD risk,” said Ryan. 

Frailty Is Reversible

The investigators examined the transition between frailty states and from frailty states to incident CVD in 18,077 community-dwelling older adults. Participants had had no previous CVD event. The population’s median age was 73.9 years, and 56% were women. All were followed for a median of 7.4 years and attended at least two in-person follow-up assessments (ie, two frailty assessments or one frailty assessment and CVD occurrence).

There is no universal definition of frailty. The researchers used the Deficit-Accumulation Frailty Index (which defines frailty by the number of diagnosed conditions, biomarkers, pathology, and physical indicators of health, well-being, and function) and a modified version of the Fried Frailty Phenotype (which defines frailty as having three of the following five factors: shrinking, weakness, exhaustion, slowness, and low activity). Participants were categorized as not frail, pre-frail, or frail.

The estimated probability for transitioning from frail to CVD increased from 3% at 1 year to 11% at 5 years and 18% at 10 years, using the Frailty Index. Conversely, the probability of transitioning from frail to pre-frail was 21% at 1 year, 34% at 5 years, and 32% at 10 years.

“We identified a substantial number who got better: that is, transitioned from frail to pre-frail and from pre-frail to not frail. This is important because it emphasizes that recovery is relatively common and associated with a reduced risk for CVD,” said Ryan.

Factors like older age and female sex also played a role. For example, a 1-year increase in chronological age was associated with an estimated 5% relative increased risk for Frailty Index-defined frailty progression, a 7%-9% increased relative risk for developing CVD, and a 3% lower relative risk for reverting to a less frail state.

Compared with males, females had a 26% higher relative risk for progressing to a more severe frailty state and were less likely to reverse it. But they also had up to a 49% lower relative risk for transitioning from another frailty state to a CVD event. In addition, higher socioeconomic status, which facilitated better healthcare access and timely management, boosted the likelihood of frailty recovery, while lower socioeconomic status and residing in a rural setting did the opposite.

Timely Intervention

There is no formal agreement about how and when to manage frailty in the clinical setting. “Frailty is not routinely screened,” Tracey Colella, PhD, RN, research scientist and clinician in the Cardiovascular Prevention and Rehabilitation Program at University Health Network in Toronto, told Medscape News Canada. “Why are we waiting until an actual event has occurred or some sort of chronic disease has manifested? We need to start early screening, especially in women.” Colella was not involved in the study.

How soon to intervene is unclear, however. First, intervention might be ideally started when patients, especially women, given their higher risk, are in their 40s, when hormone levels, muscle mass, and activity levels are changing. But intervening even earlier might be beneficial, too.

“We know that women who have pregnancy or reproductive issues are at heightened risk, two to three times higher, of future CVD,” said Colella.

Though she believes that frequent screening is better, she acknowledged that such an approach might not be feasible. Preventive interventions (eg, regular and consistent resistance training; balance, dynamic, and stability exercises; adequate, protein-rich nutrition; and ample caloric intake) thus become important. Colella also emphasized that some screening tools (eg, the Clinical Frailty Scale) are easier to use with a busy clinical visit. 

“A frailty [screen] does not have to be 64 items,” she said, noting that “tailoring interventions” is important. “It’s not one-size-fits-all.”

Nor is frailty inevitable. “It’s a dynamic state,” said Colella. “The study really reinforced the importance of screening older adults and provided meaningful context for identifying individuals at higher risk. There’s hope.”

The study, which was part of the ASPREE and ASPREE-XT (ie, post-ASPREE observational study), was mainly supported by the National Institute on Aging and the National Cancer Institute at the United States National Institutes of Health, the National Health and Medical Research Council of Australia, Monash University, and the Victorian Cancer Agency. Ryan and Colella reported having no relevant financial relationships.

Liz Scherer is an independent health and medical journalist. She frequently covers health news for Canada and Europe.