Statin Use Linked to Lower Risk of Frailty in Older Veterans

Findings from a large observational study led by researchers at Mass General Brigham support a role for existing heart drugs in preserving healthy aging.

Researchers at Mass General Brigham have demonstrated that older U.S. veterans who initiated statin therapy were significantly less likely to develop frailty over time, suggesting that the cholesterol-lowering medications may have healthy aging benefits beyond cardiovascular disease prevention. Results are published in the European Heart Journal.

“There are currently no approved medications specifically to prevent frailty,” said Saadia Qazi, DO, MPH, MSc, lead author of the study and a cardiologist at VA Boston and in the Division of Aging in Mass General Brigham’s Department of Medicine. “Our findings suggest that statins may offer an important opportunity to reduce the risk of frailty and help people preserve their health and independence as they age.”

Frailty is characterized by muscle loss, fatigue, slow walking speed, and low levels of activity. Older adults who are categorized as frail by a health care provider are more likely to experience a dramatic decline in function after a minor illness or injury. As older adults in the U.S. experience a high rate of frailty, there’s a growing need to identify prevention and treatment strategies for it. The study authors explain that statins have anti-inflammatory effects in addition to lowering cholesterol, and this may help slow processes associated with biological aging and functional decline.

In a retrospective cohort study, Qazi and colleagues analyzed Medicare and Medicaid data from 987,301 U.S. veterans receiving care through the Veterans Affairs health system between 2002 and 2018 and assessed the development of frailty in those who did not take statins and those who did. At the beginning of the analysis period, all veterans were aged 67 years and older, considered to be non-frail, and were not taking statins. Frailty was assessed using a validated 31-item Veterans Affairs Frailty Index.

Over an average follow-up period of 5.3 years, 290,729 veterans started statin therapies and more than 636,000 veterans developed frailty. After adjusting for many differences between participants, including body mass index, sex, race, smoking status, cardiovascular disease, cancer, and other factors,

statin initiation was associated with a 24% lower risk of developing frailty compared with non-statin use.

The association between statin use and reduced risk of frailty was consistent across many subgroups, including older age groups and people with diabetes, cardiovascular disease, arthritis, or dementia. The association was also found among those who were “pre-frail,” showing some early signs of frailty at the beginning of the study. This finding suggests that statins may be beneficial in preventing frailty even if they’re not taken years before frailty starts.

“While randomized trials are needed, these observational findings suggest a potential role for statins in preventing frailty,” said senior author Ariela Orkaby, MD, MPH, a geriatrician at VA Boston and Mass General Brigham. “We know that frailty and heart disease share underlying mechanisms. Our study suggests that targeting those mechanisms could help prevent both outcomes.”

Authorship: In addition to Qazi and Orkaby, Mass General Brigham authors include Michael Gaziano, Luc Djousse, and Jane A. Driver. Additional authors include Brian Charest, Nicholas M. Pajewski, Kathryn E. Callahan, Denise K. Houston, Sara E. Espinoza, Daniel E. Forman, Karen P. Alexander, and David R. Gagnon.

Funding: Funding provided by the National Institute of Aging (R03AG060169, R01AG081287, R01AG058883, R01AG060499, U19AG065188, R01AG073633, R01AG077179, and P30AG024827); VA (CSR&D IK2CX001800, RR&D 1I21RX004409 and HSR&D 1I01HX003518); and PCORI (IHS-2021C3-24147).

Paper cited: Qazi S et al. “Statins and survival free of incident frailty among older US veterans” European Heart Journal DOI: 10.1093/eurheartj/ehag451