Midlife cardiorespiratory fitness and the development of peripheral artery disease in later life

Neil Keshvani, Benjamin Willis, David Leonard, Ang Gao, Laura Defina, Mary M. McDermott, Jarett D. Berry, Dharam J. Kumbhani*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


BACKGROUND: Data are sparse on the prospective associations between physical activity and incidence of lower extremity peripheral artery disease (PAD). METHODS AND RESULTS: Linking participant data from the CCLS (Cooper Center Longitudinal Study) to Medicare claims files, we studied 19 023 participants with objectively measured midlife cardiorespiratory fitness through maximal effort on the Balke protocol who survived to receive Medicare coverage between 1999 and 2009. The study aimed to determine the association between midlife cardiorespiratory fitness and incident PAD with proportional hazards intensity models, adjusted for age, sex, body mass index, and other covariates, to PAD failure time data. During 121 288 person-years of Medicare follow-up, we observed 805 PAD-related hospitalizations/procedures among 19 023 participants (21% women, median age 50 years). Lower midlife fitness was associated with a higher rate of incident PAD in patients aged 65 years and older (low fit [quintile 1]: 11.4, moderate fit [quintile 2 to 3]: 7.8, and high fit [quintile 4 to 5]: 5.7 per 1000 person years). After multivariable adjustment for common predictors of incident PAD such as age, body mass index, hypertension, and diabetes, these findings persisted. Lower risk for PAD per greater metabolic equivalent task of fitness was observed (hazard ratio [HR], 0.93 [95% CI, 0.90– 0.97]; P<0.001). Among a subset of patients with an additional fitness assessment, each 1 metabolic equivalent task increase from baseline fitness was associated with decreased risk of incident PAD (HR, 0.90 [95% CI, 0.82– 0.99]; P=0.03). CONCLUSIONS: Cardiorespiratory fitness in healthy, middle-aged adults is associated with lower risk of incident PAD in later life, independent of other predictors of incident PAD.

Original languageEnglish (US)
Article numbere020841
JournalJournal of the American Heart Association
Issue number23
StatePublished - Dec 7 2021


  • Cardiorespiratory fitness
  • Midlife
  • Peripheral artery disease

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


Dive into the research topics of 'Midlife cardiorespiratory fitness and the development of peripheral artery disease in later life'. Together they form a unique fingerprint.

Cite this