Cardiovascular autonomic nervous system function and hip fracture risk: the Cardiovascular Health Study

Phyllis K. Stein, Petra Buzkova, Howard A. Fink, John A. Robbins, Kenneth J. Mukamal, Jane A. Cauley, Laura Carbone, Rachel Elam, David W. McMillan, Rodrigo Valderrabano, Joshua I. Barzilay

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5 Scopus citations


Summary: Among 1299 older adults with 24-h Holter monitoring data at baseline, followed for approximately 15 years, 190 incident hip fractures occurred. Increased heart rate variability was independently associated with reduced risk of hip fracture among female participants. Purpose: Autonomic nervous system function modulates bone remodeling in rodent osteoporosis models. We tested whether cardiovascular autonomic function is associated with hip fracture risk in humans. Methods: Participants were 1299 subjects from the Cardiovascular Health Study (mean age 72.8 years). Eight heart rate variability (HRV) measures (time and frequency domains, detrended fluctuation analysis variables, and heart rate turbulence) were derived from 24-h Holter monitor scans in sinus rhythm. Median follow-up for incident hip fracture was 14.7 years [IQR 9.1, 20.2]. Cox proportional hazards models were used to calculate hazard ratios (95% confidence intervals, CI). Results: There were 144 hip fractures among 714 women (1.31 [1.06, 1.61] per 100-person years) and 46 among 585 men (0.62 [0.43, 0.90] per 100 person-years). From among HRV variables examined, a one standard deviation (SD) higher variation between normal heart beats over 24 h (the SD of NN intervals [SDNN]) was associated with a multivariable-adjusted lower hip fracture risk (HR= 0.80; 95% CI 0.65–0.99; p = 0.04) in women. The adjusted association between very low frequency power, and hip fracture was borderline statistically significant in women (HR= 0.82; 95% CI, 0.66–1.00; p = 0.06). When the 8 HRV variables were considered conjointly and adjusted for each other’s association with hip fracture risk, a 1 SD higher SDNN value was significantly associated with reduced hip fracture risk in women (HR 0.74; 95% CI, 0.50–0.99; p = 0.05). No HRV variables were associated with hip fracture in men. Conclusions: In older women, increased heart rate variation is associated with hip fracture risk.

Original languageEnglish
Article number163
JournalArchives of Osteoporosis
Issue number1
StatePublished - Dec 2021


  • Detrended fluctuation analysis
  • Frequency domain
  • Heart rate turbulence
  • Heart rate variation
  • Hip fracture
  • Time domain


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