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

• Type of Material: Article
• Authors: Phyllis K Stein, Washington University School of Medicine, St. Lou; Petra Buzkova, University of Washington; Howard A Fink, University of Minnesota, Minneapolis; John A Robbins, University of California Davis; Kenneth J Mukamal, Beth Israel Deaconess Medical Center; Jane A Cauley, University of Pittsburgh; Laura Carbone, Veterans Affairs Medical Center; Rachel Elam, Veterans Affairs Medical Center; David W McMillan, University of Miami; Rodrigo Valderrabano, University of Miami; Joshua Barzilay, Emory University
• Language: English
• Date: 2021-12-01
• Publisher: SPRINGER LONDON LTD
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2021, International Osteoporosis Foundation and National Osteoporosis Foundation
• Final Published Version (URL): http://dx.doi.org/10.1007/s11657-021-01028-y
• Title of Journal or Parent Work: ARCHIVES OF OSTEOPOROSIS
• Volume: 16
• Issue: 1
• Start Page: 163
• End Page: 163
• Grant/Funding Information: This research was supported by contracts HHSN268201200036C, HHSN268200800007C, HHSN268201800001C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, 75N92021D00006, and grants U01HL080295 and U01HL130114 from the National Heart, Lung, and Blood Institute (NHLBI), with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided by R01AG023629 and K24AG065525 from the National Institute on Aging (NIA). A full list of principal CHS investigators and institutions can be found at CHS-NHLBI.org." The content is solely the responsibility of the authors and does not represent the official views of the National Institutes of Health.
• Keywords: Heart rate variation; MORTALITY; BONE-MINERAL DENSITY; Science & Technology; Hip fracture; Orthopedics; Time domain; Life Sciences & Biomedicine; Frequency domain; HEART-RATE-VARIABILITY; Heart rate turbulence; OLDER-ADULTS; Endocrinology & Metabolism; PREDICTOR; WOMEN; Detrended fluctuation analysis

Abstract

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.