Cardiovascular autonomic nervous system function and hip fracture risk: the Cardiovascular Health Study
Tóm tắt
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. 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. 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). 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. In older women, increased heart rate variation is associated with hip fracture risk.
Tài liệu tham khảo
Elefteriou F (2018) Impact of the autonomic nervous system on the skeleton. Physiol Rev 98:1083–1112. https://doi.org/10.1152/physrev.00014.2017
Takeda S, Elefteriou F, Levasseur R, Liu X, Zhao L, Parker KL et al (2002) Leptin regulates bone formation via the sympathetic nervous system. Cell 111(3):305–317
Sternberg Z (2018) Cardiovascular autonomic dysfunction: link between multiple sclerosis osteoporosis and neurodegeneration. NeuroMol Med 20:37–53
Bajayo A, Bar A, Denes A, Bachar M, Kram V, Attar-Namdar M et al (2012) Skeletal parasympathetic innervation communicates central IL-1 signals regulating bone mass accrual. Proc Natl Acad Sci USA 109(38):15455–15460
Tien D, Ohara PT, Larson AA, Jasmin L (2003) Vagal afferents are necessary for the establishment but not the maintenance of kainic acid-induced hyperalgesia in mice. Pain 102(1–2):39–49
Cappuccio FP, Meilahn E, Zmuda JM, Cauley JA (1999) Study of osteoporotic fractures research group. High blood pressure and bone-mineral loss in elderly white women: a prospective study. Lancet. 354(9183):971–975
Ang L, Dillon B, Mizokami-Stout K, Pop-Busui R (2020) Cardiovascular autonomic neuropathy: a silent killer with long reach. Auton Neurosci 225:102646. https://doi.org/10.1016/j.autneu.2020.102646
Fried LP, Borhani NO, Enright P, Furberg CD, Gardin JM, Kronmal RA, Kuller LH, Manolio TA, Mittelmark MB, Newman A et al (1991) The Cardiovascular Health Study: design and rationale. Ann Epidemiol 1(3):263–276
Stein PK, Barzilay JI, Domitrovich PP, Chaves PM, Gottdiener JS, Heckbert SR, Kronmal RM (2007) Heart rate variability and its relationship to glucose disorders and metabolic syndrome: the Cardiovascular Health Study. Diabet Med 24:855–863
Patel VN, Pierce BR, Bodapati RK, Brown DL, Ives DG, Stein PK (2017) Association of Holter-derived heart rate variability parameters with the development of congestive heart failure in the Cardiovascular Health Study. JACC Heart Fail 5(6):423–431
Lampert R, Bremner JD, Su S, Miller A, Lee F, Cheema F, Goldberg J, Vaccarino V (2008) Decreased heart rate variability is associated with higher levels of inflammation in middle-aged men. Am Heart J. 156(4):759 e1-759 e7
Theorell T, Liljeholm-Johansson Y, Björk H, Ericson M (2007) Saliva testosterone and heart rate variability in the professional symphony orchestra after “public faintings” of an orchestra member. Psychoneuroendocrinology 32(6):660–668
Taylor JA, Carr DL, Myers CW, Eckberg DL (1998) Mechanisms underlying very-low-frequency RR-interval oscillations in humans. Circulation 98:547–555
Echeverría JC, Woolfson MS, Crowe JA, Hayes-Gill BR, Croaker GDH, Vyas H (2003) Interpretation of heart rate variability via detrended fluctuation analysis and alphabeta filter. Chaos 13(2):467–475
Schmidt G, Malik M, Barthel P, Schneider R, Ulm K, Rolnitzky L, Camm AJ, Bigger JT Jr, Schömig A (1999) Heart-rate turbulence after ventricular premature beats as a predictor of mortality after acute myocardial infarction. Lancet 353(9162):1390–1396
Stein PK, Barzilay JI, Chaves PH, Mistretta SQ, Domitrovich PP, Gottdiener JS, Rich MW, Kleiger RE (2008) Novel measures of heart rate variability predict cardiovascular mortality in older adults independent of traditional cardiovascular risk factors: the Cardiovascular Health Study (CHS). J Cardiovasc Electrophysiol 19(11):1169–1174
Robinson-Cohen C, Katz R, Mozaffarian D, Dalrymple LS, de Boer I, Sarnak M, Shlipak M, Siscovick D, Kestenbaum B (2009) Physical Activity and Rapid Decline in Kidney Function Among Older Adults. Arch Intern Med 169(22):2116–2123
Massera D, Xu S, Walker MD, Valderrábano RJ, Mukamal KJ, Ix JH, Siscovick DS, Tracy RP, Robbins JA, Biggs ML, Xue X, Kizer JR (2019) Biochemical markers of bone turnover and risk of incident hip fracture in older women: the Cardiovascular Health Study. Osteoporos Int 30(9):1755–1765
Pagani F, Francucci CM, Moro L (2005) Markers of bone turnover: biochemical and clinical perspectives. J Endocrinol Invest 28(10 Suppl):8–13
Bauer 1, J Krege, N Lane, E Leary, C Libanati, P Miller, G Myers, S Silverman, H W Vesper, D Lee, M Payette, S Randall (2012) National bone health alliance bone turnover marker project: current practices and the need for US harmonization, standardization, and common reference ranges. Osteoporos Int. 23(10):2425–2433
R Development Core Team (2019) R: A Language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing
Tosun A, Doğru MT, Aydn G, Keleş I, Arslan A, Güneri M, Orkun S, Ebinç H (2011) Does autonomic dysfunction exist in postmenopausal osteoporosis? Am J Phys Med Rehabil 90(12):1012–1019
Miyasaka N, Akiyoshi M, Kubota T (2014) Relationship between autonomic nervous system activity and bone mineral density in non-medicated perimenopausal women. J Bone Miner Metab 32(5):588–592
Lavi S, Nevo O, Thaler I, Rosenfeld R, Dayan L, Hirshoren N, Gepstein L, Jacob G (2007) Effect of aging on the cardiovascular regulatory systems in healthy women. Am J Physiol Regul Integr Comp Physiol. 2(292):788–793
Shaffer F, Ginsberg JP (2017) An overview of heart rate variability metrics and norms. Front Public Health 5:258
Kaye DM, Esler MD (2008) Autonomic control of the aging heart. Neuromolecular Med 10(3):179–186
Umetani K, Singer DH, McCraty R, Atkinson M (1998) Twenty-four-hour time domain heart rate variability and heart rate: relations to age and gender over nine decades. J Am Coll Cardiol 31(3):593–601
Tsuda K, Nishio I, Masuyama Y (2001) Bone mineral density in women with essential hypertension. Am J Hypertens 14:704–707
Vestergaard P, Rejnmark L, Mosekilde L (2009) Hypertension is a risk factor for fractures. Calcif Tissue Int 84(2):103–111
Koenig J, Thayer JF (2016) Sex differences in healthy human heart rate variability: a meta-analysis. Neurosci Biobehav Rev 64:288–310
Rinonapoli G, Ruggiero C, Meccariello L, Bisaccia M, Ceccarini P, Caraffa A (2021) Osteoporosis in Men: a Review of an Underestimated Bone Condition. Int J Mol Sci 22(4):2105
Kado DM, Lui LY, Cummings SR; Study of Osteoporotic Fractures Research Group (2002) Rapid resting heart rate: a simple and powerful predictor of osteoporotic fractures and mortality in older women. J Am Geriatr Soc. 50(3):455–460
Rothem DE, Rothem L, Soudry M, Dahan A, Eliakim R (2009) Nicotine modulates bone metabolism-associated gene expression in osteoblast cells. J Bone Min Metab 27(5):555–561
Okazaki R, Reiko Watanabe R, Inoue D (2016) Osteoporosis associated with chronic obstructive pulmonary disease. J Bone Metab 23(3):111–120
Veldhuis-Vlug AG, El Mahdiui M, Endert E, Heijboer AC, Fliers E, Bisschop PH (2012) Bone resorption is increased in pheochromocytoma patients and normalizes following adrenalectomy. J Clin Endocrinol Metab 97(11):E2093–E2097
Stein PK, Barzilay JI, Chaves PH, Domitrovich PP, Gottdiener JS (2009) Heart rate variability and its changes over 5 years in older adults. Age Ageing 38(2):212–218
Barzilay JI, Bůžková P, Chen Z, de Boer IH, Carbone L, Rassouli NN, Fink HA, Robbins JA (2013) Albuminuria is associated with hip fracture risk in older adults: the cardiovascular health study. Osteoporos Int 24(12):2993–3000