@article {9004, title = {Cardiovascular autonomic nervous system function and hip fracture risk: the Cardiovascular Health Study.}, journal = {Arch Osteoporos}, volume = {16}, year = {2021}, month = {2021 10 31}, pages = {163}, abstract = {

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 [Formula: see text] 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 [Formula: see text] 0.82; 95\% CI, 0.66-1.00; p = 0.06). When the 8 HRV variables were considered conjointly and adjusted for each other{\textquoteright}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.

}, keywords = {Aged, Autonomic Nervous System, Female, Heart Rate, Hip Fractures, Humans, Osteoporosis, Proportional Hazards Models}, issn = {1862-3514}, doi = {10.1007/s11657-021-01028-y}, author = {Stein, Phyllis K and B{\r u}zkov{\'a}, Petra and Fink, Howard A and Robbins, John A and Mukamal, Kenneth J and Cauley, Jane A and Carbone, Laura and Elam, Rachel and McMillan, David W and Valderrabano, Rodrigo and Barzilay, Joshua I} } @article {9316, title = {The associations of markers of endothelial dysfunction with hip fracture risk.}, journal = {Arch Osteoporos}, volume = {18}, year = {2023}, month = {2023 Mar 02}, pages = {39}, abstract = {

UNLABELLED: Endothelial dysfunction underlies the development of atherosclerotic vascular disease, which in turn is associated with osteoporotic fractures. Here, we examined the association of two markers of endothelial dysfunction with incident hip fracture risk in older adults but found no statistically significant associations between them.

PURPOSE/INTRODUCTION: Endothelial dysfunction underlies the development of atherosclerotic vascular disease. Vascular disease, in turn, is associated with the risk of osteoporotic fractures, such as hip fractures. Here, we examine whether two measures of endothelial dysfunction are related to hip fracture risk.

METHODS: Participants for this study were 2792 individuals (mean age 78.6~years) who had flow-mediated dilation (FMD) measured after ischemia in the forearm and 2255 adults (mean age 73.3~years) with measured soluble intercellular adhesion molecule (siCAM) levels, a constitutive endothelial cell membrane protein associated with the initiation of atherosclerosis. Mean follow-up was 9.7 and 11.7~years, respectively. There were 375 and 265 incident hip fractures, respectively, in each group.

RESULTS: In Cox proportional hazards models, there was no significant association between FMD response and incident hip fracture (HR per 1\% higher FMD was 0.98 [0.93, 1.04]; p = 0.44). In exploratory analyses, when data were examined dichotomously, participants in the lowest 80\% of FMD (<= 4.5\%) had an adjusted 1.29 (0.98, 1.68; p = 0.067) higher hazard of hip fracture compared to participants in the upper 20\% of FMD change. There were no significant associations between siCAM and incident hip fracture whether examined as a continuous or dichotomized variable.

CONCLUSIONS: Among older adults, two measures of endothelial dysfunction were not significantly associated with hip fracture risk. There was a trend for higher fracture risk with lower FMD.

}, keywords = {Aged, Forearm, Hip Fractures, Humans, Osteoporotic Fractures, Vascular Diseases}, issn = {1862-3514}, doi = {10.1007/s11657-023-01226-w}, author = {Barzilay, Joshua I and B{\r u}zkov{\'a}, Petra and Fink, Howard A and Cauley, Jane A and Carbone, Laura and Elam, Rachel and Robbins, John A and Stein, Phyllis and Sheets, Kerry and Jalal, Diana and Mukamal, Kenneth J} } @article {9384, title = {Mortality Following Hip Fracture in Older Adults With and Without Coronary Heart Disease.}, journal = {Am J Med}, year = {2023}, month = {2023 Apr 24}, abstract = {

BACKGROUND: Comorbidities like coronary heart disease are common among older people who sustain an osteoporotic hip fracture. However, their impact on short- and long-term mortality post-hip fracture is not well quantified.

METHODS: We examined 4092 and 1173 older adults without and with prevalent coronary heart disease, respectively. Post-hip fracture mortality rates were computed with Poisson models and hazard ratios with Cox regression. For perspective, we compared mortality rates among participants with prevalent coronary heart disease who had either a hip fracture or incident heart failure (but no hip fracture).

RESULTS: Among participants without prevalent coronary heart disease, the mortality rate post-hip fracture was 21.83 per 100 participant years, including 49.27 per 100 participant years in the first 6 months following hip fracture. Among participants with prevalent coronary heart disease, the corresponding mortality rates were 32.52 and 79.44 per 100 participant years, respectively. Participants with prevalent coronary heart disease and incident heart failure (but no hip fracture) had corresponding post-incident heart failure mortality rates per 100 participant years of 25.62 overall and 46.4 in the first 6 months. In all 3 groups, the hazard ratio for mortality was similarly elevated: 5- to 7-fold at 6 months and 1.7- to 2.5-fold beyond 5 years.

CONCLUSION: As a case study in the absolute effects of a comorbidity on post-hip fracture mortality, hip fracture in a person with coronary heart disease carries an exceedingly high mortality rate, even higher than that following incident heart failure in individuals with coronary heart disease.

}, issn = {1555-7162}, doi = {10.1016/j.amjmed.2023.03.036}, author = {Robbins, John A and B{\r u}zkov{\'a}, Petra and Barzilay, Joshua I and Cauley, Jane A and Fink, Howard A and Carbone, Laura D and Chen, Zhao and Stein, Phyllis K and Elam, Rachel and Sheets, Kerry and Mukamal, Kenneth J} }