Impact of peri-operative frailty and operative stress on post-discharge mortality, readmission and days at home in Medicare beneficiaries.

BACKGROUND: Understanding how patients' frailty and the physiological stress of surgical procedures affect postoperative outcomes may inform risk stratification of older patients undergoing surgery. The objective of the study was to examine the association of peri-operative frailty with mortality, 30-day readmission and days at home after non-cardiac surgical procedures of different physiological stress. METHODS: This retrospective study used Medicare claims data from a 7.125% random sample of Medicare fee-for-service beneficiaries from 2015 to 2019 who were aged ≥ 65 years and underwent non-cardiac surgical procedure listed in the Operative Stress Score categories. The exposure of the study was claims-based frailty index (robust, < 0.15; pre-frail, 0.15 to < 0.25; mildly frail, 0.25 to < 0.35; and moderate-to-severely frail, ≥ 0.35) with Operative Stress Score categories being 1, very low stress to 5, very high stress. The primary outcome was all-cause mortality at 30 days and 365 days after the surgical procedure. RESULTS: In total, 1,019,938 patients (mean (SD) age of 76.1 (7.3) years; 52.3% female; 16.8% frail) were included. The cumulative incidence of mortality generally increased with Operative Stress Score category, ranging from 5.0% (Operative Stress Score 2) to 24.9% (Operative Stress Score 4) at 365 days. Within each category, increasing frailty was associated with mortality at 30 days (hazard ratio comparing moderate-to-severe frailty vs. robust ranged from 1.59-3.91) and at 365 days (hazard ratio 1.30-4.04). The variation in postoperative outcomes by patients' frailty level was much greater than the variation by the operative stress category. CONCLUSIONS: These results emphasise routine frailty screening before major and minor non-cardiac procedures and the need for greater clinician awareness of postoperative outcomes beyond 30 days in shared decision-making with older adults with frailty.

Performance of FRAX in older adults with frailty: the Framingham Heart Study.

We compared the performance of FRAX according to frailty status in 3554 individuals from the Framingham Study. During 10-year follow-up, 6.9% and 3.0% of participants with and without frailty experienced MOF. Discrimination profiles were lower in participants with frailty compared to those without, but they improved when FRAX included BMD. INTRODUCTION: Frailty increases fracture risk. FRAX was developed to predict fractures but never validated in individuals with frailty. We aimed to compare the predictive performance of FRAX (v4.3) in individuals with and without frailty. METHODS: We conducted a cohort study using the Framingham Heart Study. Frailty was defined by the Fried phenotype. Major osteoporotic fractures (MOF) were ascertained from medical records during 10-year follow-up. To evaluate discrimination and calibration of FRAX, we calculated the area-under-the-receiver-operating characteristics curves (AUC) using logistic regression models and observed-to-predicted fracture probabilities. Analyses were stratified by frailty status. RESULTS: Frailty was present in 550/3554 (15.5%) of participants. Participants with frailty were older (81.1 vs. 67.6 years), female (68.6% vs. 55.1%), and had greater mean FRAX scores (MOF: 15.9% vs. 10.1%) than participants without frailty. During follow-up, 38 participants with frailty (6.9%) and 91 without (3.0%) had MOFs. The AUC for FRAX (without BMD) was lower in participants with frailty (0.584; 95% CI 0.504-0.663) compared to those without (0.695; 95% CI 0.649-0.741); p value = 0.02. Among participants with frailty, the AUC improved when FRAX included BMD (AUC 0.658, p value < 0.01). FRAX overestimated MOF risk, with larger overestimations in individuals without frailty. Performance of FRAX for hip fracture was similar. CONCLUSION: FRAX may have been less able to identify frail individuals at risk for fracture, as compared with individuals without frailty, unless information on BMD is available. This suggests that BMD captures features important for fracture prediction in frail persons. Future fracture prediction models should be developed among persons with frailty.

Association Between Long-Term Aspirin Use and Frailty in Men: The Physicians' Health Study.

BACKGROUND: Chronic inflammation may lead to frailty, however the potential for anti-inflammatory medications such as aspirin to prevent frailty is unknown. We sought to examine the association between long-term aspirin use and prevalent frailty. METHODS: We included 12 101 men ≥60 years who participated in the Physicians' Health Study I, a completed aspirin randomized controlled trial (1982-1989). Annual questionnaires collected self-reported data on daily aspirin use, lifestyle, and clinical variables. Average aspirin use was summed into 2 categories: ≤60 days/year and >60 days/year. Frailty was assessed using a 33-item index 11 years after trial completion. A score of ≥0.21 was considered frail. Propensity score inverse probability of treatment weighting was used for statistical control of confounding. Logistic regression models estimated odds of frailty as a function of categories of average aspirin use. RESULTS: Mean age was 70.5 years (range 60-101). Following an average of 11 ± 0.6 years of follow-up, aspirin use was reported as ≤60 days/year for 15%; 2413 participants (20%) were frail. Frequency of aspirin use was associated with smoking, alcohol consumption, hypertension, and cardiovascular disease, but negatively associated with bleeding and Coumadin use. The odds ratio (95% confidence intervals) for frailty was 0.85 (0.76-0.96) for average aspirin use >60 days/year versus aspirin use ≤60 days/year. Results were similar using an alternate definition of frailty. CONCLUSIONS: Long-term regular aspirin use is inversely associated with frailty among older men, even after consideration of multimorbidity and health behaviors. Work is needed to understand the role of medications with anti-inflammatory properties on aging.

A Longitudinal Study of Trunk Muscle Properties and Severity of Thoracic Kyphosis in Women and Men: The Framingham Study.

BACKGROUND: Cross-sectional studies suggest that trunk muscle morphology in the lumbar spine is an important determinant of kyphosis severity in older adults. The contribution of age-related changes in muscle morphology in the thoracic and lumbar spine to progression of kyphosis is not known. Our objective was to determine cross-sectional and longitudinal associations of thoracic and lumbar muscle size and density with kyphosis. METHODS: Participants were 1,087 women and men (mean age: 61 years) of the Framingham Heart Study who underwent baseline and follow-up quantitative computed tomography (QCT) scanning 6 years apart. We used QCT scans to measure trunk muscle cross-sectional area (CSA, cm2) and density (HU) at the thoracic and lumbar spine and Cobb angle (degrees) from T4 to T12. Linear regression models estimated the association between muscle morphology and kyphosis. RESULTS: At baseline, smaller muscle CSA and lower density of thoracic (but not lumbar) spine muscles were associated with a larger (worse) Cobb angle in women and men. For example, each standard deviation decrease in baseline thoracic paraspinal muscle CSA was associated with a larger baseline Cobb angle in women (3.7 degrees, 95% CI: 2.9, 4.5) and men (2.5 degrees, 95% CI: 1.6, 3.3). Longitudinal analyses showed that loss of muscle CSA and density at the thoracic and lumbar spine was not associated with progression of kyphosis. CONCLUSIONS: Our findings suggest that kyphosis severity is related to smaller and lower density trunk muscles at the thoracic spine. Future studies are needed to determine how strengthening mid-back musculature alters muscle properties and contributes to preventing kyphosis progression.

Cortical and trabecular bone microarchitecture as an independent predictor of incident fracture risk in older women and men in the Bone Microarchitecture International Consortium (BoMIC): a prospective study.

BACKGROUND: Although areal bone mineral density (aBMD) assessed by dual-energy x-ray absorptiometry (DXA) is the clinical standard for determining fracture risk, most older adults who sustain a fracture have T scores greater than -2·5 and thus do not meet the clinical criteria for osteoporosis. Importantly, bone fragility is due to low BMD and deterioration in bone structure. We assessed whether indices of high-resolution peripheral quantitative CT (HR-pQCT) were associated with fracture risk independently of femoral neck aBMD and the Fracture Risk Assessment Tool (FRAX) score. METHODS: We assessed participants in eight cohorts from the USA (Framingham, Mayo Clinic), France (QUALYOR, STRAMBO, OFELY), Switzerland (GERICO), Canada (CaMos), and Sweden (MrOS). We used Cox proportional hazard ratios (HRs) to estimate the association between HR-pQCT bone indices (per 1 SD of deficit) and incident fracture, adjusting for age, sex, height, weight, and cohort, and then additionally for femoral neck DXA aBMD or FRAX. FINDINGS: 7254 individuals (66% women and 34% men) were assessed. Mean baseline age was 69 years (SD 9, range 40-96). Over a mean follow-up of 4·63 years (SD 2·41) years, 765 (11%) participants had incident fractures, of whom 633 (86%) had femoral neck T scores greater than -2·5. After adjustment for age, sex, cohort, height, and weight, peripheral skeleton failure load had the greatest association with risk of fracture: tibia HR 2·40 (95% CI 1·98-2·91) and radius 2·13 (1·77-2·56) per 1 SD decrease. HRs for other bone indices ranged from 1·12 (95% CI 1·03-1·23) per 1 SD increase in tibia cortical porosity to 1·58 (1·45-1·72) per 1 SD decrease in radius trabecular volumetric bone density. After further adjustment for femoral neck aBMD or FRAX score, the associations were reduced but remained significant for most bone parameters. A model including cortical volumetric bone density, trabecular number, and trabecular thickness at the distal radius and a model including these indices plus cortical area at the tibia were the best predictors of fracture. INTERPRETATION: HR-pQCT indices and failure load improved prediction of fracture beyond femoral neck aBMD or FRAX scores alone. Our findings from a large international cohort of men and women support previous reports that deficits in trabecular and cortical bone density and structure independently contribute to fracture risk. These measurements and morphological assessment of the peripheral skeleton might improve identification of people at the highest risk of fracture. FUNDING: National Institutes of Health National Institute of Arthritis Musculoskeletal and Skin Diseases.

Thoracic Kyphosis and Physical Function: The Framingham Study.

OBJECTIVE: To evaluate the association between thoracic kyphosis and physical function. DESIGN: Prospective cohort. SETTING: Framingham, Massachusetts. PARTICIPANTS: Framingham Heart Study Offspring and Third Generation cohort members who had computed tomography (CT) performed between 2002 and 2005 and physical function assessed a mean 3.4 years later (N = 1,100; mean age 61 ± 8, range 50-85). MEASUREMENTS: Thoracic kyphosis (Cobb angle, T4-T12) was measured in degrees using supine CT scout images. Participants were categorized according to Cobb angle to compare those in the highest quartile (Q4, most-severe kyphosis) with those in the lowest quartiles (Q1-Q3). Quick walking speed (m/s), chair-stand time (seconds), grip strength (kg), and self-reported impairments were assessed using standardized procedures. Analyses were adjusted for age, height, weight, smoking, follow-up time, vertebral fractures, and prevalent spinal degeneration. RESULTS: Thoracic kyphosis was not associated with physical function in women or men, and these results were consistent in those younger than 65 and those aged 65 and older. For example, walking speed was similar in adults younger than 65 with and without severe kyphosis (women, Q4: 1.38 m/s, Q1-Q3: 1.40 m/s, P = .69; men, Q4: 1.65 m/s, Q1-Q3: 1.60 m/s; P = .39). CONCLUSION: In healthy relatively high-functioning women and men, kyphosis severity was not associated with subsequent physical function. Individuals at risk of functional decline cannot be targeted based on supine CT thoracic curvature measures alone.

Heritability of Thoracic Spine Curvature and Genetic Correlations With Other Spine Traits: The Framingham Study.

Hyperkyphosis is a common spinal disorder in older adults, characterized by excessive forward curvature of the thoracic spine and adverse health outcomes. The etiology of hyperkyphosis has not been firmly established, but may be related to changes that occur with aging in the vertebrae, discs, joints, and muscles, which function as a unit to support the spine. Determining the contribution of genetics to thoracic spine curvature and the degree of genetic sharing among co-occurring measures of spine health may provide insight into the etiology of hyperkyphosis. The purpose of our study was to estimate heritability of thoracic spine curvature using T4 -T12 kyphosis (Cobb) angle and genetic correlations between thoracic spine curvature and vertebral fracture, intervertebral disc height narrowing, facet joint osteoarthritis (OA), lumbar spine volumetric bone mineral density (vBMD), and paraspinal muscle area and density, which were all assessed from computed tomography (CT) images. Participants included 2063 women and men in the second and third generation offspring of the original cohort of the Framingham Study. Heritability of kyphosis angle, adjusted for age, sex, and weight, was 54% (95% confidence interval [CI], 43% to 64%). We found moderate genetic correlations between kyphosis angle and paraspinal muscle area (ρˆG , -0.46; 95% CI, -0.67 to -0.26), vertebral fracture (ρˆG , 0.39; 95% CI, 0.18 to 0.61), vBMD (ρˆG , -0.23; 95% CI, -0.41 to -0.04), and paraspinal muscle density (ρˆG , -0.22; 95% CI, -0.48 to 0.03). Genetic correlations between kyphosis angle and disc height narrowing (ρˆG , 0.17; 95% CI, -0.05 to 0.38) and facet joint OA (ρˆG , 0.05; 95% CI, -0.15 to 0.24) were low. Thoracic spine curvature may be heritable and share genetic factors with other age-related spine traits including trunk muscle size, vertebral fracture, and bone mineral density. © 2016 American Society for Bone and Mineral Research.

Association between long-term air pollution and increased blood pressure and hypertension in China.

Several studies have investigated the short-term effects of ambient air pollutants in the development of high blood pressure and hypertension. However, little information exists regarding the health effects of long-term exposure. To investigate the association between residential long-term exposure to air pollution and blood pressure and hypertension, we studied 24 845 Chinese adults in 11 districts of 3 northeastern cities from 2009 to 2010. Three-year average concentration of particles with an aerodynamic diameter ≤10 µm (PM(10)), sulfur dioxide (SO(2)), nitrogen dioxides (NO(2)), and ozone (O(3)) were calculated from monitoring stations in the 11 districts. We used generalized additive models and 2-level logistic regressions models to examine the health effects. The results showed that the odds ratio for hypertension increased by 1.12 (95% confidence interval [CI], 1.08-1.16) per 19 µg/m(3) increase in PM(10), 1.11 (95% CI, 1.04-1.18) per 20 µg/m(3) increase in SO(2), and 1.13 (95% CI, 1.06-1.20) per 22 µg/m(3) increase in O(3). The estimated increases in mean systolic and diastolic blood pressure were 0.87 mm Hg (95% CI, 0.48-1.27) and 0.32 mm Hg (95% CI, 0.08-0.56) per 19 µg/m(3) interquartile increase in PM(10), 0.80 mm Hg (95% CI, 0.46-1.14) and 0.31 mm Hg (95% CI, 0.10-0.51) per 20 µg/m(3) interquartile increase in SO(2), and 0.73 mm Hg (95% CI, 0.35-1.11) and 0.37 mm Hg (95% CI, 0.14-0.61) per 22 µg/m(3) interquartile increase in O(3). These associations were only statistically significant in men. In conclusion, long-term exposure to PM(10), SO(2), and O(3) was associated with increased arterial blood pressure and hypertension in the study population.