Validation of genetic classifiers derived from mouse and human tumors to identify molecular subtypes of colorectal cancer.

Colorectal cancer (CRC) is a leading cause of cancer death in the United States. Standard treatment for advanced-stage CRC for decades has included 5-fluorouracil-based chemotherapy. More recently, targeted therapies for metastatic CRC are being used based on the individual cancer's molecular profile. In the past few years, several different molecular subtype schemes for human CRC have been developed. The molecular subtypes can be distinguished by gene expression signatures and have the potential to be used to guide treatment decisions. However, many subtyping classification methods were developed using mRNA expression levels of hundreds to thousands of genes, making them impractical for clinical use. In this study, we assessed whether an immunohistochemical approach could be used for molecular subtyping of CRCs. We validated two previously published, independent sets of immunohistochemistry classifiers and modified the published methods to improve the accuracy of the scoring methods. In addition, we evaluated whether protein and genetic signatures identified originally in the mouse were linked to clinical outcomes of patients with CRC. We found that low DDAH1 or low GAL3ST2 protein levels in human CRCs correlate with poor patient outcomes. The results of this study have the potential to impact methods for determining the prognosis and therapy selection for patients with CRC.

Joint Associations of Prevalent Radiographic Vertebral Fracture and Abdominal Aortic Calcification With Incident Hip, Major Osteoporotic, and Clinical Vertebral Fractures.

Prevalent vertebral fractures (PVFx) and abdominal aortic calcification (AAC) are both associated with incident fractures and can be ascertained on the same lateral spine images, but their joint association with incident fractures is unclear. Our objective was to estimate the individual and joint associations of PVFx and AAC with incident major osteoporotic, hip, and clinical vertebral fractures in 5365 older men enrolled in the Osteoporotic Fractures in Men (MrOS) Study, using Cox proportional hazards and Fine and Gray subdistribution hazards models to account for competing mortality. PVFx (Genant SQ grade 2 or 3) and 24-point AAC score were ascertained on baseline lateral spine radiographs. Self-reports of incident fractures were solicited every 4 months and confirmed by review of clinical radiographic reports. Compared with men without PVFx and AAC-24 score 0 or 1, the subdistribution hazard ratio (SHR) for incident major osteoporotic fracture was 1.38 (95% confidence interval [CI] 1.13-1.69) among men with AAC-24 score ≥2 alone, 1.71 (95% CI 1.37-2.14) for men with PVFx alone, and 2.35 (95% CI 1.75-3.16) for men with both risk factors, after accounting for conventional risk factors and competing mortality. Wald statistics showed improved prediction model performance by including both risk factors compared with including only AAC (chi-square = 17.3, p < .001) or including only PVFx (chi-square = 8.5, p = .036). Older men with both PVFx and a high level of AAC are at higher risk of incident major osteoporotic fracture than men with either risk factor alone. Assessing prevalent radiographic vertebral fracture and AAC on the same lateral spine images may improve prediction of older men who will have an incident major osteoporotic fracture, even after accounting for traditional fracture risk factors and competing mortality. © 2021 American Society for Bone and Mineral Research (ASBMR).

Height Loss in Old Age and Fracture Risk Among Men in Late Life: A Prospective Cohort Study.

To assess the association of height loss in old age with subsequent risk of hip and any clinical fracture in men late in life while accounting for the competing risk of mortality, we used data from 3491 community-dwelling men (mean age 79.2 years). Height loss between baseline and follow-up (mean 7.0 years between examinations) was categorized as <1 cm (referent group), ≥1 to <2 cm, ≥2 to <3 cm, and ≥3 cm. Men were contacted every 4 months after the follow-up examination to ask about fractures (confirmed by radiographic reports) and ascertain vital status (deaths verified by death certificates). Competing risk methods were used to estimate absolute probabilities of fracture outcomes by height loss category and calculate adjusted risks of fracture outcomes by height loss. During an average of 7.8 years, 158 (4.5%) men experienced a hip fracture and 1414 (40.5%) died before experiencing this event. The absolute 10-year probability of fracture events accounting for the competing risk of death increased with greater height loss. For example, the hip fracture probability was 2.7% (95% confidence interval [CI] 1.9-3.8%) among men with height loss <1 cm increasing to 11.6% (95% CI 8.0-16.0%) among men with height loss ≥3 cm. After adjustment for demographics, fall history, multimorbidity, baseline height, weight change, and femoral neck bone mineral density and considering competing mortality risk, men with height loss ≥3 cm versus <1 cm had a nearly twofold (subdistribution hazard ratio [HR] = 1.94, 95% CI 1.06-3.55) higher risk of hip fracture and a 1.4-fold (subdistribution HR = 1.42, 95% CI 1.05-1.91) increased risk of any clinical fracture. Height loss ≥3 cm in men during old age was associated with higher subsequent risk of clinical fractures, especially hip fractures, even after accounting for the competing risk of death and traditional skeletal and non-skeletal risk factors. © 2021 American Society for Bone and Mineral Research (ASBMR).

Implications of Frailty among Men with Implantable Cardioverter Defibrillators.

OBJECTIVES: Frailty is associated with adverse outcomes, but little is known of the impact of frailty on patients with implantable cardioverter defibrillators (ICDs). This study sought to determine the prevalence of frailty, based on quantitative assessment, and assessed its potential impact on outcomes among community-dwelling men with ICDs. METHODS: A total of 124 ICD-treated men presenting for a routine device clinic appointment between May and October 2016 underwent frailty assessment consisting of three components: shrinking (weight loss ≥5% during the past year), weakness (inability to rise from a chair without using their arms), and self-reported poor energy level. Patients who had no components were considered robust, those with 1 component were intermediate stage, and those with ≥2 components were deemed frail. RESULTS: Mean age was 70.4 (±9.7) years. Of the 124 men, 31 (25%) were considered to be frail, 65 (52%) were intermediate, and 28 (23%) were robust. Frail men were older and were more likely to have symptomatic heart failure, chronic kidney disease, and hypertension (P < 0.05 for all) compared with nonfrail men. During a follow-up of 16 months, frail men were significantly more likely to die compared with nonfrail men (29% vs 5.4%, P < 0.0003). The incidence of appropriate ICD shocks (16.1% vs 6.5%) or hospitalizations (38.7% vs 23.7%) tended to be higher among frail versus nonfrail patients, but neither reached statistical significance (P = 0.10). CONCLUSIONS: Almost one-fourth of men with ICD are frail. Almost one-third of frail ICD patients died within 16 months. It may be useful to assess frailty in patients with ICD.

Frailty Phenotype and Healthcare Costs and Utilization in Older Men.

OBJECTIVES: To determine the association of the frailty phenotype with subsequent healthcare costs and utilization. DESIGN: Prospective cohort study (Osteoporotic Fracture in Men [MrOS]). SETTING: Six US sites. PARTICIPANTS: A total of 1,514 community-dwelling men (mean age = 79.3 years) participating in the MrOS Year 7 (Y7) examination linked with their Medicare claims data. MEASUREMENTS: At Y7, the frailty phenotype was operationalized using five components and categorized as robust, pre-frail, or frail. Multimorbidity and a frailty indicator (approximating the deficit accumulation index) were derived from claims data. Functional limitations were assessed by asking about difficulty performing instrumental activities of daily living. Total direct healthcare costs and utilization were ascertained during 36 months following Y7. RESULTS: Mean of total annualized costs (2018 dollars) was $5,707 (standard deviation [SD] = 8,800) among robust, $8,964 (SD = 18,156) among pre-frail, and $20,027 (SD = 27,419) among frail men. Compared with robust men, frail men (cost ratio [CR] = 2.35; 95% confidence interval [CI] = 1.88-2.93) and pre-frail men (CR = 1.28; 95% CI = 1.11-1.48) incurred greater total costs after adjustment for demographics, multimorbidity, and cognitive function. Associations of phenotypic pre-frailty and frailty with higher total costs were somewhat attenuated but persisted after further consideration of functional limitations and a claims-based frailty indicator. Each individual frailty component was also associated with higher total costs. Frail vs robust men had higher odds of hospitalization (odds ratio [OR] = 2.62; 95% CI = 1.75-3.91) and skilled nursing facility (SNF) stay (OR = 3.36; 95% CI = 1.83-6.20). A smaller but significant effect of the pre-frail category on SNF stay was present. CONCLUSION: Phenotypic pre-frailty and frailty were associated with higher subsequent total healthcare costs in older community-dwelling men after accounting for a claims-based frailty indicator, functional limitations, multimorbidity, cognitive impairment, and demographics. Assessment of the frailty phenotype or individual components such as slowness may improve identification of older community-dwelling adults at risk for costly extensive care.

Self-reported poor sleep on multiple dimensions is associated with higher total health care costs in older men.

STUDY OBJECTIVES: To estimate the association of self-reported poor sleep in multiple dimensions with health care costs in older men. METHODS: Participants were 1,413 men (mean [SD] age 76.5 [5.7] years) enrolled in both the Outcomes of Sleep Disorders in Older Men (MrOS Sleep) study and Medicare Fee-for-Service. Poor sleep was characterized at the baseline MrOS Sleep visit on five dimensions (satisfaction, daytime sleepiness, timing, latency, and duration). Health care costs and utilization were ascertained over 3 years of follow-up using Medicare Claims. RESULTS: Median (interquartile range [IQR]) annualized total health care costs (2018 US dollars) rose from $3,616 (IQR 1,523-7,875) for those with no impaired sleep dimensions to $4,416 (IQR 1,854-11,343) for men with two impaired sleep dimensions and $5,819 (IQR 1,936-15,569) for those with at least three impaired sleep dimensions. After multivariable adjustment, the ratio of total health care costs (CR) was significantly higher for men with two (1.24, 95% confidence interval [CI] 1.03- to 1.48) and men with at least three impaired sleep dimensions (1.78, 95% CI 1.42 to 2.23) vs. those with no impaired sleep dimensions. After excluding 101 men who died during the 3-year follow-up period, these associations were attenuated and not significant (CR 1.22, 95% CI 0.98 to 1.53 for men ≥3 impaired sleep dimensions vs. none). CONCLUSIONS: Self-reported poor sleep on multiple dimensions is associated with higher subsequent total health care costs in older men, but this may be due to higher mortality and increased health care costs toward the end of life among those with poor sleep health.

Radical Prostatectomy or Observation for Clinically Localized Prostate Cancer: Extended Follow-up of the Prostate Cancer Intervention Versus Observation Trial (PIVOT).

BACKGROUND: Very long-term mortality in men with early prostate cancer treated with surgery versus observation is uncertain. OBJECTIVE: To determine long-term effects of surgery versus observation on all-cause mortality for men with early prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: This study evaluated long-term follow-up of a randomized trial conducted at the US Department of Veterans Affairs and National Cancer Institute sites. The participants were men (n=731) ≤75yr of age with localized prostate cancer, prostate-specific antigen (PSA) <50ng/ml, life expectancy ≥10yr, and medically fit for surgery. INTERVENTION: Radical prostatectomy versus observation. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: All-cause mortality was assessed in the entire cohort and patient and tumor subgroups. Intention-to-treat analysis was conducted using Kaplan-Meier methods with log-rank tests and Cox proportional hazard models; cumulative mortality incidence, between-group differences, and relative risks were also assessed at predefined time periods. RESULTS AND LIMITATIONS: During 22.1yr (median follow-up for survivors=18.6yr; interquartile range: 16.6-20.0), 515 men died; 246 of 346 men (68%) were assigned to surgery versus 269 of 367 (73%) assigned to observation (hazard ratio 0.84 [95% confidence interval {CI}: 0.70-1.00]; p= 0.044 [absolute risk reduction = 5.7 percentage points, 95% CI: -0.89 to 12%]; relative risk: 0.92 [95% CI: 0.84-1.01]). The restricted mean survival in the surgical group was 13.6 yr (95% CI: 12.9-14.3) versus 12.6 yr (95% CI: 11.8-13.3) in the observation group; a mean of 1 life-year was gained with surgery. Results did not significantly vary by patient or tumor characteristics, although differences were larger favoring surgery among men aged <65 yr, of white race, and having better health status, fewer comorbidities, ≥34% positive prostate biopsy cores, and intermediate-risk disease. Results were not adjusted for multiple comparisons, and we could not assess outcomes other than all-cause mortality. CONCLUSIONS: Surgery was associated with small very long-term reductions in all-cause mortality and increases in years of life gained. Absolute effects did not vary markedly by patient characteristics. Absolute effects and mean survival were much smaller in men with low-risk disease, but were greater in men with intermediate-risk disease although not in men with high-risk disease. PATIENT SUMMARY: In this randomized study, we evaluated death from any cause in men with early prostate cancer treated with either surgery or observation. Overall, surgery may provide small very long-term reductions in death from any cause and increases in years of life gained. Absolute effects were much smaller in men with low-risk disease, but were greater in men with intermediate-risk disease although not in men with high-risk disease. Strategies are needed to identify men needing and benefitting from surgery while reducing ineffective treatment and overtreatment.

Abdominal aortic calcification (AAC) and ankle-brachial index (ABI) predict health care costs and utilization in older men, independent of prevalent clinical cardiovascular disease and each other.

BACKGROUND AND AIMS: Abdominal aortic calcification (AAC) and low ankle-brachial index (ABI) are markers of multisite atherosclerosis. We sought to estimate their associations in older men with health care costs and utilization adjusted for each other, and after accounting for CVD risk factors and prevalent CVD diagnoses. METHODS: This was an observational cohort study of 2393 community-dwelling men (mean age 73.6 years) enrolled in the Osteoporotic Fractures in Men (MrOS) study and U.S. Medicare Fee for Service (FFS). AAC was scored on baseline lateral lumbar spine X-rays using a 24-point scale. ABI was measured as the lowest ratio of arm to right or left ankle blood pressure. Health care costs, hospital stays, and SNF stays were identified from Medicare FFS claims over 36 months following the baseline visit. RESULTS: Men with AAC score ≥9 (n = 519 [21.7% of analytic cohort]) had higher annualized total health care costs of $1473 (95% C.I. 293, 2654, 2017 U S. dollars) compared to those with AAC score 0-1, after multivariable adjustment. Men with ABI <0.90 (n = 154 [6.4% of analytic cohort]) had higher annualized total health care costs of $2705 (95% CI 634, 4776) compared to men with normal ABI (≥0.9 and < 1.4), after multivariable adjustment. CONCLUSIONS: High levels of AAC and low ABI in older men are associated with higher subsequent health care costs, after accounting for clinical CVD risk factors, prevalent CVD diagnoses, and each other. Further investigations of whether preventing progression of peripheral vascular disease and calcification reduces subsequent health care costs are warranted.

Multidimensional sleep health and subsequent health-care costs and utilization in older women.

STUDY OBJECTIVES: Determine the association of poor multidimensional sleep health with health-care costs and utilization. METHODS: We linked 1,459 community-dwelling women (mean age 83.6 years) participating in the Study of Osteoporotic Fractures Year 16 visit (2002-2004) with their Medicare claims. Five dimensions of sleep health (satisfaction, daytime sleepiness, timing, latency, and duration) were assessed by self-report. The number of impaired dimensions was expressed as a score (range 0-5). Total direct health-care costs and utilization were ascertained during the subsequent 36 months. RESULTS: Mean (SD) total health-care costs/year (2017 dollars) increased in a graded manner across the sleep health score ranging from $10,745 ($15,795) among women with no impairment to up to $15,332 ($22,810) in women with impairment in three to five dimensions (p = 0.01). After adjustment for age, race, and enrollment site, women with impairment in three to five dimensions vs. no impairment had greater mean total costs (cost ratio [CR] 1.34 [95% CI = 1.13 to 1.60]) and appeared to be at higher risk of hospitalization (odds ratio (OR) 1.31 [95% CI = 0.96 to 1.81]). After further accounting for number of medical conditions, functional limitations, and depressive symptoms, impairment in three to five sleep health dimensions was not associated with total costs (CR 1.02 [95% CI = 0.86 to 1.22]) or hospitalization (OR 0.91 [95% CI = 0.65 to 1.28]). Poor multidimensional sleep health was not related to outpatient costs or risk of skilled nursing facility stay. CONCLUSIONS: Older women with poor sleep health have higher subsequent total health-care costs largely attributable to their greater burden of medical conditions, functional limitations, and depressive symptoms.

Association of sleep-disordered breathing with total healthcare costs and utilization in older men: the Outcomes of Sleep Disorders in Older Men (MrOS Sleep) study.

STUDY OBJECTIVES: To determine the associations of sleep-disordered breathing (SDB) with subsequent healthcare costs and utilization including inpatient and post-acute care facility stays among community-dwelling older men. METHODS: Participants were 1,316 men (mean age 76.1 [SD = 5.7] years) in the Outcomes of Sleep Disorders in Older Men (MrOS sleep) study (from December 2003 to March 2005), who were enrolled in a Medicare Fee-For-Service plan. Primary SDB measures including apnea hypopnea index (AHI) and oxygen desaturation index (ODI) were collected using in-home level 2 polysomnography. Incident healthcare costs and utilization were determined from claims data in the subsequent 3-year period post-MrOS sleep visit. RESULTS: Five hundred and twenty-nine (40.2%) men had at least one hospitalization in the 3-year period. Compared with those without sleep apnea (AHI < 5/hour), men with moderate to severe sleep apnea (AHI ≥ 15/hour) had a higher odds of all-cause hospitalization (odds ratio [OR] adjusted for age and site 1.43, 95% confidence interval [CI]: 1.07-1.90). This association was slightly attenuated after further adjustment for traditional prognostic factors including education, body mass index, comorbid medical conditions, and health status (OR = 1.36; 95% CI: 1.01-1.83). Similar associations were observed for ODI. However, measures of SDB were not related to subsequent healthcare costs (total or outpatient) or odds of post-acute skilled nursing facility stay. CONCLUSIONS: Older men with SDB have an increased risk of hospitalization, not entirely explained by the greater prevalence of comorbid conditions, but not higher subsequent total healthcare costs. These findings indicate a need to evaluate the impact of SDB treatment on subsequent healthcare utilization.

Depressive Symptoms and Total Healthcare Costs: Roles of Functional Limitations and Multimorbidity.

OBJECTIVES: Depressive symptoms can be both a cause and a consequence of functional limitations and medical conditions. Our objectives were to determine the association of depressive symptoms with subsequent total healthcare costs in older women after accounting for functional limitations and multimorbidity. DESIGN: Prospective cohort study (Study of Osteoporotic Fractures [SOF]). SETTING: Four US sites. PARTICIPANTS: A total of 2508 community-dwelling women (mean age = 79.4 years) participating in the SOF year 10 (Y10) examination linked with their Medicare claims data. MEASUREMENTS: At Y10, depressive symptoms were measured using the 15-item Geriatric Depression Scale (GDS) and functional limitations were assessed by number (range = 0-5) of impairments in performing instrumental activities of daily living. Multimorbidity was ascertained by the Elixhauser method using claims data for the 12 months preceding the Y10 examination. Total direct healthcare costs, outpatient costs, acute hospital stays, and skilled nursing facility during the 12 months following the Y10 examination were ascertained from claims data. RESULTS: Annualized mean (SD) total healthcare costs were $4654 ($9075) in those with little or no depressive symptoms (GDS score = 0-1), $7871 ($14 534) in those with mild depressive symptoms (GDS score = 2-5), and $9010 ($15 578) in those with moderate to severe depressive symptoms (GDS score = 6 or more). After adjustment for age, site, self-reported functional limitations, and multimorbidity, the magnitudes of these incremental costs were partially attenuated (cost ratio = 1.34 [95% confidence interval {CI} = 1.14-1.59] for those with mild depressive symptoms, and cost ratio = 1.29 [95% CI = 0.99-1.69] for those with moderate to severe depressive symptoms vs women with little or no depressive symptoms). CONCLUSION: Depressive symptoms were associated with higher subsequent healthcare costs attributable, in part, to greater functional limitations and multimorbidity among those with symptoms. Importantly, even mild depressive symptoms were associated with higher healthcare costs. J Am Geriatr Soc 67:1596-1603, 2019.

Hospitalization-Associated Change in Gait Speed and Risk of Functional Limitations for Older Adults.

BACKGROUND: Hospitalization-associated functional decline is a common problem for older adults, but it is unclear how hospitalizations affect physical performance measures such as gait speed. We sought to determine hospitalization-associated change in gait speed and likelihood of new limitations in mobility and activities of daily living (ADLs). METHODS: We used longitudinal data over 5 years from the Health, Aging and Body Composition Study, a prospective cohort of black and white community-dwelling men and women, aged 70-79 years, who had no limitations in mobility (difficulty walking 1/4 mile or climbing 10 steps) or ADLs (transferring, bathing, dressing, and eating) at baseline. Gait speed, and new self-reported limitations in mobility and ADLs were assessed annually. Selected participants (n = 2,963) had no limitations at the beginning of each 1-year interval. Hospitalizations were self-reported every 6 months and verified with medical record data. Generalized estimating equations were used to examine hospitalization-associated change in gait speed and odds of new limitations over each 1-year interval. Fully adjusted models included demographics, hospitalization within the past year, health conditions, symptoms, body mass index, and health-related behaviors. RESULTS: In fully adjusted models, any hospitalization was associated with decrease in gait speed (-0.04 m/s; 95% confidence interval [CI]: -0.05 to -0.03) and higher odds of new limitations in mobility or ADLs (odds ratio = 1.97, 95% CI: 1.70-2.28), and separately with increased odds of new mobility limitation (odds ratio = 2.22, 95% CI: 1.90-2.60) and new ADL limitations (odds ratio = 1.84, 95% CI: 1.53-2.21). Multiple hospitalizations within a year were associated with gait speed decline (-0.06 m/s; 95% CI: -0.08 to -0.04) and greater odds of new limitations in mobility or ADLs (odds ratio = 2.96, 95% CI: 2.23-3.95). CONCLUSIONS: Functionally independent older adults experienced hospitalization-associated declines in gait speed and new limitations in mobility and ADLs.

The Association Between Objectively Measured Physical Activity and Subsequent Health Care Utilization in Older Men.

BACKGROUND: To examine the associations between objective physical activity measures and subsequent health care utilization. METHODS: We studied 1,283 men (mean age 79.1 years, SD 5.3) participating in the Osteoporotic Fractures in Men Study. Participants wore a SenseWear® Pro Armband monitor for 1 week. Data was summarized as daily (i) step counts, (ii) total energy expenditure, (iii) active energy expenditure, and (iv) activity time (sedentary, ≥ light, ≥ moderate). The outcome measures of 1-year hospitalizations/duration of stay from Medicare data were analyzed with a two-part hurdle model. Covariates included age, clinical center, body mass index, marital status, depressive symptoms, medical conditions, cognitive function, and prior hospitalization. RESULTS: Each 1 SD = 3,092 step increase in daily step count was associated with a 34% (95% confidence interval [CI]: 19%-46%) lower odds of hospitalization in base model (age and center) and 21% (95% CI: 4%-35%) lower odds of hospitalization in fully adjusted models. Similar but smaller associations held for other physical activity measures, but these associations were not significant in fully adjusted models. Among those hospitalized, higher step count was associated with shorter total duration of acute/postacute care stays in the base model only. There was a fourfold significant difference (from model-based estimates) in predicted care days comparing those with 2,000 versus 10,000 daily steps in the base model, but only a twofold difference (not significant) in the full model. CONCLUSION: Daily step count is an easily determined measure of physical activity that may be useful in assessment of future health care burden in older men.

Central Obesity and Visceral Adipose Tissue Are Not Associated With Incident Atherosclerotic Cardiovascular Disease Events in Older Men.

Background Visceral adipose tissue ( VAT ) and other measures of central obesity predict incident atherosclerotic cardiovascular disease ( ASCVD ) events in middle-aged individuals, but these associations are less certain in older individuals age 70 years and older. Our objective was to estimate the associations of VAT and the android-gynoid fat mass ratio, another measure of central obesity, with incident ASCVD events among a large cohort of older men. Methods and Results Two thousand eight hundred ninety-nine men (mean [ SD ] age 76.3 [5.5] years) enrolled in the Outcomes of Sleep Disorders in Older Men study had rigorous adjudication of incident ASCVD events (myocardial infarction, coronary heart disease death, or fatal or nonfatal stroke). We used proportional hazards models to estimate the hazard ratios for incident ASCVD per SD increase of VAT or android-gynoid fat mass ratio (measured at baseline with dual-energy absorptiometry), adjusted for age, race, education, systolic blood pressure, smoking status, oxidized low-density lipoprotein level, treatment for hypertension, statin use, aspirin use, presence of diabetes mellitus, and study enrollment site. Over a mean ( SD ) follow-up period of 7.9 (3.4) years, 424 men (14.6%) had an incident ASCVD event. Neither VAT nor android-gynoid fat mass ratio were associated with incident ASCVD events, either unadjusted or after multivariable-adjustment (hazard ratios [95% confidence interval ] per SD increase 1.02 [0.92-1.13] and 1.05 [0.95-1.17], respectively). Conclusions Central adipose tissue, as measured by VAT or android-gynoid fat mass ratio, was not associated with incident ASCVD events in this study of older men.

Frailty as a Risk Factor for Cardiovascular Versus Noncardiovascular Mortality in Older Men: Results From the MrOS Sleep (Outcomes of Sleep Disorders in Older Men) Study.

BACKGROUND: Frailty is associated with greater mortality; however, whether frail patients primarily die of cardiovascular disease (CVD) or non-CVD causes is unknown. METHODS AND RESULTS: We assessed the cause of death in relation to frailty status, measured at baseline, among 3135 community-dwelling older men in the MrOS Sleep (Outcomes of Sleep Disorders in Older Men) study. Absolute probability and risk of CVD mortality associated with frailty status were estimated with traditional methods that used censoring and newer methods that considered non-CVD mortality as a competing risk. Of the 3135 men (mean age: 76.4±5.6 years), 475 (15.2%) were frail. During an average follow-up of 9.2 years, 1275 (40.7%) men died, including 445 (34.9%) from CVD and 828 (64.9%) from non-CVD causes (2 deaths unadjudicated). Both CVD and non-CVD mortality risk increased with frailty. Cumulative absolute probability of CVD death at 10 years among frail men was 23.8% (20.2-27.6%) using the competing risk method versus 32.5% (27.3-37.8%) using the traditional Kaplan-Meier method (41.5% [95% confidence interval, 36.9-45.9%] and 48.6% [95% confidence interval, 43.6-53.4%], respectively, for non-CVD mortality). The multivariable-adjusted risk of CVD death among frail versus robust men was 1.38 (95% confidence interval, 0.99-1.92) using the competing risk method versus 1.84 (95% confidence interval, 1.35-2.51) using the traditional Cox proportional hazards method. CONCLUSIONS: Among community-dwelling older men, ≈35% of the deaths were due to CVD. Frail men were at increased risk of CVD death, but ignoring the competing risk of non-CVD mortality overestimated their long-term probability and relative risk of CVD death.

Impact of Competing Risk of Mortality on Association of Cognitive Impairment With Risk of Hip Fracture in Older Women.

Previous studies examining the association of cognitive impairment and dementia with fracture outcomes in older adults have usually used standard approaches that did not take into account the competing risk of mortality. However, ignoring mortality may not provide accurate estimates of risk of fracture because dementia in older adults strongly predicts death, making mortality a competing risk. A total of 1491 women (mean age 87.6 years) participating in the prospective Study of Osteoporotic Fractures (SOF) Year 20 exam were cognitively assessed and followed to ascertain vital status (deaths verified by death certificates) and hip fractures (confirmed by radiographic reports). Cognitive status was categorized as normal, mild cognitive impairment (MCI), or dementia, based on a standardized evaluation. Absolute probability of hip fracture by category of cognitive function was estimated using traditional Kaplan-Meier method and cumulative incidence function accounting for competing mortality risk. Risk of hip fracture by cognitive function category was determined using conventional Cox proportional hazards regression and subdistribution hazards models with death as a competing risk. During an average follow-up of 5.6 years, 139 (9.3%) women experienced a hip fracture and 990 (66.4%) died before experiencing this outcome. Among women with dementia, the risk of hip fracture was 11.7% (95% confidence interval [CI] 7.3-17.2) at 5 years and 18.6% (95% CI 9.1-30.9) at 10 years using traditional survival analysis versus 7.9% (95% CI 5.1-11.6) at 5 years and 8.8% (95% CI 5.8-12.8) at 9.8 years using a competing risk approach. Results were similar for women with MCI. Women with MCI and dementia have a higher risk of hip fractures than women with normal cognition. However, not taking into account the competing risk of mortality significantly overestimates the risk of hip fracture in women in the ninth and tenth decades of life with cognitive impairment. © 2018 American Society for Bone and Mineral Research.

Association of High-resolution Peripheral Quantitative Computed Tomography (HR-pQCT) bone microarchitectural parameters with previous clinical fracture in older men: The Osteoporotic Fractures in Men (MrOS) study.

High-resolution peripheral quantitative computed tomography (HR-pQCT) assesses both volumetric bone mineral density (vBMD) and trabecular and cortical microarchitecture. However, studies of the association of HR-pQCT parameters with fracture history have been small, predominantly limited to postmenopausal women, often performed limited adjustment for potential confounders including for BMD, and infrequently assessed strength or failure measures. We used data from the Osteoporotic Fractures in Men (MrOS) study, a prospective cohort study of community-dwelling men aged ≥65 years, to evaluate the association of distal radius, proximal (diaphyseal) tibia and distal tibia HR-pQCT parameters measured at the Year 14 (Y14) study visit with prior clinical fracture. The primary HR-pQCT exposure variables were finite element analysis estimated failure loads (EFL) for each skeletal site; secondary exposure variables were total vBMD, total bone area, trabecular vBMD, trabecular bone area, trabecular thickness, trabecular number, cortical vBMD, cortical bone area, cortical thickness, and cortical porosity. Clinical fractures were ascertained from questionnaires administered every 4 months between MrOS study baseline and the Y14 visit and centrally adjudicated by masked review of radiographic reports. We used multivariate-adjusted logistic regression to estimate the odds of prior clinical fracture per 1 SD decrement for each Y14 HR-pQCT parameter. Three hundred forty-four (19.2%) of the 1794 men with available HR-pQCT measures had a confirmed clinical fracture between baseline and Y14. After multivariable adjustment, including for total hip areal BMD, decreased HR-pQCT finite element analysis EFL for each site was associated with significantly greater odds of prior confirmed clinical fracture and major osteoporotic fracture. Among other HR-pQCT parameters, decreased cortical area appeared to have the strongest independent association with prior clinical fracture. Future studies should explore associations of HR-pQCT parameters with specific fracture types and risk of incident fractures and the impact of age and sex on these relationships.

Associations of recent weight loss with health care costs and utilization among older women.

The association of weight loss with health care costs among older women is uncertain. Our study aim was to examine the association of objectively measured weight change with subsequent total health care (THC) costs and other health care utilization among older women. Our study population included 2,083 women (mean age 80.2 years) enrolled in the Study of Osteoporotic Fractures and U.S. Medicare Fee for Service. Weight loss and gain were defined, respectively, as ≥5% decrease and ≥5% increase in body weight, and weight maintenance as <5% change in body weight over a period of 4.5 years. THC costs, outpatient costs, hospitalizations, and skilled nursing facility [SNF] utilization were estimated from Medicare claims for 1 year after the period during which weight change was measured. The associations of weight change with THC and outpatient costs were estimated using generalized linear models with gamma variance and log link functions, and with hospitalizations and SNF utilization using logistic models. Adjusted for age and current body mass index (BMI), weight loss compared with weight maintenance was associated with a 35% increase in THC costs ($2148 [95% CI, 745 to 3552], 2014 U.S. dollars), a 15% increase in outpatient costs ($329 [95% C.I. -1 to 660]), and odds ratios of 1.42 (95% CI, 1.14 to 1.76) for ≥1 hospital stay and 1.45 (95% CI, 1.03 to 2.03) for ≥1 SNF stay. These associations did not vary by BMI category. After additional adjustment for multi-morbidity and functional status, associations of weight loss with all four outcomes were no longer significant. In conclusion, ≥5% weight loss among older women is not associated with increased THC and outpatient costs, hospitalization, and SNF utilization, irrespective of BMI category after accounting for multi-morbidity and impaired functional status that accompany weight loss.