Frail Men Research Articles

Identifying the Biomarker Profile of Pre-Frail and Frail People: A Cross-Sectional Analysis from UK Biobank.

This study aimed to compare the biomarker profile of pre-frail and frail adults in the UK Biobank cohort by sex. In total, 202,537 participants (67.8% women, aged 37 to 73 years) were included in this cross-sectional analysis. Further, 31 biomarkers were investigated in this study. Frailty was defined using a modified version of the Frailty Phenotype. Multiple linear regression analyses were performed to explore the biomarker profile of pre-frail and frail individuals categorized by sex. Lower concentrations of apoA1, total, LDL, and HDL cholesterol, albumin, eGFRcys, vitamin D, total bilirubin, apoB, and testosterone (differences ranged from -0.30 to -0.02 per 1-SD change), as well as higher concentrations of triglycerides, GGT, cystatin C, CRP, ALP, and phosphate (differences ranged from 0.01 to 0.53 per 1-SD change), were identified both in pre-frail and frail men and women. However, some of the associations differed by sex. For instance, higher rheumatoid factor and urate concentrations were identified in pre-frail and frail women, while lower calcium, total protein, and IGF-1 concentrations were identified in pre-frail women and frail women and men. When the analyses were further adjusted for CRP, similar results were found. Several biomarkers were linked to pre-frailty and frailty. Nonetheless, some of the associations differed by sex. Our findings contribute to a broader understanding of the pathophysiology of frailty as currently defined.

The role of frailty in modifying physical function and quality of life over time in older men with metastatic castration-resistant prostate cancer

IntroductionAs treatment options for metastatic castration-resistant prostate cancer (mCRPC) expand and its patient population ages, consideration of frailty is increasingly relevant. Using a novel frailty index (FI) and two common frailty screening tools, we examined quality of life (QoL) and physical function (PF) in frail versus non-frail men receiving treatment for mCRPC. Materials and MethodsMen aged 65+ starting docetaxel chemotherapy, abiraterone, or enzalutamide for mCRPC were enrolled in a multicenter prospective cohort study. QoL, fatigue, pain, and mood were measured with the Functional Assessment of Cancer Therapy-General scale, the Edmonton Symptom Assessment System tiredness and pain subscales, and the Patient Health Questionnaire-9. PF was evaluated with grip strength, four-meter gait speed, five times Sit-to-Stand Test, and instrumental activities of daily living. Frailty was determined using the Vulnerable Elders Survey (VES-13), the Geriatric 8 (G8), and an FI constructed from 36 variables spanning laboratory abnormalities, geriatric syndromes, functional status, social support, as well as emotional, cognitive, and physical deficits. We categorized patients as non-frail (FI ≤ 0.2, VES < 3, G8 > 14), pre-frail (FI > 0.20, ≤0.35), or frail (FI > 0.35, VES ≥ 3, G8 ≤ 14); assessed correlation between the three tools; and performed linear mixed-effects regression analyses to examine longitudinal differences in outcomes (0, 3, 6 months) by frailty status. A sensitivity analysis with worst-case imputation was conducted to explore attrition. ResultsWe enrolled 175 men (mean age 74.9 years) starting docetaxel (n = 71), abiraterone (n = 37), or enzalutamide (n = 67). Our FI demonstrated moderate correlation with the VES-13 (r = 0.607, p < 0.001) and the G8 (r = −0.520, p < 0.001). Baseline FI score was associated with worse QoL (p < 0.001), fatigue (p < 0.001), pain (p < 0.001), mood (p < 0.001), PF (p < 0.001), and higher attrition (p < 0.01). Over time, most outcomes remained stable, although pain improved, on average, regardless of frailty status (p = 0.007), while fatigue (p = 0.045) and mood (p = 0.015) improved in frail patients alone. DiscussionAmong older men receiving care for mCRPC, frailty may be associated with worse baseline QoL and PF, but over time, frail patients may experience largely similar trends in QoL and PF as their non-frail counterparts. Further study with larger sample size and longer follow-up may help elucidate how best to incorporate frailty into treatment decision-making for mCRPC.

NOVEL INTERVENTIONS AND TARGETS FOR THE PREVENTION OF DEMENTIA AND FRAILTY: 2021 EDITOR’S CHOICE ARTICLES FROM JGMS

Abstract This symposium will present four 2021 “Editor’s Choice” articles from the Journal of Gerontology Medical Sciences that focus on novel interventions and targets for the prevention of dementia and frailty. Jeffrey Scherrer and colleagues, in their article “Lower Risk for Dementia Following Adult Tetanus, Diphtheria, and Pertussis (Tdap) Vaccination,” examine the links between adult vaccinations and decreased dementia risk. Katharine Brewster, Justin Golub (presenter), and colleagues, in “Age-Related Hearing Loss, Late-Life Depression, and Risk for Incident Dementia in Older Adults,” investigate hearing loss and depression as independent risk factors for eventual conversion to dementia. By understanding these potentially reversible mechanisms for dementia, targets for early interventions could be identified. “Association Between Long-Term Aspirin Use and Frailty in Men: The Physicians’ Health Study,” written by Ariela Orkaby and colleagues, examines the association between long-term aspirin use and frailty, furthering our understanding of the benefits of anti-inflammatory medications even in older adults. Kristen George and coauthors, in their article, “Impact of Cardiovascular Risk Factors in Adolescence, Young Adulthood, and Midlife on Late-Life Cognition: Study of Healthy Aging in African Americans,” examine how cardiovascular risk factors early in life may affect late life cognition in Black Americans. Beverly Gwen Windham, the discussant, will highlight commonalities and lessons learned from these studies.

Are satisfaction and performance of meaningful activities associated with frailty in older adults?

• Investigated the association between meaningful activities and frailty based on sex. • Activity satisfaction was associated with frailty in men. • Activity satisfaction and performance were associated with frailty in women. • Prevention of frailty may play a positive role in meaningful activities.

Relationship between Testosterone and Sarcopenia in Older-Adult Men: A Narrative Review.

Age-related decline in testosterone is known to be associated with various clinical symptoms among older men and it is possible that the accompanying decline in muscle mass and strength might lead to a decline in motor and physical functions. Sarcopenia is an important pathophysiological factor associated with frailty in older adults and is diagnosed in older adults as a decrease in muscle strength, muscle mass, and walking speed, which can lead to a significant decline in the quality of life and shortened healthy life expectancy. Testosterone directly interacts with the androgen receptor expressed in myonuclei and satellite cells and is also indirectly associated with muscle metabolism through various cytokines and molecules. Currently, significant correlations between testosterone and frailty in men have been confirmed by numerous cross-sectional studies. Many randomized control studies have also supported the beneficial effect of testosterone replacement therapy (TRT) on muscle volume and strength among men with low to normal testosterone levels. In the world’s aging society, TRT can be a tool for preventing the onset of sarcopenia in older-adult men. This narrative review aims to show the relationship between the decline in testosterone with age, sarcopenia, and frailty, as well as the effects of testosterone replacement therapy on muscle mass and strength.

Racial, Ethnic, and Socioeconomic Differences in a Deficit Accumulation Frailty Index in the Multiethnic Cohort Study.

Frailty status has been sparsely studied in some groups including Native Hawaiians and Asian Americans. We developed a questionnaire-based deficit accumulation frailty index (FI) in the Multiethnic Cohort (MEC) and examined frailty status (robust, FI 0 to <0.2, prefrail, FI 0.2 to <0.35, and frail FI ≥ 0.35) among 29026 men and 40756 women. After adjustment for age, demographic, lifestyle factors, and chronic conditions, relative to White men, odds of being frail was significantly higher (34%-54%) among African American, Native Hawaiian, and other Asian American men, whereas odds was significantly lower (36%) in Japanese American men and did not differ in Latino men. However, among men who had high school or less, none of the groups displayed significantly higher odds of prefrail or frail compared with White men. Relative to White women, odds of being frail were significantly higher (14%-33%) in African American and Latino women, did not differ for other Asian American women and lower (14%-36%) in Native Hawaiian and Japanese American women. These racial and ethnic differences in women were observed irrespective of education. Risk of all-cause mortality was higher in prefrail and frail men than robust men (adjusted hazard ratio [HR] = 1.69, 1.59-1.81; HR = 3.27, 3.03-3.53); results were similar in women. All-cause mortality was significantly positively associated with frailty status and frailty score across all sex, race, and ethnic groups. Frailty status differed significantly by race and ethnicity and was consistently associated with all-cause mortality. The FI may be a useful tool for aging studies in this multiethnic population.

Sex differences in frailty of geriatric outpatients with type 2 diabetes mellitus: a multicentre cross-sectional study

Frailty and type 2 diabetes mellitus (T2DM) can occur concurrently and are increasingly prevalent in older populations. There is a marked variability in frailty progression between men and women. This study aimed to investigate sex differences in the prevalence and factors associated with frailty in older outpatients with T2DM. This multicentre cross-sectional study included 638 outpatients (aged ≥ 60 years; median age 71 years [interquartile range, 66–77]; male, 55.5%) and was conducted from January 2019 to July 2020. Frailty was assessed using the Fried frailty phenotype. Factors associated with frailty were assessed using a logistic regression analysis. The overall frailty prevalence was 28.2% (men, 26.8%; women, 29.9%; P = 0.388). In the adjusted model, the factors associated with greater odds of being frail were older age (odds ratio [OR], 1.08; 95% confidence interval [CI], 1.05–1.11; P < 0.001) and body mass index (BMI) less than 20 kg/m2 (OR, 1.96; 95% CI, 1.16–3.32; P = 0.012). Higher education (OR, 0.64; 95% CI, 0.42–0.98; P = 0.041) and productive work (OR, 0.11; 95% CI, 0.03–0.36; P < 0.001) were protective factors against frailty. Frailty was associated with all four factors in women, but only with older age and productive work in men. Our study found that the prevalence of frailty in older outpatients with T2DM was 28.2%, though not significantly different between men and women. While older age and BMI less than 20 kg/m2 can increase the odds of frailty, and higher education and productive work can decrease the odds of frailty in women, only age and productive work were associated with frailty in men with T2DM.

Management of Biochemical Recurrence of Prostate Cancer After Curative Treatment: A Focus on Older Patients.

Following a treatment with curative intent, a biochemical recurrence may be diagnosed, often many years after the primary treatment. The consequences of this relapse on survival are very heterogeneous. The expected specific survival at relapse is above 50% at 10 years. Therefore, its management needs to be balanced with the individual life expectancy. The relapse needs to be categorized as either a low- or high-risk category. The latter has to be considered for salvage therapy, provided the individual life expectancy is long enough. It is evaluated through an initial geriatric assessment, starting with the G8 score as well as the mini-Cog. A comprehensive geriatric assessment might be needed based on the G8 score. Patients will then be categorized as either fit, vulnerable, or frail. If a local salvage therapy is considered, the relapse localization might be of interest in some situations. Available salvage therapies in senior adults have nothing special compared to salvage of younger men, except for aggressive local therapy, which might be less well tolerated. The key objective in managing a biochemical recurrence in senior adults is to find the right balance between under- and over-treatment in a shared decision process. In many frail and vulnerable men, a clinically oriented watchful waiting should be preferred, while fit men with an aggressive relapse and a significant life expectancy need an active therapy.

Candidate biomarkers of physical frailty in heart failure: an exploratory cross-sectional study.

Physical frailty is highly prevalent and predictive of worse outcomes in heart failure (HF). Candidate biomarker analysis may help in understanding the mechanisms underlying physical frailty in HF. We aimed to identify candidate biomarkers associated with physical frailty in HF using a multimarker strategy of distinct pathophysiological processes. We collected data and plasma samples from 113 adults with New York Heart Association Functional Class I-IV HF. Physical frailty was measured with the Frailty Phenotype Criteria. Plasma biomarkers included: N-terminal pro-B-type natriuretic peptide, norepinephrine, dihydroxyphenylglycol, soluble tumour necrosis factor alpha receptor-1, adiponectin, insulin, glucose, insulin-like growth factor-1 (IGF-1), and myostatin. Comparative statistics and multivariate linear regression were used to test group differences and associations. The average age was 63.5 ± 15.7 years, half were women (48%), and most had a non-ischaemic aetiology of HF (73%). Physical frailty was identified in 42% and associated with female sex, higher body mass index and percent body fat, more comorbidities, and HF with preserved ejection fraction. Adjusting for Seattle HF Model projected survival score, comorbidities, body composition, and sex, physical frailty was associated with significantly lower plasma adiponectin [β ± standard error (SE) -0.28 ± 0.14, P = 0.047], IGF-1 (β ± SE -0.21 ± 0.10, P = 0.032), and myostatin (β ± SE -0.22 ± 0.09, P = 0.011). In sex-stratified analyses, IGF-1 and myostatin were significantly associated with physical frailty in men but not women. We identified biomarkers involved in adipose tissue and skeletal muscle development, maintenance, and function that were associated with physical frailty in HF.

Associations between inflammation, coagulation, cardiac strain and injury, and subclinical vascular disease with frailty in older men: a cross-sectional study

BackgroundInflammation, coagulation activation, endothelial dysfunction and subclinical vascular disease are cross-sectionally associated with frailty. Cardiac-specific biomarkers are less-well characterised. We assessed associations between these and frailty, in men with, and without, cardiovascular disease (CVD).MethodsCross-sectional analysis of 1096 men without, and 303 with, CVD, aged 71–92, from the British Regional Heart Study. Multinominal logistic regression was performed to examine the associations between frailty status (robust/pre-frail/frail) and, separately, C-reactive protein (CRP), interleukin-6 (IL-6), tissue plasminogen activator (tPA), D-dimer, von Willebrand factor (vWF), high-sensitivity cardiac troponin-T (hs-cTnT), N-terminal pro B-type natriuretic peptide (NT-proBNP) (all natural log-transformed), and, in men without CVD, carotid intima-media thickness (CIMT), carotid-femoral pulse wave velocity (cfPWV), carotid distensibility coefficient (DC), and ankle-brachial pressure index (ABPI), adjusted for age, renal function, BMI, social class, smoking, polypharmacy, cognition, multimorbidity and systolic blood pressure. Explanatory variables with p < 0.05 were carried forward into mutually-adjusted analysis.ResultsIn men without CVD, higher CRP, IL-6, vWF, tPA, hs-cTnT, NT-proBNP, cfPWV, and lower DC were significantly associated with frailty; mutually-adjusted, log IL-6 (OR for frailty = 2.02, 95%CI 1.38–2.95), log hs-cTnT (OR = 1.95, 95%CI 1.24–3.05) and DC (OR = 0.92, 95%CI 0.86–0.99) retained associations. In men with CVD, higher CRP, IL-6, and hs-cTnT, but not vWF, tPA, NT-proBNP or D-dimer, were significantly associated with frailty; mutually-adjusted, log hs-cTnT (OR 3.82, 95%CI 1.84–7.95) retained a significant association.ConclusionsIn older men, biomarkers of myocardial injury are associated with frailty. Inflammation is associated with frailty in men without CVD. Carotid artery stiffness is associated with frailty in men without CVD, independently of these biomarkers.

Efficacy and safety of Androgen Deprivation Therapy (ADT) combined with modified docetaxel chemotherapy versus ADT combined with standard docetaxel chemotherapy in patients with metastatic castration-resistant prostate cancer: study protocol for a multicentre prospective randomized controlled trial

BackgroundAndrogen deprivation therapy (ADT) combined with docetaxel chemotherapy is the standard treatment for metastatic castration-resistant prostate cancer (mCRPC) patients. However, mCRPC patients are mainly frail elderly men, constantly accompanied by comorbidities and showing poor tolerance to standard docetaxel chemotherapy. Some exploratory studies administering modified chemotherapy regimens have reported noninferior oncologic outcomes with fewer adverse events, yet most are retrospective or small studies, and prospective randomized controlled trials have rarely been conducted. Therefore, we designed this modified docetaxel chemotherapy regimen in patients with mCRPC, aiming to evaluate its efficacy and safety compared with the standard docetaxel chemotherapy regimen.MethodsThis is an open-label, multi-institutional, prospective, randomized non-inferiority trial. A total of 128 patients with mCRPC will be randomized to receive ADT combined with modified docetaxel chemotherapy (experimental group, n=64) or ADT combined with standard docetaxel chemotherapy (control group, n=64). Patients in the experimental group will receive a modified regimen with docetaxel 40 mg/m2 on the 1st day and 35 mg/m2 on the 8th day, repeated every 21 days. The primary endpoint is progression-free survival at 2 years. Secondary endpoints include overall survival, prostate-specific antigen response rate, pain response rate, toxicity and quality of life.DiscussionThe expected benefit for the patient in the experimental arm is noninferior efficacy with decreased toxicity and improved quality of life compared with that in the control arm. To the best of our knowledge, this will be the first multicentre prospective randomized study to assess the efficacy and safety of modified docetaxel chemotherapy in patients with mCRPC in China. The results of this trial may provide benefit to mCRPC patients, especially those with poor performance.Trial registrationchictr.org.cn Identifier: ChiCTR2100046636 (May 24, 2021). Ongoing study.

Frailty and testosterone level in older adults: a systematic review and meta-analysis.

We conducted a systematic review to evaluate the relationship between total testosterone (TT), free testosterone (fT), or sex hormone-binding globulin (SHBG) and frailty in older adults. We systematically searched nine databases (e.g. MEDLINE, Embase, ACP Journal Club, and the Cochrane library et al.) for papers on frailty and androgen levels published up to October 10, 2021. We calculated the odds ratio (OR) for the relationship between testosterone level and frailty by performing meta-analysis. The search strategy yielded 311 hits in all databases combined. Eleven (seven cross-sectional studies and four cohort studies) met the inclusion criteria for meta-analysis. Among cross-sectional studies, meta-analysis revealed a significant association between TT and frailty in men (OR = 1.37 [95% CI 1.09, 1.72]) not women (OR = 1.06 [0.84, 1.34]). The fT was also significantly association with frailty in men (OR = 1.55 [1.06, 2.25] not women (OR = 1.35 [0.91, 2.01]). Cohort studies showed the same result in TT (OR = 1.09 [1.02, 1.18]) and fT (OR = 1.15 [1.02, 1.30]) for men. We did not find a significant association between SHBG and frailty. The findings of this systematic review and meta-analysis suggest that TT and fT were significantly associated with frailty in older men but not women.

DNA methylation is associated with muscle loss in community-dwelling older men -the Yakumo study- : a preliminary experimental study.

ABSTRACTFrailty is a state of reduced muscle strength and activity in older people. DNA methylation is associated with osteoporosis and muscle loss in murine and other animal studies, but there are no epidemiological studies in humans. This study aimed to assess the association of osteoporosis and muscle loss with DNA methylation in community-dwelling older people. This cross-sectional study was performed in a rural part of Japan. We analyzed 204 subjects (98 men and 106 women). In univariate analysis, the two groups were compared according to the presence or absence of osteoporosis and of muscle loss. Logistic regression analysis was performed to determine predictors of frailty in the muscle loss group. We used age, sex, body mass index, smoking history, drinking history, serum albumin and C-reactive protein levels, diabetes, hypertension, hyperlipidemia, heart disease history, and LINE-1 DNA methylation as the factors. Probability values < 0.05 were considered to be statistically significant. The levels of LINE-1 DNA methylation in leukocytes were associated with muscle loss in men over the age of 60. LINE-1 DNA methylation levels were not associated with bone mineral density in either the men or women over the age of 60. LINE-1 DNA methylation levels in leukocytes correlated significantly with the risk of frailty in men over the age of 60. Promoting an understanding of DNA methylation may lead to a better understanding of the pathophysiology of muscle loss.

Influence of Long-term Nonaspirin NSAID Use on Risk of Frailty in Men ≥60 Years: The Physicians' Health Study.

Inflammation is a central pathway leading to frailty but whether commonly used nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs) can prevent frailty is unknown. Prospective cohort study of male physicians ≥60 who participated in the Physicians' Health Study. Annual questionnaires collected data on NSAID use, lifestyle, and morbidity. Average annual NSAID use was categorized as 0 days/year, 1-12 days/year, 13-60 days/year, and >60 days/year. Frailty was assessed using a validated 33-item frailty index. Propensity score inverse probability of treatment weighting was used to address confounding by indication and logistic regression models estimated odds ratios (ORs) of prevalent frailty according to nonaspirin NSAID use. A total of 12 101 male physicians were included (mean age 70 ± 7 years, mean follow-up 11 years). Reported NSAID use was 0 days/year for 2 234, 1-12 days/year for 5 812, 13-60 days/year for 2 833, and >60 days/year for 1 222 participants. A total of 2 413 participants (20%) were frail. Higher self-reported NSAID use was associated with greater alcohol use, smoking, arthritis, hypertension, and heart disease, while less NSAID use was associated with coumadin use and prior bleeding. After propensity score adjustment, all characteristics were balanced. ORs (95% confidence intervals) of prevalent frailty were 0.90 (0.80-1.02), 1.02 (0.89-1.17), and 1.26 (1.07-1.49) for average NSAID use of 1-12 days/year, 13-60 days/year, and >60 days/year, compared to 0 days/year (p-trend < .001). Long-term use of NSAIDs at high frequency is associated with increased risk of frailty among older men. Additional study is needed to understand the role of anti-inflammatory medication in older adults and its implication for overall health.

Association of Frailty Index with Clinical BPH Progression and Serious Adverse Events: the MTOPS Trial

Lower urinary tract symptoms due to suspected benign prostatic hyperplasia (BPH) are increasingly treated with medications targeting obstruction among older men, but frailty may represent a novel risk factor for this condition. Our objective was to assess the associations between frailty and clinical BPH progression or serious adverse events (SAE) among 3047 men, age 50-89 years, enrolled in the Medical Therapy of Prostatic Symptoms Study, a placebo-controlled RCT of doxazosin, finasteride, or combination therapy on clinical BPH progression. We created a frailty index using 69 items collected at baseline and categorized men as fit (0-0.1), less fit (0.1-<0.25), or frail (0.25-1.0). The primary outcomes were time to 1) first composite event of clinical BPH progression, and 2) SAE requiring hospitalization. Cox proportional hazards models were adjusted for demographics, intervention, BPH surrogates, and comorbidities. At baseline, 28% men were fit, 58% were less fit, and 14% were frail. During follow-up (mean 4.5 years), the incidence rate of clinical BPH progression was 2.2/100p-y among fit, 3.0/100p-y among less fit (HR =1.28, 95% CI 0.98, 1.67), and 4.1/100p-y among frail men (HR=1.60, 95% CI 1.13, 2.26). Among men randomized to combination therapy, the SAE incidence rate was 3.4/100p-y for fit men versus 12.7/100p-y for frail men (HR=5.98, 95% CI 3.76, 9.52). In conclusion, frailty is independently associated with greater risk of both clinical BPH progression and SAE. The decision to initiate medical therapy for BPH among frail men should therefore include a discussion of both benefits and risks via shared decision making.

Assessment of Frailty and Association With Progression of Benign Prostatic Hyperplasia Symptoms and Serious Adverse Events Among Men Using Drug Therapy

Benign prostatic hyperplasia (BPH) in older men can cause lower urinary tract symptoms (LUTS), which are increasingly managed with medications. Frailty may contribute to both symptom progression and serious adverse events (SAEs), shifting the balance of benefits and harms of drug therapy. To assess the association between a deficit accumulation frailty index and clinical BPH progression or SAE. This cohort study used data from the Medical Therapy of Prostatic Symptoms trial, which compared placebo, doxazosin, finasteride, and combination therapy in men with moderate-to-severe LUTS, reduced urinary flow rate, and no prior BPH interventions, hypotension, or elevated prostate-specific antigen. Enrollment was from 1995 to 1998, and follow-up was through 2001. Data were assessed in February 2021. A frailty index (score range, 0-1) using 68 potential deficits collected at baseline was used to categorized men as robust (score ≤0.1), prefrail (score 0.1 to <0.25), or frail (score ≥0.25). Primary outcomes were time to clinical BPH progression and time to SAE, as defined in the parent trial. Adjusted hazard ratios (AHRs) were estimated using Cox proportional hazards regressions adjusted for demographic variables, treatment group, measures of obstruction, and comorbidities. Among 3047 men (mean [SD] age, 62.6 [7.3] years; range, 50-89 years) in this analysis, 745 (24%) were robust, 1824 (60%) were prefrail, and 478 (16%) were frail at baseline. Compared with robust men, frail men were older (age ≥75 years, 12 men [2%] vs 62 men [13%]), less likely to be White (646 men [87%] vs 344 men [72%]), less likely to be married (599 men [80%] vs 342 men [72%]), and less likely to have 16 years or more of education (471 men [63%] vs 150 men [31%]). During mean (SD) follow-up of 4.0 (1.5) years, the incidence rate of clinical BPH progression was 2.2 events per 100 person-years among robust men, 2.9 events per 100 person-years among prefrail men (AHR, 1.36; 95% CI, 1.02-1.83), and 4.0 events per 100 person-years among frail men (AHR, 1.82; 95% CI, 1.24-2.67; linear P = .005). Larger point estimates were seen among men who received doxazosin or combination therapy, although the test for interaction between frailty index and treatment group did not reach statistical significance (P for interaction = .06). Risk of SAE was higher among prefrail and frail men (prefrail vs robust AHR, 1.81; 95% CI, 1.48-2.23; frail vs robust AHR, 2.86; 95% CI, 2.21-3.69; linear P < .001); this association was similar across treatment groups (P for interaction = .76). These findings suggest that frailty is independently associated with greater risk of both clinical BPH progression and SAEs. Older frail men with BPH considering initiation of drug therapy should be counseled regarding their higher risk of progression despite combination therapy and their likelihood of experiencing SAEs regardless of treatment choice.

The contribution of musculoskeletal factors to physical frailty: a cross-sectional study

BackgroundMusculoskeletal conditions and physical frailty have overlapping constructs. We aimed to quantify individual contributions of musculoskeletal factors to frailty.MethodsParticipants included 347 men and 360 women aged ≥60 yr (median ages; 70.8 (66.1–78.6) and 71.0 (65.2–77.5), respectively) from the Geelong Osteoporosis Study. Frailty was defined as ≥3, pre-frail 1–2, and robust 0, of the following; unintentional weight loss, weakness, low physical activity, exhaustion, and slowness. Measures were made of femoral neck BMD, appendicular lean mass index (ALMI, kg/m2) and whole-body fat mass index (FMI, kg/m2) by DXA (Lunar), SOS, BUA and SI at the calcaneus (Lunar Achilles Insight) and handgrip strength by dynamometers. Binary and ordinal logistic regression models and AUROC curves were used to quantify the contribution of musculoskeletal parameters to frailty. Potential confounders included anthropometry, smoking, alcohol, prior fracture, FMI, SES and comorbidities.ResultsOverall, 54(15.6%) men and 62(17.2%) women were frail. In adjusted-binary logistic models, SI, ALMI and HGS were associated with frailty in men (OR = 0.73, 95%CI 0.53–1.01; OR=0.48, 0.34–0.68; and OR = 0.11, 0.06–0.22; respectively). Muscle measures (ALMI and HGS) contributed more to this association than did bone (SI) (AUROCs 0.77, 0.85 vs 0.71, respectively). In women, only HGS was associated with frailty in adjusted models (OR = 0.30 95%CI 0.20–0.45, AUROC = 0.83). In adjusted ordinal models, similar results were observed in men; for women, HGS and ALMI were associated with frailty (ordered OR = 0.30 95%CI 0.20–0.45; OR = 0.56, 0.40–0.80, respectively).ConclusionMuscle deficits appeared to contribute more than bone deficits to frailty. This may have implications for identifying potential musculoskeletal targets for preventing or managing the progression of frailty.

Cardiovascular risk score associations with frailty in men and women with or at risk for HIV.

To understand the relationship between cardiovascular disease (CVD) risk and frailty among men (MWH) and women living with HIV (WWH), or at risk for HIV. We considered 10-year coronary heart disease and atherosclerotic CVD risk by Framingham risk score (FRS, 2001 National Cholesterol Education Program Adult Treatment Program III) and Pooled Cohort Equations (PCE, 2013 American College of Cardiology/American Heart Association) in relation to the Fried Frailty Phenotype (FFP) in the Multicenter AIDS Cohort Study (MACS) and Women's Interagency HIV Study (WIHS). FFP was ascertained in MACS from 2004 to 2019 and in WIHS from 2005 to 2006 and 2011-2019. FFP score at least three of five components defined frailty. Repeated measures logistic regression (both cohorts) and Cox proportional hazards regression (MACS) were performed, controlled for education, income, cholesterol medication and hepatitis C virus serostatus, and among MWH and WWH, CD4+ cell count/μl, antiretroviral therapy, and HIV viral load. There were 5554 participants (1265 HIV seronegative/1396 MWH; 768 seronegative/1924 WWH) included. Among men, high-risk FRS was associated with increased risk of incident frailty among seronegative [adjusted hazard ratio (aHR)) = 2.12, 95% confidence interval (CI):1.22-3.69] and MWH (aHR = 2.19, 95% CI: 1.33-3.61). Similar associations were seen with high-risk PCE and incident frailty among SN (aHR = 1.88, 95% CI: 1.48-2.39) and MWH (aHR = 1.59, 95% CI: 1.26-2.00). Among women, high-risk PCE was associated with frailty in SN [adjusted odds ratio (aOR) = 1.43, 95% CI: 1.02-2.00] and WWH (aOR = 1.36, 95% CI: 1.08-1.71); however, high-risk FRS was not (seronegative: aOR = 1.03, 95% CI: 0.30-3.49; WWH: aOR = 0.86, 95% CI: 0.23-3.20). Higher CVD risk was associated with increased frailty regardless of HIV serostatus among men and women. These findings may inform clinical practices of screening for frailty.

Subclinical cardiovascular disease and risk of incident frailty: The British Regional Heart Study.

Subclinical cardiovascular disease (CVD) is cross-sectionally associated with frailty, but the relationship between subclinical CVD and incident frailty has not been reported. We aimed to assess this prospective association. Longitudinal analysis of data from the British Regional Heart Study, a prospective cohort study. 1057 men, aged 71-92years, robust or pre-frail at baseline, and without a clinical diagnosis of CVD. Participants underwent baseline measurement of carotid-femoral pulse wave velocity (cfPWV), carotid intima-media thickness (CIMT), carotid distensibility coefficient (DC), and ankle-brachial pressure index (ABPI), and had questionnaire-based frailty assessment after three years. Frailty status was based on the Fried phenotype. Multivariate logistic regressions examined associations between incident frailty and tertile of cfPWV, CIMT, DC, and ABPI group (<0.9, 0.9-1.4, ≥1.4). 865 men were examined and completed the 3year follow-up questionnaire, of whom 78 became frail. Adjusted for age, prefrailty, body mass index, diabetes, smoking, atrial fibrillation, blood pressure, renal function, and incident CVD, higher CIMT was associated with greater odds of incident frailty (2nd tertile OR 1.62, 95% CI 0.78-3.35, 3rd tertile OR 2.61, 95% CI 1.30-5.23, p=0.007, trend p=0.006). cfPWV showed a weaker, non-significant association (2nd tertile OR 1.79, 95% CI 0.85-3.78, 3rd tertile OR 1.73, OR 0.81-3.72, p=0.16, trend p=0.20). There was no clear association between incident frailty and DC or ABPI. In subgroup analyses, CIMT was significantly associated with incident frailty in men ≥80years (3rd tertile OR 6.99, 95%CI 1.42-34.5), but not in men aged 75-80 or<75years. Subclinical CVD, as measured by CIMT, is associated with greater risk of incident frailty in older men over three year follow-up, independent of the development of clinically-apparent stroke, heart failure, or myocardial infarction, and may be a modifiable risk factor for frailty. This association may be stronger in very old age.

Bidirectional relationship between insomnia and frailty in older adults: A 2-year longitudinal study

BackgroundMost previous studies that examined the association of insomnia with frailty used cross-sectional designs. The temporal relationship between these factors is therefore largely unknown. This study aimed to examine the bidirectional relationship between insomnia and frailty by sex. MethodsA 2-year longitudinal study involving all community-dwelling older adults living in a rural area in Japan (n = 3844). Validated measures of insomnia and frailty were employed. Insomnia was assessed using the Athens insomnia scale, and frailty using the Kihon checklist. We performed a cross-lagged panel model, adjusted for age, sex, years of education, employment status, self-rated health, complications (hypertension, diabetes, stroke, or osteoarthritis), BMI, physical activity, alcohol consumption, and smoking status, and assessed differences by sex. ResultsPoor sleep predicted the onset and worsening of frailty during follow up (standardized coefficient [95% confidence interval]: 0.076 [0.045, 0.107]). Frailty also predicted severe insomnia symptoms (0.074 [0.044, 0.104]). However, the temporal association between these conditions varied by sex. In older men, the effect of frailty on insomnia was stronger than that of insomnia on frailty. However, in women, the impact of insomnia on frailty was stronger than that of frailty on insomnia. ConclusionsThe primary potential cause of the association between insomnia and frailty may vary by sex, being frailty in men and insomnia in women. Sex-specific interventions to improve sleep quality and duration, and maintain functional abilities in daily life may contribute to the prevention and management of both frailty and insomnia in older adults.