Chronotropic Incompetence among People with HIV Improves with Exercise Training in the Exercise for Healthy Aging Study.

BACKGROUND: People with HIV (PWH) have lower exercise capacity compared to peers without HIV, which may be explained by chronotropic incompetence (CI), the inability to increase heart rate during exercise. METHODS: The Exercise for Healthy Aging Study included adults ages 50-75 with and without HIV. Participants completed 12 weeks of moderate intensity exercise, before randomization to moderate or high intensity for 12 additional weeks. We compared adjusted heart rate reserve (AHRR; CI <80%) on cardiopulmonary exercise testing by HIV serostatus and change from baseline to 12 and 24 weeks using mixed effects models. RESULTS: Among 32 PWH and 37 controls (median age 56, 7% female, mean BMI 28 kg/m2), 28% of PWH compared to 11% of controls had CI at baseline (p = 0.067). AHRR was lower among PWH (91 vs 101%; difference 10%, 95% CI 1.9-18.9; p = 0.02). At week 12, AHRR normalized among PWH (+8%, 95% CI 4-11; p < 0.001) and was sustained at week 24 (+5, 95%CI 1-9; p = 0.008) compared to no change among controls (95%CI -4 to 4; p = 0.95; pinteraction = 0.004). After 24 weeks of exercise, only 15% PWH and 10% of controls had CI (p = 0.70). CONCLUSIONS: Chronotropic incompetence contributes to reduced exercise capacity among PWH and improves with exercise training.

A Multiomics Assessment of Preoperative Exercise in Pancreatic Cancer Survivors Receiving Neoadjuvant Therapy: A Case Series.

To molecularly characterize the impact of exercise on mitigating neoadjuvant treatment (NAT)-induced physical decline in pancreatic ductal adenocarcinoma (PDAC) patients, a multi-omics approach was employed for the analysis of plasma samples before and after a personalized exercise intervention. Consisting of personalized aerobic and resistance exercises, this intervention was associated with significant molecular changes that correlated with improvements in lean mass, appendicular skeletal muscle index (ASMI), and performance in the 400-m walk test (MWT) and sit-to-stand test. These alterations indicated exercise-induced modulation of inflammation and mitochondrial function markers. This case study provides proof-of-principal application for multiomics-based assessments of supervised exercise, thereby supporting this intervention as a feasible and beneficial intervention for PDAC patients to potentially enhance treatment response and patient quality of life. The molecular changes observed here underscore the importance of physical activity in cancer treatment protocols, advocating for the development of accessible multiomics-guided exercise programs for cancer patients.

Skeletal muscle DNA methylation: Effects of exercise and HIV.

Aging, human immunodeficiency virus (HIV) infection, and antiretroviral therapy modify the epigenetic profile and function of cells and tissues, including skeletal muscle (SkM). In some cells, accelerated epigenetic aging begins very soon after the initial HIV infection, potentially setting the stage for the early onset of frailty. Exercise imparts epigenetic modifications in SkM that may underpin some health benefits, including delayed frailty, in people living with HIV (PWH). In this first report of exercise-related changes in SkM DNA methylation among PWH, we investigated the impact of 24 weeks of aerobic and resistance exercise training on SkM (vastus lateralis) DNA methylation profiles and epigenetic age acceleration (EAA) in older, virally suppressed PWH (n = 12) and uninfected controls (n = 18), and associations of EAA with physical function at baseline. We identified 983 differentially methylated positions (DMPs) in PWH and controls at baseline and 237 DMPs after training. The influence of HIV serostatus on SkM methylation was more pronounced than that of exercise training. There was little overlap in the genes associated with the probes most significantly differentiated by exercise training within each group. Baseline EAA (mean ± SD) was similar between PWH (-0.4 ± 2.5 years) and controls (0.2 ± 2.6 years), and the exercise effect was not significant (p = 0.79). EAA and physical function at baseline were not significantly correlated (all p ≥ 0.10). This preliminary investigation suggests HIV-specific epigenetic adaptations in SkM with exercise training but confirmation in a larger study that includes transcriptomic analysis is warranted.

Chronotropic Incompetence among People with HIV Improves with Exercise Training in the Exercise for Healthy Aging Study.

Background: People with HIV (PWH) have lower exercise capacity compared to HIV-uninfected peers, which may be explained by chronotropic incompetence (CI), the inability to increase heart rate during exercise. Methods: The Exercise for Healthy Aging Study included adults ages 50-75 with and without HIV. Participants completed 12 weeks of moderate intensity exercise, before randomization to moderate or high intensity for 12 additional weeks. We compared adjusted heart rate reserve (AHRR; CI <80%) on cardiopulmonary exercise testing by HIV serostatus, and change from baseline to 12 and 24 weeks using mixed effects models. Results: Among 32 PWH and 37 controls (median age 56, 7% female, mean BMI 28 kg/m2), 28% of PWH compared to 11% of controls had CI at baseline (p=0.067). AHRR was lower among PWH (91 vs 102%; difference 11%, 95% CI 2.5-19.7; p=0.01). At week 12, AHRR normalized among PWH (+8%, 95% CI 4-11; p<0.001) and was sustained at week 24 (+5, 95%CI 1-9; p=0.008) compared to no change among controls (95%CI -4 to 4; p=0.95; pinteraction=0.004). After 24 weeks of exercise, only 15% PWH and 10% of controls had CI (p=0.70). Conclusions: Chronotropic incompetence contributes to reduced exercise capacity among PWH and improves with exercise training.

The use of non-invasive imaging modalities for the assessment of skeletal muscle quantity and quality in people with HIV: A narrative review.

BACKGROUND: People with HIV (PWH) are prone to mobility impairments and physical dysfunction, with the loss of skeletal muscle quantity and quality being a major contributor to the dysfunction. Assessment of skeletal muscle is an important component of care for this patient population for early intervention and treatment. The use of non-invasive imaging techniques to evaluate skeletal muscle, such as dual X-ray absorptiometry, computer tomography and magnetic resonance imaging, has increased in popularity in recent years. PURPOSE: This narrative review synthesizes the use of these techniques and summarizes the associations between outcomes from these imaging modalities and physical function in PWH.

Heart Failure Family Caregivers' Perspectives of Physical Activity Engagement: A Qualitative Study.

Research on caregiver burden and related psychological distress has been widely studied. However, little research has focused on perspectives and experiences of older family caregivers of persons with heart failure on engaging in physical exercise to improve their health and wellness. We investigated barriers and facilitators influencing physical activity engagement for older family caregivers of persons with heart failure through a qualitative descriptive study design utilizing participant interviews. The social cognitive theory framework guided the thematic analysis. Identified themes and subthemes that emerged were centered around the framework's interrelated personal, environmental, and behavioral factors. Self-efficacy emerged as a central construct facilitating engagement in physical activity. The older family caregivers embraced technology for physical activity interventions more readily since the COVID-19 pandemic encouraged increased technology use. The age-related and caregiving barriers to physical activity found in this study highlight considerations for an older family caregiver and guide interventions for future family caregivers' engagement.

Development of a reference chart for monitoring cancer-related fatigue throughout a supervised exercise program.

BACKGROUND: Cancer-related fatigue (CRF) is one of the most reported and functionally limiting symptoms experienced by individuals living with and beyond cancer. Exercise is effective at reducing CRF, though currently it is not possible to predict the magnitude and time course of improvement for an individual participating in an exercise program. OBJECTIVE: To develop a reference chart of CRF improvement for individuals participating in a 3-month cancer-specific exercise program. METHODS: In this retrospective cohort study, CRF was assessed every two weeks (using the FACIT - Fatigue scale, range: 0 - 52 with lower scores indicating greater fatigue) in 173 individuals participating in a 3-month supervised exercise program (741 observations). No cancer types were excluded and individuals were either undergoing chemotherapy and/or radiation, or within 6 months of completing treatment. The reference chart was developed using Generalized Additive Models for Location Scale and Shape. RESULTS: Each participant had an average of four CRF observations. Lower centiles demonstrated greater improvement than higher centiles (11 points over the duration of the program for the 10th and 4 points for the 90th percentiles). LIMITATIONS: The population is biased to individuals self-selecting or being referred to a clinical exercise program. CONCLUSIONS: This reference chart provides a novel method of monitoring CRF improvement during a cancer-specific exercise program. Setting appropriate expectations and informing exercise prescription adaptation are discussed in the context of representative data from three participants. Future research can investigate improvements in clinical outcomes and the remote monitoring of CRF through the implementation of the reference chart.

Lipidome Alterations with Exercise Among People With and Without HIV: An Exploratory Study.

Age-related comorbidities and physical function impairments in aging people with HIV (PWH) can be improved through exercise interventions. The mechanisms underlying these improvements, including lipidomic changes, are unknown. Sedentary adults (50-75 years old) with or without HIV participated in supervised endurance/resistance exercise for 24 weeks. Plasma lipid concentrations (∼1,200 lipid species from 13 lipid classes) at baseline and week 24 were measured by mass spectrometry. Given multiple comparisons, unadjusted and Benjamini-Hochberg corrected p values are reported. Analyses are considered exploratory. Twenty-five PWH and 24 controls had paired samples at baseline and week 24. The change in total triacylglycerol (TAG) concentrations after exercise intervention differed between groups (unadj-p = 0.006, adj-p = 0.078) with concentrations increasing among controls, but not among PWH. Changes in concentrations of TAG species composed of long-chain fatty acids differed between groups (unadj-p < 0.04) with increases among controls, but not among PWH. Changes in total diacylglycerol (DAG) concentration from baseline to week 24 differed between groups (unadj-p = 0.03, adj-p = 0.2) with an increase in PWH and a nonsignificant decrease in controls. Baseline to week 24 changes in DAGs composed of palmitic acid (16:0), palmitoleic acid (16:1), and stearic acid (18:0) differed by serostatus (unadj-p = 0.009-0.03; adj-p 0.10-0.12), with nonsignificant increases and decreases in concentrations in PWH and controls, respectively. Concentrations of individual lysophosphatidylcholine (LPC) and ceramide (CER) species also differed by HIV serostatus (unadj-p < = 0.05). Although exploratory, the effects of exercise on the lipidome may differ among people with and without HIV, potentially due to underlying alterations in lipid processing and fatty acid oxidation in PWH. Clinical Trials NCT02404792.

Feasibility of Implementing Physical Activity Behavior Change Counseling in an Existing Cancer-Exercise Program.

PURPOSE: This study examined the feasibility and acceptability of implementing research-tested physical activity (PA) behavior change counseling (BCC) sessions in an existing cancer-exercise program, and the preliminary effects on cancer survivor's self-efficacy and PA. METHODS: Participants were cancer survivors undergoing or within six-months of completing cancer treatment(s), and exercise program staff. Cancer survivors were randomized to receive the exercise program plus PABCC, or the standard exercise program. Feasibility and acceptability were assessed by recruitment, adherence, satisfaction, and a focus group with program staff. Qualitative data were analyzed using descriptive thematic analysis. Self-report questionnaires measured PA and exercise self-efficacy. RESULTS: Recruitment was 33 out of 93 (36.7%), and n = 13 (39%) provided post-program data. Cancer survivors enjoyed PABCC sessions, but reported face-to-face delivery was an added time burden. Program staff expressed desire to implement PABCC, but perceived staff capacity and time as barriers to sustainability. Exercise self-efficacy increased by 21.5% in the PABCC group vs. 4.2% in the control. PA increased by 81.3% in the PABCC group vs. 16.6% in the control group. CONCLUSIONS: Implementing PABCC in an existing cancer-exercise program was acceptable and promising for increasing moderate to vigorous PA, but additional research is needed to enhance the feasibility and sustainability of translating efficacious behavioral interventions into existing cancer-exercise programs.

An exercise intervention alters stool microbiota and metabolites among older, sedentary adults.

BACKGROUND: Physiologic aging has been associated with gut dysbiosis. Although short exercise interventions have been linked to beneficial changes in gut microbiota in younger adults, limited data are available from older populations. We hypothesized that exercise would produce beneficial shifts in microbiota and short-chain fatty acid (SCFA) levels in older persons. METHODS: Stool samples were collected before and at completion of a supervised 24-week cardiovascular and resistance exercise intervention among 50-75-year-old participants. SCFA levels were analyzed by gas chromatography and microbiome by 16S rRNA gene sequencing. Negative binomial regression models compared pre- and post-differences using false discovery rates for multiple comparison. RESULTS: A total of 22 participants provided pre-intervention samples; 15 provided samples at study completion. At baseline, the majority of participants were men (95%), mean age 58.0 (8.8) years, mean body mass index 27.4 (6.4) kg/m2. After 24 weeks of exercise, at the genus level, exercise was associated with significant increases in Bifidobacterium (and other unidentified genera within Bifidobacteriaceae), Oscillospira, Anaerostipes, and decreased Prevotella and Oribacterium (p < 0.001). Stool butyrate increased with exercise [5.44 (95% confidence interval 1.54, 9.24) mmol/g, p = 0.02], though no significant differences in acetate or propionate (p ⩾ 0.09) were seen. CONCLUSION: Our pilot study suggested that an exercise intervention is associated with changes in the microbiome of older adults and a key bacterial metabolite, butyrate. Although some of these changes could potentially reverse age-related dysbiosis, future studies are required to determine the contribution of changes to the microbiome in the beneficial effect of exercise on overall health of older adults. Clinical Trials NCT02404792.

Ibuprofen taken before exercise blunts the IL-6 response in older adults but does not alter bone alkaline phosphatase or c-telopeptide.

INTRODUCTION: Non-steroidal anti-inflammatory drugs (NSAIDs) taken before exercise have been shown to impair bone formation. NSAIDs also suppress inflammatory cytokines, such as interleukin-6 (IL-6), that can have pro-resorptive effects. It is unclear how taking NSAIDs timed around exercise influences inflammatory and bone biomarkers following an acute exercise bout in older adults. PURPOSE: To determine if timing of ibuprofen use relative to a single exercise bout has acute effects on serum IL-6, bone-specific alkaline phosphatase (BAP, marker of bone formation), and c-telopeptide of type I collagen (CTX, marker of bone resorption). METHODS: As part of a 36-week exercise intervention, participants aged 60 to 75 years were randomized to 3 groups: placebo before and after exercise (PP), ibuprofen before and placebo after exercise (IP), or placebo before and ibuprofen after exercise (PI). Acute responses were studied in a subset of participants (12 PP, 17 IP, 13 PI). Blood was sampled before and immediately, 30 min, and 60 min after exercise for IL-6, BAP, and CTX. RESULTS: The exercise-induced increase in IL-6 was blunted in response to IP when compared to PI 60-min after exercise (p < 0.001). There were no significant differences in the change in BAP or CTX between groups at any time points CONCLUSION: Ibuprofen taken before exercise dampened the inflammatory response to exercise but had no effects on bone biomarkers in older adults. It may be necessary to monitor changes for a longer time interval after an acute exercise bout to determine whether bone turnover is altered by ibuprofen or other NSAIDs. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00462722; Posted 04/19/2007.

A Unique Gut Microbiome-Physical Function Axis Exists in Older People with HIV: An Exploratory Study.

Impairments in physical function and increased systemic levels of inflammation have been observed in middle-aged and older persons with HIV (PWH). We previously demonstrated that in older persons, associations between gut microbiota and inflammation differed by HIV serostatus. To determine whether relationships between the gut microbiome and physical function measurements would also be distinct between older persons with and without HIV, we reanalyzed existing gut microbiome and short chain fatty acid (SCFA) data in conjunction with previously collected measurements of physical function and body composition from the same cohorts of older (51-74 years), nonfrail PWH receiving effective antiretroviral therapy (N = 14) and age-balanced uninfected controls (N = 22). Associations between relative abundance (RA) of the most abundant bacterial taxa or stool SCFA levels with physical function and body composition were tested using HIV-adjusted linear regression models. In older PWH, but not in controls, greater RA of Alistipes, Escherichia, Prevotella, Megasphaera, and Subdoligranulum were associated with reduced lower extremity muscle function, decreased lean mass, or lower Short Physical Performance Battery (SPPB) scores. Conversely, greater RA of Dorea, Coprococcus, and Phascolarctobacterium in older PWH were associated with better muscle function, lean mass, and SPPB scores. Higher levels of the SCFA butyrate associated with increased grip strength in both PWH and controls. Our findings indicate that in older PWH, both negative and positive associations exist between stool microbiota abundance and physical function. Different relationships were observed in older uninfected persons, suggesting features of a unique gut-physical function axis in PWH.

Bone Mineral Density in Different Menopause Stages is Associated with Follicle Stimulating Hormone Levels in Healthy Women.

Although estradiol (E2) has been believed to be the most critical factor in the menopause-associated decrease in bone mineral density (BMD), the role of increasing follicle stimulating hormone (FSH) during menopause is relatively unclear. We determined the extent to which hip and lumbar spine BMD differ among the stages of menopause in healthy women, and whether BMD is associated with FSH and E2 levels. A cross-sectional study of 141 healthy women classified as premenopausal (Pre; 38 ± 6 yrs; mean ± SD, n = 30), early perimenopausal (EPeri; 50 ± 3yrs, n = 31), late perimenopausal (LPeri; 50 ± 4yrs, n = 30), early postmenopausal (EPost; 55 ± 3yrs, n = 24), or late postmenopausal (LPost; 62 ± 4 yrs, n = 26), was conducted. Spine/hip BMD and sex hormones were measured using dual-energy X-ray absorptiometry and enzymatic/colorimetric methods, respectively. Compared to EPeri, spine BMD was lower (p < 0.05) in LPeri, EPost, and LPost and hip BMD was lower (p < 0.05) in EPost and LPost. BMD was inversely associated with FSH (spine: r = -0.341; hip: r = -0.271, p < 0.05) and directly associated with E2 (spine: r = 0.274; hip: r = 0.256, p < 0.05). The menopause-related loss of spine and hip BMD is associated not only with low E2 but also higher FSH. Future studies are essential to delineating the mechanisms by which FSH regulates bone health in aging women.

Associations Between Tenofovir Diphosphate in Dried Blood Spots, Impaired Physical Function, and Fracture Risk.

BACKGROUND: In this study, we evaluate associations between cumulative antiretroviral adherence/exposure, quantified using tenofovir diphosphate (TFV-DP) in dried blood spots (DBS), and human immunodeficiency virus (HIV)-related aging factors. METHODS: This is a cross-sectional analysis of younger (ages 18-35) and older (ages ≥60) persons with HIV (PWH) taking TFV disoproxil fumarate. Tenofovir diphosphate concentrations were quantified in DBS. Linear and logistic regression models were used to evaluate associations between TFV-DP and bone mineral density (BMD), physical function, frailty, and falls. RESULTS: Forty-five PWH were enrolled (23 younger, 22 older). Every 500 fmol/punch (equivalent to an increase in ~2 doses/week) increase in TFV-DP was associated with decreased hip BMD (-0.021 g/cm2; 95% confidence interval [CI], -0.040 to -0.002; P = .03). Adjusting for total fat mass, every 500 fmol/punch increase in TFV-DP was associated with higher odds of Short Physical Performance Battery impairment (score ≤10; adjusted odds ratio [OR], 1.6; 95% CI, 1.0-2.5; P = .04). Every 500 fmol/punch increase in TFV-DP was associated with slower 400-meter walk time (14.8 seconds; 95% CI, 3.8-25.8; P = .01) and remained significant after adjusting for age, lean body mass, body mass index (BMI), and fat mass (all P ≤ .01). Every 500 fmol/punch increase in TFV-DP was associated with higher odds of reporting a fall in the prior 6 months (OR, 1.8; 95% CI, 1.1-2.8; P = .02); this remained significant after adjusting for age, lean body mass, BMI, and total fat mass (all P < .05). CONCLUSIONS: Higher TFV-DP levels were associated with lower hip BMD, poorer physical function, and greater risk for falls, a concerning combination for increased fracture risk.

Blunted Muscle Mitochondrial Responses to Exercise Training in Older Adults With HIV.

BACKGROUND: Muscle mitochondrial dysfunction associated with HIV and antiretroviral therapy (ART) may improve with exercise. METHODS: Muscle specimens obtained before and after 24 weeks of exercise in older people with HIV (PWH; n = 18; ART >2 years) and uninfected controls (n = 21) were analyzed for citrate synthase (CS) activity and complexes (C) I-V, manganese superoxide dismutase (MnSOD), peroxisome proliferator-activated receptor-γ coactivator-1 (PGC1α), and voltage-dependent anion channel 1 (VDAC1) content. RESULTS: Only controls had increased CS, MnSOD, PGC1α, and CIV (P ≤ .01; P < .01 vs PWH) after training. CONCLUSIONS: The blunted mitochondrial adaptations to training in PWH suggests the need for different types of exercise-induced stimulation. CLINICAL TRIALS REGISTRATION: NCT02404792.

The Impact of Moderate or High-Intensity Combined Exercise on Systemic Inflammation Among Older Persons With and Without HIV.

BACKGROUND: We investigated whether higher-intensity exercise provided greater decrease in markers of inflammation, and whether responses differed by HIV serostatus. METHODS: People with HIV (PWH; n = 32) and controls (n = 37) aged 50-75 years completed 12 weeks moderate-intensity exercise, then were randomized to moderate- or high-intensity exercise for 12 additional weeks (n = 27 and 29, respectively). Inflammation biomarkers were measured at 0, 12, 24 weeks. Mixed and multiple regression models were adjusted for baseline inflammation, age, and body mass index. RESULTS: Baseline tumor necrosis factor-α (TNF-α), soluble TNF receptor 2 (sTNFR2), and soluble CD14 (sCD14) were significantly higher among PWH than controls (P < .04). From week 0-12, changes in interleukin-6 (IL-6), TNF-α, and sTNFR1 were not significantly different by HIV serostatus. We found no significant interaction between HIV serostatus/exercise intensity on week 12-24 changes in IL-6, TNF-α, and sTNFR1. Among high-intensity exercisers, PWH and controls had significant increases in sCD14 (P ≤ .003), controls significant increases in IL-10 (P = .01), and PWH nonsignificant decrease in highly sensitive C-reactive protein (P = .07). Other markers were not significantly different by serostatus or intensity. CONCLUSIONS: Moderate and high-intensity exercise elicited similar effects on inflammation among PWH and controls, with additional beneficial effects seen among high-intensity exercisers. Increase in sCD14 and attenuated IL-10 increase (PWH only) merit further study. CLINICAL TRIALS REGISTRATION: NCT02404792.

A supervised exercise intervention fails to improve subjective and objective sleep measures among older adults with and without HIV.

BACKGROUND: Chronic sleep disruption can have significant negative health effects and prior studies suggest that people with HIV (PWH) have disproportionately higher rates of sleep problems. METHODS: We evaluated baseline sleep of sedentary, older adults (50-75 years) with (n = 28) and without HIV (n = 29) recruited into a 24-week exercise study. Subjective sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI); objective sleep parameters were assessed using wrist-worn actigraphy. Regression models were used to investigate changes in outcomes. RESULTS: Fifty-seven participants completed the intervention. At baseline, PWH had significantly lower sleep efficiency (88.7 [95% CI 86, 91]%) compared to controls (91.8 [95% CI 91, 93]%; p = 0.02); other sleep measures indicated poorer sleep among PWH but did not reach statistical significance (p ≥ 0.12). Overall, sleep outcomes did not significantly change with the exercise intervention (all p > 0.05). In adjusted analyses, PWH demonstrated a decrease in total sleep time (-22.1 [-43.7, -0.05] p = 0.045) and sleep efficiency (-1.3 [-2.5, -.01], p = 0.03) during the 24 weeks of exercise; these differences were attenuated and no longer significant after adjusting for exercise intensity. At the completion of the intervention, compared to controls, PWH had significantly poorer sleep by PSQI score (2.2 [0.6, 3.8]; p = 0.006) and sleep efficiency (-2.8 [-5.4,-0.2]%; p = 0.04). CONCLUSIONS: In this study, sleep disturbance was more prevalent in sedentary older PWH compared to uninfected controls. An exercise intervention had minimal effect on sleep impairments among PWH nor controls. Among older adults, interventions beyond cardiovascular and resistance exercise may be needed to significantly alter subjective and objective sleep outcomes.

Physical Function and Frailty Tools in Mortality Prediction of Middle-Aged Adults With HIV.

BACKGROUND: Frailty and physical function impairments occur at an earlier than expected age in people with HIV (PWH). The goal of this study was to determine which tools or combination of tools assessing frailty/physical function were most predictive of mortality in a middle-aged population of PWH. METHODS: Using electronic health records, we determined survival, death, or loss to follow-up for 359 PWH, aged 45-65 years originally enrolled in a 2009-2010 cross-sectional cohort study. The predictive accuracy of various physical function measures [frailty score, Veterans Aging Cohort Study (VACS) index, 400-m walk, Short Physical Performance Battery (SPPB), grip strength, and falls] were compared using integrated time-dependent receiver operating characteristic area under the curve (AUC) in single variable models. Two-variable models were compared with the best single-variable model to determine if AUC improved with additional physical function variables. RESULTS: At 8-year follow-up, frailty, 400-m walk pace, SPPB, chair rise pace, VACS score, and falls were associated with increased hazard of mortality; grip strength was only predictive in sex-adjusted models. The VACS index and 400-m walk pace were the best individual predictors of mortality with time-dependent receiver operating characteristic AUC scores of 0.82, followed by SPPB (0.73), chair-rise pace (0.68), falls (0.65), frailty (0.63), and grip strength (0.55). Addition of the 400-m walk to VACS index yielded the only significant improvement in the prediction of survival compared with the VACS index alone (P = 0.04). CONCLUSION: Our study highlights several clinically applicable physical function measures predictive of mortality in middle-aged PWH that can be tailored to specific patient subpopulations and clinical or research encounters.

Body Composition Changes in Response to Moderate- or High-Intensity Exercise Among Older Adults With or Without HIV Infection.

BACKGROUND: People with HIV (PWH) are at an increased risk for adiposity and sarcopenia, despite effective antiretroviral therapy. Our objective was to compare the effects of prescribed exercise on body composition in older PWH and uninfected controls. SETTING: Academic medical center. METHODS: Sedentary PWH (n = 27) and uninfected controls (n = 28) aged 50-75 years completed 24 weeks of cardiovascular and resistance exercise. Participants completed 12 weeks of moderate-intensity exercise and then were randomized to moderate- or high-intensity exercise for 12 additional weeks. Total lean (LEAN) and fat mass (FAT), and visceral adipose tissue area (VAT) were measured using dual-energy x-ray absorptiometry at baseline and 24 weeks; baseline and intervention differences were compared by HIV serostatus using multivariable regression analyses adjusted for baseline values, age, and exercise adherence. RESULTS: At baseline, PWH had significantly lower FAT (P = 0.003), but no significant differences in LEAN or VAT compared with controls (P > 0.20). Changes over 24 weeks were not significantly different by HIV serostatus, although controls tended to gain more LEAN (0.8 kg; range, 0-1.6 kg; P = 0.04] than PWH (0.6 kg; range, -0.2 to 1.4 kg; P = 0.12) and lose less FAT and VAT (controls: (-0.9 kg; range, -1.8 to 0.0 kg and -10.3 cm; range, -19.6, 1.0) cm; both P = 0.03 vs PWH: -2.0 kg; range, -2.9 to -1.1 kg and -17.7 cm; range, -27.1 to -8.2 cm; both P < 0.001). Exercise intensity differences were not apparent for LEAN, FAT, or VAT. CONCLUSIONS: Exercise reduced total and visceral fat in older PWH and controls. Minimal gains in lean mass suggest that greater emphasis on resistance exercise may be needed to more effectively increase muscle in PWH.

Appendicular lean mass is lower in late compared with early perimenopausal women: potential role of FSH.

Age-related declines in skeletal muscle mass (i.e., sarcopenia) contribute to physical disability in older women. Although a menopause-related increase in fat mass is well documented, whether menopause influences muscle mass and sarcopenia is unclear. We determined the extent to which skeletal muscle mass differs across the stages of the menopause transition in women and whether these differences are associated with estradiol or other sex hormones. This was a cross-sectional study of 144 healthy women (aged 30-70 yr) classified as premenopausal [n = 30, 38 ± 6 yr (means ± SD)], early (n = 31, 50 ± 3 yr) and late (n = 30, 50 ± 4 yr) perimenopausal, and early (n = 26, 55 ± 3 yr) and late (n = 27, 62 ± 4 yr) postmenopausal. Appendicular lean mass (ALM) adjusted by the square of height in meters (ALM index; ALMi) was assessed by dual-energy X-ray absorptiometry. ALMi was lower (P < 0.05) in late perimenopausal and postmenopausal compared with early perimenopausal, with no significant differences between other groups (premenopausal 6.6 ± 0.6, early perimenopausal 6.8 ± 0.8, late perimenopausal 6.1 ± 0.8, early postmenopausal 6.5 ± 1.1, and late postmenopausal 6.2 ± 0.9 kg/m2). The prevalence of sarcopenia (ALMi ≤ 5.67 kg/m2) was 7%, 3%, 30%, 27%, and 32% in premenopausal, early and late perimenopausal, and early and late postmenopausal groups, respectively. ALMi measured across menopause stages was inversely correlated to follicle-stimulating hormone (FSH; r = -0.28, P = 0.003) but not to estradiol (r = 0.088, P = 0.34). The menopause transition appears to be a vulnerable period for the loss of skeletal muscle mass that may begin during the late perimenopausal transition. Future studies are necessary to investigate the potential effect of FSH on skeletal muscle.NEW & NOTEWORTHY Our data suggest that the late perimenopausal stage may be a vulnerable period for the loss of skeletal muscle, potentially related to elevations in FSH.