Association of chronotropic incompetence with reduced cardiorespiratory fitness in older adults with HIV.

OBJECTIVE: Understanding the physiological drivers of reduced cardiorespiratory fitness in people with HIV (PWH) will inform strategies to optimize healthspan. Chronotropic incompetence is common in heart failure and associated with low cardiorespiratory fitness yet is understudied in PWH. The objective was to determine the prevalence of chronotropic incompetence and its relationship with cardiorespiratory fitness. DESIGN: Participants were PWH at least 50 years of age with no prior history of heart failure or coronary heart disease who were enrolled in a randomized exercise trial. Baseline cardiopulmonary exercise testing (CPET) was used to measure cardiorespiratory fitness as peak oxygen consumption (VO2peak) and calculate the chronotropic index from heart rate values. Chronotropic incompetence was defined as an index less than 80%. RESULTS: The 74 participants were on average 61 years old, 80% Black or African American, and 93% men. Chronotropic incompetence was present in 31.1%. VO2peak was significantly lower among participants with chronotropic incompetence compared with participants without chronotropic incompetence [mean (SD) ml/min/kg: 20.9 (5.1) vs. 25.0 (4.5), P = 0.001]. Linear regression showed that chronotropic incompetence and age were independent predictors of VO2peak, but smoking and comorbidity were not. The chronotropic index correlated with VO2peak (r = 0.48, P < 0.001). CONCLUSION: Among older PWH without heart failure or coronary heart disease, chronotropic incompetence was present in approximately one-third of individuals and was associated with clinically relevant impaired cardiorespiratory fitness. Investigation of chronotropic incompetence in large cohorts which includes PWH and heart failure may contribute to strategies that promote healthy aging with HIV infection and offer a preclinical window for intervention.

Healthy aging: Linking causal mechanisms with holistic outcomes.

Identifying and understanding the impact of differing exposures over the lifecourse necessitates contextualizing different levels of influence ranging from genetics, epigenetics, geography, and psychosocial networks.

Update in Human Immunodeficiency Virus and Aging.

Effective and consistent antiretroviral therapy has enabled people with human immunodeficiency virus (HIV) (PWH) to survive longer than previously encountered earlier in the epidemic. Consequently, PWH are subject to the struggles and clinical conditions typically associated with aging. However, the aging process in PWH is not the same as for those who do not have HIV. There is a complex interplay of molecular, microbiologic, and pharmacologic factors that leads to accelerated aging in PWH; this leads to increased risk for certain age-related comorbidities requiring greater vigilance and interventions in routine care.

Pilot study of functional circuit exercise in older adults.

Sustainable exercise strategies are needed for older adults to maintain aerobic capacity and strength. The objective of this pilot in 6 adults ≥ 65 years of age was to determine the feasibility and preliminary efficacy of high-intensity functional circuit training which does not require stationary equipment. Instructor-led small group exercise classes were held 3x/week for 12 weeks using weight-bearing exercises performed in a circuit format at ratings of perceived exertion (RPE) of 6-8/10. All 6 participants completed the pilot and showed significant improvements by the Wilcoxon signed-rank test. The six-minute walk distance increased 10.5%. Timed arm curl and chair stands increased 26.8% and 30.3% (all p ≤ 0.03). These preliminary findings suggest that high-intensity functional circuit exercise is feasible in older adults and increases functional measures of aerobic capacity and strength. Further research is warranted to develop this strategy which has the potential for broad dissemination without the need for a traditional exercise facility.

Epigenetic Age Acceleration Markers Are Associated With Physiologic Frailty and All-Cause Mortality in People With Human Immunodeficiency Virus.

BACKGROUND: Biomarkers that provide insight into drivers of aging are needed for people with human immunodeficiency virus (PWH). The study objective was to determine if epigenetic age acceleration (EAA) markers are associated with physiologic frailty measured by the Veterans Aging Cohort Study (VACS) Index and predict all-cause mortality for PWH. METHODS: Epigenome-wide DNA methylation was profiled in VACS total white blood cell samples collected during 2005-2007 from 531 PWH to generate 6 established markers of EAA. The association of each EAA marker was tested with VACS Index 2.0. All-cause mortality was assessed over 10 years. For each EAA marker, the hazard ratio per increased year was determined using Cox regression. To evaluate mortality discrimination, C-statistics were derived. RESULTS: Participants were mostly men (98.5%) and non-Hispanic Black (84.4%), with a mean age of 52.4 years (standard deviation [SD], 7.8 years). Mean VACS Index score was 59.3 (SD, 16.4) and 136 deaths occurred over a median follow-up of 8.7 years. Grim age acceleration (AA), PhenoAA, HannumAA, and extrinsic epigenetic AA were associated with the VACS Index and mortality. HorvathAA and intrinsic epigenetic AA were not associated with either outcome. GrimAA had the greatest mortality discrimination among EAA markers and predicted mortality independently of the VACS Index. One-year increase in GrimAA was associated with a 1-point increase in VACS Index and a 10% increased hazard for mortality. CONCLUSIONS: The observed associations between EAA markers with physiologic frailty and mortality support future research to provide mechanistic insight into the accelerated aging process and inform interventions tailored to PWH for promoting increased healthspan.

Combining Charlson comorbidity and VACS indices improves prognostic accuracy for all-cause mortality for patients with and without HIV in the Veterans Health Administration.

Introduction: As people age with HIV (PWH), many comorbid diseases are more common than among age matched comparators without HIV (PWoH). While the Veterans Aging Cohort (VACS) Index 2.0 accurately predicts mortality in PWH using age and clinical biomarkers, the only included comorbidity is hepatitis C. We asked whether adding comorbid disease groupings from the Charlson Comorbidity Index (CCI) improves the accuracy of VACS Index. Methods: To maximize our ability to model mortality among older age groups, we began with PWoH in Veterans Health Administration (VA) from 2007-2017, divided into development and validation samples. Baseline predictors included age, and components of CCI and VACS Index (excluding CD4 count and HIV RNA). Patients were followed until December 31, 2021. We used Cox models to develop the VACS-CCI score and estimated mortality using a parametric (gamma) survival model. We compared accuracy using C-statistics and calibration curves in validation overall and within subgroups (gender, age

Biological ageing with HIV infection: evaluating the geroscience hypothesis.

Although people with HIV are living longer, as they age they remain disproportionately burdened with multimorbidity that is exacerbated in resource-poor settings. The geroscience hypothesis postulates that a discrete set of between five and ten hallmarks of biological ageing drive multimorbidity, but these processes have not been systematically examined in the context of people with HIV. We examine four major hallmarks of ageing (macromolecular damage, senescence, inflammation, and stem-cell dysfunction) as gerodrivers in the context of people with HIV. As a counterbalance, we introduce healthy ageing, physiological reserve, intrinsic capacity, and resilience as promoters of geroprotection that counteract gerodrivers. We discuss emerging geroscience-based diagnostic biomarkers and therapeutic strategies, and provide examples based on recent advances in cellular senescence, and other, non-pharmacological approaches. Finally, we present a conceptual model of biological ageing in the general population and in people with HIV that integrates gerodrivers and geroprotectors as modulators of homoeostatic reserves and organ function over the lifecourse.

Telehealth Exercise Intervention in Older Adults With HIV: Protocol of a Multisite Randomized Trial.

ABSTRACT: People with HIV (PWH) have reduced cardiorespiratory fitness, but a high intensity, easily disseminated exercise program has not yet been successfully developed in older PWH. The purpose of this article is to describe a synchronous telehealth exercise intervention in older PWH, delivered from one medical center to two other centers. Eighty older PWH (≥50 years) on antiretroviral therapy will be randomized to exercise or delayed entry control groups. Functional circuit exercise training, which does not entail stationary equipment, will be provided by real-time videoconferencing, 3 times weekly for 12 weeks, to small groups. Continuous remote telemonitoring of heart rate will ensure high exercise intensity. We hypothesize that telehealth exercise will be feasible and increase cardiorespiratory fitness and reduce sarcopenia and frailty. Findings will provide new insight to target successful aging in older PWH and can also be widely disseminated to PWH of any age or other patient populations.

Assessing Moderate to Vigorous Physical Activity in Older Adults: Validity of a Commercial Activity Tracker.

Purpose: Despite the potential for commercial activity devices to promote moderate to vigorous physical activity (MVPA), limited information is available in older adults, a high-priority target population with unique gait dynamics and energy expenditure. The study purpose was to investigate the content validity of the Garmin Vivosmart HR device for step counts and MVPA in adults ≥65 years of age in free-living conditions. Methods: Thirty-five participants (M age= 73.7 (6.3) years) wore Garmin and ActiGraph GT3X+ devices for a minimum of 2 days. Accuracy and intra-person reliability were tested against a hip worn ActiGraph device. Separate analyses were conducted using different accelerometer cut-off values to define MVPA, a population-based threshold (≥2,020 counts/minute) and a recommended threshold for older adults (≥1,013 counts/minute). Results: Overall, the Garmin device overestimated MVPA compared with the hip-worn ActiGraph. However, the difference was small using the lower, age-specific, MVPA cut-off value [median (IQR) daily minutes; 50(85) vs. 32(49), p = 0.35] in contrast to the normative standard (50(85) vs. 7(24), p < 0.001). Regardless of the MVPA cut-off, intraclass correlation showed poor reliability [ICC (95% CI); 0.16(-0.40, 0.55) to 0.35(-0.32, 0.7)] which was supported by Bland-Altman plots. Garmin step count was both accurate (M step difference: 178.0, p = 0.22) and reliable [ICC (95% CI; 0.94) (0.88, 0.97)]. Conclusion: Results support the accuracy of a commercial activity device to measure MVPA in older adults but further research in diverse patient populations is needed to determine clinical utility and reliability over time.

Feasibility and effects of high-intensity interval training in older adults living with HIV.

Adults with HIV on therapy can live a normal lifespan but exhibit advanced ageing which includes reduced cardiorespiratory fitness. Our objective was to determine the feasibility and effects of high-intensity interval training (HIIT) combined with resistance training (RT) in older adults with HIV. We conducted a cross-over pilot study within a randomized exercise trial in sedentary adults with HIV ≥50 years of age. First, participants were randomized to 4 months of continuous high-intensity aerobic exercise (AEX) and RT 3x/week or standard of care control. Then, the control group completed 4 months of HIIT + RT (3x/week). Among the 32 individuals enrolled, 26 eligible participants were randomized. Most participants were African American (63%) and male (95%) with a mean (SD) age of 61.5 (6.7) years and VO2peak of 24.5 (4.9) ml/kg/min. Attendance and adherence to both exercise training interventions were high. The clinically significant increases in VO2peak (ml/kg/min) after HIIT (3.09 ±1.04, p=0.02) and AEX (2.09 ±0.72, p=0.01) represented improvements of 17.1% and 7.7%, respectively. Both groups had improvements in exercise endurance (time on the treadmill) and strength (all p< 0.01). This pilot study supports HIIT as an efficient means to deliver high-intensity AEX to improve cardiorespiratory fitness toward the goal of attenuating the accelerated ageing process in adults with HIV.

Polypharmacy and frailty among persons with HIV.

Polypharmacy is associated with frailty in the general population, but little is known about polypharmacy among persons living with HIV (PLWH) on antiretroviral (ARV) therapy. We determined the association between polypharmacy and an adapted frailty-related phenotype (aFRP) via a cross-sectional study in FY 2009 of 1762 PLWH on ARV with suppressed viral load and 2679 uninfected participants in the Veterans Aging Cohort Study. The primary predictor was number of chronic outpatient non-ARV medications using pharmacy fill/refill data. The outcome was self-report of four aFRP domains: shrinking, exhaustion, slowness, low physical activity. Frailty was defined as reporting 3-4 domains while pre-frailty was 1-2. Frailty was uncommon (2% PLWH, 3% uninfected); a larger proportion demonstrated any aFRP domain (31% PLWH, 41% uninfected). Among PLWH and uninfected, median chronic non-ARV medications was 6 and 16 respectively if having any aFRP domain, and 4 and 10 when without aFRP domains. In adjusted analyses, each additional chronic non-ARV medication conferred an 11% increased odds of having any aFRP domain in PLWH (OR [95% CI] = 1.11 [1.08, 1.14]), and a 4% increase in those uninfected (OR [95% CI] = 1.04 [1.03, 1.04]). The stronger association between polypharmacy and frailty in PLWH warrants further study and potential deprescribing of medications.

Rapid Transition to Telehealth Group Exercise and Functional Assessments in Response to COVID-19.

Exercise is critical for health maintenance in late life. The COVID-19 shelter in place and social distancing orders resulted in wide-scale interruptions of exercise therapies, placing older adults at risk for the consequences of decreased mobilization. The purpose of this paper is to describe rapid transition of the Gerofit facility-based group exercise program to telehealth delivery. This Gerofit-to-Home (GTH) program continued with group-based synchronous exercise classes that ranged from 1 to 24 Veterans per class and 1 to 9 classes offered per week in the different locations. Three hundred and eight of 1149 (27%) Veterans active in the Gerofit facility-based programs made the transition to the telehealth delivered classes. Participants' physical performance testing continued remotely as scheduled with comparisons between most recent facility-based and remote testing suggesting that participants retained physical function. Detailed protocols for remote physical performance testing and sample exercise routines are described. Translation to remote delivery of exercise programs for older adults could mitigate negative health effects.

Adapting the "Resist Diabetes" Resistance Training Intervention for Veterans.

PURPOSE: The Resist Diabetes trial demonstrated that twice-per-week resistance training reduced prediabetes prevalence and improved strength among older adults with prediabetes. Our objective was to determine initial perceptions of patients and care providers in a Veterans Affairs Medical Center (VAMC) regarding Resist Diabetes (RD), and ultimately, inform adaptations to improve uptake of RD in the Veterans Health Administration. METHODS: A mixed-methods approach was utilized. Care providers (n=20) and veterans with prediabetes (n=12) were recruited to gauge perceptions of the RD program and identify barriers and facilitators to the program referral process and program implementation. Care provider perceptions of the acceptability, appropriateness and feasibility were determined using a validated survey. Open-ended questionnaires and interview guides, based upon the Consolidated Framework for Implementation Research, were utilized to determine major and minor themes within the provider and veteran responses. To identify the dissemination potential of RD, the availability of onsite fitness facilities at VAMC facilities nationally (n=159) was assessed. RESULTS: Providers rated (scaled 1-5; 1=completely disagree, 5=completely agree) the RD program as appealing (4.8+/-0.1), appropriate (4.8+/-0.0), and feasible (4.6+/-0.2). Providers reported that prediabetes/diabetes is a significant problem in the VAMC, and that different prevention programs will appeal to different types of VAMC patients. Patients (n=12; 58% female; aged 65+/-10yrs; BMI 34+/-6 kg/m2; HbA1c 5.7+/-1.8%) expressed interest in an exercise-focused diabetes prevention program and defined key barriers: travel, transportation, and time constraints. Among the responding national VAMC sites, 85% (97/114) reported having an onsite fitness facility. CONCLUSION: Salem VAMC care providers and veteran patients demonstrated positive perceptions of the Resist Diabetes program. Program adaptations are needed to address barriers to patient participation including travel, transportation and time constraints.

Short Communication: Low Muscle Mass Is Associated with Osteoporosis in Older Adults Living with HIV.

Sarcopenia, age-related low muscle mass and function, is a well-established independent risk factor for bone fracture in the geriatric population but is understudied in older people living with HIV (PLWH). The objective of this cross-sectional study was to investigate in older PLWH the relationship between muscle mass and bone mineral density (BMD). Sedentary PLWH who were ≥50 years of age, receiving antiretroviral therapy, and enrolled in an exercise intervention trial were included. Established definitions for sarcopenia and osteopenia/osteoporosis were applied to muscle mass data and BMD collected by dual-energy X-ray absorptiometry before exercise training. Participants were 93% male and 33% Caucasian race with median age 61 years, and median CD4 lymphocytes 707 cells/µL. The majority (64%) were overweight and obese by body mass index. Appendicular skeletal muscle index (ASMI) correlated with BMD at the femoral neck (r = 0.49, p < .01), total hip (r = 0.54, p < .01), and lumbar spine (r = 0.48, p < .05). Low BMD at the femoral neck was present in 39% (26% osteopenia, 13% osteoporosis). ASMI was lower among those with low BMD compared with normal BMD (p = .02). Low muscle mass measured by ASMI is associated with low BMD in clinically stable older PLWH. Detailed body composition assessment may help guide lifestyle recommendations to prevent bone fractures in older PLWH.

Association of Diastolic Dysfunction with Reduced Cardiorespiratory Fitness in Adults Living with HIV.

Despite the high prevalence of diastolic dysfunction in adults living with HIV, the impact on cardiorespiratory fitness (CRF) is understudied. The objective of this cross-sectional study was to investigate the relationship between cardiac function and CRF in adults with HIV. Adults receiving antiretroviral therapy with no history of coronary artery disease (CAD) or heart failure were eligible to participate. Cardiac function was assessed by resting Doppler echocardiography. CRF was measured by oxygen utilization at peak exercise (VO2peak). The majority of participants were African American (86%) and male (97%) with a mean [standard deviation (SD)] age of 56.6 (7.1) years and median CD4 lymphocyte count of 492 cells/mL. The mean (SD) VO2peak was 26.1 (5.5) mL/(kg·min). Age, diabetes, hypertension, and hemoglobin were associated with VO2peak. Overall, diastolic dysfunction was present in 38% and was associated with lower VO2peak (p < 0.05). VO2peak was lower among those with impaired myocardial relaxation (e' <8 cm/s) compared with normal relaxation [mean ± SE mL/(kg·min), 25.2 ± 0.6 vs. 27.7 ± 0.9, p < 0.05]. Adjusted for age and clinical factors, each unit increase in left ventricular relaxation (E/A) was associated with an average 4.4 mL/(kg·min) higher VO2peak, representing more than one metabolic equivalent. We conclude that diastolic dysfunction is independently associated with clinically significant low CRF in adults with HIV and no history of CAD or heart failure. These results highlight the importance of recognizing diastolic dysfunction in individuals living with HIV regardless of their cardiovascular disease history.

Gait and Balance Biomechanics in Older Adults With and Without Human Immunodeficiency Virus.

Balance deficits impose limitations and can impede safe walking contributing to falls and falls-related complications. The objective of this study was to perform an in-depth balance assessment and compare domains of limitations in older men with and without HIV infection. Fifteen sedentary African American men either with HIV (n = 6) or without HIV (n = 9 controls) participated. Standing balance was assessed under quiet stance on dual synchronized force plates during three 30 s trials with eyes open. Participants also completed standardized clinical instruments of balance, including the Berg Balance Scale (BBS) and Dynamic Gait Index (DGI). Older participants with HIV have lower BBS and DGI scores than controls (both p < .05). Adults with HIV have nearly twice the magnitude greater center of pressure (COP) sway variability than controls (1.42 ± 1.20 cm2 vs. 0.71 ± 0.1 cm2, p < .05). These data demonstrating differences in COP sway area between groups may further support evidence of potential fall risk and contribute to frailty in older adults with HIV.

The effect of isolated nocturnal oxygen desaturations on serum hs-CRP and IL-6 in patients with chronic obstructive pulmonary disease.

INTRODUCTION: A majority of patients with chronic obstructive pulmonary disease (COPD) die of cardiovascular disease (CVD), yet the mechanisms responsible for this association are not fully understood. It remains unknown if isolated nocturnal oxygen desaturation (iNOD) could be one of the potential pathways by which the 'inflammatory COPD' phenotype leads to CVD. OBJECTIVES: We aimed to evaluate if COPD patients who meet the Medicare guidelines for nocturnal oxygen therapy (iNOT+) had higher serum hs-CRP and IL-6 than those who did not meet the guidelines for iNOT (iNOT-). METHODS: Patients with moderate to severe COPD (ie FEV1 < 80% and FEV1/FVC < 70), who were not on oxygen, underwent nocturnal oximetry on room air. Serum IL-6 and hs-CRP were collected the morning after the nocturnal oximetry testing. RESULTS: A total of 28 patients were included in the study, 8 of whom had more than 5 minutes and 5% of their sleep time spent at oxygen saturation less than 88% and constituted the iNOT+ group. Only serum hs-CRP was significantly higher in iNOT+ than iNOT- (P = 0.050). There was no difference in the rate of COPD exacerbations at one and three months, or five-year survival between the groups (P > 0.3). CONCLUSION: COPD patients who have more than 5 minutes and 5% of their sleep time spent at oxygen saturation less than 88% have increased hs-CRP, which is associated with increased risk of future CVD.

A pilot randomized aerobic exercise trial in older HIV-infected men: Insights into strategies for successful aging with HIV.

BACKGROUND: HIV-infected adults have increased risk for age-related diseases and low cardiorespiratory fitness that can be prevented and improved with exercise. Yet, exercise strategies have not been well studied in older adults with HIV and may require substantial adaptation to this special population. OBJECTIVE: To determine the safety and efficacy of aerobic exercise in older HIV-infected men in a randomized trial comparing different levels of exercise intensity. METHODS: We conducted a pilot exercise trial in 22 HIV-infected men ≥50 years of age receiving antiretroviral therapy who were randomized 1:1 to moderate-intensity aerobic exercise (Mod-AEX) or high-intensity aerobic exercise (High-AEX) that was performed three times weekly for 16 weeks in a supervised setting. Primary outcome was cardiorespiratory fitness (VO2peak) measured by treadmill testing. Secondary outcomes were exercise endurance, six-minute walk distance (6-MWD), body composition measured by Dual-energy X-ray absorptiometry (DXA), and fasting plasma levels of lipids and glucose. RESULTS: VO2peak increased in the High-AEX group (3.6 ±1.2 mL/kg/min, p = 0.02) but not in the Mod-AEX group (0.4 ±1.4 mL/kg/min, p = 0.7) with a significant between group difference (p<0.01). Exercise endurance increased in both the High-AEX group (27 ±11%, p = 0.02) and the Mod-AEX group (11 ±4%, p = 0.04). The 6-MWD increased in both the High-AEX (62 ±18m, p = 0.01) and the Mod-AEX group (54 ±14m, p = 0.01). Changes in VO2peak and 6-MWD were clinically relevant. There were no serious exercise-related adverse events. Dropouts were similar between group (27% overall) and were related to joint pain. CONCLUSIONS: This pilot exercise trial demonstrates that moderate to high-intensity aerobic exercise in older HIV-infected men increases endurance and ambulatory function. However, increased cardiorespiratory fitness was observed only with high-intensity aerobic exercise despite substantial baseline impairment. Future research is needed to determine exercise strategies in older HIV-infected adults that address advanced aging and comorbidity yet are durable and feasible.

Providing Rural Veterans With Access to Exercise Through Gerofit.

Clinical video telehealth can be used to deliver functional circuit exercise training to older veterans in remote locations.