The relationship of cardiorespiratory function, fatigue and depressive symptoms in PLHIV.

Fatigue and depressive symptoms are prevalent and associated with poor clinical outcomes, though the underlying physiological mechanisms of fatigue and depression are poorly understood. We examined the impact of cardiorespiratory fitness (CRF) on fatigue and depressive symptoms in one-hundred and nine PLHIV. CRF was examined by maximal cardiorespiratory stress test and determined by peak oxygen uptake. Patient-reported fatigue was examined utilizing the HIV-Related Fatigue Scale. Depressive symptoms were examined with the Beck Depression Inventory and PROMISE 29. Data was collected at baseline and six months. Generalized estimating equations were used to determine the effect of CRF on fatigue and depressive symptoms over time. Participants were approximately 53 years old, 86% African American (n = 93), and 65% male (n = 70). After controlling for age and sex, fatigue was inversely associated with CRF (ß = -0.163; p = .005). Depressive symptoms were not associated with CRF as measured by the BeckDepression Inventory (p = .587) nor PROMIS 29 (p = .290), but over time, depressive symptoms decreased (p = .051). Increased CRF was associated with decreased fatigue levels, but was not associated with depressive symptoms. These results should guide future research aimed at how CRF might inform interventions to improve fatigue in PLHIV.

Relationship of HIV Status and Fatigue, Cardiorespiratory Fitness, Myokines, and Physical Activity.

People living with HIV (PLWH) experience high rates of fatigue, which can be improved with physical activity. We examined relationships between HIV infection, fatigue, cardiorespiratory fitness, physical activity, and myokines. Twenty PLWH and 20 HIV-uninfected adults completed a fatigue assessment, a maximal cardiometabolic exercise test, serum measures of myokines, and wore an accelerometer for 7 days. Measures were completed at baseline, 3 months, and 6 months. At baseline, PLWH had more fatigue (4.7 ± 2.6 vs. 2.8 ± 2.5, p = .01) and higher peak ventilatory efficiency (VE/VCO2; 33 ± 5.5 vs. 30.2 ± 2.5; p = .06). Half of PLWH engaged in at least one 10-minute bout of physical activity in the previous week, compared with control subjects (65%). Over time, HIV infection and fibroblast growth factor 21 were associated with fatigue (p < .05). People living with HIV have more fatigue and a higher ventilatory efficiency; expression of fibroblast growth factor 21 may underpin this relationship.

Cardiorespiratory fitness is associated with inflammation and physical activity in HIV+ adults.

OBJECTIVE: Our objective was to examine the effect of a lifestyle diet and exercise intervention on cardiorespiratory fitness (CRF) and to examine predictors of change in CRF. DESIGN: People living with HIV (PLHIV) are at increased risk for cardiovascular disease. CRF is a better predictor of cardiovascular disease-related mortality than established risk factors yet very little is known about CRF in PLHIV. METHODS: One-hundred and seven virally suppressed PLHIV were randomized to a group-based intervention to improve lifestyle behaviors or a control condition. All PLHIV maximal cardiorespiratory stress test to determine VO2 peak, VO2 at anaerobic threshold, and ventilatory efficiency/VCO2, at baseline and 6 months later. Participants wore an accelerometer to measure physical activity, completed waist-hip circumference measures, and had a fasting lipid profile, IL-6, and high sensitivity C-reactive protein analyzed. Generalized estimating equations were used to examine the effect of the intervention on CRF and predictors of change in CRF. RESULTS: Participants were approximately 53 years old, 65% male (n = 70), and 86% African-American (n = 93). There was no effect of the intervention on markers of CRF over time (P > 0.05). After controlling for age, sex, waist-hip-ratio, the inflammatory biomarker IL-6 was inversely associated with a decline in both VO2 peak (P = 0.03) and VO2 at anaerobic threshold (P = 0.03). In addition, participants who walked an additional 10 000 steps per day had a 2.69 ml/kg per min higher VO2 peak (P = 0.02). CONCLUSION: Despite HIV viral suppression, PLHIV had remarkably poor CRF and inflammation was associated with a clinically adverse CRF profile. However, increased physical activity was associated with improved CRF.

Occult peripheral artery disease is common and limits the benefit achieved in cardiac rehabilitation.

Cardiac rehabilitation (CR) has proven morbidity and mortality benefits in cardiovascular disease, which directly correlates with exercise performance achieved. Many patients in CR exercise at sub-optimal levels, without obvious limitations. Occult lower-extremity peripheral artery disease (PAD) may be a determinant of diminished exercise capacity and reduced benefit obtained from traditional CR. In this prospective study of 150 consecutive patients enrolled in Phase II CR, we describe the prevalence of PAD, the utility of externally validated screening questionnaires, and the observed impact on CR outcomes. Abnormal ankle-brachial indices (ABI) (< 0.9 and >1.4) were observed in 19% of those studied. The Edinburgh Claudication Questionnaire was insensitive for detecting PAD by low ABI in this population, and the Walking Impairment Questionnaire and a modified Gardner protocol demonstrated a lack of typical symptoms with low levels of activity. Importantly, at completion of traditional CR, exercise improvement measured in metabolic equivalents (METs) was worse in those with a low ABI compared to those with a normal ABI (+1.39 vs +2.41 METs, p = 0.002). In conclusion, PAD is common in patients in Phase II CR and often clinically occult. Screening based on standard questionnaires appears insensitive in this population, suggesting a need for a broad-based screening strategy with ABI measurements. In this study, undiagnosed PAD significantly attenuated improvements in exercise performance, which potentially has bearings on future clinical events.

Variables Measured During Cardiopulmonary Exercise Testing as Predictors of Mortality in Chronic Systolic Heart Failure.

BACKGROUND: Data from a cardiopulmonary exercise (CPX) test are used to determine prognosis in patients with chronic heart failure (HF). However, few published studies have simultaneously compared the relative prognostic strength of multiple CPX variables. OBJECTIVES: The study sought to describe the strength of the association among variables measured during a CPX test and all-cause mortality in patients with HF with reduced ejection fraction (HFrEF), including the influence of sex and patient effort, as measured by respiratory exchange ratio (RER). METHODS: Among patients (n = 2,100, 29% women) enrolled in the HF-ACTION (HF-A Controlled Trial Investigating Outcomes of exercise traiNing) trial, 10 CPX test variables measured at baseline (e.g., peak oxygen uptake [Vo2], exercise duration, percent predicted peak Vo2 [%ppVo2], ventilatory efficiency) were examined. RESULTS: Over a median follow-up of 32 months, there were 357 deaths. All CPX variables, except RER, were related to all-cause mortality (all p < 0.0001). Both %ppVo2 and exercise duration were equally able to predict (Wald chi-square: ∼141) and discriminate (c-index: 0.69) mortality. Peak Vo2 (ml·kg(-1)·min(-1)) was the strongest predictor of mortality among men (Wald chi-square: 129) and exercise duration among women (Wald chi-square: 41). Multivariable analyses showed that %ppVo2, exercise duration, and peak Vo2 (ml·kg(-1)·min(-1)) were similarly able to predict and discriminate mortality. In men, a 10% 1-year mortality rate corresponded to a peak Vo2 of 10.9 ml·kg(-1)·min(-1) versus 5.3 ml·kg(-1)·min(-1) in women. CONCLUSIONS: Peak Vo2, exercise duration, and % ppVo2 carried the strongest ability to predict and discriminate the likelihood of death in patients with HFrEF. The prognosis associated with a given peak Vo2 differed by sex. (Exercise Training Program to Improve Clinical Outcomes in Individuals With Congestive Heart Failure; NCT00047437).

A randomized controlled trial of high dose vitamin D3 in patients with heart failure.

OBJECTIVE: To investigate the effect of Vitamin D3 on physical performance in patients with HF. BACKGROUND: HF is associated with functional decline and frailty. Vitamin D deficiency is associated with loss of muscle strength and poor outcomes in patients with HF. METHODS: Sixty-four patients participated in a 6-month parallel design double blind RCT to test the hypothesis that oral vitamin D3 would improve physical performance. Vitamin D3 50,000 IU or placebo was given weekly; all received daily calcium. Patients were included regardless of EF and 25OHD ≤ 37.5 ng/ml. The primary outcome was peak VO2, and secondary outcomes were the 6MW, TGUG and knee isokinetic muscle strength. Between group comparisons were made using ANCOVA models that adjust for baseline measures. RESULTS: Patients were age 65.9 ± 10.4 years old, 48% women, 64% African American, EF 37.6±13.9, 36% NYHA III, the remainder NYHA II. At baseline the vitamin D group 25OHD was 19.1 ± 9.3 ng/ml and increased to 61.7 ± 20.3 ng/ml; in the placebo group baseline 25OHD was 17.8 ± 9.0 ng/ml and decreased to 17.4 ± 9.8 ng/ml at 6 months (between groups p<0.001). There was no significant change from baseline to 6 months in peak VO2, 6MW, TGUG or isokinetic muscle strength. CONCLUSIONS: Vitamin D3 did not improve physical performance for patients with HF despite a robust increase in serum 25OHD. Vitamin D repletion in patients with HF should conform to standard adult guidelines for vitamin D supplementation.

Modest increase in peak VO2 is related to better clinical outcomes in chronic heart failure patients: results from heart failure and a controlled trial to investigate outcomes of exercise training.

BACKGROUND: The prognostic ability of a single measurement of peak oxygen uptake (VO(2)) is well established in patients with chronic heart failure. The relation between a change in peak VO(2) and clinical outcomes is not well defined. METHODS AND RESULTS: This investigation determined whether an increase in peak VO(2) was associated with a lower risk of the primary end point of time to all-cause mortality or all-cause hospitalization and 3 secondary end points. In Heart Failure and a Controlled Trial to Investigate Outcomes of Exercise Training, an exercise training trial for patients with systolic heart failure, cardiopulmonary exercise tests were performed at baseline and ≈3 months later in 1620 participants. Median peak VO(2) in the combined sample increased from 15.0 (11.9-18.0 Q1-Q3) to 15.4 (12.3-18.7 Q1-Q3) mL·kg(-1)·min(-1). Every 6% increase in peak VO(2,) adjusted for other significant predictors, was associated with a 5% lower risk of the primary end point (hazard ratio=0.95; CI=0.93-0.98; P<0.001); a 4% lower risk of the secondary end point of time to cardiovascular mortality or cardiovascular hospitalization (hazard ratio=0.96; CI=0.94-0.99; P<0.001); an 8% lower risk of cardiovascular mortality or heart failure hospitalization (hazard ratio=0.92; CI=0.88-0.96; P<0.001); and a 7% lower all-cause mortality (hazard ratio=0.93; CI=0.90-0.97; P<0.001). CONCLUSIONS: Among patients with chronic systolic heart failure, a modest increase in peak VO(2) over 3 months was associated with a more favorable outcome. Monitoring the change in peak VO(2) for such patients may have benefit in assessing prognosis.

Body mass index and 25 hydroxyvitamin D status in patients with and without heart failure.

The purpose of this pilot study was to assess the association between 25-hydroxyvitamin D (25[OH]D) concentrations, vitamin D intake, and sunlight exposure in patients with heart failure (HF) compared with healthy volunteers. Fourteen healthy volunteers 50 and older were recruited to compare with 14 patients with HF. Healthy volunteers were compared with HF patients by serum 25(OH)D concentrations, dietary vitamin D intake, weekly sunlight exposure, and other covariates. Independent sample t tests and linear regression models were used to compare differences between healthy volunteers and patients with HF. The mean serum 25(OH)D concentration was not significantly different between groups (healthy volunteers 25.7 ± 11.1 ng/mL, patients with HF 20.4 ± 10.2 ng/mL; P=.2) and no group effect was found in any multivariable models. Body mass index regardless of group was found to be inversely associated with serum 25(OH)D concentrations (P=.025). There was no difference in the dietary intake of vitamin D or calcium between groups. The healthy volunteers had a significantly greater amount of sunlight exposure but this did not result in higher 25(OH)D when compared with those with HF. Our findings suggest that body mass index has an important relationship with 25(OH)D concentrations regardless of a person being healthy or having HF.

Serum 25-hydroxyvitamin D concentration is associated with functional capacity in older adults with heart failure.

BACKGROUND: Vitamin D is a fat-soluble hormone necessary for calcium homeostasis. Recently, studies have demonstrated that vitamin D may be important to the health of the cardiovascular system. METHODS: Adults ≥ 50 years of age with heart failure were recruited for assessment of serum 25-hydroxyvitamin D (25OHD) concentrations. Cardiopulmonary exercise testing was used to assess functional capacity. Proximal muscle strength was evaluated with a Biodex isokinetic dynamometer [corrected] (Biodex, Shirley, NY), and health status was assessed with the Kansas City Cardiomyopathy Questionnaire. Univariate associations between physical performance and health status measures and 25OHD followed by a linear regression model were used to study associations, adjusting for other potential explanatory variables. RESULTS: Forty adults 67.8 ± 10.9 years of age (55% women and 57.5% African American) with mean ejection fraction 40% were analyzed (New York Heart Association class II in 70% and class III in 30%). Comorbidities included 77.5% hypertension and 47.5% diabetes. The mean 25OHD concentration was 18.5 ± 9.1 ng/mL, and mean peak Vo2, 14 ± 4 mL/kg/min. In univariate regression analysis, 25OHD was positively associated with peak Vo2 (P = .045). Multivariable regression analysis sustained positive association between 25OHD and peak Vo2 (P = .044) after adjusting for age, race, and respiratory exchange ratio (adjusted R² = 0.32). Association between proximal muscle strength with the 25OHD concentration was not significant. The Kansas City Cardiomyopathy Questionnaire physical limitation domain score was negatively associated with 25OHD (P = .04) but was not sustained in multivariable analysis. CONCLUSIONS: 25-Hydroxyvitamin D may be an important marker or modulator of functional capacity in patients with heart failure. Randomized controlled trials are needed to assess the effect of vitamin D repletion on functional performance.

Baseline differences in the HF-ACTION trial by sex.

BACKGROUND: In patients with heart failure (HF), assessment of functional capacity plays an important prognostic role. Both 6-minute walk and cardiopulmonary exercise testing have been used to determine physical function and to determine prognosis and even listing for transplantation. However, as in HF trials, the number of women reported has been small, and the cutoffs for transplantation have been representative of male populations and extrapolated to women. It is also well known that peak VO(2) as a determinant of fitness is inherently lower in women than in men and potentially much lower in the presence of HF. Values for a female population from which to draw for this important determination are lacking. METHODS: The HF-ACTION trial randomized 2,331 patients (28% women) with New York Heart Association class II-IV HF due to systolic dysfunction to either a formal exercise program in addition to optimal medical therapy or to optimal medical therapy alone without any formal exercise training. To characterize differences between men and women in the interpretation of final cardiopulmonary exercise testing models, the interaction of individual covariates with sex was investigated in the models of (1) VE/VCO(2), (2) VO(2) at ventilatory threshold (VT), (3) distance on the 6-minute walk, and (4) peak VO(2). RESULTS: The women were younger than the men and more likely to have a nonischemic etiology and a higher ejection fraction. Dose of angiotensin converting enzyme inhibitor (ACEI) was lower in the women, on average. The lower ACEI dose may reflect the higher use of angiotensin II receptor blocker (ARB) in women. Both the peak VO(2) and the 6-minute walk distance were significantly lower in the women than in the men. Perhaps the most significant finding in this dataset of baseline characteristics is that the peak VO(2) for women was significantly lower than that for men with similar ventricular function and health status. CONCLUSION: Therefore, in a well-medicated, stable, class II-IV HF cohort of patients who are able to exercise, women have statistically significantly lower peak VO(2) and 6-minute walk distance than men with similar health status and ventricular function. These data should prompt careful thought when considering prognostic markers for women and listing for cardiac transplant.