Year Of Exercise Training Research Articles

The effects of short-term, progressive exercise training on disease activity in smouldering multiple myeloma and monoclonal gammopathy of undetermined significance: a single-arm pilot study.

High levels of physical activity are associated with reduced risk of the blood cancer multiple myeloma (MM). MM is preceded by the asymptomatic stages of monoclonal gammopathy of undetermined significance (MGUS) and smouldering multiple myeloma (SMM) which are clinically managed by watchful waiting. A case study (N = 1) of a former elite athlete aged 44 years previously indicated that a multi-modal exercise programme reversed SMM disease activity. To build from this prior case study, the present pilot study firstly examined if short-term exercise training was feasible and safe for a group of MGUS and SMM patients, and secondly investigated the effects on MGUS/SMM disease activity. In this single-arm pilot study, N = 20 participants diagnosed with MGUS or SMM were allocated to receive a 16-week progressive exercise programme. Primary outcome measures were feasibility and safety. Secondary outcomes were pre- to post-exercise training changes to blood biomarkers of MGUS and SMM disease activity- monoclonal (M)-protein and free light chains (FLC)- plus cardiorespiratory and functional fitness, body composition, quality of life, blood immunophenotype, and blood biomarkers of inflammation. Fifteen (3 MGUS and 12 SMM) participants completed the exercise programme. Adherence was 91 ± 11%. Compliance was 75 ± 25% overall, with a notable decline in compliance at intensities > 70% V̇O2PEAK. There were no serious adverse events. There were no changes to M-protein (0.0 ± 1.0g/L, P =.903), involved FLC (+ 1.8 ± 16.8mg/L, P =.839), or FLC difference (+ 0.2 ± 15.6mg/L, P =.946) from pre- to post-exercise training. There were pre- to post-exercise training improvements to diastolic blood pressure (- 3 ± 5 mmHg, P =.033), sit-to-stand test performance (+ 5 ± 5 repetitions, P =.002), and energy/fatigue scores (+ 10 ± 15%, P =.026). Other secondary outcomes were unchanged. A 16-week progressive exercise programme was feasible and safe, but did not reverse MGUS/SMM disease activity, contrasting a prior case study showing that five years of exercise training reversed SMM in a 44-year-old former athlete. Longer exercise interventions should be explored in a group of MGUS/SMM patients, with measurements of disease biomarkers, along with rates of disease progression (i.e., MGUS/SMM to MM). https://www.isrctn.com/ISRCTN65527208 (14/05/2018).

Older Adult Aerobic Capacity, Muscular Strength, Fitness and Body Composition After 20+ Years of Exercise Training: A Systematic Review and Meta-Analysis

Older Adult Aerobic Capacity, Muscular Strength, Fitness and Body Composition After 20+ Years of Exercise Training: A Systematic Review and Meta-Analysis

Abstract 12741: Effect of One Year of Exercise Training on Left Ventricular Relaxation in Patients With Stage B Heart Failure

Introduction: Left ventricular hypertrophy (LVH) is a risk factor for developing heart failure (HF). Exercise training decreases LV stiffness in individuals with LVH, but the effects of exercise training on LV relaxation in these individuals are unknown. Methods: Patients with LVH (> 11 mm) and elevated cardiac biomarkers (N-terminal pro- B-type natriuretic peptide [>40 pg/mL] or high-sensitivity troponin T [>0.6 pg/mL]) were randomized 2:1 to 1 year of monitored exercise training 4-5 days a week, including high intensity intervals, and 1-2 days of strength training or an attention control. Isovolumetric relaxation time (IVRT) was measured with pulse wave Doppler echocardiography and pulmonary capillary wedge pressure (PCWP) was consecutively measured with right heart catheterization before and after intervention. LV relaxation time constant, Tau, was estimated by Tau = IVRT / (Ln End-systolic pressure (ESP) - Ln PCWP) (Figure). Maximal oxygen uptake (VO 2 Max; Douglas bags) was measured with an incremental treadmill test. LV Stiffness was significantly improved in exercise arm, previously reported. Results: Thirty-one participants completed the study (Control: n=11, 51±6 years, 55% men, Exercise: n=20 53±6, 65% men). VO 2 Max increased by 18.2% in the exercise arm (2.2±0.6 L/min to 2.5±0.6, but not in controls; group x time p<0.001). Exercise training did not change Tau (exercise 38.2±6.5 to 39.8±8.7 ms) compared to control(40.3 ± 5.9 to 39.2±6.8 ms, group x time p = 0.84, Figure ). Exercise training resulted in no significant changes in IVRT (p = 0.35), SBP (p=0.89) or PCWP (p=0.69). Conclusions: In patients with LVH at risk for HF, one year of high intensity exercise training did not improve LV relaxation despite significant improvement in ventricular stiffness and exercise capacity. These results suggest the primary mechanism for HF risk reduction with exercise training is by lowering LV stiffness, and not necessarily altering LV relaxation.

Effect of 5 years of exercise training on the cardiovascular risk profile of older adults: the Generation 100 randomized trial.

AimsThe aim of this study was to compare the effects of 5 years of supervised exercise training (ExComb), and the differential effects of subgroups of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT), with control on the cardiovascular risk profile in older adults.Methods and resultsOlder adults aged 70–77 years from Trondheim, Norway (n = 1567, 50% women), able to safely perform exercise training were randomized to 5 years of two weekly sessions of HIIT [∼90% of peak heart rate (HR), n = 400] or MICT (∼70% of peak HR, n = 387), together forming ExComb (n = 787), or control (instructed to follow physical activity recommendations, n = 780). The main outcome was a continuous cardiovascular risk score (CCR), individual cardiovascular risk factors, and peak oxygen uptake (VO2peak). CCR was not significantly lower [−0.19, 99% confidence interval (CI) −0.46 to 0.07] and VO2peak was not significantly higher (0.39 mL/kg/min, 99% CI −0.22 to 1.00) for ExComb vs. control. HIIT showed higher VO2peak (0.76 mL/kg/min, 99% CI 0.02–1.51), but not lower CCR (−0.32, 99% CI −0.64 to 0.01) vs. control. MICT did not show significant differences compared to control or HIIT. Individual risk factors mostly did not show significant between-group differences, with some exceptions for HIIT being better than control. There was no significant effect modification by sex. The number of cardiovascular events was similar across groups. The healthy and fit study sample, and contamination and cross-over between intervention groups, challenged the possibility of detecting between-group differences.ConclusionsFive years of supervised exercise training in older adults had little effect on cardiovascular risk profile and did not reduce cardiovascular events.RegistrationClinicalTrials.gov: NCT01666340.

One-Year Committed Exercise Training Reverses Abnormal Left Ventricular Myocardial Stiffness in Patients With Stage B Heart Failure With Preserved Ejection Fraction.

Individuals with left ventricular (LV) hypertrophy and elevated cardiac biomarkers in middle age are at increased risk for the development of heart failure with preserved ejection fraction. Prolonged exercise training reverses the LV stiffening associated with healthy but sedentary aging; however, whether it can also normalize LV myocardial stiffness in patients at high risk for heart failure with preserved ejection fraction is unknown. In a prospective, randomized controlled trial, we hypothesized that 1-year prolonged exercise training would reduce LV myocardial stiffness in patients with LV hypertrophy. Forty-six patients with LV hypertrophy (LV septum >11 mm) and elevated cardiac biomarkers (N-terminal pro-B-type natriuretic peptide [>40 pg/mL] or high-sensitivity troponin T [>0.6 pg/mL]) were randomly assigned to either 1 year of high-intensity exercise training (n=30) or attention control (n=16). Right-heart catheterization and 3-dimensional echocardiography were performed while preload was manipulated using both lower body negative pressure and rapid saline infusion to define the LV end-diastolic pressure-volume relationship. A constant representing LV myocardial stiffness was calculated from the following: P=S×[Exp {a (V-V0)}-1], where "P" is transmural pressure (pulmonary capillary wedge pressure - right atrial pressure), "S" is the pressure asymptote of the curve, "V" is the LV end-diastolic volume index, "V0" is equilibrium volume, and "a" is the constant that characterizes LV myocardial stiffness. Thirty-one participants (exercise group [n=20]: 54±6 years, 65% male; and controls (n=11): 51±6 years, 55% male) completed the study. One year of exercise training increased max by 21% (baseline 26.0±5.3 to 1 year later 31.3±5.8 mL·min-1·kg-1, P<0.0001, interaction P=0.0004), whereas there was no significant change in max in controls (baseline 24.6±3.4 to 1 year later 24.2±4.1 mL·min-1·kg-1, P=0.986). LV myocardial stiffness was reduced (right and downward shift in the end-diastolic pressure-volume relationship; LV myocardial stiffness: baseline 0.062±0.020 to 1 year later 0.031±0.009), whereas there was no significant change in controls (baseline 0.061±0.033 to 1 year later 0.066±0.031, interaction P=0.001). In patients with LV hypertrophy and elevated cardiac biomarkers (stage B heart failure with preserved ejection fraction), 1 year of exercise training reduced LV myocardial stiffness. Thus, exercise training may provide protection against the future risk of heart failure with preserved ejection fraction in such patients. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03476785.

Vascular improvements in individuals with type 2 diabetes following a 1year randomised controlled exercise intervention, irrespective of changes in cardiorespiratory fitness.

Vascular changes in individuals with type 2 diabetes mellitus majorly contribute to the development of cardiovascular disease. Increased cardiorespiratory fitness (CRF) has been associated with improvements in vascular health. Although CRF tends to improve with exercise training, there remains a portion of participants with little or no improvement. Given the importance of vascular function in individuals with type 2 diabetes, we assessed whether individuals who failed to improve CRF following a 1year exercise intervention also failed to improve arterial stiffness and structural indices. Individuals with type 2 diabetes with no major micro- and macrovascular complications and aged between 30 and 75years old (n = 63) participated in a three-arm, 1year, randomised controlled exercise intervention in Lisbon, Portugal. The study involved a non-exercise control group, a moderate continuous training combined with resistance training (RT) group and a high-intensity interval training with RT group. Allocation of participants into the intervention and control groups was done using a computer-generated list of random numbers. An improvement in CRF was defined as a change in [Formula: see text] ≥5%. Vascular stiffness and structural indices were measured using ultrasound imaging and applanation tonometry. Generalised estimating equations were used to compare changes in vascular measures across individuals in the control group (n = 22) and those in the exercise groups who either had improved CRF (CRF responders; n = 14) or whose CRF did not improve (CRF non-responders; n = 27) following 1year of exercise training. Compared with the control group, exercisers, with and without improvements in CRF, had decreased carotid intima-media thickness (IMT) (CRF responders: β = -2.84 [95% CI -5.63, -0.04]; CRF non-responders: β = -5.89 [95% CI -9.38, -2.40]) and lower-limb pulse wave velocity (PWV) (CRF responders: β = -0.14 [95% CI -0.25, -0.03]; CRF non-responders: β = -0.14 [95% CI -0.25, -0.03]), the latter being an indicator of peripheral arterial stiffness. Only CRF responders had decreased PWV of the upper limb compared with control participants (β = -0.12 [95% CI -0.23, -0.01]). As for central stiffness, CRF non-responders had increased aortic PWV compared with CRF responders (β = 0.19 [95% CI 0.07, 0.31]), whereas only the CRF non-responders had altered carotid distensibility coefficient compared with the control group (β = 0.00 [95% CI 3.01 × 10-5, 0.00]). No interaction effects between the CRF responders and non-responders vs control group were found for the remaining stiffness or haemodynamic indices (p>0.05). Regardless of improvements in CRF, individuals with type 2 diabetes had significant improvements in carotid IMT and lower-limb arterial stiffness following a 1year exercise intervention. Thus, a lack of improvement in CRF following exercise in people with type 2 diabetes does not necessarily entail a lack of improvement in vascular health. ClinicalTrials.gov NCT03144505 FUNDING: This work was supported by fellowships from the Portuguese Foundation for Science and Technology. This work is also financed by a national grant through the Fundação para a Ciência e Tecnologia (FCT), within the unit I&D 472.

One year of exercise training promotes distinct adaptations in right and left ventricle of female Sprague-Dawley rats.

Aerobic exercise training induces a unique cardioprotective phenotype, but it is becoming clear that it does not promote the same structural, functional, and molecular adaptations in both ventricles. In the present study, we aimed to better characterize and compare the molecular pathways involved in the exercise-induced remodeling of both ventricles. Female Sprague-Dawley rats were randomly assigned to control and exercise groups. Animals in the exercise group were submitted to low-intensity treadmill exercise for 54weeks. After the experimental period, biventricular hemodynamic analysis was performed and right and left ventricles were harvested for morphological and biochemical analyses. Data showed that long-term low-intensity exercise training improves cardiac function, especially left ventricular diastolic function; however, the expression of connexin-43, CCAAT-enhancer binding protein β, and c-kit did not change in none of the ventricles. In the right ventricle, long-term exercise training induced an increase of manganese superoxide dismutase and sirtuin 3 protein expression, suggestive of improved antioxidant capacity. Our results also support that long-term aerobic exercise training imposes greater metabolic remodeling to the right ventricle, mainly by increasing mitochondrial ability to produce ATP, with no association to estrogen-related receptor α regulation.

The impact of 2years of high-intensity exercise training on a model of integrated cardiovascular regulation.

Heart rate variability, a common and easily measured index of cardiovascular dynamics, is the output variable of complicated cardiovascular and respiratory control systems. Both neural and non-neural control mechanisms may contribute to changes in heart rate variability. We previously developed an innovative method using transfer function analysis to assess the effect of prolonged exercise training on integrated cardiovascular regulation. In the present study, we modified and applied this to investigate the effect of 2years of high-intensity training on circulatory components to tease out the primary effects of training. Our method incorporated the dynamic Starling mechanism, dynamic arterial elastance and arterial-cardiac baroreflex function. The dynamic Starling mechanism gain and arterial-cardiac baroreflex gain were significantly increased in the exercise group. These parameters remained unchanged in the controls. Conversely, neither group experienced a change in dynamic arterial elastance. The integrated cardiovascular regulation gain in the exercise group was 1.34-fold larger than that in the control group after the intervention. In these previously sedentary, otherwise healthy, middle-aged adults, 2 years of high-intensity exercise training improved integrated cardiovascular regulation by enhancing the dynamic Starling mechanism and arterial-cardiac baroreflex sensitivity. Assessing the effects of exercise training on cardiovascular variability is challenging because of the complexity of multiple mechanisms. In a prospective, parallel-group, randomized controlled study, we examined the effect of 2years of high-intensity exercise training on integrated cardiovascular function, which incorporates the dynamic Starling mechanism, dynamic arterial elastance and arterial-cardiac baroreflex function. Sixty-one healthy participants (48% male, aged 53years, range 52-54years) were randomized to either 2years of exercise training (exercise group: n= 34) or control/yoga group (controls: n= 27). Before and after 2years, subjects underwent a 6min recording of beat-by-beat pulmonary artery diastolic pressure (PAD), stroke volume index (SVindex), systolic blood pressure (sBP) and RR interval measurements with controlled respiration at 0.2Hz. The dynamic Starling mechanism, dynamic arterial elastance and arterial-cardiac baroreflex function were calculated by transfer function gain between PAD and SVindex; SVindex and sBP; and sBP and RR interval, respectively. Fifty-three participants (controls: n= 25; exercise group: n= 28) completed the intervention. After 2years, the dynamic Starling mechanism gain (Group× Time interaction: P= 0.008) and the arterial-cardiac baroreflex gain (P= 0.005) were significantly increased in the exercise group but remained unchanged in the controls. There was no change in dynamic arterial elastance in either of the two groups. The integrated cardiovascular function gain in the exercise group increased 1.34-fold, whereas there was no change in the controls (P= 0.02). In these previously sedentary, otherwise healthy middle-aged adults, a 2year programme of high-intensity exercise training improved integrated cardiovascular regulation by enhancing the dynamic Starling mechanism and arterial-cardiac baroreflex sensitivity, without changing dynamic arterial elastance.

Reversing the Cardiac Effects of Sedentary Aging in Middle Age-A Randomized Controlled Trial: Implications For Heart Failure Prevention.

Poor fitness in middle age is a risk factor for heart failure, particularly heart failure with a preserved ejection fraction. The development of heart failure with a preserved ejection fraction is likely mediated through increased left ventricular (LV) stiffness, a consequence of sedentary aging. In a prospective, parallel group, randomized controlled trial, we examined the effect of 2 years of supervised high-intensity exercise training on LV stiffness. Sixty-one (48% male) healthy, sedentary, middle-aged participants (53±5 years) were randomly assigned to either 2 years of exercise training (n=34) or attention control (control; n=27). Right heart catheterization and 3-dimensional echocardiography were performed with preload manipulations to define LV end-diastolic pressure-volume relationships and Frank-Starling curves. LV stiffness was calculated by curve fit of the diastolic pressure-volume curve. Maximal oxygen uptake (Vo2max) was measured to quantify changes in fitness. Fifty-three participants completed the study. Adherence to prescribed exercise sessions was 88±11%. Vo2max increased by 18% (exercise training: pre 29.0±4.8 to post 34.4±6.4; control: pre 29.5±5.3 to post 28.7±5.4, group×time P<0.001) and LV stiffness was reduced (right/downward shift in the end-diastolic pressure-volume relationships; preexercise training stiffness constant 0.072±0.037 to postexercise training 0.051±0.0268, P=0.0018), whereas there was no change in controls (group×time P<0.001; pre stiffness constant 0.0635±0.026 to post 0.062±0.031, P=0.83). Exercise increased LV end-diastolic volume (group×time P<0.001), whereas pulmonary capillary wedge pressure was unchanged, providing greater stroke volume for any given filling pressure (loading×group×time P=0.007). In previously sedentary healthy middle-aged adults, 2 years of exercise training improved maximal oxygen uptake and decreased cardiac stiffness. Regular exercise training may provide protection against the future risk of heart failure with a preserved ejection fraction by preventing the increase in cardiac stiffness attributable to sedentary aging. URL: https://www.clinicaltrials.gov. Unique identifier: NCT02039154.

Are There Clinical Cardiac Complications From Too Much Exercise?

The dose-response association between physical activity and cardiovascular outcomes is well described (10). As little as 15 min·d−1 of moderate-intensity exercise significantly lowers the risk for cardiovascular morbidity and mortality. Greater volumes yield greater cardiovascular benefit. However, the impact of extreme volumes of exercise on cardiovascular health is under debate (9), because some studies present evidence of adverse clinical outcomes in endurance athletes who perform exercise volumes at the extreme upper end of the physical activity continuum. These observations raise the possibility that high doses of exercise have deleterious cardiac effects.

Effects of exercise training on carotid intima-media thickness in patients with type 2 diabetes and coronary artery disease. Influence of carotid plaques.

BackgroundCarotid intima-media thickness (cIMT) holds prognostic information for future cardiovascular disease and is associated with the extent of coronary atherosclerosis. We investigated the effect of exercise on cIMT progression in patients with both type 2 diabetes and coronary artery disease (CAD).MethodsPatients with type 2 diabetes and CAD (n = 137) were randomized to exercise training or standard follow-up. The 12 month exercise program contained 150 min weekly of combined aerobic and resistance training. High-resolution ultrasonography of the distal part of the common carotid artery (CCA) was performed to measure cIMT before and after the intervention. The CCA and the carotid bulb were scanned for the presence of atherosclerotic plaques. Differences in changes between the randomized groups were calculated by one-way ANCOVA.ResultsIn the total population no difference in changes of cIMT from baseline to 12 months was observed between the exercise group and controls [−0.016 mm (95 % CI −0.037 to 0.006) vs. −0.007 mm (95 % CI −0.029 to 0.015), p = 0.57]. However, there was a significant interaction between the effect of exercise training and the presence of carotid plaques (p = 0.013), and significant reduced cIMT was demonstrated in the exercise group compared with controls in patients without identified carotid plaques (n = 65) [−0.034 mm (95 % CI −0.060 to 0.008) vs. 0.013 mm (95 % CI −0.011 to 0.038), p = 0.010].ConclusionOne year of exercise training in patients with type 2 diabetes and CAD did not significantly change cIMT progression. However, in patients without identified carotid plaques, beneficial effect of exercise training on cIMT progression was demonstrated.

Effects of exercise training on HbA1c and VO2peak in patients with type 2 diabetes and coronary artery disease: A randomised clinical trial.

Few exercise trials have focused on patients with both type 2 diabetes and coronary artery disease. We investigated the effects of 1 year of exercise training on HbA1c and VO(2peak) in these patients. Patients with type 2 diabetes and coronary artery disease (n = 137) were randomised to combined exercise training or control group. HbA(1c) was measured at the beginning and end of the study. Changes in VO(2peak), and also ventilatory threshold and time to exhaustion, were assessed by cardiopulmonary exercise testing. No differences in changes between the randomised groups were observed in HbA1c and VO(2peak), whereas ventilatory threshold and time to exhaustion increased significantly in the exercise group compared with the controls (p = 0.046 and p = 0.034). In patients without previous acute myocardial infarction and diabetes microvascular complications (n = 46), the exercise group did improve HbA1c and VO(2peak) compared with the controls (p = 0.052 and p = 0.035). No significant effects of exercise training on HbA(1c) or VO(2peak) were observed in patients with type 2 diabetes and coronary artery disease, although improvements were seen in patients without vascular complications beyond coronary artery disease, implying that the degree of vascular disease may influence exercise responses. Ventilatory threshold and time to exhaustion did increase significantly, indicating improved exercise performance despite the minor change in VO(2peak).

A randomised controlled study of the long-term effects of exercise training on mortality in elderly people: study protocol for the Generation 100 study

IntroductionEpidemiological studies suggest that exercise has a tremendous preventative effect on morbidity and premature death, but these findings need to be confirmed by randomised trials. Generation 100 is a randomised,...

Circulation: Heart Failure Editors’ Picks

Summary : Lifelong exercise training maintains a youthful compliance of the left ventricle (LV), whereas a year of exercise training started later in life fails to reverse LV stiffening, possibly because of accumulation of irreversible advanced glycation end products. Alagebrium is a novel drug that breaks advanced glycation end product crosslinks and improves LV stiffness in aged animals. In this study, the authors prescribed alagebrium (200 mg daily) or placebo combined with aerobic exercise training or contact control in healthy, sedentary older individuals for 1 year. The authors evaluated overall cardiac function by the use of several modalities, including invasive pressure–volume measurements, exercise testing, and cardiac MRI before and after the training. To the authors’ knowledge, this is the first study to evaluate the effects of alagebrium and exercise training in healthy aged humans. After intervention, exercise training significantly increased exercise capacity, LV mass, and LV end-diastolic volume. Conversely, alagebrium had little effect on exercise capacity or LV geometry. However, alagebrium showed a modest improvement in LV stiffness compared with placebo. This favorable effect of alagebrium on LV stiffness was most prominent in individuals with combined alagebrium and exercise training. Conclusions : Alagebrium had no effect on hemodynamics, LV geometry, or exercise capacity in healthy, previously sedentary seniors. However, it did show a modestly favorable effect on age-associated LV stiffening.1 Summary : Maximum oxygen consumption (peak VO2) and efficiency of ventilation (VE) during exercise (VE/VCO2 slope) are known to stratify adults in heart failure for 1-year survival. On the basis of adult data, a recent American Heart Association scientific statement suggested that peak VO2<50% predicted for age and sex should be considered substantial impairment in exercise performance in children with heart disease and therefore a class I indication for heart transplant listing. This single-center study examined the association of …

The effect of an advanced glycation end-product crosslink breaker and exercise training on vascular function in older individuals: A randomized factorial design trial

Aging leads to accumulation of irreversible advanced glycation end-products (AGEs), contributing to vascular stiffening and endothelial dysfunction. When combined with the AGE-crosslink breaker Alagebrium, exercise training reverses cardiovascular aging in experimental animals. This study is the first to examine the effect of Alagebrium, with and without exercise training, on endothelial function, arterial stiffness and cardiovascular risk in older individuals. Forty-eight non-exercising individuals (mean age 70±4years) without manifest diseases or use of medication were allocated into 4 groups for a 1-year intervention: Exercise training & Alagebrium (200mg/day); exercise training & placebo; no exercise training & Alagebrium (200mg/day); and no exercise training & placebo. We performed a maximal exercise test (VO2max) and measured endothelial function using venous occlusion plethysmography and intra-arterial infusion of acetylcholine, sodium nitroprusside and NG-monomethyl-l-arginine. Arterial stiffness was measured using pulse wave velocity. Cardiovascular risk was calculated using the Lifetime Risk Score (LRS). In the exercise training groups, LRS and VO2max improved significantly (23.9±4.5 to 27.2±4.6mLO2/min/kg, p<0.001). Endothelial response to the vasoactive substances did not change, nor did arterial stiffness in any of the four groups. In conclusion, one year of exercise training significantly improved physical fitness and lifetime risk for cardiovascular disease without affecting endothelial function or arterial stiffness. The use of the AGE-crosslink breaker Alagebrium had no independent effect on vascular function, nor did it potentiate the effect of exercise training. Despite the clinical benefits of exercise training for older individuals, neither exercise training nor Alagebrium (alone or in combination) was able to reverse the vascular effects of decades of sedentary aging.

Cardiovascular Effects of 1 Year of Alagebrium and Endurance Exercise Training in Healthy Older Individuals

Lifelong exercise training maintains a youthful compliance of the left ventricle (LV), whereas a year of exercise training started later in life fails to reverse LV stiffening, possibly because of accumulation of irreversible advanced glycation end products. Alagebrium breaks advanced glycation end product crosslinks and improves LV stiffness in aged animals. However, it is unclear whether a strategy of exercise combined with alagebrium would improve LV stiffness in sedentary older humans. Sixty-two healthy subjects were randomized into 4 groups: sedentary+placebo; sedentary+alagebrium (200 mg/d); exercise+placebo; and exercise+alagebrium. Subjects underwent right heart catheterization to define LV pressure-volume curves; secondary functional outcomes included cardiopulmonary exercise testing and arterial compliance. A total of 57 of 62 subjects (67 ± 6 years; 37 f/20 m) completed 1 year of intervention followed by repeat measurements. Pulmonary capillary wedge pressure and LV end-diastolic volume were measured at baseline, during decreased and increased cardiac filling. LV stiffness was assessed by the slope of LV pressure-volume curve. After intervention, LV mass and end-diastolic volume increased and exercise capacity improved (by ≈8%) only in the exercise groups. Neither LV mass nor exercise capacity was affected by alagebrium. Exercise training had little impact on LV stiffness (training × time effect, P=0.46), whereas alagebrium showed a modest improvement in LV stiffness compared with placebo (medication × time effect, P=0.04). Alagebrium had no effect on hemodynamics, LV geometry, or exercise capacity in healthy, previously sedentary seniors. However, it did show a modestly favorable effect on age-associated LV stiffening. http://www.clinicaltrials.gov. Unique identifier: NCT01014572.

Effect of exercise training combined with isoflavone supplementation on bone and lipids in postmenopausal women: A randomized clinical trial

We determined the effects of 2 years of exercise training and soy isoflavone supplementation on bone mass and lipids in postmenopausal women provided with calcium and vitamin D. Women were randomized to four groups: exercise training (Ex); isoflavone supplementation (Iso: 165 mg/d [105 mg/d aglycone equivalent]); combined Ex and Iso (ExIso); and placebo (control). Exercise included resistance training (2 days/week) and walking (4 days/week). Our primary outcomes were lumbar spine and hip bone mineral density (BMD). Secondary outcomes included hip geometry, tibia and radius speed of sound (SOS), dynamic balance (6 m backward tandem walking), blood lipids, mammography, and endometrial thickness. A total of 351 women (Ex = 86, Iso = 90, ExIso = 87, control = 88) were randomized, with 298 analyzed at 2 years (Ex = 77, Iso = 76, ExIso = 72, control = 73). There was a significant interaction for total hip BMD (p < 0.001) such that ExIso had a greater rate of decrease (absolute change [95% confidence interval] = -0.018 [-0.024, -0.012] g/cm(2) ) than either the Ex or Iso groups alone (-0.005 [-0.01, 0.001] and -0.005 [-0.011, 0.001] g/cm(2) , respectively). There were no differences between groups for changes in lumbar spine BMD and minimal significant changes in hip geometric properties and bone SOS. Exercise groups improved dynamic balance as measured by a decrease in backward tandem walking time over 6 m (p = 0.017). Isoflavone groups decreased low density lipoproteins (Iso: -0.20 [-0.37, -0.02] mmol/L; ExIso: -0.23 [-0.40, -0.06] mmol/L; p = 0.003) compared to non-isoflavone groups (Ex: 0.01 [-0.16, 0.18] mmol/L; control: -0.09 [-0.27, 0.08] mmol/L) and had lower adverse reports of menopausal symptoms (14% versus 33%; p = 0.01) compared to non-isoflavone groups. Isoflavone supplementation did not increase endometrial thickness or abnormal mammograms. We conclude exercise training and isoflavone supplementation maintain hip BMD compared to control, but these two interventions interfere with each other when combined. Isoflavone supplementation decreased LDL and adverse events related to menopausal symptoms.

Physical Activity Is the Key Determinant of Skeletal Muscle Mitochondrial Function in Type 2 Diabetes

Conflicting data exist on mitochondrial function and physical activity in type 2 diabetes mellitus (T2DM) development. The aim was to assess mitochondrial function at different stages during T2DM development in combination with physical exercise in longstanding T2DM patients. We performed cross-sectional analysis of skeletal muscle from 12 prediabetic 11 longstanding T2DM male subjects and 12 male controls matched by age and body mass index. One-year intrasubject controlled supervised exercise training intervention was done in longstanding T2DM patients. Extensive ex vivo analyses of mitochondrial quality, quantity, and function were collected and combined with global gene expression analysis and in vivo ATP production capacity after 1 yr of training. Mitochondrial density, complex I activity, and the expression of Krebs cycle and oxidative phosphorylation system-related genes were lower in longstanding T2DM subjects but not in prediabetic subjects compared with controls. This indicated a reduced capacity to generate ATP in longstanding T2DM patients only. Gene expression analysis in prediabetic subjects suggested a switch from carbohydrate toward lipid as an energy source. One year of exercise training raised in vivo skeletal muscle ATP production capacity by 21 ± 2% with an increased trend in mitochondrial density and complex I activity. In addition, expression levels of β-oxidation, Krebs cycle, and oxidative phosphorylation system-related genes were higher after exercise training. Mitochondrial dysfunction is apparent only in inactive longstanding T2DM patients, which suggests that mitochondrial function and insulin resistance do not depend on each other. Prolonged exercise training can, at least partly, reverse the mitochondrial impairments associated with the longstanding diabetic state.

Comparison Of Aerobic To Resistance Exercise In Older Breast Cancer Survivors: Preliminary Findings From A One-year RCT

Exercise may be particularly important for older breast cancer survivors (BCS) because of the combined impact of treatment plus aging on their physical health; however, studies specific to older BCS are lacking. PURPOSE: The purpose of this study was to compare the relative benefits of aerobic exercise and resistance exercise on physical functioning and body size in inactive, older (aged 65+) BCS who had completed primary treatment. METHODS: Early-stage, older BCS (mean age: 73 yrs) who were at least 2 years past radiation and/or chemotherapy were randomized to one year of strength training (STR), aerobic training (AER) or a control program of flexibility training (FLEX). Data from BCS who completed baseline, 6 and 12 month testing were used for preliminary analysis (STR: n=30, AER: n=29; FLEX: n=25). Primary outcomes were lower and upper body strength measured by 1-RM leg press (LPmax) and bench press (BPmax); time to rise from a chair 5 times (Chair); time to walk 4m at an usual pace (UW; m/s); distance walked in 6 min (6MW); and body weight. Separate 3 × 3 repeated measures ANOVAs were used to determine significant main effects of time and group × time interactions for each primary outcome. RESULTS: There were significant main effects for all outcome measures, except for weight, where improvements occurred over time for all groups (Table 1). There were no significant group x time interactions for any measure. CONCLUSIONS: These preliminary findings suggest that one year of exercise training, independent of exercise mode, may improve physical function in older BCS. However, it remains possible that observed changes simply represent population changes over time or a learning effect on effort-dependent tests. Supported by NIH grant R01 CA120123Table 1: Percent improvement in physical function and body weight after one year of exercise training in older BCS.

Cardiovascular Effects of 1 Year of Progressive and Vigorous Exercise Training in Previously Sedentary Individuals Older Than 65 Years of Age

Healthy but sedentary aging leads to cardiovascular stiffening, whereas life-long endurance training preserves left ventricular (LV) compliance. However, it is unknown whether exercise training started later in life can reverse the effects of sedentary behavior on the heart. Twelve sedentary seniors and 12 Masters athletes were thoroughly screened for comorbidities. Subjects underwent invasive hemodynamic measurements with pulmonary artery catheterization to define Starling and LV pressure-volume curves; secondary functional outcomes included Doppler echocardiography, magnetic resonance imaging assessment of cardiac morphology, arterial stiffness (total aortic compliance and arterial elastance), and maximal exercise testing. Nine of 12 sedentary seniors (70.6±3 years; 6 male, 3 female) completed 1 year of endurance training followed by repeat measurements. Pulmonary capillary wedge pressures and LV end-diastolic volumes were measured at baseline, during decreased cardiac filling with lower-body negative pressure, and increased filling with saline infusion. LV compliance was assessed by the slope of the pressure-volume curve. Before training, Vo(2)max, LV mass, LV end-diastolic volume, and stroke volume were significantly smaller and the LV was less compliant in sedentary seniors than Masters athletes. One year of exercise training had little effect on cardiac compliance. However, it reduced arterial elastance and improved Vo(2)max by 19% (22.8±3.4 versus 27.2±4.3 mL/kg/mL; P<0.001). LV mass increased (10%, 64.5±7.9 versus 71.2±12.3 g/m(2); P=0.037) with no change in the mass-volume ratio. Although 1 year of vigorous exercise training did not appear to favorably reverse cardiac stiffening in sedentary seniors, it nonetheless induced physiological LV remodeling and imparted favorable effects on arterial function and aerobic exercise capacity.