Cardiac functional adaptation to resistance and endurance exercise training: a randomized crossover study.

Few training studies have assessed the impact of different modes of exercise on changes in cardiac function. This study investigated changes in left ventricular (LV) systolic and diastolic function following endurance (END) and resistance (RES) training in healthy participants. Sixty-four individuals participated in a randomized crossover design trial, involving 12 wk of END and RES training, separated by a 12-wk washout. Echocardiograms assessed systolic function [ejection fraction (EF) and global longitudinal strain (GLS)], diastolic function [mitral valve early velocity (E), tissue Doppler velocity (e'), their ratio (E/e')], and left atrial volume indexed to body surface area (LA ESVi). LV mass (LVM) increased with both RES (Δ5.3 ± 11.9, P = 0.001) and END (Δ7.5 ± 13.9, P < 0.001). Once adjusted for lean body mass (LVMi), changes remained significant following END. E/e' improved following END (Δ-0.35 ± 0.98, P = 0.011) not RES (Δ0.35 ± 1.11, P =0.157; P = 0.001 between modes). LA ESVi increased with END (Δ2.0 ± 6.1, P = 0.019) but not RES (Δ1.7 ± 5.7, P = 0.113). EF and GLS were not impacted significantly by either mode of training. Adaptation in LVM and LA volumes, as well as diastolic function, was exercise mode specific. Twelve weeks of intensive END increased LVM, LA volumes, and increased diastolic function. Following RES, LVM increased, although this was attenuated after accounting for changes in lean body mass. There were no changes in systolic function following either mode of exercise training.NEW & NOTEWORTHY Different types of exercise training induce distinct physiological adaptations however few exercise training studies have assessed the impact of different modes of exercise on cardiac function. This study investigated changes in left ventricular systolic and diastolic function following exercise training. Participants completed both endurance and resistance training separated by a 12-wk washout period so each participant is their own control. We present adaptations in cardiac structure and diastolic function are exercise mode specific.

Exercise and Artery Function in Twins: Sex Differences in a Cross-Over Trial.

BACKGROUND: Physical activity reduces cardiovascular risk, partly via direct effects on the arterial wall. We hypothesized that vascular function responses would be modality-specific, sex-dependent, and express a high degree of heritability. METHODS: We recruited 90 same-sex twins (31 monozygotic, 14 dizygotic dizygotic pairs; 25.8±6.0 years) and randomized 70 (25 monozygotic, 10 dizygotic) to complete, as pairs, 3 months each of resistance and endurance training, separated by a 3-month washout. RESULTS: Brachial artery flow-mediated (FMD%) and glyceryl-trinitrate induced dilation (GTN%) both increased following endurance (FMD%: ∆1.46%, P<0.001; GTN%: ∆1.76%, P=0.004) and resistance (FMD%: ∆1.73%, P<0.001; GTN%: ∆1.68%, P=0.045). About one-third of participants failed to respond to one or other mode; 10% failed to respond to both for FMD% (17% for GTN%). FMD% and GTN% increased significantly in response to both resistance and endurance in females (P<0.05), but not males. Twin analysis revealed that responses to both FMD% and GTN% with exercise training for both modalities were dependent on factors shared by monozygotic pairs and that a large contribution from genetic effects is unlikely. CONCLUSIONS: Our findings indicate that both endurance and resistance can enhance vascular function and that responses in females were more marked. Most individuals respond to one or other form of training, with few unresponsive to both; a finding that has implications for optimizing exercise-based approaches for individualized benefit. Focusing on characteristics of exercise prescription may be more important than the impact of distinct candidate genes when considering exercise as a form of vascular medicine. REGISTRATION: URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=371222; Unique identifier: ACTRN 12616001095459.

Sex differences in cardiovascular risk factor responses to resistance and endurance training in younger subjects.

This study compared differences in cardiovascular (CV) risk factor responses between males and females following endurance (END) and resistance (RES) training. We present the frequency of responders to each training modality and the magnitude of response. Using a randomized crossover design, 68 healthy adults [age: female (F): 24.5 ± 4.6; male (M): 27.3 ± 6.6] completed 3 mo of RES and END, with 3 mo washout. Peak oxygen consumption (V̇o2peak), strength, body composition, blood pressure, glucose, insulin, and lipids were measured. V̇o2peak (L/min) significantly increased in both sexes following END, but not RES. The magnitude of change was larger in males (F: +0.20 L/min; M: +0.32 L/min), although this did not achieve statistical significance (P = 0.051). Strength significantly increased in both sexes following RES (P < 0.01), with a larger increase in males (Leg press: F: +39 kg; M: +63 kg; P < 0.05). Lean mass significantly increased in both sexes (P < 0.01) following RES and fat mass decreased in females following END (P = 0.019). The change in C-reactive protein following END was significantly different between sexes (F: -0.4 mg/L; M: +0.5 mg/L; P = 0.035). There were no differences between sexes in the proportion of individuals who responded positively to any variable following RES or END; differences between sexes were due to the magnitude of change. Males had a larger increase in V̇o2peak following END and strength following RES. There were no sex differences in other CV risk factors. This suggests differences in physiological responses to strength and V̇o2peak may not translate to changes in CV risk in healthy subjects.NEW & NOTEWORTHY This study investigated sex differences in cardiovascular risk factors in response to different exercise training modalities. Males had a larger improvement in peak oxygen consumption following endurance training and strength following resistance training compared with females. These changes in peak oxygen consumption and strength did not translate to changes in other cardiovascular risk factors. Despite the greater magnitude of change in males, there were no sex differences in the proportion of individuals who responded to training.

Endurance versus resistance training in treatment of cardiovascular risk factors: A randomized cross-over trial.

BACKGROUND: Individual variability in traditional cardiovascular risk factor responses to different exercise modalities has not been directly addressed in humans using a randomized cross-over design. METHODS: Body weight and body mass index, resting blood pressure, blood glucose, insulin and lipids were assessed in 68 healthy untrained adults (26±6 years) who underwent three-months of exercise training targeted at improving cardiopulmonary fitness (endurance) and skeletal muscle function (resistance), separated by three-months washout. RESULTS: There were significant increases in weight and body mass index following resistance (+0.8 kg, P<0.01; and +0.26 kg/m2, P<0.01, respectively), but not endurance (+0.1 kg, P = 0.75; and +0.03 kg/m2, P = 0.70, respectively). Although no significant group changes resulted from training in other cardiovascular risk factors, the positive response rate for all variables ranged from 27-49% for resistance and 42-58% for endurance. Between 39-59% of individuals who did not respond to resistance nonetheless responded to endurance, and 28-54% who did not respond to endurance responded to resistance. CONCLUSION: Whilst, on average, 12 weeks of resistance or endurance did not change most cardiovascular risk factors, many subjects showed robust positive responses. Exercise modality had an impact on the proportion of subjects who responded to training, and non-response to one mode of training did not imply non-response to the alternate mode. Although the effect of exercise on a single risk factor may be modest, the effect on overall cardiovascular risk profile can be dramatic. STUDY REGISTRATION: The study was registered at the Australian New Zealand Clinical Trials Registry, which was published prior to recruitment and randomization (ACTRN12616001095459).

Studies of Twin Responses to Understand Exercise THerapy (STRUETH): cerebrovascular function.

We studied monozygotic (MZ) and dizygotic (DZ) twin pairs following resistance (RES) and endurance (END) training to assess genetic and environmental contributions to cerebrovascular function. Cerebrovascular function (rest, autoregulation, hypercapnia, exercise) was assessed in 86 healthy same-sex MZ (30 pairs) and DZ (13 pairs) twins, who underwent 3 months of END and RES. Carbon dioxide ( PETCO2${P_{{\rm{ETC}}{{\rm{O}}_{\rm{2}}}}}$ ), mean arterial pressure (MAP) and middle cerebral artery velocity (MCAv) were measured and MCAv resistance (MCACVRi ) was calculated. Resting MCAv reduced by -2.8 cm/s following RES (P = 0.024), with no change following END (-0.3 cm/s, P = 0.758). Change in MCACVRi following RES was +0.11 mmHg/cm/s (P < 0.001), which was significantly greater than END (+0.02 mmHg/cm/s, P = 0.030). MAP also increased following RES (+4 mmHg, P = 0.010), but not END (+1 mmHg, P = 0.518). No changes were apparent in PETCO2${P_{{\rm{ETC}}{{\rm{O}}_{\rm{2}}}}}$ . At rest, positive response rates following RES ranged from 27 to 71% and from 40 to 64% following END. Intraclass correlations between twins were moderate for most variables at baseline. In response to training, only MZ pairs were significantly correlated for a change in MCAv (P = 0.005) and low frequency phase (P = 0.047) following RES.This study is the first to compare cerebrovascular function following RES and END in MZ and DZ twins. Most individuals who did not respond to one modality were able to respond by switching modality, and baseline heritability estimates were higher than training response. Exercise professionals should therefore consider modality and environmental factors when optimising interventions. KEY POINTS: Characterising individual responses to resistance and endurance exercise training can inform optimal strategies for exercise prescription. This study utilised monozygotic and dizygotic twins in a randomised cross-over study to determine individual responsiveness to different modalities of exercise training. The influence of environment vs. genetics on cerebrovascular responses to training was determined. It is apparent that individuals respond differently to distinct exercise stimuli and that switching modality may be a beneficial way to obtain positive responses in cerebrovascular function. This study has implications for improving individualised exercise prescription to maintain or improve cerebrovascular structure and function.

Left Ventricular Adaptation to Exercise Training via Magnetic Resonance Imaging: Studies of Twin Responses to Understand Exercise THerapy.

PURPOSE: Changes in left ventricular mass (LVM) and end-diastolic volume (EDV) in response to exercise training are important determinants of functional capacity in health and disease, but the impact of different exercise modalities remains unclear. METHODS: Using a randomized crossover design we studied the impact of resistance (RES) and endurance (END) training using cardiac magnetic resonance imaging in previously untrained monozygotic (MZ) and dizygotic (DZ) twin pairs (n = 72; 22 MZ pairs, 14 DZ same-sex pairs; 26.1 ± 5.4 yr). Twins, as pairs, undertook 3 months of RES and 3 months of END training (order randomized), separated by a 3-month washout. RESULTS: Group results revealed that END increased LVM (P < 0.001) and EDV (P = 0.007), whereas RES did not (P > 0.05). A higher proportion of individuals responded to END than RES for LVM (72% vs 38%, P < 0.001) and EDV (67% vs 40%, P = 0.003). Baseline cross-sectional intraclass correlations were higher for MZ than DZ twin pairs for all variables (e.g., LVM heritability = 0.42), but no significant correlations were apparent between pairs for change in any variable in response to either RES or END (P > 0.05). CONCLUSIONS: Our findings indicate that cardiac adaptation in response to exercise is modality-specific and that low responders to one mode of exercise can be high responders to an alternative. Heritability estimates based on cross-sectional data, which suggested a genetic contribution to LVM, do not accord with estimates based on training effects, which indicated limited genetic impact on adaptation in this 3-month study of exercise training. This study has implications for understanding the physiological and health impacts of typically used exercise modalities on cardiac adaptation in previously untrained individuals.

Resistance, but not endurance exercise training, induces changes in cerebrovascular function in healthy young subjects.

It is generally considered that regular exercise maintains brain health and reduces the risk of cerebrovascular diseases such as stroke and dementia. Since the benefits of different "types" of exercise are unclear, we sought to compare the impacts of endurance and resistance training on cerebrovascular function. In a randomized and crossover design, 68 young healthy adults were recruited to participate in 3 mo of resistance and endurance training. Cerebral hemodynamics through the internal carotid, vertebral, middle and posterior cerebral arteries were measured using Duplex ultrasound and transcranial Doppler at rest and during acute exercise, dynamic autoregulation, and cerebrovascular reactivity (to hypercapnia). Following resistance, but not endurance training, middle cerebral artery velocity and pulsatility index significantly decreased (P < 0.01 and P = 0.02, respectively), whereas mean arterial pressure and indices of cerebrovascular resistance in the middle, posterior, and internal carotid arteries all increased (P < 0.05). Cerebrovascular resistance indices in response to acute exercise and hypercapnia also significantly increased following resistance (P = 0.02), but not endurance training. Our findings, which were consistent across multiple domains of cerebrovascular function, suggest that episodic increases in arterial pressure associated with resistance training may increase cerebrovascular resistance. The implications of long-term resistance training on brain health require future study, especially in populations with pre-existing cerebral hypoperfusion and/or hypotension.NEW & NOTEWORTHY Three months of endurance exercise did not elicit adaptation in any domain of cerebrovascular function in young healthy inactive volunteers. However, resistance training induced decreased pulsatility in the extracranial arteries and increased indices of cerebrovascular resistance in cerebral arteries. This increase in cerebrovascular resistance, apparent at baseline and in response to both hypercapnia and acute exercise, may reflect a protective response in the face of changes in arterial pressure during resistance exercise.

Sex Differences in Cardiac Adaptation to Distinct Modalities of Exercise: A Cardiac Magnetic Resonance Study.

PURPOSE: No previous study has described sex differences in chronic cardiac adaptation in response to distinct modalities of exercise training in humans. METHODS: Cardiac magnetic resonance imaging (1.5 T) was used to assess left ventricular (LV) outcomes in 78 untrained subjects (46F, 26 M; 26.1 ± 5.4 yr). Subjects underwent 3 months of closely supervised and monitored resistance (RES) and endurance (END) training, separated by a 3-month washout period. RESULTS: LV mass (LVM) increased in response to END in both sexes (females △3.98 ± 7.98 g, P = 0.002; males △5.99 ± 10.67 g, P = 0.005), whereas LV end-diastolic volume (EDV) increased in males (△7.48 ± 11.91 mL, P = 0.002) but not females (△1.54 ± 10.49 mL, P = 0.373). In response to RES, LVM and EDV did not increase in either sex. The proportion of subjects exhibiting a positive response to training (i.e., a change >0) for LVM and EDV did not differ between sexes for either training modality. CONCLUSION: Eccentric hypertrophy in response to END training was more apparent in males than females, whereas there were no notable cardiac changes between sexes for RES training. The proportion of low versus high responders to training was not sex specific for LVM or EDV in response to either commonly prescribed exercise training modality.

Studies of Twin Responses to Understand Exercise Therapy (STRUETH): Body Composition.

PURPOSE: We studied individual variability in exercise responses in twins. We hypothesized that 1) endurance (END) training would reduce fat mass whereas resistance (RES) training would increase lean mass, 2) individuals who did not respond to one modality would respond to the other, and 3) cross-sectional heritability estimates would be higher than estimates based on training responses. METHODS: DXA was undertaken in 84 same-sex untrained twins (30 monozygotic [MZ], 12 dizygotic [DZ]). Participants underwent 3 months of END and RES training, separated by 3 months washout. Twins trained in pairs. RESULTS: RES (P < 0.001) and END (P = 0.002) increased lean mass, with a greater change in RES (P < 0.001). Similarly, RES (P = 0.04) and END (P = 0.006) decreased fat mass. Eighty-four percent of subjects responded positively to RES for lean mass and 58% to END (P < 0.001). For fat mass, RES and END induced 56% and 66% responder rates, respectively (P = 0.28). Cross-sectional intraclass correlations, used to assess the similarity in twin responses, were higher for MZ than DZ pairs for all variables. Following training, only MZ pairs were significantly correlated (P < 0.001) for change in lean mass to RES. CONCLUSION: To our knowledge, this study is the first to report individual responsiveness in body composition to both RES and END in the same subjects. Although RES and END induced favorable changes in fat mass, RES was superior for lean mass. The frequency of lean mass responders to RES exceeded that for END, whereas response rates for fat mass were similar. Cross-sectional heritability estimates were higher than training response estimates, and shared environment had the largest influence on changes in body composition. This study suggests that exercise professionals should consider modality and environmental factors when optimizing exercise interventions.

Assessment of cerebrovascular responses to physiological stimuli in identical twins using multimodal imaging and computational fluid dynamics.

There is acknowledged variability in the Circle of Willis (CoW) in the general population, yet the structure and function relationship of the cerebrovasculature is poorly understood. We aimed to demonstrate the feasibility of combining high-resolution imaging techniques and computational fluid dynamics (CFD) to describe cerebrovascular structure and function in vivo. We tested our methodology by examining the null hypothesis that monozygotic twins (18-30 yr) would exhibit similar CoW structure and function. Six twin pairs underwent 3T magnetic resonance angiography of the head and neck and B-mode Doppler ultrasound for velocity and diameter recordings in the vertebral and internal carotid arteries under three conditions (rest, hypercapnia, and exercise). Artery diameter, length, tortuosity, and bifurcation angle were assessed in regions of interest of the CoW. We simulated hemodynamics to determine the cardiac-cycle time-averaged wall shear stress (TAWSS), oscillatory shear index (OSI), and relative residence time (RRT). We observed low and insignificant intraclass correlations (ICC) between twins in all regions for diameter (ICC range 0.000-0.657, P > 0.05), two of four regions for length (ICC range 0.355-0.368, P > 0.05), all regions for tortuosity (ICC range 0.270-0.505, P > 0.05), and all bifurcation angles (ICC range 0.000-0.547, P > 0.05). Similarly, no significant correlations were apparent for cerebral blood flow or CFD-derived measures of TAWSS, OSI, and RRT, at rest or in response to hypercapnia or exercise. Therefore, differences exist in CoW structure and associated shear stress in response to physiological stimulation. These data suggest that the structure, function, and health of cerebrovascular arteries are not primarily genetically dependent.NEW & NOTEWORTHY There is acknowledged variability in the Circle of Willis in the general population, yet the structure and function relationship of the cerebrovasculature is poorly understood. Using a combination of magnetic resonance imaging, high-resolution Doppler ultrasound, and computational fluid dynamic modeling, we show that monozygotic twins exhibit differences in cerebrovascular structure and function when exposed to physiological stimuli. These data suggest that the morphology, function, and health of cerebrovascular arteries are not primarily genetically determined.

Visualizing and quantifying cutaneous microvascular reactivity in humans by use of optical coherence tomography: impaired dilator function in diabetes.

The pathophysiology and time course of impairment in cutaneous microcirculatory function and structure remain poorly understood in people with diabetes, partly due to the lack of investigational tools capable of directly imaging and quantifying the microvasculature in vivo. We applied a new optical coherence tomography (OCT) technique, at rest and during reactive hyperemia (RH), to assess the skin microvasculature in people with diabetes with foot ulcers (DFU, n = 13), those with diabetes without ulcers (DNU, n = 9), and matched healthy controls (CON, n = 13). OCT images were obtained from the dorsal part of the foot at rest and following 5 min of local ischemia induced by inflating a cuff around the thigh at suprasystolic level (220 mmHg). One-way ANOVA was used to compare the OCT-derived parameters (diameter, speed, flow rate, and density) at rest and in response to RH, with repeated-measures two-way ANOVA performed to analyze main and interaction effects between groups. Data are means ± SD. At rest, microvascular diameter in the DFU (84.89 ± 14.84 µm) group was higher than CON (71.25 ± 7.6 µm, P = 0.012) and DNU (71.33 ± 12.04 µm, P = 0.019) group. Speed in DFU (65.56 ± 4.80 µm/s, P = 0.002) and DNU (63.22 ± 4.35 µm/s, P = 0.050) were higher than CON (59.58 ± 3.02 µm/s). Microvascular density in DFU (22.23 ± 13.8%) was higher than in CON (9.83 ± 2.94%, P = 0.008), but not than in the DNU group (14.8 ± 10.98%, P = 0.119). All OCT-derived parameters were significantly increased in response to RH in the CON group (all P < 0.01) and DNU group (all P < 0.05). Significant increase in the DFU group was observed in speed (P = 0.031) and density (P = 0.018). The change in density was lowest in the DFU group (44 ± 34.1%) compared with CON (199.2 ± 117.5%, P = 0.005) and DNU (148.1 ± 98.4, P = 0.054). This study proves that noninvasive OCT microvascular imaging is feasible in people with diabetes, provides powerful new physiological insights, and can distinguish between healthy individuals and patients with diabetes with distinct disease severity.

Exploring human trainability: Design and rationale of Studies of Twin Responses to Understand Exercise as a Therapy (STRUETH) study.

BACKGROUND: Exercise confers myriad health benefits and physical inactivity is a modifiable risk factor for many non-communicable chronic diseases. However, individual responsiveness to guideline-based exercise programs is idiosyncratic for health and fitness outcomes. It is not known whether the response of individuals to distinct exercise modalities tend to be concordant or whether there is a genetic contribution to variation in exercise responsiveness. METHODS/DESIGN: Healthy, young adult (16-40yrs) monozygotic (MZ) and dizygotic (DZ) twin pairs were recruited and randomly assigned to 3 months of endurance or resistance exercise training. Twin pairs trained together. After 3 months of training in their randomly assigned mode, a washout period of 3 months was observed before twin pairs crossed over to complete 3 months of the alternate exercise intervention. Measures of cardiac morphology and function, cerebrovascular function, cognitive performance, peripheral artery function, biochemistry, blood pressure, body composition, skeletal muscle strength and cardiopulmonary fitness were collected before and after each exercise intervention (i.e. at weeks 0, 12, 24 and 36). DISCUSSION: We adopted exercise modalities that produce distinct haemodynamic and physiological stimuli for physiological adaptation and recruited MZ and DZ twin pairs to address questions such as; do individuals exhibit concordant responses to distinct exercise modalities? and what is the genetic contribution to adaptation resulting from distinct training modalities? The results of this study will provide insight into the genetic and environmental contribution to exercise response to distinct modes of training, with implications for determining the optimal approaches to exercise prescription.

Fitness and strength responses to distinct exercise modes in twins: Studies of Twin Responses to Understand Exercise as a THerapy (STRUETH) study.

KEY POINTS: Exercise is considered medicine; however, the individual degree of responsiveness to a standardized dose of exercise is idiosyncratic. Individual responsiveness between distinct exercise modalities and the genetic/environmental contributions to exercise response are not well understood. In this novel randomized cross-over design study, monozygotic and dizygotic twins, as pairs, underwent 3 months of resistance and endurance training, separated by a 3 month washout period, aiming to assess training responses in strength and fitness outcomes to dichotomous training modalities, as well as the genetic/environmental contributions to exercise response. Our findings indicate that (i) individual responsiveness differs between exercise modalities; (ii) low-responders to one mode may be 'rescued' by switching to an alternate mode of exercise; and (iii) genes may not play as large a role, as previously estimated from cross-sectional data, for exercise training adaptation. The present study has implications for those charged with optimizing the benefits of exercise by means of individualizing the exercise prescription. ABSTRACT: Exercise response is idiosyncratic, although the degree of responsiveness, concordance in response between modalities and genetic contribution to responsiveness are not well understood. We investigated this using a novel randomized cross-over design of dichotomous exercise interventions in mono-(MZ) and di-zygotic (DZ) twin pairs. We studied strength (1RM) and fitness ( V̇O2max ) responses in 84 same-sex untrained twins (30 MZ, 12 DZ pairs; 24.9 ± 5.4 years). Twins, as pairs, underwent 3 months of resistance (RES) and endurance (END) training, separated by a 3 month washout period. Training responses and genetic/environmental contributions to responses were assessed. Leg strength 1RM increased following RES but not END (△47 ± 29 vs. 3 ± 26 kg; P < 0.001), whereas V̇O2max increased following END but not RES (△0.25 ± 0.26 vs. 0.04 ± 0.25 L min-1 ; P < 0.001). A higher percentage of individuals responded to RES for strength and to END for V̇O2max (P < 0.0001). Within-individual responses to each mode were not correlated (P > 0.05). Cross-sectional intraclass correlations were higher for MZ than DZ pairs for all variables, largely as a result of shared environment. Following training, MZ, but not DZ pairs, were significantly correlated for strength change to RES (rMZ = 0.62, P = 0.002) and END (rMZ = 0.36, P = 0.04), and for V̇O2max change to END (L min-1 , rMZ = 0.45, P = 0.02) with a mixture of unshared/shared environmental contributions. Our findings indicate that individual responsiveness differs between modalities and low-responders to one mode may be 'rescued' by switching to an alternate mode. Additionally, genes may not play as large a role as previously estimated from cross-sectional data for training adaptation, and/or cross-sectional data do not reflect longitudinal training effects. The present study has implications for optimizing the individualization of exercise prescription.

Early markers of cardiovascular injury in childhood leukaemia survivors treated with anthracycline chemotherapy.

BACKGROUND: Cardiovascular disease (CVD) is the leading non-malignant cause of death in childhood cancer survivors. Heightened risk of CVD is often attributable to treatment with anthracycline chemotherapy. Anthracycline-mediated cardiac injury may lie latent for years following cessation of treatment and is therefore often not detected until disease is advanced and aggressive therapy is required. Symptomatic CVD may be preceded by subclinical cardiac and vascular dysfunction. This study aimed to determine whether such dysfunction could be detected in healthy, anthracycline-treated survivors of childhood leukaemia. METHODS: Cardiac magnetic resonance imaging (cMRI) with late gadolinium enhancement and endothelial function were used to characterise pre-clinical stages of CVD. Twenty-two long-term (>5 years survival; age 21 ± 3 years) childhood leukaemia survivors were assessed. All survivors were asymptomatic and had normal resting echocardiography. To exclude potential confounding effects of radiotherapy, no survivors had received this treatment. Twenty-two similarly aged (25 ± 3 years) gender-matched controls were recruited for comparison. RESULTS: Left ventricular ejection fraction was lower in the survivors (55.0 ± 4.6%) compared to the controls (59.4 ± 6.2%; p = 0.010). Further, five survivors (23%) had clinically reduced (<50%) left ventricular ejection fraction. Normalised left ventricular end systolic volume was augmented in survivors (40.0 ± 9.1 mL·m2 vs. 34.5 ± 7.5 mL·m2; p = 0.038). Cardiac MRI did not show any late gadolinium enhancement. High resolution, ultrasound-derived flow mediated dilation was impaired in survivors (6.7 ± 2.1% vs. 8.60 ± 1.91%, p = 0.005). CONCLUSIONS: We detected subclinical changes in cardiovascular structure and function indicative of early disease in anthracycline-treated childhood leukaemia survivors with normal echocardiography. Early detection and characterisation of underlying disease allows for timely intervention and improved outcomes in this at-risk population.

Brachial and Cerebrovascular Functions Are Enhanced in Postmenopausal Women after Ingestion of Chocolate with a High Concentration of Cocoa.

Background: Cocoa contains polyphenols that are thought to be beneficial for vascular health.Objective: We assessed the impact of chocolate containing distinct concentrations of cocoa on cerebrovascular function and cognition.Methods: Using a counterbalanced within-subject design, we compared the acute impact of consumption of energy-matched chocolate containing 80%, 35%, and 0% single-origin cacao on vascular endothelial function, cognition, and cerebrovascular function in 12 healthy postmenopausal women (mean ± SD age: 57.3 ± 5.3 y). Participants attended a familiarization session, followed by 3 experimental trials, each separated by 1 wk. Outcome measures included cerebral blood flow velocity (CBFv) responses, recorded before and during completion of a computerized cognitive assessment battery (CogState); brachial artery flow-mediated dilation (FMD); and hemodynamic responses (heart rate and blood pressure).Results: When CBFv data before and after chocolate intake were compared between conditions through the use of 2-factor ANOVA, an interaction effect (P = 0.003) and main effects for chocolate (P = 0.043) and time (P = 0.001) were evident. Post hoc analysis revealed that both milk chocolate (MC; 35% cocoa; P = 0.02) and dark chocolate (DC; 80% cocoa; P = 0.003) induced significantly lower cerebral blood flow responses during the cognitive tasks, after normalizing for changes in arterial pressure. DC consumption also increased brachial FMD compared with the baseline value before chocolate consumption (P = 0.002), whereas MC and white chocolate (0% cocoa) caused no change (P-interaction between conditions = 0.034).Conclusions: Consumption of chocolate containing high concentrations of cocoa enhanced vascular endothelial function, which was reflected by improvements in FMD. Cognitive function outcomes did not differ between conditions; however, cerebral blood flow responses during these cognitive tasks were lower in those consuming MC and DC. These findings suggest that chocolate containing high concentrations of cocoa may modify the relation between cerebral metabolism and blood flow responses in postmenopausal women. This trial was registered at www.ANZCTR.orgau as ACTRN12616000990426.

Consumption of dark chocolate attenuates subsequent food intake compared with milk and white chocolate in postmenopausal women.

BACKGROUND: Chocolate has a reputation for contributing to weight gain due to its high fat, sugar and calorie content. However, the effect of varying concentrations of cocoa in chocolate on energy intake and appetite is not clear. OBJECTIVE: To compare the acute effect of consuming an isocaloric dose of dark, milk and white chocolate on subsequent energy intake, appetite and mood in postmenopausal women. METHODS: Fourteen healthy postmenopausal women (57.6 ± 4.8yr) attended an introductory session followed by three experimental trials performed in a counterbalanced order at a standardised time of day, each separated by one week. Ad libitum energy intake, perceived appetite, mood and appetite-related peptides were assessed in response to consumption of 80% cocoa [dark chocolate], 35% cocoa [milk chocolate] and cocoa butter [white chocolate] (2099 kJ), prepared from a single-origin cacao bean. RESULTS: Ad libitum energy intake was significantly lower following dark (1355 ± 750 kJ) compared with both milk (1693 ± 969 kJ; P = 0.008) and white (1842 ± 756 kJ; P = 0.001) chocolate consumption. Blood glucose and insulin concentrations were transiently elevated in response to white and milk chocolate consumption compared with the dark chocolate (P < 0.05), while pancreatic polypeptide was elevated in response to higher cocoa content chocolate (dark and milk) compared with white chocolate (P < 0.05). No differences in active ghrelin or leptin were observed between conditions, nor was mood altered between conditions (P > 0.05). CONCLUSIONS: Dark chocolate attenuates subsequent food intake in postmenopausal women, compared to the impact of milk and white chocolate consumption.