Physical activity, inactivity and sleep in older patients with coronary artery disease following percutaneous coronary intervention: a longitudinal, observational study.

OBJECTIVES: Physical activity presents an important cornerstone in the management and care of coronary artery disease (CAD) patients following percutaneous coronary intervention (PCI) and research in older patients continues to be overlooked. This study evaluated differences in physical activity, inactivity and sleep of CAD patients following PCI for acute coronary syndrome consisting of ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) and elective admission of stable angina patients over 12 months. METHODS: This was an observational, longitudinal study. Fifty-eight patients were recruited (STEMI, n  = 20, NSTEMI, n  = 18 and stable angina, n  = 20) and completed 7-day monitoring (physical activity, inactivity and sleep) using wrist-worn tri-axial accelerometers (GENEActiv, ActivInsights Ltd, Kimbolton, Cambridgeshire, UK) upon discharge from a tertiary centre and repeated measurements at 3 months ( n  = 43), 6 months ( n  = 40) and 12 months ( n  = 33). RESULTS: Following PCI, CAD patients showed a general trend of increasing light and moderate-vigorous physical activity over the 12-month follow-up. Time in inactivity remained high but decreased over time. Sleep duration and sleep efficiency remained consistent. NSTEMI patients spent less time asleep, more time inactive and less time in light and moderate-vigorous physical activity in comparison to STEMI and stable angina patients. Differences between the groups over time were minimal. CONCLUSION: These findings suggest that older patients with CAD spend long periods in inactivity but the increasing trend of both light and moderate-vigorous physical activity over time presents a positive change in behaviour in the year following PCI.

Muscle Function, Body Composition, Insulin Sensitivity and Physical Activity in Adolescents Born Preterm: Impact of Gestation and Vitamin D Status.

Whilst several studies have explored adolescent metabolic and cognitive function after preterm birth, few have explored muscle function and physical activity. We set out to examine the relationship between gestational age and muscle metabolism in a cohort of adolescents who were born preterm. Participants were recruited from the Newcastle preterm birth growth study cohort. They did not have severe neurological disease and were not on daily medication. Participants underwent an assessment of oxidative muscle function using phosphorus magnetic resonance spectroscopy that included the half-time for recovery of equilibrium of phosphocreatine, τ½PCr. In addition, we measured key variables that might affect muscle function including physical activity levels determined by 3-day accelerometry, body composition using air displacement plethysmography, insulin sensitivity using the homeostatic model assessment/Matsuda index and serum vitamin D concentrations. 60 adolescents (35F) median age 15.6 years (range 12.1−18.8) with a median gestation of 31 weeks (range 24 to 34 weeks) underwent a single assessment. Males were more active and spent less time in sedentary mode. Time spent in light activity was associated with insulin sensitivity (IS) (Matsuda Index; p < 0.05) but there were no strong correlations between activity levels and gestational age. Greater fat mass, waist circumference and body mass index were all associated with lower IS. Gestational age was negatively associated with adjusted measures of oxidative muscle function (τ½PCr). In a stepwise multivariate linear regression model, gestational age at birth was the most significant predictor of oxidative muscle function (p = 0.005). Higher serum vitamin D levels were also associated with faster phosphocreatine recovery time (p = 0.045). Oxidative function in the skeletal muscle of adolescents born preterm is associated with gestational age and vitamin D concentrations. Our study suggests that being born preterm may have a long-term impact on muscle metabolism.

Movement as Medicine for Cardiovascular Disease Prevention: Pilot Feasibility Study of a Physical Activity Promotion Intervention for At-Risk Patients in Primary Care.

BACKGROUND: Physical activity (PA) can reduce cardiovascular disease (CVD) risk factors, and although primary care settings offer a large reach to promote PA and reduce CVD risk, primary health care professionals may lack self-efficacy and tools to effectively promote PA in practice. Movement as Medicine for CVD Prevention is a suite of 2 theory-based, web-based behavioral interventions-one for health care professionals and one for patients-which may offer a pathway for promoting PA and reducing CVD risk in primary care. OBJECTIVE: This study aims to examine the feasibility and possible effects of Movement as Medicine for CVD Prevention. METHODS: This nonrandomized pilot study recruited participants from primary care organizations in the Northeast of England. Enrolled health care professionals followed a theory-based, web-based course on PA counseling and motivational interviewing techniques. After the course, health care professionals delivered behavior change consultations based on motivational interviewing to inactive individuals with >20% risk of developing CVD within 10 years. Patients were then given access to a website based on self-determination and self-regulation theories, which targeted increased levels of PA. Outcomes were assessed at baseline and after 3 months, and patient data were analyzed on an intention-to-treat basis in a multiple imputation data set. RESULTS: Recruitment rates of primary care organizations fell below expectations. A total of 11 health care professionals from 3 enrolled primary care organizations completed the web-based course and reported increases in important theoretical determinants of PA promotion in practice (eg, self-efficacy, Cohen d=1.24, 95% CI 0.67-1.80; and planning, Cohen d=0.85, 95% CI -0.01 to 1.69). A total of 83 patients were enrolled in the study, and 58 (70%) completed both the baseline and 3-month assessments. Compared with baseline, patients had higher levels of objective (Cohen d=0.77, 95% CI 0.13-1.41) but not subjective (Cohen d=0.40, 95% CI -0.03 to 0.83) moderate to vigorous PA at 3 months. Patients also reported higher levels of the PA determinants of intention, self-efficacy, intrinsic motivation, and action planning and action control at 3 months (effect sizes ranged from Cohen d=0.39 to 0.60). CONCLUSIONS: The Movement as Medicine for CVD Prevention intervention seems to have the potential to improve patient PA behaviors and important determinants of health care professionals' PA promotion practices. However, the recruitment rates of primary care organizations in this study were low and would need to be increased to examine the efficacy of the program. This study offers several insights into improving the feasibility of this primary care PA promotion pathway. TRIAL REGISTRATION: ISRCTN Registry ISRCTN14582348; http://www.isrctn.com/ISRCTN14582348.

Feasibility of a Very Low Calorie Diet to Achieve a Sustainable 10% Weight Loss in Patients With Nonalcoholic Fatty Liver Disease.

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is the most common liver condition worldwide. A weight loss goal of ≥10% is the recommended treatment for NAFLD; however, only a minority of patients achieve this level of weight reduction with standard dietary approaches. This study aimed to determine whether a very low calorie diet (VLCD) is an acceptable and feasible therapy to achieve and maintain a ≥10% weight loss in patients with clinically significant NAFLD. METHODS: Patients with clinically significant NAFLD were recruited to a VLCD (∼800 kcal/d) intervention using meal replacement products. Anthropometrics, blood tests (liver and metabolic), liver stiffness, and cardiovascular disease risk were measured at baseline, post-VLCD, and at 9-month follow-up. RESULTS: A total of 45 patients were approached of which 30 were enrolled 27 (90%) completed the VLCD intervention, and 20 (67%) were retained at 9-month follow-up. The VLCD was acceptable to patients and feasible to deliver. Intention-to-treat analysis found that 34% of patients achieved and sustained ≥10% weight loss, 51% achieved ≥7% weight loss, and 68% achieved ≥5% weight loss at 9-month follow-up. For those completing the VLCD, liver health (liver enzymes and liver stiffness), cardiovascular disease risk (blood pressure and QRISK2), metabolic health (fasting glucose, HbA1c, and insulin), and body composition significantly improved post-VLCD and was maintained at 9 months. DISCUSSION: VLCD offers a feasible treatment option for some patients with NAFLD to enable a sustainable ≥10%, weight loss, which can improve liver health, cardiovascular risk, and quality of life in those completing the intervention.

Assessing the feasibility and acceptability of Changing Health for the management of prediabetes: protocol for a pilot study of a digital behavioural intervention.

BACKGROUND: The prevalence of prediabetes is rapidly rising in the UK, largely associated with an increase in obesity. Lifestyle programmes that provide support to make and sustain dietary and physical activity behavioural changes are necessary to initiate and maintain weight loss. However, these programmes are often intensive and time consuming. Given the magnitude of the problem, there is a need for behavioural interventions that can be delivered at scale. Digital interventions can address some of the aforementioned issues. The primary aim of the present study is to assess the feasibility and acceptability of a digital intervention called Changing Health that provides structured education and lifestyle behaviour change support to adults with prediabetes. METHODS: A single-group pilot study will be undertaken. We aim to recruit 40 participants with prediabetes defined by HbA1c or fasting plasma glucose (FPG), aged between 18 and 75 years with a BMI ≥ 25. Participants will receive the digital intervention (a mobile phone app incorporating structured education and behavioural tools to support lifestyle behaviour change) with the aim of losing and maintaining 5-6% of their baseline body weight. Each participant will receive 100 min of lifestyle coaching over the 9-month intervention period and will have continued access to the digital intervention. Clinical outcome measures will be collected during four visits to our clinical research facility: two visits at baseline, one visit at month 3, and one visit at month 9. These secondary outcome measures will include diet, physical activity, sleep, metabolic control, body composition, cardiorespiratory fitness, and cardiovascular function. To measure primary outcomes, an embedded qualitative study will be conducted to obtain data on feasibility and acceptability of the intervention. DISCUSSION: This pilot study will establish whether Changing Health is feasible and acceptable to adults with prediabetes. Clinical outcome measures will provide estimates of variability to inform sample size calculations, and qualitative data generated will inform any necessary refinements to the intervention. This will provide a platform for a larger evaluation to assess the effectiveness of Changing Health for changing diet and physical activity to initiate and maintain weight loss in adults with prediabetes. TRIAL REGISTRATION: ISRCTN Registry: ISRCTN69270299.

The degree of hepatic steatosis associates with impaired cardiac and autonomic function.

BACKGROUND & AIMS: Cardiovascular disease is the principle cause of death in patients with elevated liver fat unrelated to alcohol consumption, more so than liver-related morbidity and mortality. The aim of this study was to evaluate the relationship between liver fat and cardiac and autonomic function, as well as to assess how impairment in cardiac and autonomic function is influenced by metabolic risk factors. METHODS: Cardiovascular and autonomic function were assessed in 96 sedentary individuals: i) non-alcoholic fatty liver disease (NAFLD) (n = 46, hepatic steatosis >5% by magnetic resonance spectroscopy), ii) Hepatic steatosis and alcohol (dual aetiology fatty liver disease [DAFLD]) (n = 16, hepatic steatosis >5%, consuming >20 g/day of alcohol) and iii) CONTROL (n = 34, no cardiac, liver or metabolic disorders, <20 g/day of alcohol). RESULTS: Patients with NAFLD and DAFLD had significantly impaired cardiac and autonomic function when compared with controls. Diastolic variability and systolic variability (LF/HF-sBP [n/1]; 2.3 (1.7) and 2.3 (1.5) vs. 3.4 (1.5), p <0.01) were impaired in patients with NAFLD and DAFLD when compared to controls, with DAFLD individuals showing a decrease in diastolic variability relative to NAFLD patients. Hepatic steatosis and fasting glucose were negatively correlated with stroke volume index. Fibrosis stage was significantly negatively associated with mean blood pressure (r = -0.47, p = 0.02), diastolic variability (r = -0.58, p ≤0.01) and systolic variability (r = -0.42, p = 0.04). Hepatic steatosis was independently associated with cardiac function (p ≤0.01); TNF-α (p ≤0.05) and CK-18 (p ≤0.05) were independently associated with autonomic function. CONCLUSION: Cardiac and autonomic impairments appear to be dependent on level of liver fat, metabolic dysfunction, inflammation and fibrosis staging, and to a lesser extent alcohol intake. Interventions should be sought to moderate the excess cardiovascular risk in patients with NAFLD or DAFLD. LAY SUMMARY: Increased levels of fat in the liver impair the ability of the cardiovascular system to work properly. The amount of fat in the liver, metabolic control, inflammation and alcohol are all linked to the degree that the cardiovascular system is affected.

High intensity interval training protects the heart during increased metabolic demand in patients with type 2 diabetes: a randomised controlled trial.

AIM: The present study assessed the effect of high intensity interval training on cardiac function during prolonged submaximal exercise in patients with type 2 diabetes. METHODS: Twenty-six patients with type 2 diabetes were randomized to a 12 week of high intensity interval training (3 sessions/week) or standard care control group. All patients underwent prolonged (i.e. 60 min) submaximal cardiopulmonary exercise testing (at 50% of previously assess maximal functional capacity) with non-invasive gas-exchange and haemodynamic measurements including cardiac output and stroke volume before and after the intervention. RESULTS: At baseline (prior to intervention) there was no significant difference between the intervention and control group in peak exercise oxygen consumption (20.3 ± 6.1 vs. 21.7 ± 5.5 ml/kg/min, p = 0.21), and peak exercise heart rate (156.3 ± 15.0 vs. 153.8 ± 12.5 beats/min, p = 0.28). During follow-up assessment both groups utilized similar amount of oxygen during prolonged submaximal exercise (15.0 ± 2.4 vs. 15.2 ± 2.2 ml/min/kg, p = 0.71). However, cardiac function i.e. cardiac output during submaximal exercise decreased significantly by 21% in exercise group (16.2 ± 2.7-12.8 ± 3.6 L/min, p = 0.03), but not in the control group (15.7 ± 4.9-16.3 ± 4.1 L/min, p = 0.12). Reduction in exercise cardiac output observed in the exercise group was due to a significant decrease in stroke volume by 13% (p = 0.03) and heart rate by 9% (p = 0.04). CONCLUSION: Following high intensity interval training patients with type 2 diabetes demonstrate reduced cardiac output during prolonged submaximal cardiopulmonary exercise testing. Ability of patients to maintain prolonged increased metabolic demand but with reduced cardiac output suggests cardiac protective role of high intensity interval training in type 2 diabetes. TRIAL REGISTRATION: ISRCTN78698481. Registered 23 January 2013, retrospectively registered.

Unsupervised high-intensity interval training improves glycaemic control but not cardiovascular autonomic function in type 2 diabetes patients: A randomised controlled trial.

BACKGROUND: This is the first randomised controlled trial to assess the impact of unsupervised high-intensity interval training on cardiovascular autonomic function in adults with type 2 diabetes. METHODS: A total of 22 individuals with type 2 diabetes (age 60 ± 2 years, 17 males) lay in a supine position for 20 min for evaluation of cardiovascular autonomic function, which included (1) time domain measures of heart rate variability, (2) frequency domain measures of heart rate variability and blood pressure variability and (3) baroreflex receptor sensitivity. Participants were randomised into 12 weeks of high-intensity interval training (3 sessions/week) or standard care control group. RESULTS: After 12 weeks, the between-group change in HbA1c (%) was significant (high-intensity interval training: 7.13 ± 0.31 to 6.87 ± 0.29 vs Control: 7.18 ± 0.17 to 7.36 ± 0.21, p = 0.03). There were no significant changes in measures of heart rate variability; R-R interval (ms) (high-intensity interval training: 954 ± 49 to 973 ± 53 vs Control: 920 ± 6 to 930 ± 32, p = 0.672), low frequency/high frequency (high-intensity interval training: 0.90 ± 0.21 to 0.73 ± 0.07 vs Control: 1.20 ± 0.29 to 1.00 ± 0.17, p = 0.203), or blood pressure variability; systolic blood pressure low frequency/high frequency (high-intensity interval training: 0.86 ± 0.21 to 0.73 ± 0.10 vs Control: 1.06 ± 0.26 to 0.91 ± 0.14, p = 0.169). At baseline, HbA1c was negatively correlated with baroreflex receptor sensitivity ( r = -0.592, p < 0.01). CONCLUSION: High-intensity interval training improves glycaemic control but has limited effect on cardiovascular autonomic regulation in patients with type 2 diabetes.

Adiposity predicts low cardiorespiratory fitness in individuals with metabolic diseases.

Cardiorespiratory fitness (CRF) is impaired in those with metabolic diseases and strongly predicts mortality. We found that adiposity, not glycaemic control or disease type, is the strongest predictor of low CRF in those with metabolic diseases. We discuss how adiposity and metabolic health may relate to outcomes in obesity.

Accelerometer-derived physical activity in those with cardio-metabolic disease compared to healthy adults: a UK Biobank study of 52,556 participants.

AIM: Cardio-metabolic disease and physical activity are closely related but large-scale objective studies which measure physical activity are lacking. Using the largest accelerometer cohort to date, we aimed to investigate whether there is an association between disease status and accelerometer variables after a 5-year follow-up. METHODS: 106,053 UK Biobank participants wore a wrist-worn GENEactiv monitor. Those with acceptable wear time (> 3 days) were split into 4 cardio-metabolic disease groups based on self-report disease status which was collected 5 ± 1 years prior. Multiple linear regression models were used to investigate associations, controlling for confounders and stratified for gender. RESULTS: Average daily acceleration was lower in men ('healthy'-42 ± 15 mg v 'Type 2 diabetes + cardiovascular disease (CVD)'-31 ± 12 mg) and women ('healthy'-44 ± 13 mg v 'Type 2 diabetes + CVD'-31 ± 11 mg) with cardio-metabolic disease and this was consistent across both week and weekend days. Men and women with the worst cardio-metabolic disease perform around half of moderate to vigorous physical activity on a daily basis compared to healthy individuals, and spend almost 7 h per day in 30 min inactivity bouts. Significant associations were seen between cardio-metabolic disease and accelerometer variables 5 years on when controlling for confounders. CONCLUSION: In the largest accelerometer cohort to date, there are significant associations between cardio-metabolic disease and physical activity variables after 5 years of follow-up. Triaxial accelerometers provide enhanced measurement opportunities for measuring lifestyle behaviours in chronic disease.

Skeletal muscle mitochondrial oxidative phosphorylation function in idiopathic pulmonary arterial hypertension: in vivo and in vitro study.

Mitochondrial dysfunction within the pulmonary vessels has been shown to contribute to the pathology of idiopathic pulmonary arterial hypertension (IPAH). We investigated the hypothesis of whether impaired exercise capacity observed in IPAH patients is in part due to primary mitochondrial oxidative phosphorylation (OXPHOS) dysfunction in skeletal muscle. This could lead to potentially new avenues of treatment beyond targeting the pulmonary vessels. Nine clinically stable participants with IPAH underwent cardiopulmonary exercise testing, in vivo and in vitro assessment of mitochondrial function by 31P-magnetic resonance spectroscopy (31P-MRS) and laboratory muscle biopsy analysis. 31P-MRS showed abnormal skeletal muscle bioenergetics with prolonged recovery times of phosphocreatine and abnormal muscle pH handling. Histochemistry and quadruple immunofluorescence performed on muscle biopsies showed normal function and subunit protein abundance of the complexes within the OXPHOS system. Our findings suggest that there is no primary mitochondrial OXPHOS dysfunction but raises the possibility of impaired oxygen delivery to the mitochondria affecting skeletal muscle bioenergetics during exercise.

Systematic review assessing the effectiveness of dietary intervention on gut microbiota in adults with type 2 diabetes.

AIMS/HYPOTHESIS: Despite improved understanding of the pathophysiology of type 2 diabetes mellitus, explanations for individual variability in disease progression and response to treatment are incomplete. The gut microbiota has been linked to the pathophysiology of type 2 diabetes mellitus and may account for this variability. We conducted a systematic review to assess the effectiveness of dietary and physical activity/exercise interventions in modulating the gut microbiota and improving glucose control in adults with type 2 diabetes mellitus. METHODS: A systematic search was conducted to identify studies reporting on the effect of dietary and physical activity/exercise interventions on the gut microbiota and glucose control in individuals with a confirmed diagnosis of type 2 diabetes mellitus. Study characteristics, methodological quality and details relating to interventions were captured using a data-extraction form. Meta-analyses were conducted where sufficient data were available, and other results were reported narratively. RESULTS: Eight studies met the eligibility criteria of the systematic review. No studies were found that reported on the effects of physical activity/exercise on the gut microbiota and glucose control. However, studies reporting on dietary interventions showed that such interventions were associated with modifications to the composition and diversity of the gut microbiota. There was a statistically significant improvement in HbA1c (standardised mean difference [SMD] -2.31 mmol/mol [95% CI -2.76, -1.85] [0.21%; 95% CI -0.26, -0.16]; I2 = 0%, p < 0.01), but not in fasting blood glucose (SMD -0.25 mmol/l [95% CI -0.85, 0.35], I2 = 87%, p > 0.05), fasting insulin (SMD -1.82 pmol/l [95% CI -7.23, 3.60], I2 = 54%, p > 0.05) or HOMA-IR (SMD -0.15 [95% CI -0.63, 0.32], I2 = 69%, p > 0.05) when comparing dietary interventions with comparator groups. There were no significant changes in the relative abundance of bacteria in the genera Bifidobacterium (SMD 1.29% [95% CI -4.45, 7.03], I2 = 33%, p > 0.05), Roseburia (SMD -0.85% [95% CI -2.91, 1.21], I2 = 79%, p > 0.05) or Lactobacillus (SMD 0.04% [95% CI -0.01, 0.09], I2 = 0%, p > 0.05) when comparing dietary interventions with comparator groups. There were, however, other significant changes in the gut microbiota, including changes at various taxonomic levels, including phylum, family, genus and species, Firmicutes:Bacteroidetes ratios and changes in diversity matrices (α and ß). Dietary intervention had minimal or no effect on inflammation, short-chain fatty acids or anthropometrics. CONCLUSIONS/INTERPRETATION: Dietary intervention was found to modulate the gut microbiota and improve glucose control in individuals with type 2 diabetes. Although the results of the included studies are encouraging, this review highlights the need for further well-conducted interventional studies to inform the clinical use of dietary interventions targeting the gut microbiota.

Comparison of cardiac output estimates by bioreactance and inert gas rebreathing methods during cardiopulmonary exercise testing.

PURPOSE: This study assessed the agreement between cardiac output estimated by inert gas rebreathing and bioreactance methods at rest and during exercise. METHODS: Haemodynamic measurements were assessed in 20 healthy individuals (11 females, nine males; aged 32 ± 10 years) using inert gas rebreathing and bioreactance methods. Gas exchange and haemodynamic data were measured simultaneously under rest and different stages (i.e. 30, 60, 90, 120, 150 and 180 W) of progressive graded cardiopulmonary exercise stress testing using a bicycle ergometer. RESULTS: At rest, bioreactance produced significantly higher cardiac output values than inert gas rebreathing (7·8 ± 1·4 versus 6·5 ± 1·7 l min-1 , P = 0·01). At low-to-moderate exercise intensities (i.e. 30-90 W), bioreactance produced significantly higher cardiac outputs compared with rebreathing method (P<0·05). At workloads of 120 W and above, there was no significant difference in cardiac outputs between the two methods (P = 0·10). There was a strong relationship between the two methods (r = 0·82, P = 0·01). Bland-Altman analysis including rest and exercise data showed that inert gas rebreathing reported 1·95 l min-1 lower cardiac output than bioreactance, with lower and upper limits of agreement of -3·1-7·07 l min-1 . Analysis of peak exercise data showed a mean difference of 0·4 l min-1 (lower and upper limits of agreement of -4·9-5·7 l min-1 ) between both devices. CONCLUSION: Bioreactance and inert gas rebreathing methods show acceptable levels of agreement for estimating cardiac output at higher levels of metabolic demand. However, they cannot be used interchangeably due to strong disparity in results at rest and low-to-moderate exercise intensity.

Impact of Age-Related Mitochondrial Dysfunction and Exercise on Intestinal Microbiota Composition.

Mitochondrial dysfunction is prevalent in the aging gastrointestinal tract. We investigated whether mitochondrial function in aging colonic crypts and exercise influences microbial gut communities in mice. Twelve PolgAmut/mut mice were randomly divided into a sedentary and exercise group at 4 months. Seven-aged matched PolgA+/+ mice remained sedentary throughout. Stool samples were collected at 4, 7, and 11 months, and bacterial profiling was achieved through 16S rRNA sequencing profiling. Mitochondrial enzyme activity was assessed in colonic epithelial crypts at 11 months for PolgAmut/mut and PolgA+/+ mice. Sedentary and exercised PolgAmut/mut mice had significantly higher levels of mitochondrial dysfunction than PolgA+/+ mice (78%, 77%, and 1% of crypts, respectively). Bacterial profiles of sedentary PolgAmut/mut mice were significantly different from the sedentary PolgA+/+ mice, with increases in Lactobacillus and Mycoplasma, and decreases in Alistipes, Odoribacter, Anaeroplasma, Rikenella, Parabacteroides, and Allobaculum in the PolgAmut/mut mice. Exercise did not have any impact upon gut mitochondrial dysfunction; however, exercise did increase gut microbiota diversity and significantly increased bacterial genera Mucispirillum and Desulfovibrio. Mitochondrial dysfunction is associated with changes in the gut microbiota. Endurance exercise moderated some of these changes, establishing that environmental factors can influence gut microbiota, despite mitochondrial dysfunction.

Impact of age on the association between cardiac high-energy phosphate metabolism and cardiac power in women.

OBJECTIVE: Diminished cardiac high-energy phosphate metabolism (phosphocreatine-to-ATP (PCr:ATP) ratio) and cardiac power with age may play an important roles in development of cardiac dysfunction and heart failure. The study defines the impact of age on PCr:ATP ratio and cardiac power and their relationship. METHODS: Thirty-five healthy women (young≤50 years, n=20; and old≥60 years, n=15) underwent cardiac MRI with 31P spectroscopy to assess PCr:ATP ratio and performed maximal graded cardiopulmonary exercise testing with simultaneous gas-exchange and central haemodynamic measurements. Peak cardiac power output, as the best measure of pumping capability and performance of the heart, was calculated as the product of peak exercise cardiac output and mean arterial blood pressure. RESULTS: PCr:ATP ratio was significantly lower in old compared with young age group (1.92±0.48 vs 2.29±0.55, p=0.03), as were peak cardiac power output (3.35±0.73 vs 4.14±0.81W, p=0.01), diastolic function (ie, early-to-late diastolic filling ratio, 1.33±0.54 vs 3.07±1.84, p<0.01) and peak exercise oxygen consumption (1382.9±255.0 vs 1940.3±434.4 mL/min, p<0.01). Further analysis revealed that PCr:ATP ratio shows a significant positive relationship with early-to-late diastolic filling ratio (r=0.46, p=0.02), peak cardiac power output (r=0.44, p=0.02) and peak oxygen consumption (r=0.51, p=0.01). CONCLUSIONS: High-energy phosphate metabolism and peak power of the heart decline with age. Significant positive relationship between PCr:ATP ratio, early-to-late diastolic filling ratio and peak cardiac power output suggests that cardiac high-energy phosphate metabolism may be an important determinant of cardiac function and performance.

The cardio-metabolic impact of taking commonly prescribed analgesic drugs in 133,401 UK Biobank participants.

OBJECTIVE: There has been a significant increase in the prescribing of medication for chronic non-cancer pain. In a UK population sample, we aimed to assess cardio-metabolic (CM) health in those taking these chronic pain medications. METHODS: 133,401 participants from the UK Biobank cohort were studied. BMI, waist cm and hypertension were compared between those on drugs prescribed for chronic pain and CM drugs to those on CM drugs only. Multiple confounders were controlled for. RESULTS: Those taking opiates and CM drugs had the worst CM health profile with a 95%, 82% and 63% increased odds of reporting obesity, 'very high risk' waist circumference and hypertension, respectively (OR [95% CI] 1.95 [1.75-2.17], 1.82 [1.63-2.03], 1.63 [1.45-1.84]), compared to those on CM drugs alone. Those taking neuropathic pain medications and CM drugs also demonstrate worse CM profile than those taking CM drugs only. CONCLUSIONS: The impact of medications for chronic pain and sleep upon CM health and obesity is of concern for these classes of drugs which have been recently labelled as dependency forming medications. The results from this cross sectional study warrants further investigation and adds further support to calls for these medications to be prescribed for shorter periods.

Pathophysiology of exercise intolerance in chronic diseases: the role of diminished cardiac performance in mitochondrial and heart failure patients.

OBJECTIVE: Exercise intolerance is a clinical hallmark of chronic conditions. The present study determined pathophysiological mechanisms of exercise intolerance in cardiovascular, neuromuscular, and metabolic disorders. METHODS: In a prospective cross-sectional observational study 152 patients (heart failure reduced ejection fraction, n=32; stroke, n=34; mitochondrial disease, n=28; type two diabetes, n=28; and healthy controls, n=30) performed cardiopulmonary exercise testing with metabolic and haemodynamic measurements. Peak exercise O2 consumption and cardiac power output were measures of exercise tolerance and cardiac performance. RESULTS: Exercise tolerance was significantly diminished in patients compared with controls (ie, by 45% stroke, 39% mitochondria disease, and 33% diabetes and heart failure, p<0.05). Cardiac performance was only significantly reduced in heart failure (due to reduced heart rate, stroke volume, and blood pressure) and mitochondrial patients (due reduced stroke volume) compared with controls (ie, by 53% and 26%, p<0.05). Ability of skeletal muscles to extract oxygen (ie, arterial-venous O2 difference) was diminished in mitochondrial, stroke, and diabetes patients (by 24%, 22%, and 18%, p<0.05), but increased by 21% in heart failure (p<0.05) compared with controls. Cardiac output explained 65% and 51% of the variance in peak O2 consumption (p<0.01) in heart failure and mitochondrial patients, whereas arterial-venous O2 difference explained 69% (p<0.01) of variance in peak O2 consumption in diabetes, and 65% and 48% in stroke and mitochondrial patients (p<0.01). CONCLUSIONS: Different mechanisms explain exercise intolerance in patients with heart failure, mitochondrial dysfunction, stroke and diabetes. Their better understanding may improve management of patients, their stress tolerance and quality of life.

Effects of Exercise on Liver Fat and Metabolism in Alcohol Drinkers.

BACKGROUND & AIMS: Exercise is an important component of obesity-associated disorders and has been shown to reduce markers of nonalcoholic fatty liver disease (NAFLD). However, little is known about how these effects are influenced by alcohol intake. The authors performed a randomized controlled trial to investigate the effects of exercise on hepatic triglyceride content (HTGC) and metabolism in overweight or obese patients who consume alcohol. METHODS: The authors performed a prospective study of 27 patients (mean 54 ± 11 years of age, body mass index [BMI] 31 ± 4 kg/m2) with >5% HTGC in the United Kingdom, consuming alcohol (mean 221 ± 75 g/week). Anthropometry, body composition, HTGC, and abdominal fat were measured using plethysmography and magnetic resonance imaging. Subjects were assigned to groups that exercised (3 times/week on nonconsecutive days) for 12 weeks (n = 14) or continued standard care (control group, n = 13), maintaining baseline weight and alcohol consumption. The exercise program consisted of aerobic exercise (static cycling) and a circuit of resistance exercise (free weights and machines). Patients were examined at baseline and at 12 weeks; data collected on HTGC, body composition, metabolic control, circulating inflammatory, and fibrosis markers were assessed at baseline and at 12 weeks. Between-group differences were evaluated using an unpaired t test and within-group differences using a paired t test. The primary outcomes for this study were changes in HTGC between baseline and 12 weeks. RESULTS: After 12 weeks, there was no significant difference between the exercise and control groups in HTGC (reduction of 0.1% ± 2.1% in exercisers vs increase of 0.5 ± 2.1% in control group; P > .05). At week 12, the exercise group had significant reductions in subcutaneous fat (loss of 23 ± 28 cm2 in the exercisers vs increase of 12 ± 19 cm2 in the control group; P < .01), and whole body fat (loss of 2.1 ± 1.1 kg in the exercisers vs increase of 0.2 ± 2.1 kg; P < .01). The exercise group also had a significantly greater increase in lean body mass (increase of 1.9 ± 1.4 kg for the exercisers vs increase of 0.7 ± 1.5 kg for the control group; P < .01) and a significantly greater reduction in level of cytokeratin 18 (reduction of 49 ± 82 U/L in exercisers vs increase of 17 ± 38 U/L in control group; P < .05). There were no differences between groups in changes in metabolic factors or markers of inflammation. CONCLUSIONS: In a randomized controlled trial of obese individuals who consume alcohol, exercise significantly improved body composition and reduced hepatocyte apoptosis (cytokeratin 18), but did not reduce HTGC. This finding could indicate that alcohol consumption reduces the effects of exercise on NAFLD observed in previous studies. Clinical care teams should look to use exercise as part of the management strategy for people consuming alcohol, but optimal benefit may be as an adjunct to alcohol reduction and weight management strategies. (ISRCTN.com, Number: ISRCTN90597099).

Low physical activity, high television viewing and poor sleep duration cluster in overweight and obese adults; a cross-sectional study of 398,984 participants from the UK Biobank.

BACKGROUND: An unhealthy lifestyle is one of the greatest contributors to obesity. A number of behaviours are linked with obesity, but are often measured separately. The UK Biobank cohort of >500,000 participants allows us to explore these behaviours simultaneously. We therefore aimed to compare physical activity, television (TV) viewing and sleep duration across body mass index (BMI) categories in a large sample of UK adults. METHODS: UK Biobank participants were recruited and baseline measures were taken between 2007 and 2010 and data analysis was performed in 2015. BMI was measured objectively using trained staff. Self-report questionnaires were used to measure lifestyle behaviours including the international physical activity questionnaire (IPAQ-short form) for physical activity. During data analysis, six groups were defined based on BMI; 'Underweight' (n = 2026), 'Normal weight' (n = 132,372), 'Overweight (n = 171,030), 'Obese I' (n = 67,903), 'Obese II' (n = 18,653) and 'Obese III' (n = 7000). The odds of reporting unhealthy lifestyle behaviours (low physical activity, high TV viewing or poor sleep duration) were compared across BMI groups using logistic regression analysis. RESULTS: Overweight and obese adults were more likely to report low levels of physical activity (≤967.5 MET.mins/wk) ('Overweight'-OR [95% CI]: 1.23 [1.20 to 1.26], 'Obese I' 1.66 [1.61-1.71], 'Obese II' 2.21 [2.12-2.30], and 'Obese III' 3.13 [2.95 to 3.23]) compared to 'Normal weight' adults. The odds of reporting high TV viewing (3 h/day) was greater in 'Overweight' (1.52 [1.48 to 1.55]) and obese adults ('Obese I' 2.06 [2.00-2.12], 'Obese II' 2.69 [2.58-2.80], 'Obese III' 3.26 [3.07 to 3.47]), and poor sleep duration (<7, >8 h/night) was higher in 'Overweight' (1.09 [1.07 to 1.12]) and obese adults ('Obese I' 1.31 [1.27-1.34], 'Obese II' 1.50 [1.44-1.56], 'Obese III' (1.78 [1.68 to 1.89]) compared to the 'Normal weight' group. These lifestyle behaviours were clustered, the odds of reporting simultaneous low physical activity, high TV viewing and poor sleep (unhealthy behavioural phenotype) was higher than reporting these behaviours independently, in overweight and obese groups. 'Obese III' adults were almost six times more likely (5.47 [4.96 to 6.05]) to report an unhealthy behavioural phenotype compared to the 'Normal weight' group. CONCLUSIONS: Overweight and obese adults report low levels of physical activity, high TV viewing and poor sleep duration. These behaviours seem to cluster and collectively expose individuals to greater risk of obesity. Multiple lifestyle behaviours should be targeted in future interventions.