Ian M. Lahart

Physical activity, risk of death and recurrence in breast cancer survivors: A systematic review and meta-analysis of epidemiological studies

Abstract Strong evidence exists supporting the effect of lack of physical activity on the risk of developing breast cancer. However, studies examining the effects of physical activity on breast cancer outcomes, including survival and prognosis have been inconclusive. Therefore, the aim of the current study was to provide a systematic review and meta-analysis of studies investigating the association between physical activity and breast cancer recurrence and death. Methods. PubMed, EMBASE, and CENTRAL databases were searched up to 18 October 2014. Reference lists of retrieved articles and relevant previous reviews were also searched. Observational studies that reported risk estimates for all-cause and/or breast cancer-related death and/or breast cancer recurrences by levels of physical activity, were included in the review. Random effects models were used to calculate pooled hazard ratios (HR) and 95% confidence intervals (CI) and to incorporate variation between studies. The Newcastle-Ottawa scale was used to critically appraise the risk of bias across studies. Results. Twenty-two prospective cohort studies were eligible in this meta-analysis. During average follow-up periods ranging from 4.3 to 12.7 years there were 123 574 participants, 6898 all-cause deaths and 5462 breast cancer outcomes (i.e. breast cancer-related deaths or recurrences). The average Newcastle-Ottawa score was six stars (range 4–8). Compared to those who reported low/no lifetime recreational pre-diagnosis physical activity, participants who reported high lifetime recreational pre-diagnosis physical activity levels had a significantly lower risk of all-cause (HR = 0.82, 95% CI 0.70–0.96, p < 0.05) and breast cancer-related death (HR = 0.73, 95% CI 0.54–0.98, p < 0.05). Significant risk reductions for all-cause and breast cancer-related death was also demonstrated for more recent pre-diagnosis recreational physical activity (HR = 0.73, 95% CI 0.65–0.82, p < 0.001; and HR = 0.84, 95% CI 0.73–0.97, p < 0.05, respectively), post-diagnosis physical activity (HR = 0.52, 95% CI 0.43–0.64, p < 0.01; and HR = 0.59, 95% CI 0.45–0.78, p < 0.05, respectively) and meeting recommended physical activity guidelines (i.e. ≥ 8 MET-h/wk) post-diagnosis (HR = 0.54, 95% CI 0.38–0.76, p < 0.01; and HR = 0.67, 95% CI 0.50–0.90, p < 0.01, respectively). However, there was evidence of heterogeneity across lifetime recreational pre- and post-diagnosis physical activity analyses. Both pre-diagnosis (lifetime and more recent combined) and post-diagnosis physical activity were also associated with reduced risk of breast cancer events (breast cancer progression, new primaries and recurrence combined) (HR = 0.72 95% CI 0.56–0.91, p < 0.01; and HR = 0.79, 95% CI 0.63–0.98, p < 0.05, respectively). Conclusion. There is an inverse relationship between physical activity and all-cause, breast cancer-related death and breast cancer events. The current meta-analysis supports the notion that appropriate physical activity may be an important intervention for reducing death and breast cancer events among breast cancer survivors.

Energy expenditure in the Race Across America (RAAM).

Energy Expenditure was measured with doubly labelled water technique during heavy sustained exercise with an official finishing team in the Race Across America. Energy Intake was also calculated to produce an energy balance for the race. A team of 4 cyclists (Mean +/-SD age: 37+4 yr; body height: 182+8 cm; body mass: 80.8+6.6 kg) completed the race in a relay fashion. The team completed the race in 6 days 10 h and 51 min. Total mean energy expenditure was found to be 43,401 kcals (181,711 kJ) with a mean daily energy expenditure of 6,420 kcals (26,879 kJ). Total mean energy intake from all food and drink consumed was calculated at 29,506 kcals (123,536 kJ) with a mean daily energy intake of 4 918 kcals (20,591 kJ). This resulted in a total mean energy deficit of 13,878 kcals (58,104 kJ) with a mean daily energy deficit of 1,503 kcals (6,293 kJ). The high energy expenditure highlights the need for correct and practical dietary strategies and challenges nutritionists to devise high energy diets that not only contain the correct macronutrient balance, but are also palatable to the cyclists, thus encouraging a high energy intake.

Scaling waist girth for differences in body size reveals a new improved index associated with cardiometabolic risk.

Our aim was to examine whether a new ratio, waist divided by height0.5 (WHT.5R), is both independent of stature and a stronger predictor of cardiometabolic risk (CMR) than other anthropometric indices. Subjects (4117 men and 646 women), aged 20–69 years, were assessed for stature (cm), mass (kg), waist, and hip girths (cm) from which body mass index (BMI), waist‐to‐hip ratio (WHR), waist‐to‐height ratio (WHTR), and two new indices, a body shape index (ABSI) and WHT.5R, were determined. We used the allometric power law, W = a.HTb, to obtain a simple body shape index for waist girth (W) to be independent of stature (HT). Physical activity was determined using self‐report, and physical fitness was determined using the Bruce protocol. Glucose, total cholesterol, low‐density lipoprotein, high‐density lipoprotein, triglycerides, and TC/HDL ratio were determined from fasting venous blood samples. A single CMR composite score was derived from log‐transformed z‐scores of Triglycerides + average blood pressure ((diastolic + systolic)/2) + glucose + HDL (*−1). Results confirmed WHT.5R to be independent of stature and the strongest predictor of CMR, compared with BMI, WC, WHR, ABSI, and WHTR. We also found that CMR scores decline significantly with increasing fitness and physical activity, confirming that being fit and active can compensate for the adverse effects of being fat as measured by all other anthropometric indices. In conclusion, WHT.5R was the best anthropometric index associated with CMR, and being both physically fit and active has a protective effect on CMR, irrespective of weight status.

A Unique Case Series of Novel Biomarkers of Cardiac Damage in Cyclists Completing the 4800 km Race Across America (RAAM)

Prolonged strenuous exercise is associated with the appearance of biomarkers of cardiac cell damage and a decline in cardiac function during recovery. Few studies have assessed repeated bouts of prolonged exercise and whether this results in further biomarker accumulation and greater dysfunction. Further, it may be useful to describe the changes in a range of biomarkers that may provide additional insight into the clinical significance of cardiac biomarker release. Four highly trained cyclists completed the 4800 km Race Across America (RAAM) in 7 days. Venous blood samples and echocardiograms were taken prior to, every 24 hours during and immediately after the RAAM. Venous blood was analysed for cardiac troponin I (cTnI), creatine kinase MB (CK-MB), fatty acid binding protein (HFABP), glycogen phosphorylase BB (GPBB) and N-Terminal Brain Natriuretic Peptide (NTproBNP). Echocardiograms allowed analysis of septal, left ventricular free wall and right ventricular free wall tissue velocities during systole and diastole. Before the RAAM cTnI levels were below the assay detection level (0.02 ng.ml⁻¹). In three riders cTnI peaked on day one (0.03 ng.ml⁻¹) and returned below detection levels post race. In the 4th rider cTnI peaked on day 5 (0.08 ng.ml⁻¹) and was still elevated post-race. Both CK-MB and H-FABP were increased during the RAAM in all 4 cyclists. In three riders H-FABP peaked on day one (3.49 to 5.09 ng.ml⁻¹) and declined over the rest of the RAAM. In the final rider H-FABP peaked on day two (5.90 ng.ml⁻¹) and then dropped back to baseline by the post-RAAM assessment. Interestingly, changes in H-FABP mirrored, temporally, changes in CK-MB in places and this may reflect an association with skeletal muscle damage. Data for GPBB value to (2.9 - 149.6 ng.ml⁻¹) and NTproBNP value to (27.3 - 310.0 ng.L⁻¹) were variable but again was elevated in all riders during the course of the RAAM. Changes in ventricular wall tissue velocities were minor and not cumulative. Peak atrial diastolic tissue velocity in the left ventricular free wall increased (P < 0.05) from 11 to 18 cm.s⁻¹ over the last two race days but this did not significantly impact the ratio of early to late diastolic wall motion. Cardiac biomarkers were elevated during the completion of the RAAM in all 4 cyclist but changes were not cumulative which suggest that the hearts of the cyclists coped well with the extreme cardiac work demanded by this ultra-endurance exercise challenge.

Physical Activity Levels in Women Attending Breast Screening, Receiving Chemotherapy and Post-Breast Cancer Treatment; A Cross-Sectional Study

Background: A lack of physical activity (PA) is a well-recognised risk factor in the development of breast cancer (BC) and evidence-base research on the impact of PA on BC survival is consolidating. However, evidence reveals that BC survivors have low levels of PA, suggesting the need of targeted interventions to enhance the PA behaviour of BC survivors. Unfortunately, there is lack of data from the UK about the PA behaviours of women at various stages of diagnosis and treatment of BC. Therefore, the aim of the present study was to assess PA levels in women at different stages of BC pathway. Patients and Methods: A convenient sample of patients was selected at various stages of presentation and treatment of BC. Patients attending for breast screening for NHSBSP (n = 188), post-operative patients attending for chemotherapy (n = 41) and BC patients within one year’s post-treatment (n = 80) were invited to take part in this cross-sectional study. Results: Based on the odds ratio, the likelihood of a chemotherapy participant not meeting PA guidelines (i.e., being in the low activity category) were three times higher than the odds of a NHSBPS attendee not meeting PA guidelines, and compared to post-treatment participants, the chemotherapy patient’s odds of not meeting PA guidelines was four times higher. The odds of NHSBPS attendees being in the high activity category compared to the moderate category were three times higher than that of a post-treatment participant. Conclusions: The current study suggests the need to establish robust PA interventions to enhance the PA behaviour of breast cancer survivors.

Effects of physical activity on the link between PGC-1a and FNDC5 in muscle, circulating Ιrisin and UCP1 of white adipocytes in humans: A systematic review

Background: Exercise may activate a brown adipose-like phenotype in white adipose tissue. The aim of this systematic review was to identify the effects of physical activity on the link between peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1a) and fibronectin type III domain-containing protein 5 (FNDC5) in muscle, circulating Irisin and uncoupling protein one (UCP1) of white adipocytes in humans. Methods: Two databases (PubMed 1966 to 08/2016 and EMBASE 1974 to 08/2016) were searched using an appropriate algorithm. We included articles that examined physical activity and/or exercise in humans that met the following criteria: a) PGC-1a in conjunction with FNDC5 measurements, and b) FNDC5 and/or circulating Irisin and/or UCP1 levels in white adipocytes. Results: We included 51 studies (12 randomised controlled trials) with 2474 participants. Out of the 51 studies, 16 examined PGC-1a and FNDC5 in response to exercise, and only four found increases in both PGC-1a and FNDC5 mRNA and one showed increased FNDC5 mRNA. In total, 22 out of 45 studies that examined circulating Irisin in response to exercise showed increased concentrations when ELISA techniques were used; two studies also revealed increased Irisin levels measured via mass spectrometry. Three studies showed a positive association of circulating Irisin with physical activity levels. One study found no exercise effects on UCP1 mRNA in white adipocytes. Conclusions: The effects of physical activity on the link between PGC-1a, FNDC5 mRNA in muscle and UCP1 in white human adipocytes has attracted little scientific attention. Current methods for Irisin identification lack precision and, therefore, the existing evidence does not allow for conclusions to be made regarding Irisin responses to physical activity. We found a contrast between standardised review methods and accuracy of the measurements used. This should be considered in future systematic reviews.

Scaling children's waist circumference for differences in body size

Both waist circumference (WC) and body size (height) increase with age throughout childhood. Hence, there is a need to scale WC in children to detect differences in adiposity status (eg, between populations and different age groups), independent of body size/height.

Cardiorespiratory fitness and activity explains the obesity-deprivation relationship in children

This study examined the association between obesity and deprivation in English children and whether cardiorespiratory fitness or physical activity (PA) can explain this association. Obesity was assessed using IOTF criteria in 8,398 10-16 year olds. Social deprivation was measured using the Index of Multiple Deprivation (IMD) (subdivided into 3 groups; high, mid and low deprivation). Obesity was analysed using binary logistic regression with stature, age and sex incorporated as confounding variables. Childrens fitness levels were assessed using predicted VO2 max (20-metre shuttle run test) and PA was estimated using the PA Questionnaire for Adolescents or Children (PAQ). A strong association was found between obesity and deprivation. When fitness and PA were added to the logistic regression models, increasing levels in both were found to reduce the odds of obesity, although it was only by including fitness into the model that the association between obesity and deprivation disappeared. Including estimated PA into the model was found to be curvilinear. Initial increases in PA increase the odds of obesity. Only by increasing PA to exceed the 71st percentile (PAQ = 3.22) did the odds of being obese start to decline. In order to reduce deprivation inequalities in childrens weight-status, health practitioners should focus on increasing cardiorespiratory fitness via physical activity levels in areas of greater deprivation.

Environmental Influences on Elite Sport Athletes Well Being: From Gold, Silver, and Bronze to Blue Green and Gold

This paper considers the environmental impact on well-being and performance in elite athletes during Olympic competition. The benefits of exercising in natural environments are recognized, but less is known about the effects on performance and health in elite athletes. Although some Olympic events take place in natural environments, the majority occur in the host city, usually a large densely populated area where low exposure to natural environments is compounded by exposure to high levels of air, water, and noise pollution in the ambient environment. By combining methods and expertise from diverse but inter-related disciplines including environmental psychology, exercise physiology, biomechanics, environmental science, and epidemiology, a transdisciplinary approach will facilitate a greater understanding of the effects of the environment on Olympic athletes.

Modelling the association between weight status and social deprivation in English school children: Can physical activity and fitness affect the relationship?

Abstract Background: The association between being overweight/obese and deprivation is a serious concern in English schoolchildren. Aim: To model this association incorporating known confounders and to discover whether physical fitness and physical activity may reduce or eliminate this association. Subjects and methods: Cross-sectional data were collected between 2007–2009, from 8053 10–16 year old children from the East-of-England Healthy Heart Study. Weight status was assessed using waist circumference (cm) and body mass (kg). Deprivation was measured using the Index of Multiple Deprivation (IMD). Confounding variables used in the proportional, allometric models were hip circumference, stature, age and sex. Children’s fitness levels were assessed using predicted VO2 max (20-metre shuttle-run test) and physical activity was estimated using the Physical Activity Questionnaire for Adolescents or Children. Results: A strong association was found between both waist circumference and body mass and the IMD. These associations persisted after controlling for all confounding variables. When the children’s physical activity and fitness levels were added to the models, the association was either greatly reduced or, in the case of body mass, absent. Conclusions: To reduce deprivation inequalities in children’s weight-status, health practitioners should focus on increasing physical fitness via physical activity in areas of greater deprivation.