Diet and physical activity interventions to improve cardiovascular disease risk factors in liver transplant recipients: Systematic review and meta-analysis.

BACKGROUND AND AIMS: Cardiovascular disease, associated risk factors and obesity are prevalent after liver transplant and modifiable through lifestyle changes. Understanding what lifestyle interventions and their respective components are effective is essential for translation to clinical practice. We aimed to investigate the effects of diet and physical activity interventions on weight, body mass index and other cardiovascular disease risk factors in liver transplant recipients, and systematically describe the interventions. METHODS: We systematically searched Embase, MEDLINE, Psycho Info, CINAHL, Cochrane central register of controlled trials, PeDro, AMED, BNI, Web of Science, OpenGrey, ClinicalTrials.gov and the international clinical trials registry from inception to 31 May 2023. Search results were screened by two independent reviewers: randomised control trials with interventions that targeted diet and physical activity behaviours in liver transplant recipients were considered eligible. Two independent reviewers extracted and synthesised data for study, participant and intervention details and results. We used the Revised Cochrane Risk of Bias Tool for Randomised Trials to assess risk of bias for outcomes and the GRADE approach to rate the quality of the body of evidence. When two or more studies reported findings for an outcome, we pooled data using random-effects meta-analysis. RESULTS: Six studies were included, reporting three physical activity and three combined diet and physical activity interventions. Participants were 2 months-4 years post-transplant. Interventions lasted 12 weeks-10 months and were delivered remotely and/or in-person, most commonly delivered to individual participants by health care or sports professionals. Five studies described individual tailoring, e.g. exercise intensity. Adherence to interventions ranged from 51% to 94%. No studies reported fidelity. Intervention components were not consistently reported. In meta-analysis, diet and physical activity interventions did not significantly reduce weight or body mass index compared to control groups, however no studies targeted participants with obesity. Diet and physical activity interventions reduced percentage body fat and triglycerides compared to control groups but did not reduce total cholesterol or increase activity. The GRADE quality of evidence was low or very low. CONCLUSION: Diet and physical activity interventions reduced percentage body fat and triglycerides in liver transplant recipients. Further good quality research is needed to evaluate their effect on other cardiovascular disease risk factors, including weight and BMI. Interventions need to be better described and evaluated to improve evidence base and inform patient care.

Resistance to thyroid hormone induced tachycardia in RTHα syndrome.

Mutations in thyroid hormone receptor α1 (TRα1) cause Resistance to Thyroid Hormone α (RTHα), a disorder characterized by hypothyroidism in TRα1-expressing tissues including the heart. Surprisingly, we report that treatment of RTHα patients with thyroxine to overcome tissue hormone resistance does not elevate their heart rate. Cardiac telemetry in male, TRα1 mutant, mice indicates that such persistent bradycardia is caused by an intrinsic cardiac defect and not due to altered autonomic control. Transcriptomic analyses show preserved, thyroid hormone (T3)-dependent upregulation of pacemaker channels (Hcn2, Hcn4), but irreversibly reduced expression of several ion channel genes controlling heart rate. Exposure of TRα1 mutant male mice to higher maternal T3 concentrations in utero, restores altered expression and DNA methylation of ion channels, including Ryr2. Our findings indicate that target genes other than Hcn2 and Hcn4 mediate T3-induced tachycardia and suggest that treatment of RTHα patients with thyroxine in high dosage without concomitant tachycardia, is possible.

Association of Accelerometer-Measured Sedentary Accumulation Patterns With Incident Cardiovascular Disease, Cancer, and All-Cause Mortality.

Background Emerging evidence suggests accruing sedentary behavior (SB) in relatively more prolonged periods may convey additional cardiometabolic risks, but few studies have examined prospective outcomes. We examined the association of SB accumulation patterns with incident cardiovascular disease (CVD), cancer, and all-cause mortality (ACM). Methods and Results Data were from 7671 EPIC-Norfolk (European Prospective Investigation Into Cancer and Nutrition-Norfolk) cohort middle- to older-aged adults who wore accelerometers on the right hip for 4 to 7 days. Cox proportional hazards regression modeled associations between 2 measures of SB accumulation and incident CVD, cancer, and ACM. These were usual SB bout duration (the midpoint of each individual's SB accumulation curve, fitted using nonlinear regression) and alpha (hybrid measure of bout frequency and duration, with higher values indicating relatively shorter bouts and fewer long bouts). Models were adjusted for potential confounders, then further for 24-hour time-use compositions. During mean follow-up time of 6.4 years, 339 ACM, 1106 CVD, and 516 cancer events occurred. Elevated rates of incident cancer and ACM were seen with more prolonged SB accumulation (lower alpha, higher usual SB bout duration) but not CVD. For usual SB bout duration and alpha, respectively, the confounder-adjusted hazard ratios per SD of the exposure were 1.12 (95% CI, 1.02-1.23) and 0.88 (95% CI, 0.79-0.98) with incident cancer and 1.16 (95% CI, 1.07-1.26) and 0.80 (95% CI, 0.72-0.89) with ACM (all P<0.05). Further adjustment for 24-hour time use weakened associations with ACM for usual bout duration (hazard ratio, 1.06; 95% CI, 0.97-1.16; P=0.209) and partially for alpha (hazard ratio, 0.87; 95% CI, 0.77-0.99; P=0.029). Conclusions Accruing SB in longer bout durations was associated with higher rates of incident cancer and ACM but not with incident CVD, with some evidence of direct SB accumulation effects independent of 24-hour time use. Findings provide some support for considering SB accumulation as an adjunct target of messaging to "sit less and move more."

Assessing tobacco use in an African population: Serum and urine cotinine cut-offs from South Africa.

BACKGROUND: Cotinine, a nicotine metabolite, is used to measure tobacco use and exposure, but recommended cut-offs to differentiate tobacco users from those exposed through the environment range from 3 to 58 ng/ml in serum, and 2.5 to 550 ng/ml in urine. Cut-offs may differ by ethnicity, sex and age. As data from adults in Africa are scarce, our aim was to evaluate cut-offs for serum and urine cotinine that best predict self-reported tobacco use in South African adults. METHODS: Two datasets were explored: African-PREDICT (n = 941 black and white healthy young adults, 20-30 years, serum cotinine); and WHO SAGE Wave 2 (n = 604 adults, 18-102 years, urine cotinine). Population specific cut-offs (ROC analyses) were compared with published cut-offs and self-reported tobacco use. RESULTS: Overall, 19% (293 of 1545) reported current tobacco use. The following cotinine cut-offs showed the highest sensitivity and specificity: serum ≥15 ng/ml in black and white men, and white women; serum ≥10 ng/ml in black women; urine ≥300 ng/ml for black, mixed ancestry, and older adults (50-plus years); urine ≥500 ng/ml for younger adults (18-49 years). Specificity was lower for urine than for serum cotinine. CONCLUSION: Our study suggests that a serum cotinine level of ≥15 ng/ml and a urine cotinine level of ≥300 ng/ml best distinguish current tobacco users from non-users generally in the South African adult population.

Body mass index cut-points to identify cardiometabolic risk in black South Africans.

PURPOSE: To determine optimal body mass index (BMI) cut-points for the identification of cardiometabolic risk in black South African adults. METHODS: We performed a cross-sectional study of a weighted sample of healthy black South Africans aged 25-65 years (721 men, 1386 women) from the North West and Free State Provinces. Demographic, lifestyle and anthropometric measures were taken, and blood pressure, fasting serum triglycerides, high-density lipoprotein (HDL) cholesterol and blood glucose were measured. We defined elevated cardiometabolic risk as having three or more risk factors according to international metabolic syndrome criteria. Receiver operating characteristic curves were applied to identify an optimal BMI cut-point for men and women. RESULTS: BMI had good diagnostic performance to identify clustering of three or more risk factors, as well as individual risk factors: low HDL-cholesterol, elevated fasting glucose and triglycerides, with areas under the curve >.6, but not for high blood pressure. Optimal BMI cut-points averaged 22 kg/m2 for men and 28 kg/m2 for women, respectively, with better sensitivity in men (44.0-71.9 %), and in women (60.6-69.8 %), compared to a BMI of 30 kg/m2 (17-19.1, 53-61.4 %, respectively). Men and women with a BMI >22 and >28 kg/m2, respectively, had significantly increased probability of elevated cardiometabolic risk after adjustment for age, alcohol use and smoking. CONCLUSION: In black South African men, a BMI cut-point of 22 kg/m2 identifies those at cardiometabolic risk, whereas a BMI of 30 kg/m2 underestimates risk. In women, a cut-point of 28 kg/m2, approaching the WHO obesity cut-point, identifies those at risk.

Associations of physical activity with inflammatory factors, adipocytokines, and metabolic syndrome in middle-aged and older chinese people.

BACKGROUND: Inflammatory factors, adipocytokines, and the metabolic syndrome are important determinants of cardiometabolic disease. It remains unclear how physical activity is related to these risk factors. Our objective was to investigate single and joint associations of physical activity with inflammatory factors, adipocytokines, and the metabolic syndrome among middle-aged and older Chinese people. METHODS AND RESULTS: A total of 3289 individuals (1458 men, 1831 women) 50 to 70 years of age participated in a population-based cross-sectional survey in Beijing and Shanghai, China. Levels of total physical activity were assessed with the International Physical Activity Questionnaire. High-sensitivity C-reactive protein, interleukin-6, tumor necrosis factor-alpha receptor 2, adiponectin, and retinol-binding protein 4 were measured. The metabolic syndrome was defined using the updated National Cholesterol Education Program/Adult Treatment Panel III criteria for Asian Americans. Plasma concentrations of high-sensitivity C-reactive protein were 1.58, 1.74, and 1.27 mg/L (P=0.0138) and of adiponectin were 16.12, 16.20, and 17.21 mg/L (P=0.0078) among individuals with low, medium, and high levels of total physical activity, respectively, with adjustment for potential confounders. In the multivariable-adjusted logistic regression analyses, participants with higher levels of total physical activity had a lower risk of having the metabolic syndrome (odds ratio, 0.68; 95% confidence interval, 0.54 to 0.85; P for trend=0.001) compared with those with lower levels. CONCLUSIONS: Being physically active is associated with a better profile of inflammatory factors and adipocytokines and a reduced risk of having the metabolic syndrome among Chinese people.

Obesity related metabolic abnormalities: distribution and geographic differences among middle-aged and older Chinese populations.

OBJECTIVE: To investigate geographic differences in obesity related metabolic abnormalities in middle-aged and older Chinese people with different levels of adiposity. METHOD: Data from 3289 individuals aged 50-70 years who participated in a cross-sectional survey in 2005 (1641 from northern [Beijing] and 1648 from southern [Shanghai] China) were analyzed. Overweight or obesity and abdominal obesity were classified as body mass index > or =24 kg/m2 and waist circumference > or =90 cm for men and > or =80 cm for women. Metabolic abnormalities (metabolic syndrome, dyslipidemia, hypertension and diabetes) were defined using the NCEP/ATPIII criteria. RESULTS: The overall prevalence of overweight and obesity was 53.4%, and the prevalence of abdominal obesity was 48.0%, respectively. The prevalence of the metabolic abnormalities was significantly higher among obese individuals than their normal weight counterparts. The association between obesity and the higher prevalence of the metabolic abnormalities was more pronounced among people who were overweight or obese in the north, especially for those living in rural areas. CONCLUSION: The prevalence of obesity and associated metabolic abnormalities varies substantially among Chinese people in different geographic region. Individuals who were overweight or obese living in rural areas in the north contribute importantly to the north-south differences in obesity-related metabolic abnormalities among Chinese populations.

Independent associations of body-size adjusted fat mass and fat-free mass with the metabolic syndrome in Chinese.

BACKGROUND: Excess fat leads to adverse health outcomes. Most previous studies investigating body fatness using BMI or fat percentage, which contain both fat mass and fat-free mass, were not able to differentiate the exposure. AIM: The present study assessed the independent association of fat and fat-free mass with metabolic syndrome (MetS) in Chinese. SUBJECTS AND METHODS: A population-based study of 1144 subjects aged 50-70 from urban and rural areas of Shanghai in 2005-2006 was employed. Body composition was measured with DEXA. Fat mass index (FMI) and fat-free mass index (FFMI) were calculated. MetS was defined using the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria without waist circumference for its high correlation with body composition. RESULTS: Both FMI and FFMI were significantly related with higher odds of MetS (OR 3.97, 95% CI 2.58-6.09 for FMI; OR 2.67, 95% CI 1.70-4.18 for FFMI, the highest quartile vs the lowest group) after adjusting for age, residence, sex, smoking, drinking, physical activity, medication, family history of chronic diseases, and fat-free mass (for FMI) or fat mass (for FFMI). CONCLUSION: Both FMI and FFMI are independently associated with increased MetS risks. Proper expression of body composition is essential in assessing body composition and disease risk association.

Differences in bone mineral status between urban and rural Chinese men and women.

BACKGROUND: Few studies have investigated differences in bone health and associated lifestyle factors between urban and rural populations in countries, such as China, undergoing rapid nutrition transition. Such a study may help to identify risk factors of osteoporosis and provide evidence for future preventive strategies. OBJECTIVE: To determine primarily whether differences in bone mineral content (BMC) and bone mineral density (BMD) exist between urban and rural Chinese men and women and secondly whether any urban-rural differences could be explained by body size or lifestyle factors. METHODS: In total, 490 men and 689 women aged 50-70 were included in the study. 535 of them were from urban Shanghai and 644 from surrounding rural areas. Anthropometric measurements were conducted and spine lumber 1-4 BMC measurements were determined by dual-energy X-ray absorptiometry (DEXA). Information on socioeconomic status, medical history, smoking and drinking habits and physical activity were collected. RESULTS: Urban men and women had significantly higher spine BMC, BMD and bone area than their rural counterparts (P<0.01). After controlling body size, the differences between urban-rural spine BMC and BMD remained in women (P<0.001), but were no longer significant in men. The urban and rural differences of BMC and BMD in women could not be explained by including the lifestyle factors such as income, intake of milk, vitamin D and calcium, total physical activity level, walking and social activity. CONCLUSION: This study found the significant differences in both spine BMC and BMD between urban and rural men and women in Shanghai, China. This difference could be explained by the body size in men; however, it remained unexplained in women after adjusting for body size and certain lifestyle risk factors.

The effect of physical activity on body fatness in children and adolescents.

With the increasing prevalence of childhood obesity, there is an urgent need to identify risk factors that are amenable to preventative action. However, there is a remarkable lack of consistency between studies that have investigated the relationships between measurements of physical activity and energy expenditure and body fatness in children. This disparity could be because energy intake is a more important determinant in preventing obesity. Alternatively, some of the conflicting results could be related to methodological limitations in assessing activity and body composition. Erroneous conclusions may be drawn if physical activity energy expenditure is not adjusted for differences in body composition, or body fat is not appropriately adjusted for body size. For public health purposes it may be more informative to evaluate the amount and intensity of physical activity required to prevent fat-mass gain than to assess energy expended in physical activity. The lack of consensus in the cut-off points applied to define intensity levels is severely hindering comparisons between studies using accelerometers that have examined relationships between activity intensity and body fatness. Thus, it is not currently possible to develop a firm evidence base on which to establish physical activity recommendations until the limitations are addressed and more prospective studies undertaken. In order to turn research into effective prevention strategies a clearer understanding of the psycho-social, behavioural and environmental factors that influence activity is needed, including the interactions between physical activity and other behaviours such as time spent sedentary, sleeping and eating.

Association of physical activity with body-composition indexes in children aged 6-8 y at varied risk of obesity.

BACKGROUND: Physical inactivity increases the risk of obesity, but the relations between reported levels of physical activity (PA) and measures of body fatness (BF) in children are remarkably inconsistent. OBJECTIVE: We examined the relation between objective measures of PA and body-composition indexes in nonobese children. DESIGN: A cross-sectional study was conducted in 100 children aged 6-8 y who were recruited according to their risk of future obesity: high-risk children had >/=1 obese parent [body mass index (BMI; in kg/m(2)): >30] and low-risk children had 2 nonobese biological parents (BMI: <30). Free-living activity energy expenditure (AEE) and PA level were calculated from 7-d doubly labeled water measurements, time spent in light-intensity activity was assessed by heart rate monitoring, and body composition was determined from isotopic dilution. To adjust for body size, fat mass and fat-free mass were normalized for height and expressed as fat mass index (FMI) and lean mass index (LMI), respectively. RESULTS: High-risk children had significantly higher BMI, LMI, and FMI than did low-risk children, but no group differences in PA were found. AEE and PA level were positively associated with LMI and, after adjustment for sex and fat-free mass, negatively associated with FMI but not with BMI. Boys who spent more than the median time in light-intensity activities had significantly higher FMI than did less sedentary boys. This difference was not observed in girls. CONCLUSIONS: AEE and PA level were negatively associated with BF in nonobese children. Accurate measures of body composition are essential to appropriate assessment of relations between PA and obesity risk.

Effects of moderate and vigorous physical activity on heart rate variability in a British study of civil servants.

Physical inactivity and low resting heart rate variability (HRV) are associated with increased coronary heart disease incidence. In the Whitehall II study of civil servants aged 45-68 years (London, United Kingdom, 1997-1999), the strength of the association of moderate and vigorous activity with higher HRV was examined. Five-minute recordings of heart rate and HRV measures were obtained from 3328 participants. Calculated were time domain (standard deviation of NN intervals) and high-frequency-power measures as indicators of cardiac parasympathetic activity and low-frequency power of parasympathetic-sympathetic balance. Leisure-time physical activity (metabolic equivalent-hours per week) was categorized as moderate (>or=3-<5) and vigorous (>or=5). Moderate and vigorous physical activity were associated with higher HRV and lower heart rate. For men, linear trends of higher low-frequency power with increasing quartile of vigorous activity (304.6 (low), 329.0, 342.4, 362.5 (high); p < 0.01) and lower heart rate with increasing quartile of moderate activity (69.6 (low), 69.2, 68.9, 67.8 (high); p < 0.05) were found. These associations remained significant after adjustment for smoking and high alcohol intake. For men whose body mass index was >25 kg/m(2), vigorous activity was associated with HRV levels similar to those for normal-weight men who engaged in no vigorous activity. Vigorous activity was associated with higher HRV, representing a possible mechanism by which physical activity reduces coronary heart disease risk.

Validity and repeatability of a simple index derived from the short physical activity questionnaire used in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

OBJECTIVE: To assess the validity and repeatability of a simple index designed to rank participants according to their energy expenditure estimated by self-report, by comparison with objectively measured energy expenditure assessed by heart-rate monitoring with individual calibration. DESIGN: Energy expenditure was assessed over one year by four separate episodes of 4-day heart-rate monitoring, a method previously validated against whole-body calorimetry and doubly labelled water. Cardio-respiratory fitness was assessed by four repeated measures of sub-maximum oxygen uptake. At the end of the 12-month period, participants completed a physical activity questionnaire that assessed past-year activity. A simple four-level physical activity index was derived by combining occupational physical activity together with time participating in cycling and other physical exercise (such as keep fit, aerobics, swimming and jogging). SUBJECTS: One hundred and seventy-three randomly selected men and women aged 40 to 65 years. RESULTS: The repeatability of the physical activity index was high (weighted kappa=0.6, ). There were positive associations between the physical activity index from the questionnaire and the objective measures of the ratio of daytime energy expenditure to resting metabolic rate and cardio-respiratory fitness As an indirect test of validity, there was a positive association between the physical activity index and the ratio of energy intake, assessed by 7-day food diaries, to predicted basal metabolic rate. CONCLUSIONS: The summary index of physical activity derived from the questions used in the European Prospective Investigation into Cancer and Nutrition (EPIC) study suggest it is useful for ranking participants in terms of their physical activity in large epidemiological studies. The index is simple and easy to comprehend, which may make it suitable for situations that require a concise, global index of activity.

Validity and repeatability of the EPIC-Norfolk Physical Activity Questionnaire.

BACKGROUND: Physical activity is an important lifestyle which is often poorly assessed in epidemiological studies. The European Prospective Investigation into Cancer Study-Norfolk cohort (EPIC-Norfolk), a large population-based cohort study, has developed a comprehensive questionnaire to assess activity in different domains of life aimed at assessing total energy expenditure. We report the repeatability of this instrument and its validity against repeated objective measures of fitness and energy expenditure undertaken throughout the time frame of reference of the questionnaire. METHODS: The validity of the instrument was measured in 173 individuals randomly selected from a continuing population-based cohort study. Energy expenditure was assessed by four separate episodes of 4-day heart-rate monitoring, a method previously validated against whole body calorimetry and doubly-labelled water. Cardio-respiratory fitness was assessed by four repeated measures of sub-maximum oxygen uptake. At the end of the 12-month period, participants completed the physical activity questionnaire that assesses past-year activity at home, work and in recreation. Repeatability was assessed in a separate group of 399 randomly selected participants in EPIC who completed the physical activity questionnaire twice with a 3-month interval. RESULTS: The age- and sex-adjusted correlation between the objective measure of daytime energy expenditure and the sum of recreational and occupational reported physical activity (in MET h per week) was 0.28 (P < 0.001). The reported time spent in vigorous activity was correlated with cardio-respiratory fitness (0.16, P < 0.05) and with the proportion of time when energy expenditure was more than five times basal (0.17, P < 0.05). The repeatability of the sum of recreational and occupational reported activity was high, r = 0.73. CONCLUSIONS: The indices of physical activity derived from this questionnaire have levels of validity and repeatability comparable to other physical activity instruments that are used in large epidemiological studies and which have undergone such intense development and testing.