Light-intensity physical activity and cardiometabolic biomarkers in US adolescents

Associations of low- and high-intensity light activity with cardiometabolic biomarkers

Light-intensity physical activity (LIPA) accounts for much of adults' waking hours (≈40%) and substantially contributes to overall daily energy expenditure. Encompassing activity behaviours of low intensity (standing with little movement) through to those with a higher intensity (slow walking), LIPA is ubiquitous, yet little is known about how associations with health may vary depending on its intensity. We examined the associations of objectively assessed LIPA, categorized as either low- or high- LIPA, and MVPA, with cardiometabolic risk biomarkers.

Exploring the potential role of allostatic load biomarkers in risk assessment of patients presenting with depressive symptoms

Background: Depression is a major health problem worldwide and the majority of patients presenting with depressive symptoms are managed in primary care. Current approaches for assessing depressive symptoms in primary care are not accurate in predicting future clinical outcomes, which may potentially lead to over or under treatment. The Allostatic Load (AL) theory suggests that by measuring multi-system biomarker levels as a proxy of measuring multi-system physiological dysregulation, it is possible to identify individuals at risk of having adverse health outcomes at a prodromal stage. Allostatic Index (AI) score, calculated by applying statistical formulations to different multi-system biomarkers, have been associated with depressive symptoms. Aims and Objectives: To test the hypothesis, that a combination of allostatic load (AL) biomarkers will form a predictive algorithm in defining clinically meaningful outcomes in a population of patients presenting with depressive symptoms. The key objectives were: 1. To explore the relationship between various allostatic load biomarkers and prevalence of depressive symptoms in patients, especially in patients diagnosed with three common cardiometabolic diseases (Coronary Heart Disease (CHD), Diabetes and Stroke). 2 To explore whether allostatic load biomarkers predict clinical outcomes in patients with depressive symptoms, especially in patients with three common cardiometabolic diseases (CHD, Diabetes and Stroke). 3 To develop a predictive tool to identify individuals with depressive symptoms at highest risk of adverse clinical outcomes. Methods: Datasets used: ‘DepChron’ was a dataset of 35,537 patients with existing cardiometabolic disease collected as a part of routine clinical practice. ‘Psobid’ was a research data source containing health related information from 666 participants recruited from the general population. The clinical outcomes for 3 both datasets were studied using electronic data linkage to hospital and mortality health records, undertaken by Information Services Division, Scotland. Cross-sectional associations between allostatic load biomarkers calculated at baseline, with clinical severity of depression assessed by a symptom score, were assessed using logistic and linear regression models in both datasets. Cox’s proportional hazards survival analysis models were used to assess the relationship of allostatic load biomarkers at baseline and the risk of adverse physical health outcomes at follow-up, in patients with depressive symptoms. The possibility of interaction between depressive symptoms and allostatic load biomarkers in risk prediction of adverse clinical outcomes was studied using the analysis of variance (ANOVA) test. Finally, the value of constructing a risk scoring scale using patient demographics and allostatic load biomarkers for predicting adverse outcomes in depressed patients was investigated using clinical risk prediction modelling and Area Under Curve (AUC) statistics. Key Results: Literature Review Findings. The literature review showed that twelve blood based peripheral biomarkers were statistically significant in predicting six different clinical outcomes in participants with depressive symptoms. Outcomes related to both mental health (depressive symptoms) and physical health were statistically associated with pre-treatment levels of peripheral biomarkers; however only two studies investigated outcomes related to physical health. Cross-sectional Analysis Findings: In DepChron, dysregulation of individual allostatic biomarkers (mainly cardiometabolic) were found to have a non-linear association with increased probability of co-morbid depressive symptoms (as assessed by Hospital Anxiety and Depression Score HADS-D≥8). A composite AI score constructed using five biomarkers did not lead to any improvement in the observed strength of the association. In Psobid, BMI was found to have a significant cross-sectional association with the probability of depressive symptoms (assessed by General Health Questionnaire GHQ-28≥5). BMI, triglycerides, highly sensitive C - reactive 4 protein (CRP) and High Density Lipoprotein-HDL cholesterol were found to have a significant cross-sectional relationship with the continuous measure of GHQ-28. A composite AI score constructed using 12 biomarkers did not show a significant association with depressive symptoms among Psobid participants. Longitudinal Analysis Findings: In DepChron, three clinical outcomes were studied over four years: all-cause death, all-cause hospital admissions and composite major adverse cardiovascular outcome-MACE (cardiovascular death or admission due to MI/stroke/HF). Presence of depressive symptoms and composite AI score calculated using mainly peripheral cardiometabolic biomarkers was found to have a significant association with all three clinical outcomes over the following four years in DepChron patients. There was no evidence of an interaction between AI score and presence of depressive symptoms in risk prediction of any of the three clinical outcomes. There was a statistically significant interaction noted between SBP and depressive symptoms in risk prediction of major adverse cardiovascular outcome, and also between HbA1c and depressive symptoms in risk prediction of all-cause mortality for patients with diabetes. In Psobid, depressive symptoms (assessed by GHQ-28≥5) did not have a statistically significant association with any of the four outcomes under study at seven years: all cause death, all cause hospital admission, MACE and incidence of new cancer. A composite AI score at baseline had a significant association with the risk of MACE at seven years, after adjusting for confounders. A continuous measure of IL-6 observed at baseline had a significant association with the risk of three clinical outcomes- all-cause mortality, all-cause hospital admissions and major adverse cardiovascular event. Raised total cholesterol at baseline was associated with lower risk of all-cause death at seven years while raised waist hip ratio- WHR at baseline was associated with higher risk of MACE at seven years among Psobid participants. There was no significant interaction between depressive symptoms and peripheral biomarkers (individual or combined) in risk prediction of any of the four clinical outcomes under consideration. Risk Scoring System Development: In the DepChron cohort, a scoring system was constructed based on eight baseline demographic and clinical variables to predict the risk of MACE over four years. The AUC value for the risk scoring system was modest at 56.7% (95% CI 55.6 to 57.5%). In Psobid, it was not possible to perform this analysis due to the low event rate observed for the clinical outcomes. Conclusion: Individual peripheral biomarkers were found to have a cross-sectional association with depressive symptoms both in patients with cardiometabolic disease and middle-aged participants recruited from the general population. AI score calculated with different statistical formulations was of no greater benefit in predicting concurrent depressive symptoms or clinical outcomes at follow-up, over and above its individual constituent biomarkers, in either patient cohort. SBP had a significant interaction with depressive symptoms in predicting cardiovascular events in patients with cardiometabolic disease; HbA1c had a significant interaction with depressive symptoms in predicting all-cause mortality in patients with diabetes. Peripheral biomarkers may have a role in predicting clinical outcomes in patients with depressive symptoms, especially for those with existing cardiometabolic disease, and this merits further investigation.

Dietary patterns and cardiometabolic risk among older adults

This thesis examines dietary patterns among older adults, including how they change over time, predictors of change and associations with cardiometabolic biomarkers. It explores methodological issues in dietary patterns research and provides an understanding of the dietary patterns of older adults which may be used to inform public health interventions.

A cluster randomized controlled trial to reduce office workers' sitting time: impact on activity outcomes

PURPOSE: To evaluate, compared to usual practice, the initial and long-term effectiveness of a workplace intervention targeting reducing sitting on activity outcomes.

METHODS: Office worksites (≥1km apart) from a single organization in Victoria, Australia were cluster randomized to intervention (n=7) or control (n=7). Participants were 231 desk-based office workers (5 to 39 participants per worksite) working at least 0.6 full time equivalent. The workplace-delivered intervention addressed organizational, physical environment, and individual behavioural change to reduce sitting time. Assessments occurred at baseline, three-, and 12-months, with the primary outcome participants' objectively measured (activPAL3 device) workplace sitting time (mins/8-h workday). Secondary activity outcomes were: workplace time spent standing, stepping (light, moderate-vigorous and total) and in prolonged (≥30min) sitting bouts (h/8-h workday); usual duration of workplace sitting bouts; and, overall sitting, standing and stepping time (mins/16-h day). Analysis was by linear mixed models, accounting for repeated measures and clustering and adjusting for baseline values and potential confounders.

RESULTS: At baseline, on average, participants (68% women; mean±SD age = 45.6±9.4 years) sat, stood and stepped for 78.8±9.5%, 14.3±8.2%, and 6.9±2.9% of work hours respectively. Workplace sitting time was significantly reduced in the intervention group compared to the controls at three months (-99.1 [95% CI -116.3 to -81.8] min/8-h workday) and 12 months (-45.4 [-64.6 to -26.2] min/8-h workday). Significant intervention effects (all favoring intervention) were observed for standing, prolonged sitting, and usual sitting bout duration at work, as well as overall sitting and standing time, with no significant nor meaningful effects observed for stepping.

CONCLUSIONS: This workplace-delivered multicomponent intervention was successful at reducing workplace and overall daily sitting time in both the short- and long- term.

Deleterious associations of sitting time and television viewing time with cardiometabolic risk biomarkers

We examined the associations of sitting time and television (TV) viewing time with continuously measured biomarkers of cardio-metabolic risk in Australian adults. Waist circumference, BMI, resting blood pressure, triglycerides, HDL cholesterol, fasting and 2-h postload plasma glucose, and fasting insulin were measured in 2,761 women and 2,103 men aged ≥30 years (mean age 54 years) without clinically diagnosed diabetes from the 2004-2005 Australian Diabetes, Obesity and Lifestyle (AusDiab) study. Multivariate linear regression analyses examined associations of self-reported sitting time and TV viewing time (hours per day) with these biomarkers, adjusting for potential confounding variables. For both women and men, sitting time was detrimentally associated with waist circumference, BMI, systolic blood pressure, fasting triglycerides, HDL cholesterol, 2-h postload plasma glucose, and fasting insulin (all P < 0.05), but not with fasting plasma glucose and diastolic blood pressure (men only). With the exception of HDL cholesterol and systolic blood pressure in women, the associations remained significant after further adjustment for waist circumference. TV viewing time was detrimentally associated with all metabolic measures in women and all except HDL cholesterol and blood pressure in men. Only fasting insulin and glucose (men only) remained deleteriously associated with TV viewing time after adjustment for waist circumference. In women and men, sitting time and TV viewing time were deleteriously associated with cardio-metabolic risk biomarkers, with sitting time having more consistent associations in both sexes and being independent of central adiposity. Preventive initiatives aimed at reducing sitting time should focus on both nonleisure and leisure-time domains.

Cardiometabolic effects of genetic upregulation of the interleukin 1 receptor antagonist: A Mendelian randomisation analysis

Background To investigate potential cardiovascular and other effects of long-term pharmacological interleukin 1 (IL-1) inhibition, we studied genetic variants that produce inhibition of IL-1, a master regulator of inflammation. Methods We created a genetic score combining the effects of alleles of two common variants (rs6743376 and rs1542176) that are located upstream of IL1RN, the gene encoding the IL-1 receptor antagonist (IL-1Ra; an endogenous inhibitor of both IL-1α and IL-1β); both alleles increase soluble IL-1Ra protein concentration. We compared effects on inflammation biomarkers of this genetic score with those of anakinra, the recombinant form of IL-1Ra, which has previously been studied in randomised trials of rheumatoid arthritis and other inflammatory disorders. In primary analyses, we investigated the score in relation to rheumatoid arthritis and four cardiometabolic diseases (type 2 diabetes, coronary heart disease, ischaemic stroke, and abdominal aortic aneurysm; 453 411 total participants). In exploratory analyses, we studied the relation of the score to many disease traits and to 24 other disorders of proposed relevance to IL-1 signalling (746 171 total participants). Findings For each IL1RN minor allele inherited, serum concentrations of IL-1Ra increased by 0·22 SD (95% CI 0·18–0·25; 12·5%; p=9·3 × 10−33), concentrations of interleukin 6 decreased by 0·02 SD (−0·04 to −0·01; −1·7%; p=3·5 × 10−3), and concentrations of C-reactive protein decreased by 0·03 SD (−0·04 to −0·02; −3·4%; p=7·7 × 10−14). We noted the effects of the genetic score on these inflammation biomarkers to be directionally concordant with those of anakinra. The allele count of the genetic score had roughly log-linear, dose-dependent associations with both IL-1Ra concentration and risk of coronary heart disease. For people who carried four IL-1Ra-raising alleles, the odds ratio for coronary heart disease was 1·15 (1·08–1·22; p=1·8 × 10−6) compared with people who carried no IL-1Ra-raising alleles; the per-allele odds ratio for coronary heart disease was 1·03 (1·02–1·04; p=3·9 × 10−10). Per-allele odds ratios were 0·97 (0·95–0·99; p=9·9 × 10−4) for rheumatoid arthritis, 0·99 (0·97–1·01; p=0·47) for type 2 diabetes, 1·00 (0·98–1·02; p=0·92) for ischaemic stroke, and 1·08 (1·04–1·12; p=1·8 × 10−5) for abdominal aortic aneurysm. In exploratory analyses, we observed per-allele increases in concentrations of proatherogenic lipids, including LDL-cholesterol, but no clear evidence of association for blood pressure, glycaemic traits, or any of the 24 other disorders studied. Modelling suggested that the observed increase in LDL-cholesterol could account for about a third of the association observed between the genetic score and increased coronary risk. Interpretation Human genetic data suggest that long-term dual IL-1α/β inhibition could increase cardiovascular risk and, conversely, reduce the risk of development of rheumatoid arthritis. The cardiovascular risk might, in part, be mediated through an increase in proatherogenic lipid concentrations. Funding UK Medical Research Council, British Heart Foundation, UK National Institute for Health Research, National Institute for Health Research Cambridge Biomedical Research Centre, European Research Council, and European Commission Framework Programme 7.

Role of dietary fats in modulating cardiometabolic risk during moderate weight gain : a randomized double-blind overfeeding trial (LIPOGAIN study)

BACKGROUND: Whether the type of dietary fat could alter cardiometabolic responses to a hypercaloric diet is unknown. In addition, subclinical cardiometabolic consequences of moderate weight gain require further study. METHODS AND RESULTS: In a 7-week, double-blind, parallel-group, randomized controlled trial, 39 healthy, lean individuals (mean age of 27±4) consumed muffins (51% of energy [%E] from fat and 44%E refined carbohydrates) providing 750 kcal/day added to their habitual diets. All muffins had identical contents, except for type of fat; sunflower oil rich in polyunsaturated fatty acids (PUFA diet) or palm oil rich in saturated fatty acids (SFA diet). Despite comparable weight gain in the 2 groups, total: high-density lipoprotein (HDL) cholesterol, low-density lipoprotein:HDL cholesterol, and apolipoprotein B:AI ratios decreased during the PUFA versus the SFA diet (-0.37±0.59 versus +0.07±0.29, -0.31±0.49 versus +0.05±0.28, and -0.07±0.11 versus +0.01±0.07, P=0.003, P=0.007, and P=0.01 for between-group differences), whereas no significant differences were observed for other cardiometabolic risk markers. In the whole group (ie, independently of fat type), body weight increased (+2.2%, P<0.001) together with increased plasma proinsulin (+21%, P=0.007), insulin (+17%, P=0.003), proprotein convertase subtilisin/kexin type 9, (+9%, P=0.008) fibroblast growth factor-21 (+31%, P=0.04), endothelial markers vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and E-selectin (+9, +5, and +10%, respectively, P<0.01 for all), whereas nonesterified fatty acids decreased (-28%, P=0.001). CONCLUSIONS: Excess energy from PUFA versus SFA reduces atherogenic lipoproteins. Modest weight gain in young individuals induces hyperproinsulinemia and increases biomarkers of endothelial dysfunction, effects that may be partly outweighed by the lipid-lowering effects of PUFA. CLINICAL TRIAL REGISTRATION URL: http://ClinicalTrials.gov. Unique identifier: NCT01427140.

Increased cardiometabolic risk is associated with increased TV viewing time

Purpose: Television viewing time, independent of leisure time physical activity, has cross-sectional relationships with the metabolic syndrome and its individual components. We examined whether baseline and 5-yr changes in self-reported television viewing time are associated with changes in continuous biomarkers of cardiometabolic risk (waist circumference, triglycerides, HDL-cholesterol, systolic and diastolic blood pressure, fasting plasma glucose, and a clustered cardiometabolic risk score) in Australian adults.


Methods: The Australian Diabetes, Obesity and Lifestyle Study (AusDiab) is a prospective, population-based cohort study with biological, behavioral, and demographic measures collected in 1999-2000 and 2004-2005. Noninstitutionalized adults aged >=25 yr were measured at baseline (11,247; 55% of those completing an initial household interview); 6400 took part in the 5-yr follow-up biomedical examination, and 3846 met the inclusion criteria for this analysis. Multiple linear regression analysis was used, and unstandardized B coefficients (95% confidence intervals (CI)) are provided.


Results: Baseline television viewing time (10 h·wk-1 unit) was not significantly associated with change in any of the biomarkers of cardiometabolic risk. Increases in television viewing time over 5 yr (10 h·wk-1 unit) were associated with increases in waist circumference (men: 0.43 cm, 95% CI = 0.08-0.78 cm, P = 0.02; women: 0.68 cm, 95% CI = 0.30-1.05, P < 0.001), diastolic blood pressure (women: 0.47 mm Hg, 95% CI = 0.02-0.92 mm Hg, P = 0.04), and the clustered cardiometabolic risk score (women: 0.03, 95% CI = 0.01-0.05, P = 0.007). These associations were independent of baseline television viewing time and baseline and change in physical activity and other potential confounders.


Conclusions: These findings indicate that an increase in television viewing time is associated with adverse cardiometabolic biomarker changes. Further prospective studies using objective measures of several sedentary behaviors are required to confirm causality of the associations found.

The effects of progressive resistance training combined with a whey-protein drink and vitamin D supplementation on glycaemic control, body composition and cardiometabolic risk factors in older adults with type 2 diabetes: study protocol for a randomized c

While physical activity, energy restriction and weight loss are the cornerstone of type 2 diabetes management, less emphasis is placed on optimizing skeletal muscle mass. As muscle is the largest mass of insulin-sensitive tissue and the predominant reservoir for glucose disposal, there is a need to develop safe and effective evidence-based, lifestyle management strategies that optimize muscle mass as well as improve glycaemic control and cardiometabolic risk factors in people with this disease, particularly older adults who experience accelerated muscle loss.

Associations of sedentary time patterns and TV viewing time with inflammatory and endothelial function biomarkers in children

OBJECTIVE: Investigate associations of TV viewing time and accelerometry-derived sedentary time with inflammatory and endothelial function biomarkers in children.

METHODS: Cross-sectional analysis of 164 7-10-year-old children. TV viewing time was assessed by parental proxy report and total and patterns of sedentary time accumulation (e.g. prolonged bouts) were assessed by accelerometry. C-reactive protein (CRP), homeostasis model assessment of insulin resistance, interleukin-2, -6, -8, -10, tumour necrosis factor alpha, adiponectin, resistin, brain-derived neurotrophic factor, soluble intercellular and vascular adhesion molecule 1, plasminogen activator inhibitor 1 and soluble E-selectin were assessed. Generalised linear models assessed the associations of TV viewing and sedentary time with biomarkers, adjusting for sex, waist circumference, moderate- to vigorous-intensity physical activity and diet density.

RESULTS: Each additional h week(-1) of TV viewing was associated with 4.4% (95% CI: 2.1, 6.7) greater CRP and 0.6% (0.2, 1.0) greater sVCAM-1 in the fully adjusted model. The association between frequency and duration of 5-10 min bouts of sedentary time and CRP was positive after adjustment for sex and waist circumference but attenuated after adjustment for diet density.

CONCLUSIONS: This study suggests that TV viewing was unfavourably associated with several markers of inflammation and endothelial dysfunction. The detrimental association between 5 and 10 min bouts of sedentary time and CRP approached significance, suggesting that further research with a stronger study design (longitudinal and/or experimental) is needed to better understand how the accumulation of sedentary time early in life may influence short and longer term health.

Influence of obesity and cardiometabolic makers on lipoprotein-associated phospholipase A2 (Lp-PLA2) activity in adolescents: the healthy young cross-sectional study

Abstract Background Lipoprotein-associated phospholipase A2 activity (Lp-PLA2) is a good marker of cardiovascular risk in adults. It is strongly associated with stroke and many others cardiovascular events. Despite this, the impact of obesity on this enzyme activity and its relation to biomarkers of cardiovascular disease in adolescents is not very well investigated. The purpose of this article is to evaluate the influence of obesity and cardiometabolic markers on Lp-PLA2 activity in adolescents. Results This cross-sectional study included 242 adolescents (10–19 years) of both gender. These subjects were classified in Healthy Weight (n = 77), Overweight (n = 82) and Obese (n = 83) groups. Lipid profile, glucose, insulin, HDL size, LDL(−) and anti-LDL(−) antibodies were analyzed. The Lp-PLA2 activity was determined by a colorimetric commercial kit. Body mass index (BMI), waist circumference and body composition were monitored. Food intake was evaluated using three 24-hour diet recalls. The Lp-PLA2 activity changed in function to high BMI, waist circumference and fat mass percentage. It was also positively associated with HOMA-IR, glucose, insulin and almost all variables of lipid profile. Furthermore, it was negatively related to Apo AI (β = −0.137; P = 0.038) and strongly positively associated with Apo B (β = 0.293; P < 0.001) and with Apo B/Apo AI ratio (β = 0.343; P < 0.001). The better predictor model for enzyme activity, on multivariate analysis, included Apo B/Apo AI (β = 0.327; P < 0.001), HDL size (β = −0.326; P < 0.001), WC (β = 0.171; P = 0.006) and glucose (β = 0.119; P = 0.038). Logistic regression analysis demonstrated that changes in Apo B/Apo AI ratio were associated with a 73.5 times higher risk to elevated Lp-PLA2 activity. Conclusions Lp-PLA2 changes in function of obesity, and that it shows important associations with markers of cardiovascular risk, in particular with waist circumference, glucose, HDL size and Apo B/Apo AI ratio. These results suggest that Lp-PLA2 activity can be a cardiovascular biomarker in adolescence.

Socioeconomic position, gender, health behaviours and biomarkers of cardiovascular disease and diabetes

Socio-economic gradients in cardiovascular disease (CVD) and diabetes have been found throughout the developed world and there is some evidence to suggest that these gradients may be steeper for women. Research on social gradients in biological risk factors for CVD and diabetes has received less attention and we do not know the extent to which gradients in biomarkers vary for men and women. We examined the associations between two indicators of socio-economic position (education and household income) and biomarkers of diabetes and cardiovascular disease (CVD) for men and women in a national, population-based study of 11,247 Australian adults. Multi-level linear regression was used to assess associations between education and income and glucose tolerance, dyslipidaemia, blood pressure (BP) and waist circumference before and after adjustment for behaviours (diet, smoking, physical activity, TV viewing time, and alcohol use). Measures of glucose tolerance included fasting plasma glucose and insulin and the results of a glucose tolerance test (2 h glucose) with higher levels of each indicating poorer glucose tolerance. Triglycerides and High Density Lipoprotein (HDL) Cholesterol were used as measures of dyslipidaemia with higher levels of the former and lower levels of the later being associated with CVD risk. Lower education and low income were associated with higher levels of fasting insulin, triglycerides and waist circumference in women. Women with low education had higher systolic and diastolic BP and low income women had higher 2 h glucose and lower HDL cholesterol. With only one exception (low income and systolic BP), all of these estimates were reduced by more than 20% when behavioural risk factors were included. Men with lower education had higher fasting plasma glucose, 2 h glucose, waist circumference and systolic BP and, with the exception of waist circumference, all of these estimates were reduced when health behaviours were included in the models. While low income was associated with higher levels of 2-h glucose and triglycerides it was also associated with better biomarker profiles including lower insulin, waist circumference and diastolic BP. We conclude that low socio-economic position is more consistently associated with a worse profile of biomarkers for CVD and diabetes for women.