Netherlands Epidemiology Of Obesity Study Research Articles

Hypertension and diabetes, but not leptin and adiponectin, mediate the relationship between body fat and chronic kidney disease

Abstract Purpose Obesity may promote kidney damage through hemodynamic and hormonal effects. We investigated the association between body mass index (BMI), total body fat (TBF) and chronic kidney disease (CKD) and whether hypertension, diabetes, leptin and adiponectin mediated these associations. Methods In this cross-sectional analysis of the Netherlands Epidemiology of Obesity study, 6671 participants (45–65 y) were included. We defined CKD as eGFR <60 ml/min/1.73 m2 and/or moderately increased albuminuria. The percentage of mediation was calculated using general structural equation modeling, adjusted for potential confounding factors age, sex, smoking, ethnicity, physical activity and Dutch healthy diet index. Results At baseline mean (SD) age was 56 (6), BMI 26.3 (4.4), 44% men, and 4% had CKD. Higher BMI and TBF were associated with 1.08 (95%CI 1.05; 1.11) and 1.05-fold (95%CI 1.02; 1.08) increased odds of CKD, respectively. As adiponectin was not associated with any of the outcomes, it was not studied further as a mediating factor. The association between BMI and CKD was 8.5% (95%CI 0.5; 16.5) mediated by diabetes and 22.3% (95%CI 7.5; 37.2) by hypertension. In addition, the association between TBF and CKD was 9.6% (95%CI −0.4; 19.6) mediated by diabetes and 22.4% (95%CI 4.2; 40.6) by hypertension. We could not confirm mediation by leptin in the association between BMI and CKD (35.6% [95%CI −18.8; 90.3]), nor between TBF and CKD (59.7% [95%CI −7.1; 126.6]). Conclusion Our results suggest that the relations between BMI, TBF and CKD are in part mediated by diabetes and hypertension.

Per- and Polyfluoroalkyl Substances Concentrations are Associated with an Unfavorable Cardio-Metabolic Risk Profile: Findings from Two Population-Based Cohort Studies

AbstractPer- and polyfluoroalkyl substances (PFAS) are widely used and persistent chemicals, leading to ubiquitous exposure. Although high PFAS levels have been associated with an adverse cardiovascular risk profile, the distribution of levels and relations with cardio-metabolic risk markers in the general population have not been fully characterized. We assessed the association between blood levels of perfluorooctaneic acid (PFOA), perfluorooctane sulfonic acid (PFOS), and perfluorohexanesulfonic acid (PFHxS) and a range of lipoproteins and metabolites as well as clinical lipid measurements. We used data from participants of the Netherlands Epidemiology of Obesity study (NEO) (n = 584) and the Rhineland Study (n = 1962), jointly spanning an age range of 30 to 89 years. PFAS were measured with the Metabolon HD4 platform, and lipoprotein and metabolite profiles were measured using Nightingale’s nuclear magnetic resonance-spectroscopy platform, and mainly comprised lipoprotein markers. Using linear regression analyses, we quantified age-, sex-, and education-adjusted associations of PFOA, PFOS, and PFHxS with clinical lipid measurements and 224 lipoproteins and metabolites. Higher levels of PFAS, particularly PFOS and PFHxS, were associated with higher concentrations of total lipid, cholesterol and phospholipid content in most HDL, IDL, LDL, and VLDL subclasses. The effect sizes were age-dependent for the majority of the associations, with the deleterious effects of PFAS being generally stronger in people below compared to those above median age. Our observation that in the general population even low PFAS concentrations are associated with an unfavorable lipid profile, calls for further critical regulation of PFAS substances.

Association between venous thromboembolism-associated genetic variants, coagulation factor levels, and thrombin generation potential.

Recently three large meta-analyses of genome-wide association studies for venous thromboembolism (VTE) identified over 130 genetic variants. However, mechanisms by which newly identified and therefore underexplored VTE-associated genetic variants influence VTE remain unclear. To elucidate the mechanism, we investigated the association between 61 newly identified VTE-associated genetic variants and the levels of coagulation factor (F) VIII, FIX, FXI, and fibrinogen as well as thrombin generation parameters (lag time, peak, endogenous thrombin potential, time-to-peak, and velocity), which are well-known biological traits associated with VTE. This study was conducted on 5341 participants of the Netherlands Epidemiology of Obesity study. The associations between VTE-associated genetic variants and coagulation factor levels and thrombin generation parameters were examined using linear regression analyses, adjusted for age, sex, body mass index, oral contraceptive use, hormone replacement therapy, and menopausal status. Of 61 genetic variants, 33 were associated with one or more of the coagulation factor levels and thrombin generation parameters. Following multiple testing corrections, five genetic variants remained significant, of which MAP1A rs55707100 exhibited the most robust association with thrombin generation parameters and FXI levels (β=-5.33%, 95% confidence interval: -8.44, -2.22). Our findings shed light on the underlying mechanisms by which these genetic variants influence the risk of VTE.

PB1410 The Association between Microvascular Health and Coagulation Parameters: The Netherlands Epidemiology of Obesity Study

PB1410 The Association between Microvascular Health and Coagulation Parameters: The Netherlands Epidemiology of Obesity Study

Sex-specific association between microvascular health and coagulation parameters: the Netherlands Epidemiology of Obesity study

BackgroundMicrovascular dysfunction is a growing determinant of sex differences in coronary heart disease (CHD). Dysregulation of the coagulation system is involved in CHD pathogenesis and can be induced by endothelial glycocalyx (EG) perturbation. However, little is known about the link between EG function and coagulation parameters in population-based studies on sex specificity. ObjectivesWe sought to examine the sex differences in the relationship between EG function and coagulation parameters in a middle-aged Dutch population. MethodsUsing baseline measurements of 771 participants from the Netherlands Epidemiology of Obesity study (age, 56 years [IQR, 51-61 years]; 53% women; body mass index, 27.9 kg/m2 [IQR, 25.1-30.9 kg/m2]), associations between glycocalyx-related perfused boundary region (PBR) derived using sidestream dark-field imaging and coagulation parameters (factor [F]VIII/IX/XI; thrombin generation parameters; and fibrinogen) were investigated using linear regression analyses, adjusting for possible confounders (including C-reactive protein, leptin, and glycoprotein acetyls), followed by sex-stratified analyses. ResultsThere was a sex difference in the associations between PBR and coagulation parameters. Particularly in women, 1-SD PBR (both total and feed vessel, indicating poorer glycocalyx status) was associated with higher FIX activity ([1.8%; 95% CI, 0.3%-3.3%] and [2.0%; 95% CI, 0.5%-3.4%], respectively) and plasma fibrinogen levels ([5.1 mg/dL; 95% CI, 0.4-9.9 mg/dL] and [5.8 mg/dL; 95% CI, 1.1-10.6 mg/dL], respectively). Furthermore, 1-SD PBRcapillary was associated with higher FVIII activity (3.5%; 95% CI, 0.4%-6.5%) and plasma fibrinogen levels (5.3 mg/dL; 95% CI, 0.6-10.0 mg/dL). ConclusionWe revealed a sex-specific association between microcirculatory health and procoagulant status, which suggests that microvascular health be considered during early development of CHD in women.

"Short Questionnaire To Assess Health-Enhancing Physical Activity" Versus Actiheart-Measured Physical Activity In The Middle Aged General Population: The Netherlands Epidemiology Of Obesity Study

"Short Questionnaire To Assess Health-Enhancing Physical Activity" Versus Actiheart-Measured Physical Activity In The Middle Aged General Population: The Netherlands Epidemiology Of Obesity Study

The association between leptin and subclinical cardiovascular disease explained by body fat: Observational and Mendelian randomization analyses

Background and aimsLeptin has been associated with adverse effects on cardiovascular disease, but the effect of confounding by body fat in these associations remains unclear. To investigate associations between leptin and heart function and subclinical cardiovascular disease adjusted for total body fat, and to investigate the causal relation between leptin and cardiovascular disease using Mendelian randomisation. Methods and resultsLeptin concentrations, total body fat and diverse measures of subclinical cardiovascular disease were determined in participants of the Netherlands Epidemiology of Obesity study. Linear regression between leptin concentration and measures of heart function, ECG measures, and carotid intima media thickness as a measure of subclinical atherosclerosis was adjusted for potential confounding factors, and additionally including total body fat. We analysed the combined effects of genetic variants from a GWAS on leptin concentrations in publicly-available summary statistics of coronary heart disease GWAS (CARDIoGRAMplusC4D, n = 184,305). As many as 6107 men and women, mean (SD) age 56 (6) years, BMI 26 (4) kg/m2, and median leptin concentration 12.1 μg (IQR: 6.7–22.6) were included.In observational analyses, leptin was weakly associated with heart function and subclinical cardiovascular disease, but these associations attenuated when adjusting for total body fat. A doubling of genetically-determined leptin concentration was associated with an odds ratio of cardiovascular disease of 0.69 (0.37, 1.27). ConclusionObservational associations between leptin and subclinical measures of cardiovascular disease were largely explained by differences in total body fat. Results of analyses of genetically-determined leptin and coronary heart disease risk were inconclusive due to a large confidence interval.

Agreement between nicotine metabolites in blood and self-reported smoking status: The Netherlands Epidemiology of Obesity study

IntroductionSelf-report and nicotine detection are methods to measure smoking exposure and can both lead to misclassification. It is important to highlight discrepancies between these two methods in the context of epidemiological research. ObjectiveThe aim of this cross-sectional study is to assess the agreements between self-reported smoking status and nicotine metabolite detection. MethodsData of 599 participants from the Netherlands Epidemiology of Obesity study were used to compare serum metabolite levels of five nicotine metabolites (cotinine, hydroxy-cotinine, cotinine N-Oxide, norcotinine, 3-hydroxy-cotinine-glucuronide) between self-reported never smokers (n = 245), former smokers (n = 283) and current smokers (n = 71). We assessed whether metabolites were absent or present and used logistic regression to discriminate between current and never smokers based on nicotine metabolite information. A classification tree was derived to classify individuals into current smokers and non/former smokers based on metabolite information. ResultsIn 94% of the self-reported current smokers, at least one metabolite was present, versus in 19% of the former smokers and in 10% of the never smokers. In none of the never smokers, cotinine-n-oxide, 3-hydroxy-cotinine-n-glucorinide or norcotinine was present, while at least one of these metabolites was detected in 68% of the self-reported current smokers. The classification tree classified 95% of the participants in accordance to their self-reported smoking status. All self-reported smokers who were classified as non-smokers according to the metabolite profile, had reported to be occasional smokers. ConclusionThe agreement between self-reported smoking status and metabolite information was high. This indicates that self-reported smoking status is generally reliable.

Apolipoprotein A-V is a potential target for treating coronary artery disease: evidence from genetic and metabolomic analyses

Triglyceride (TG)-lowering LPL variants in combination with genetic LDL-C-lowering variants are associated with reduced risk of coronary artery disease (CAD). Genetic variation in the APOA5 gene encoding apolipoprotein A-V also strongly affects TG levels, but the potential clinical impact and underlying mechanisms are yet to be resolved. Here, we aimed to study the effects of APOA5 genetic variation on CAD risk and plasma lipoproteins through factorial genetic association analyses. Using data from 309,780 European-ancestry participants from the UK Biobank, we evaluated the effects of lower TG levels as a result of genetic variation in APOA5 and/or LPL on CAD risk with or without a background of reduced LDL-C. Next, we compared lower TG levels via APOA5 and LPL variation with over 100 lipoprotein measurements in a combined sample from the Netherlands Epidemiology of Obesity study (N = 4,838) and the Oxford Biobank (N = 6,999). We found that lower TG levels due to combined APOA5 and LPL variation and genetically-influenced lower LDL-C levels afforded the largest reduction in CAD risk (odds ratio: 0.78 (0.73–0.82)). Compared to patients with genetically-influenced lower TG via LPL, genetically-influenced lower TG via APOA5 had similar and independent, but notably larger, effects on the lipoprotein profile. Our results suggest that lower TG levels as a result of APOA5 variation have strong beneficial effects on CAD risk and the lipoprotein profile, which suggest apo A-V may be a potential novel therapeutic target for CAD prevention.

Evaluation of the Value of Waist Circumference and Metabolomics in the Estimation of Visceral Adipose Tissue.

Visceral adipose tissue (VAT) is a strong prognostic factor for cardiovascular disease and a potential target for cardiovascular risk stratification. Because VAT is difficult to measure in clinical practice, we estimated prediction models with predictors routinely measured in general practice and VAT as outcome using ridge regression in 2,501 middle-aged participants from the Netherlands Epidemiology of Obesity study, 2008–2012. Adding waist circumference and other anthropometric measurements on top of the routinely measured variables improved the optimism-adjusted R2 from 0.50 to 0.58 with a decrease in the root-mean-square error (RMSE) from 45.6 to 41.5 cm2 and with overall good calibration. Further addition of predominantly lipoprotein-related metabolites from the Nightingale platform did not improve the optimism-corrected R2 and RMSE. The models were externally validated in 370 participants from the Prospective Investigation of Vasculature in Uppsala Seniors (PIVUS, 2006–2009) and 1,901 participants from the Multi-Ethnic Study of Atherosclerosis (MESA, 2000–2007). Performance was comparable to the development setting in PIVUS (R2 = 0.63, RMSE = 42.4 cm2, calibration slope = 0.94) but lower in MESA (R2 = 0.44, RMSE = 60.7 cm2, calibration slope = 0.75). Our findings indicate that the estimation of VAT with routine clinical measurements can be substantially improved by incorporating waist circumference but not by metabolite measurements.

Illness perceptions and health-related quality of life in individuals with overweight and obesity.

To understand how individuals (self-)manage obesity, insight is needed into how patients perceive their condition and how this perception translates into health outcomes (e.g., health-related quality of life, HRQOL). Our objectives were (1) to examine illness perceptions in individuals with overweight and obesity, and (2) to investigate associations of these perceptions with physical and mental HRQOL. In a cross-sectional analysis of the Netherlands Epidemiology of Obesity Study (n = 6432; 52% women), illness perceptions were assessed using the Brief Illness Perception Questionnaire, and HRQOL was assessed using the 36-Item Short-Form Health Survey. Illness perceptions were calculated for different categories of overall, abdominal, and metabolically unhealthy obesity. We investigated associations of illness perceptions with HRQOL using BMI-stratified multivariable linear regression analyses. Compared to individuals with normal weight, individuals with obesity believed to a higher extent that their condition had more serious consequences [Mean Difference (95%CI): 1.8 (1.6-2.0)], persisted for a longer time [3.4 (3.2-3.6)], manifested in more symptoms [3.8 (3.6-4.0)], caused more worry [4.2 (3.9-4.4)] and emotional distress [2.0 (1.8-2.2)], but was more manageable with medical treatment [3.1 (2.9-3.4)]. They perceived to a lesser extent that they had personal control [-2.2 (-2.4, -2.0)] and understanding [-0.3 (-0.5, -0.1)] regarding their condition. These negative perceptions were less pronounced in individuals with abdominal obesity. Behaviour/Lifestyle was attributed by 73% of participants to be the cause of their obesity. Stronger negative illness perceptions were associated with impaired HRQOL, particularly the physical component. Individuals with obesity perceived their conditions as threatening, and this seemed somewhat stronger in individuals with overall obesity than those with abdominal obesity. Behaviour/Lifestyle is a crucial target intervention and empowering self-management behaviour to achieve a healthy body weight may deliver promising results. In addition, strategies that aim to change negative perceptions of obesity into more adaptive ones may improve HRQOL.

Factors associated with physical activity among COPD patients with mild or moderate airflow obstruction.

Physical inactivity is already present among patients with chronic obstructive pulmonary disease (COPD) of mild or moderate airflow obstruction. Most previous studies that reported on determinants of physical activity in COPD included patients with severe COPD. Therefore, the aim of this study was to explore which patient characteristics were related with physical activity in COPD patients with mild or moderate airflow obstruction. Cross-sectional analyses were performed on patients selected from the population-based Netherlands Epidemiology of Obesity study. Patients were included if they had a physician-diagnosed COPD GOLD 0-2 or had newly diagnosed COPD GOLD 1-2. Physical activity was evaluated using the Short Questionnaire to Assess Health-Enhancing Physical Activity (SQUASH) questionnaire and reported in hours per week of metabolic equivalents (MET-h/week). Associations between sociodemographic, lifestyle, clinical and functional characteristics were examined using regression analysis. 323 patients were included in research (77 with physician-diagnosed and 246 with newly diagnosed COPD). We found that physical activity was positively associated with pulmonary function: FEV1 (regression coefficient 0.40 (95% CI 0.09,0.71)) and FVC (regression coefficient 0.34 (95% CI 0.06,0.61)). Physical activity was associated with anxiety (regression coefficient =0.9 (95% CI 0.3,1.6)) only for physician-diagnosed patients.Lung function and anxiety level determine level of physical activity among COPD patients with mild or moderate airflow obstruction. Thus, integrating it into the physical activity plans could help to increase physical activity level of the patients.

Microvascular differences in individuals with obesity at risk of developing cardiovascular disease.

ObjectiveThis study aimed to investigate microvascular differences in individuals with obesity at risk for developing cardiovascular disease.MethodsIn this cross‐sectional Netherlands Epidemiology of Obesity study, participant sublingual microcirculation was assessed with a newly developed GlycoCheck software (Microvascular Health Solutions Inc., Salt Lake City, Utah), which integrates red blood cell velocity within the smallest capillaries (4‐7 µm) and feed vessels (>10 µm). Framingham Risk Score was used to calculate 10‐year cardiovascular risk, divided into low‐, intermediate‐, and high‐risk groups. ANOVA was used to evaluate microvascular differences among the groups.ResultsA total of 813 participants were included. The high‐risk group (n = 168) was characterized by differences in the microvasculature compared with the low‐risk group (n = 392): the high‐risk group had a 49% reduction in the number of smallest capillaries and a 9.1‐µm/s (95% CI: 5.2‐12.9) higher red blood cell velocity in the feed vessels. No differences in velocity‐corrected perfused boundary regions were found.ConclusionsIt was observed that, with adding red blood cell velocity to the software, sidestream dark field imaging is able to detect microcirculatory differences in a cohort of individuals with obesity at risk for developing cardiovascular disease.

Estimated pulse wave velocity (ePWV) as a potential gatekeeper for MRI-assessed PWV: a linear and deep neural network based approach in 2254 participants of the Netherlands Epidemiology of Obesity study

Pulse wave velocity (PWV) assessed by magnetic resonance imaging (MRI) is a prognostic marker for cardiovascular events. Prediction modelling could enable indirect PWV assessment based on clinical and anthropometric data. The aim was to calculate estimated-PWV (ePWV) based on clinical and anthropometric measures using linear ridge regression as well as a Deep Neural Network (DNN) and to determine the cut-off which provides optimal discriminative performance between lower and higher PWV values. In total 2254 participants from the Netherlands Epidemiology of Obesity study were included (age 45–65 years, 51% male). Both a basic and expanded prediction model were developed. PWV was estimated using linear ridge regression and DNN. External validation was performed in 114 participants (age 30–70 years, 54% female). Performance was compared between models and estimation accuracy was evaluated by ROC-curves. A cut-off for optimal discriminative performance was determined using Youden’s index. The basic ridge regression model provided an adjusted R2 of 0.33 and bias of < 0.001, the expanded model did not add predictive performance. Basic and expanded DNN models showed similar model performance. Optimal discriminative performance was found for PWV < 6.7 m/s. In external validation expanded ridge regression provided the best performance of the four models (adjusted R2: 0.29). All models showed good discriminative performance for PWV < 6.7 m/s (AUC range 0.81–0.89). ePWV showed good discriminative performance with regard to differentiating individuals with lower PWV values (< 6.7 m/s) from those with higher values, and could function as gatekeeper in selecting patients who benefit from further MRI-based PWV assessment.

Genetic Susceptibility Loci in Genomewide Association Study of Cluster Headache.

ObjectiveIdentifying common genetic variants that confer genetic risk for cluster headache.MethodsWe conducted a case–control study in the Dutch Leiden University Cluster headache neuro‐Analysis program (LUCA) study population (n = 840) and unselected controls from the Netherlands Epidemiology of Obesity Study (NEO; n = 1,457). Replication was performed in a Norwegian sample of 144 cases from the Trondheim Cluster headache sample and 1,800 controls from the Nord‐Trøndelag Health Survey (HUNT). Gene set and tissue enrichment analyses, blood cell‐derived RNA‐sequencing of genes around the risk loci and linkage disequilibrium score regression were part of the downstream analyses.ResultsAn association was found with cluster headache for 4 independent loci (r 2 < 0.1) with genomewide significance (p < 5 × 10−8), rs11579212 (odds ratio [OR] = 1.51, 95% confidence interval [CI] = 1.33–1.72 near RP11‐815 M8.1), rs6541998 (OR = 1.53, 95% CI = 1.37–1.74 near MERTK), rs10184573 (OR = 1.43, 95% CI = 1.26–1.61 near AC093590.1), and rs2499799 (OR = 0.62, 95% CI = 0.54–0.73 near UFL1/FHL5), collectively explaining 7.2% of the variance of cluster headache. SNPs rs11579212, rs10184573, and rs976357, as proxy SNP for rs2499799 (r 2 = 1.0), replicated in the Norwegian sample (p < 0.05). Gene‐based mapping yielded ASZ1 as possible fifth locus. RNA‐sequencing indicated differential expression of POLR1B and TMEM87B in cluster headache patients.InterpretationThis genomewide association study (GWAS) identified and replicated genetic risk loci for cluster headache with effect sizes larger than those typically seen in complex genetic disorders. ANN NEUROL 2021;90:203–216

The Relation Between Adult Weight Gain, Adipocyte Volume, and the Metabolic Profile at Middle Age.

ContextWeight gain during adulthood increases cardiometabolic disease risk, possibly through adipocyte hypertrophy.ObjectiveWe aimed to study the specific metabolomic profile of adult weight gain, and to examine its association with adipocyte volume.MethodsNuclear magnetic resonance–based metabolomics were measured in the Netherlands Epidemiology of Obesity (NEO) study (n = 6347, discovery) and Oxford Biobank (n = 6317, replication). Adult weight gain was calculated as the absolute difference between body mass index (BMI) at middle age and recalled BMI at age 20 years. We performed linear regression analyses with both exposures BMI at age 20 years and weight gain, and separately with BMI at middle age in relation to 149 serum metabolomic measures, adjusted for age, sex, and multiple testing. Additionally, subcutaneous abdominal adipocyte biopsies were collected in a subset of the Oxford Biobank (n = 114) to estimate adipocyte volume.ResultsMean (SD) weight gain was 4.5 (3.7) kg/m2 in the NEO study and 3.6 (3.7) kg/m2 in the Oxford Biobank. Weight gain, and not BMI at age 20 nor middle age, was associated with concentrations of 7 metabolomic measures after successful replication, which included polyunsaturated fatty acids, small to medium low-density lipoproteins, and total intermediate-density lipoprotein. One SD weight gain was associated with 386 μm3 (95% CI, 143-629) higher median adipocyte volume. Adipocyte volume was associated with lipoprotein particles specific for adult weight gain.ConclusionAdult weight gain is associated with specific metabolomic alterations of which the higher lipoprotein concentrations were likely contributed by larger adipocyte volumes, presumably linking weight gain to cardiometabolic disease.

Differential effect of statin use on coagulation markers: an active comparative analysis in the NEO study

BackgroundStatins are a potential treatment for venous thromboembolism (VTE) prophylaxis complementary to conventional anticoagulants without associated bleeding complications. This study aimed to compare pro-thrombotic activities of different classes of lipid-lowering drugs in an active comparator design and determine whether there is a relation between statin versus fibrate/niacin use and pro-coagulant factor outcomes.MethodsThis is a cross-sectional analysis of participants from the Netherlands Epidemiology of Obesity study using any class of lipid-lowering drugs, including any types of statins, niacin, and fibrates. We performed linear regression analyses to determine fibrinogen, factor (F) VIII, FIX, and FXI activity in statins versus fibrate/niacin users and adjusted for age, sex, tobacco smoking, body mass index (BMI), hypertension, diabetes, and prevalent cardiovascular disease.ResultsAmong 1043 participants, the mean age was 58.4 ± 5.2 years, 61% were men, and the mean BMI was 31.3 ± 4.5 kg/m2. Clinical characteristics were balanced between statin and fibrate/niacin users. Statin users had lower mean FXI (18.3 IU/dL, 95% confidence interval (CI) 9.4 to 27.3) levels compared to fibrate/niacin users. The level of FVIII (15.8 IU/dL, 95% CI − 0.003 to 31.6), and FIX (11.3 IU/dL, 95% CI − 0.4 to 23.2) were lower in statin users than fibrate/niacin users with marginal statistical significance.ConclusionCurrent statin use was associated with lower plasma levels of FXI than fibrate/niacin use. The effects on coagulation factors may, in part, explain the benefit of statin therapy rendered in primary and secondary prevention of VTE.

Objectively Measured Physical Activity and Body Fatness: Associations with Total Body Fat, Visceral Fat, and Liver Fat.

It remains unclear to what extent habitual physical activity and sedentary time (ST) are associated with visceral fat and liver fat. We studied the substitution of ST with time spent physically active and total body fat (TBF), visceral adipose tissue (VAT), and hepatic triglyceride content (HTGC) in middle-age men and women. In this cross-sectional analysis of the Netherlands Epidemiology of Obesity study, physical activity was assessed in 228 participants using a combined accelerometer and heart rate monitor. TBF was assessed by the Tanita bioelectrical impedance, VAT by magnetic resonance imaging, and HTGC by proton-MR spectroscopy. Behavioral intensity distribution was categorized as ST, time spent in light physical activity (LPA), and moderate to vigorous physical activity (MVPA). To estimate the effect of replacing 30 min·d-1 of ST with 30 min·d-1 LPA or MVPA, we performed isotemporal substitution analyses, adjusted for sex, age, ethnicity, education, the Dutch Healthy Diet index, and smoking. Included participants (41% men) had a mean ± SD age of 56 ± 6 yr and spent 88 ± 56 min in MVPA and 9.0 ± 2.1 h of ST. Replacing 30 min·d-1 of ST with 30 min of MVPA was associated with 1.3% less TBF (95% confidence interval = -2.0 to -0.7), 7.8 cm2 less VAT (-11.6 to -4.0), and 0.89 times HTGC (0.82-0.97). Replacement with LPA was not associated with TBF (-0.03%; -0.5 to 0.4), VAT (-1.7 cm2; -4.4 to 0.9), or HTGC (0.98 times; 0.92-1.04). Reallocation of time spent sedentary with time spent in MVPA, but not LPA, was associated with less TBF, visceral fat, and liver fat. These findings contribute to the development of more specified guidelines on ST and physical activity.

The associations of leptin and adiponectin with the metabolic syndrome in an Indonesian and a Dutch population

Background and aimsAt the same BMI, Asian populations develop cardiometabolic complications earlier than Western populations. We hypothesized that a different secretion of the adipocyte-derived hormones leptin and adiponectin plays a role and investigated the associations of the two hormones with the metabolic syndrome (MetS) in an Indonesian and a Dutch population. Methods and resultsWe performed cross-sectional analyses of the Netherlands Epidemiology of Obesity Study (n = 6602) and the SUGAR Scientific Programme Indonesia–Netherlands Study (n = 1461). We examined sex-stratified associations of leptin and adiponectin with MetS, using multivariate logistic regression including adjustment for total body fat. The mean (SD) leptin (mcg/L) were 4.7 (6.0) in Indonesian men, 18.6 (12.0) in Indonesian women, 9.1 (7.7) in Dutch men, and 23.4 (17.4) in Dutch women. The mean (SD) adiponectin (mg/L) were 5.7 (5.4), 7.5 (7.1), 6.6 (3.3), and 11.3 (4.9), respectively. Within the same BMI category, leptin concentrations were similar in the two populations, whereas adiponectin was lower in the Indonesian population. Per SD of leptin, adjusted prevalence odds ratios (ORs, 95%CI) of MetS were 0.9 (0.6–1.2) in Indonesian men, 1.1 (0.9–1.4) in Indonesian women, 2.2 (1.6–2.8) in Dutch men, and 1.2 (1.0–1.5) in Dutch women. Per SD of adiponectin, the ORs were 0.9 (0.7–1.2), 0.8 (0.7–1.0), 0.6 (0.6–0.8), and 0.4 (0.4–0.5), respectively. ConclusionsDespite lower adiponectin levels, adiponectin was not related to the MetS in the Indonesian population and can not explain their increased cardiometabolic risk at the same BMI.

Association of measures of body fat with serum alpha-tocopherol and its metabolites in middle-aged individuals

Background and aimsThe accumulation of fat increases the formation of lipid peroxides, which are partly scavenged by alpha-tocopherol (α-TOH). Here, we aimed to investigate the associations between different measures of (abdominal) fat and levels of urinary α-TOH metabolites in middle-aged individuals. Methods and resultsIn this cross-sectional analysis in the Netherlands Epidemiology of Obesity study (N = 511, 53% women; mean [SD] age of 55 [6.1] years), serum α-TOH and α-TOH metabolites from 24-h urine were measured as alpha-tocopheronolactone hydroquinone (α-TLHQ, oxidized) and alpha-carboxymethyl-hydroxychroman (α-CEHC, enzymatically converted) using liquid-chromatography-tandem mass spectrometry. Body mass index and total body fat were measured, and abdominal subcutaneous and visceral adipose tissue (aSAT and VAT) were assessed using magnetic resonance imaging. Using multivariable-adjusted linear regression analyses, we analysed the associations of BMI, TBF, aSAT and VAT with levels of urinary α-TOH metabolites, adjusted for confounders. We observed no evidence for associations between body fat measures and serum α-TOH. Higher BMI and TBF were associated with lower urinary levels of TLHQ (0.95 [95%CI: 0.90, 1.00] and 0.94 [0.88, 1.01] times per SD, respectively) and with lower TLHQ relative to CEHC (0.93 [0.90, 0.98] and 0.93 [0.87, 0.98] times per SD, respectively). We observed similar associations for VAT (TLHQ: 0.94 [0.89, 0.99] times per SD), but not for aSAT. ConclusionsOpposite to our research hypothesis, higher abdominal adiposity was moderately associated with lower levels of oxidized α-TOH metabolites, which might reflect lower vitamin E antioxidative activity in individuals with higher abdominal fat instead.