Sex-specific associations of childhood maltreatment with obesity-related traits - The Study of Health in Pomerania (SHIP).

BACKGROUND: Child maltreatment (CM) is linked to obesity in adulthood. However, sex-differences and direct measurements of body fat have previously been insufficiently considered in this context. OBJECTIVE: To assess sex-specific associations of CM with anthropometric markers of overweight/obesity and direct measures of body fat. PARTICIPANTS AND SETTING: Analyses were conducted in 4006 adults from a population-based cohort in Northeastern Germany (SHIP-TREND-0). METHODS: CM was assessed using the Childhood Trauma Questionnaire (CTQ). Obesity-related traits included anthropometric indicators (i.e., height, weight, body mass index [BMI], waist [WC] and hip circumference [HC], waist-to-hip ratio [WHR], waist-to-height ratio [WHtR]), fat mass (FM) and fat-free mass (FFM) derived from bioelectrical impedance analysis (BIA), and subcutaneous (SAT) and visceral adipose tissue (VAT) ascertained using magnetic resonance imaging (MRI). Sex-stratified linear regression models predicting obesity-related traits from total CTQ scores were adjusted for age and education. Exploratory analyses investigated effects of CTQ subscales on obesity-related traits. RESULTS: In men, CM was positively associated with WHtR (ß = 0.04; p = .030) and VAT (ß = 0.02; p = .031) and inversely with body height (ß = -0.05; p = .010). In women, CM-exposure was positively associated with body weight (ß = 0.07; p = .018), BMI (ß = 0.03; p = .013), WC (ß = 0.07; p = .005), HC (ß = 0.05; p = .046), WHR (ß = 0.03; p = .015), WHtR (ß = 0.04; p = .006), FM (ß = 0.04; p = .006), and SAT (ß = 0.06; p = .041). In both sexes, effects were mainly driven by exposure to emotional and physical abuse. CONCLUSIONS: Results suggest that associations between CM-exposure and obesity-related traits in adulthood are primarily present in women. This may have implications for sex-specific obesity-related cardiometabolic risk after CM.

The Association Between C24:0/C16:0 Ceramide Ratio and Cardiorespiratory Fitness is Robust to Effect Modifications by Age and Sex.

Ceramides and cardiorespiratory (CR) fitness are both related to cardiovascular diseases. The associations of three blood plasma ceramides (C16:0, C22:0, and C24:0) with CR fitness in the population-based Study of Health in Pomerania (SHIP-START-1; n = 1,102; mean age 50.3 years, 51.5% women) are investigated. In addition, subgroup analysis according to age (

High Thyroid-Stimulating Hormone and Low Free Triiodothyronine Levels Are Associated with Chronic Kidney Disease in Three Population-Based Studies from Germany.

High serum thyroid-stimulating hormone (TSH) levels have previously been associated with a low estimated glomerular filtration rate (eGFR), but studies associating thyroid hormone levels with albuminuria revealed inconsistent results. We used cross-sectional data from 7933 individuals aged 20 to 93 years of the Berlin Aging Study II and the Study of Health in Pomerania to associate serum TSH, fT3, and fT4 levels with eGFR and albuminuria. In multivariable analyses adjusted for confounding, we found inverse non-linear associations of serum TSH levels with eGFR, while serum fT3 levels showed a positive association with eGFR. High as well as low serum fT4 levels were associated with a lower eGFR. Age but not sex modified the association between thyroid hormone levels and eGFR. The inverse associations between serum TSH levels and eGFR were strongest in the youngest age groups, while the positive associations between serum fT3 levels and eGFR were strongest in older individuals. No significant associations between thyroid hormone levels and albuminuria were found. Our results indicate that hypothyroidism might be associated with a reduced kidney function. Thyroid function might be more tightly related to the eGFR than to albuminuria in the general population.

Association of plasma chemerin with all-cause and disease-specific mortality - results from a population-based study.

BACKGROUND AND OBJECTIVES: Various cross-sectional studies have observed an association between high circulating concentrations of the adipokine chemerin and an unfavorable metabolic profile. However, the prognostic value of chemerin for the risk of associated diseases and mortality was examined only in a few studies mostly using small and highly selected patient populations. We aimed to analyze the association between plasma chemerin concentrations and all-cause as well as cause-specific mortality in the general population. STUDY DESIGN AND METHODS: From the Study of Health in Pomerania (SHIP), participants of two independent cohorts (SHIP-START-1 [n = 3037], SHIP-TREND-0 [n = 4193]) were followed up for 15 and 9 years (median), respectively. The association between plasma chemerin and all-cause mortality was analyzed using multivariable Cox proportional hazard regression models. Additionally, cause-specific hazards for cardiovascular disease (CVD) and cancer mortality were modeled considering competing events. RESULTS: A total number of 507 and 208 deaths occurred during follow-up in SHIP-START-1 and SHIP-TREND-0, respectively. Multivariable regression analyses revealed a significant association between high plasma chemerin concentrations and greater overall mortality that was independent of major confounders. Each 30 ng/mL increase in chemerin was associated with a 17% higher risk of all-cause mortality (95%-confidence interval: 1.10-1.26). Cause-specific analyses further showed that the chemerin concentration was significantly associated with cancer mortality but not with CVD mortality. CONCLUSION: The present study detected a positive association between plasma chemerin concentrations and all-cause mortality in a large population-based study sample. Cause-specific analyses have shown that chemerin is likely to play a decisive role in cancer-related deaths. However, a direct association with cardiovascular mortality could not be established.

Body surface scan anthropometrics are related to cardiorespiratory fitness in the general population.

The assessment of cardiorespiratory fitness (CRF) is an important tool for prognosis evaluation of cardiovascular events. The gold standard to measure CRF is cardiopulmonary exercise testing (CPET) to determine peak oxygen uptake (VO2peak). However, CPET is not only time consuming but also expensive and is therefore not widely applicable in daily practice. The aim of our study was to analyze, whether and which anthropometric markers derived from a 3D body scanner were related to VO2peak in a general population-based study. We analyzed data (SHIP-START-3) from 3D body scanner and CPET of 1035 subjects (529 women; 51.1%, age range 36-93). A total of 164 anthropometric markers were detected with the 3D body scanner VITUS Smart XXL using the software AnthroScan Professional. Anthropometric measurements were standardized and associated with CRF by sex-stratified linear regression models adjusted for age and height. Anthropometric markers were ranked according to the - log- p values derived from these regression models. In men a greater left and right thigh-knee-ratio, a longer forearm-fingertip length, a greater left thigh circumference and greater left upper arm circumference were most strongly associated with a higher VO2peak. In women a greater left and right thigh circumference, left calf circumference, thigh thickness and right calf circumference were most strongly associated with a higher VO2peak. The detected VO2peak-related anthropometric markers could be helpful in assessing CRF in clinical routine. Commonly used anthropometric markers, e.g. waist and hip circumference, were not among the markers associated with VO2peak.

Sphingosine-1-phosphate and vascular disease in the general population.

BACKGROUND AND AIMS: Sphingosine-1-phosphate (S1P) is a sphingolipid which influences the immune and vascular system. The relationship between S1P and vascular disease in the general population is currently unclear. We explored the relation between S1P and vascular markers, (i.e. ankle-brachial index (ABI), carotid intima-media thickness (cIMT), presence of carotid atherosclerotic plaques and brachial artery flow-mediated dilation (FMD). METHODS: S1P was measured by liquid chromatography-tandem mass spectrometry in the population-based Study of Health in Pomerania (SHIP-TREND-0). Subjects with prevalent cancer, severe renal insufficiency, history of myocardial infarction and extreme values for S1P were excluded. Sex stratified linear regression models adjusted for age, smoking and waist-to-hip ratio were used. RESULTS: A total of n = 3643 participants (52% women, median age 51, 25th and 75th percentiles 39 and 63 years) were included. In men, a 1 standard deviation higher S1P concentration was associated with a significantly greater cIMT (ß: 0.0057 95%-confidence interval [CI]: 0.00027-0.0112 mm; p = 0.04) and a lower ABI (ß: -0.0090 95% CI: -0.0153 to -0.0029; p < 0.01). In women, S1P was also positively associated with cIMT (ß: 0.0044 95% CI: 0.0001-0.0086 mm; p = 0.04). CONCLUSIONS: We found that S1P was positively related to a greater cIMT in both sexes and a lower ABI in men. There was no association of S1P with any of the other investigated markers. Future studies are warranted to assess the suitability of S1P as a biomarker for vascular disease.

Variability of biomarkers used for the classification of metabolic syndrome: A repeated measurements study.

BACKGROUND AND AIMS: The definition of the metabolic syndrome consists of five components. The underlying measurements are subject to intra-individual variability. This repeated measurements study investigated the impact of intra-individual measurement variability on the stability of the diagnosis of metabolic syndrome over 12 months. METHODS AND RESULTS: Twenty-five employees of the University Medicine Greifswald aged 22-70 years were examined once a month over one year. Examinations included blood sampling and anthropometric and blood pressure measurements. Laboratory measurements included glucose, cholesterol (high-density lipoprotein [HDL], and low-density lipoprotein [LDL]), and triglycerides. The metabolic syndrome was defined according to the International Diabetes Federation modified for non-fasting blood samples. Variations in continuous metabolic markers were assessed using coefficients of variation (CV) and intra-class correlation coefficients (ICC). Overall eight participants (32%) were categorized at least once within 12 months as having a metabolic syndrome; in none of those metabolic syndrome was found consistently over the study follow-ups. The Cohen's Kappa for metabolic syndrome was 0.57. CV was highest for triglycerides (27.5%) followed by glucose (10.1%), LDL- (9.5%), and HDL-cholesterol (8.6%). ICC's were lowest for glucose (0.51), triglycerides (0.65), systolic (0.68), and diastolic blood pressure (0.69). CONCLUSION: We showed that the measurement of biomarkers defining the metabolic syndrome is a time-varying condition with implications for the concept of the metabolic syndrome. To account for this uncertainty in prevalence studies we propose to identify uncertain cases according to the current definition of the metabolic syndrome. For analysing associations we recommend to apply probabilistic sensitivity analyses.

Lipoprotein(a) and Metabolic Syndrome.

BACKGROUND: An inverse association between lipoprotein(a) (Lp[a]) and type 2 diabetes mellitus is well documented. However, data on the association of the metabolic syndrome (MetS) with Lp(a) are sparse. METHODS: Cross-sectional data for MetS and Lp(a) were available for 5743 BASE-II and SHIP-0 participants (48.7% men; age 58 [20-85] years) (BASE, Berlin Aging Study; SHIP, Study of Health in Pomerania). The association of MetS and its components with Lp(a) was analyzed by means of median regression adjusted for age, sex, and study. Associations were evaluated for the total population as well as stratified by sex and menopausal status. RESULTS: Overall, 27.6% (n = 1573) of the participants in the two studies had MetS and 22.5% (n = 1291) were premenopausal women. There was an inverse association between MetS and Lp(a) in the whole study sample (ß = -11.9, 95% confidence interval [-21.3; -2.6]) as well as in men (ß = -16.5 [-28.6; -4.3]). Participants with MetS (whole study sample) had 11.9 mmol/L lower Lp(a). Analogous results were found in postmenopausal women (ß = -25.4 [-46.0; -4.8]). In premenopausal women with MetS, Lp(a) levels were higher by 39.1 mg/L on average [12.3; 65.9]) than in premenopausal women without MetS. CONCLUSION: Hormonal aspects and menopausal alterations seem to affect the association between MetS and Lp(a), as the expected inverse association was not present in premenopausal women.

Association of thyroid function with insulin resistance: data from two population-based studies.

OBJECTIVE: Thyroid dysfunction is associated with relevant disturbances in glucose metabolism. Moreover, thyroid function undergoes important changes with ageing. The objective of this study was to investigate the association of thyroid function with insulin resistance with particular consideration of possible age-related effect modifications. DESIGN: A sample of 4193 participants from two independent epidemiological studies, the Study of Health in Pomerania-TREND-0 and the Berlin Aging Study II, was included in this cross-sectional analysis. METHODS: Insulin resistance was estimated by homeostasis model of insulin resistance (HOMA-IR) and the insulin sensitivity index (ISI). Associations of thyroid biomarkers (thyroid-stimulating hormone, free thyroxine, and free triiodothyronine (fT3)) with parameters of glucose metabolism were analysed by regression models adjusted for age, sex, smoking status, and study site. RESULTS: A higher fT3 was significantly associated with higher fasting glucose and higher fasting and 2-h postload insulin levels, a higher HOMA-IR, and lower ISI. A higher fT3 was also associated with a higher risk for impaired fasting glucose (RR 1.09, 95 CI 1.02; 1.18; P = 0.017). Many of these associations between thyroid markers and parameters of glucose metabolism were significant in young and middle-aged participants but not in older individuals. CONCLUSIONS: The main finding of this study was a consistent association of fT3 with almost all markers of insulin resistance. However, this effect seems to be wearing off in higher age highlighting a potential age-related modification of the interaction between thyroid function and glucose metabolism. Further studies are needed to clarify causal relationships.

Association between thyroid function and assessment of hepatic fat and iron contents by magnetic resonance imaging.

The associations of thyroid function parameters with non-alcoholic fatty liver disease (NAFLD) and hepatic iron overload are not entirely clear. We have cross-sectionally investigated these associations among 2734 participants of two population-based cross-sectional studies of the Study of Health in Pomerania. Serum levels of thyroid-stimulating hormone (TSH), free tri-iodothyronine (fT3), and free thyroxine (fT4) levels were measured. Liver fat content (by proton-density fat fraction) as well as hepatic iron content (by transverse relaxation rate; R2*) were assessed by quantitative MRI. Thyroid function parameters were associated with hepatic fat and iron contents by median and logistic regression models adjusted for confounding. There were no associations between serum TSH levels and liver fat content, NAFLD, or hepatic iron overload. Serum fT4 levels were inversely associated with liver fat content, NAFLD, hepatic iron contents, and hepatic iron overload. Serum fT3 levels as well as the fT3 to fT4 ratio were positively associated with hepatic fat, NAFLD, hepatic iron contents, but not with hepatic iron overload. Associations between fT3 levels and liver fat content were strongest in obese individuals, in which we also observed an inverse association between TSH levels and NAFLD. These findings might be the result of a higher conversion of fT4 to the biologically active form fT3. Our results suggest that a subclinical hyperthyroid state may be associated with NAFLD, particularly in obese individuals. Furthermore, thyroid hormone levels seem to be more strongly associated with increased liver fat content compared to hepatic iron content.

Associations of liver volume and other markers of hepatic steatosis with all-cause mortality in the general population.

AIMS: We examined the associations between liver volume and other quantitative and qualitative markers of hepatic steatosis with all-cause mortality in the general population. METHODS: We included 2769 German middle-aged individuals with a median follow-up of 8.9 years (23,898 person-years). Quantitative markers used were serum liver enzymes and FIB-4 score, while qualitative markers of hepatic steatosis included magnetic resonance imaging (MRI) measurements of liver fat content and total liver volume. Cox proportional hazards models, adjusted for confounding factors, were undertaken to investigate the associations of liver volume and other markers of hepatic steatosis with all-cause mortality. RESULTS: A larger MRI-assessed liver volume was associated with a nearly three-fold increased risk of all-cause mortality (Hazard Ratio = 3.16; 95% confidence interval 1.88; 5.30), independent of age, sex, body mass index, food frequency score, alcohol consumption and education level. This association was consistent in all subgroups considered (men vs. women; presence or absence of overweight/obesity, metabolic syndrome or diabetes). Higher serum liver enzyme levels and FIB-4 score were also significantly associated with higher all-cause mortality in the total population and in all subgroups. No independent associations were found between other quantitative and qualitative markers of hepatic steatosis and the risk of all-cause mortality. CONCLUSIONS: We showed for the first time that larger liver volume was associated with a three-fold increase in long-term risk of all-cause mortality. This association remained significant after adjustment for age, sex, alcohol consumption, obesity and other coexisting metabolic disorders.

Lower Cardiorespiratory Fitness Is Associated With Right Ventricular Geometry and Function - The Sedentary's Heart: SHIP.

Background Lower cardiorespiratory fitness (CRF) is associated with an increased risk for cardiovascular disease. However, very little information is available about the association between lower CRF and right ventricular (RV) remodeling. We investigated the relationship between CRF and RV structure and function in a large, aging, and largely sedentary adult population-based cohort. Methods and Results We used cross-sectional data of 2844 subjects (1486 women; median age, 51 years; interquartile range, 40-62 years) from the population-based cohort SHIP (Study of Health in Pomerania) with echocardiography, of which 941 also had cardiac magnetic resonance imaging. We analyzed the associations of peak oxygen uptake with RV parameters determined by both imaging techniques using multivariable-adjusted linear regression models. In echocardiography, a 1 L/min lower peak oxygen uptake was associated with a 1.18 mm (95% CI, 0.66-1.71; P<0.001) smaller RV end-diastolic diameter and a 1.41 mm (95% CI, 0.90-1.92; P<0.001) narrower RV end-diastolic outflow tract diameter. Similarly, using cardiac magnetic resonance imaging measurements, a 1 L/min lower peak oxygen uptake was associated with a 23.5 mL (95% CI, 18.7-28.4; P<0.001) smaller RV end-diastolic volume, a 13.0 mL (95% CI, 9.81-16.2; P<0.001) lower RV end-systolic volume, and a 10.7 mL/beat (95% CI, 8.10-13.3; P<0.001) lower RV stroke volume. Conclusions Our results indicate a significant association between CRF and RV remodeling. Lower CRF was associated with smaller RV chamber and lower RV systolic function, stroke volume, and cardiac output.

Low serum TSH levels are associated with low values of fat-free mass and body cell mass in the elderly.

Previous studies on the association between thyroid function and body composition are conflicting and showed strong differences across age groups. Our aim was to clarify age-specific associations of serum thyroid-stimulating hormone (TSH) levels with markers of body composition including body mass index (BMI), waist circumference, fat mass (FM), fat-free mass (FFM) and body cell mass (BCM). We used data from two independent population-based cohorts within the framework of the Study of Health in Pomerania. The study population included 5656 individuals aged 20 to 90 years. Markers of body composition were measured by bioelectrical impedance analysis. Serum TSH levels were significantly positively associated with BMI (ß = 0.16; 95% confidence interval [CI]: 0.06 to 0.27), waist circumference (ß = 0.35; 95% CI: 0.08 to 0.62) and FM (ß = 0.32; 95% CI: 0.12 to 0.52), but not with FFM and BCM. Interaction analysis revealed positive associations of serum TSH levels with BMI, waist circumference, FM, FFM and BCM in individuals older than 60 years, while no such associations were observed in younger individuals. We demonstrated that lower serum TSH levels were accompanied with lower values of BMI, waist circumference, FM, FFM, and BCM in the elderly, while no such associations were observed in younger individuals.

Hepatic steatosis and hepatic iron overload modify the association of iron markers with glucose metabolism disorders and metabolic syndrome.

BACKGROUND: Iron status has been linked with impaired glucose metabolism (IGM), type 2 diabetes mellitus (T2DM) and the metabolic syndrome (MetS), but the role of hepatic steatosis or iron overload on these associations remains uncertain. METHODS: We analysed data from 2310 participants without known T2DM of the population-based Study of Health in Pomerania (SHIP-TREND, Germany) through logistic regression models. We tested additive and multiplicative interactions between ferritin and hepatic steatosis or iron overload. RESULTS: Serum ferritin was positively associated with IGM (OR per 100 µg/L: 1.11 [1.01, 1.23]), T2DM (OR per 100 µg/L: 1.20 [1.06, 1.36]) and MetS (OR per 100 µg/L: 1.11 [1.02, 1.20]) in the total population as well as in participants without hepatic iron overload. However, the synergistic effect of higher ferritin concentrations and hepatic iron overload showed stronger associations with IGM and T2DM. Similarly, while ferritin was positively associated with T2DM and MetS even in the absence of hepatic steatosis, the synergistic effect of higher ferritin concentrations and hepatic steatosis showed stronger associations with IGM, T2DM and MetS. Transferrin was associated with isolated impaired glucose tolerance but not with T2DM and MetS. CONCLUSIONS: Our study suggests that ferritin may be associated with glucose metabolism disorders and MetS even in people without hepatic steatosis or iron overload. However, in individuals with higher ferritin concentrations, the presence of hepatic steatosis may indicate stronger risk for glucose metabolism disorders and MetS, while the presence of hepatic iron overload may indicate stronger risk only for glucose metabolism disorders.

Genetic loci associated with prevalent and incident myocardial infarction and coronary heart disease in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium.

BACKGROUND: Genome-wide association studies have identified multiple genomic loci associated with coronary artery disease, but most are common variants in non-coding regions that provide limited information on causal genes and etiology of the disease. To overcome the limited scope that common variants provide, we focused our investigation on low-frequency and rare sequence variations primarily residing in coding regions of the genome. METHODS AND RESULTS: Using samples of individuals of European ancestry from ten cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, both cross-sectional and prospective analyses were conducted to examine associations between genetic variants and myocardial infarction (MI), coronary heart disease (CHD), and all-cause mortality following these events. For prevalent events, a total of 27,349 participants of European ancestry, including 1831 prevalent MI cases and 2518 prevalent CHD cases were used. For incident cases, a total of 55,736 participants of European ancestry were included (3,031 incident MI cases and 5,425 incident CHD cases). There were 1,860 all-cause deaths among the 3,751 MI and CHD cases from six cohorts that contributed to the analysis of all-cause mortality. Single variant and gene-based analyses were performed separately in each cohort and then meta-analyzed for each outcome. A low-frequency intronic variant (rs988583) in PLCL1 was significantly associated with prevalent MI (OR = 1.80, 95% confidence interval: 1.43, 2.27; P = 7.12 × 10-7). We conducted gene-based burden tests for genes with a cumulative minor allele count (cMAC) ≥ 5 and variants with minor allele frequency (MAF) < 5%. TMPRSS5 and LDLRAD1 were significantly associated with prevalent MI and CHD, respectively, and RC3H2 and ANGPTL4 were significantly associated with incident MI and CHD, respectively. No loci were significantly associated with all-cause mortality following a MI or CHD event. CONCLUSION: This study identified one known locus (ANGPTL4) and four new loci (PLCL1, RC3H2, TMPRSS5, and LDLRAD1) associated with cardiovascular disease risk that warrant further investigation.

Cardiorespiratory Fitness and Gray Matter Volume in the Temporal, Frontal, and Cerebellar Regions in the General Population.

OBJECTIVE: To analyze the association between cardiorespiratory fitness (CRF) and global and local brain volumes. PARTICIPANTS AND METHODS: We studied 2103 adults (21-84 years old) from 2 independent population-based cohorts (Study of Health in Pomerania, examinations from June 25, 2008, through September 30, 2012). Cardiorespiratory fitness was measured using peak oxygen uptake (VO2peak), oxygen uptake at the anaerobic threshold (VO2@AT), and maximal power output from cardiopulmonary exercise testing on a bicycle ergometer. Magnetic resonance imaging brain data were analyzed by voxel-based morphometry using regression models with adjustment for age, sex, education, smoking, body weight, systolic blood pressure, glycated hemoglobin level, and intracranial volume. RESULTS: Volumetric analyses revealed associations of CRF with gray matter (GM) volume and total brain volume. After multivariable adjustment, a 1-standard deviation increase in VO2peak was related to a 5.31 cm³ (95% CI, 3.27 to 7.35 cm³) higher GM volume. Whole-brain voxel-based morphometry analyses revealed significant positive relations between CRF and local GM volumes. The VO2peak was strongly associated with GM volume of the left middle temporal gyrus (228 voxels), the right hippocampal gyrus (146 voxels), the left orbitofrontal cortex (348 voxels), and the bilateral cingulate cortex (68 and 43 voxels). CONCLUSION: Cardiorespiratory fitness was positively associated with GM volume, total brain volume, and specific GM and white matter clusters in brain areas not primarily involved in movement processing. These results, from a representative population sample, suggest that CRF might contribute to improved brain health and might, therefore, decelerate pathology-specific GM decrease.

Brain-derived neurotrophic factor is related with adverse cardiac remodeling and high NTproBNP.

The brain-derived neurotrophic factor (BDNF) is a neuronal growth factor essential for normal cardiac contraction and relaxation. Alterations in BDNF signaling are related to the development of cardiovascular disease. Whether BDNF is related to subclinical cardiac remodeling is unclear. We related BDNF with echocardiographic parameters and NTproBNP in a large population-based cohort (n = 2,976, median age 48 years; 45% male). Transthoracic echocardiography was performed on all subjects and BDNF was measured by ELISA. Study participants with severe kidney dysfunction, previous myocardial infarction, and LV ejection fraction <40% were excluded. Linear regression models were adjusted for age, sex, lean mass, fat mass, current smoking, systolic blood pressure and depression. Low BDNF was associated with high NTproBNP. A 10,000 pg/ml lower BDNF was related with a 2.5 g higher (95%-confidence interval [CI]: 0.2 to 4.9; p = 0.036) LV mass, 0.01 cm posterior wall thickness (0.003 to 0.022; p = 0.007) and 0.02 E/A ratio (0.003 to 0.042, p = 0.026). Here we show that low BDNF levels are related with adverse cardiac remodeling and higher levels of NTproBNP. Further research is warranted to assess if BDNF may be used to monitor neuronal-cardiac damage during CVD progression.

Sex-Specific Associations of Brain-Derived Neurotrophic Factor and Cardiorespiratory Fitness in the General Population.

The brain-derived neurotrophic factor (BDNF) was initially considered to be neuron-specific. Meanwhile, this neurotrophin is peripherally also secreted by skeletal muscle cells and increases due to exercise. Whether BDNF is related to cardiorespiratory fitness (CRF) is currently unclear. We analyzed the association of serum BDNF levels with CRF in the general population (Study of Health in Pomerania (SHIP-TREND) from Northeast Germany; n = 1607, 51% female; median age 48 years). Sex-stratified linear regression models adjusted for age, height, smoking, body fat, lean mass, physical activity, and depression analyzed the association between BDNF and maximal oxygen consumption (VO2peak), maximal oxygen consumption normalized for body weight (VO2peak/kg), and oxygen consumption at the anaerobic threshold (VO2@AT). In women, 1 mL/min higher VO2peak, VO2peak/kg, and VO2@AT were associated with a 2.43 pg/mL (95% confidence interval [CI]: 1.16 to 3.69 pg/mL; p = 0.0002), 150.66 pg/mL (95% CI: 63.42 to 237.90 pg/mL; p = 0.0007), and 2.68 pg/mL (95% CI: 0.5 to 4.8 pg/mL; p = 0.01) higher BDNF serum concentration, respectively. No significant associations were found in men. Further research is needed to understand the sex-specific association between CRF and BDNF.

Changes in fat mass and fat-free-mass are associated with incident hypertension in four population-based studies from Germany.

BACKGROUND: We estimated the association of changes in body weight, waist circumference (WC), fat mass (FM) and fat-free mass (FFM) with changes in blood pressure and incident hypertension using data from four German population-based studies. METHODS: We analyzed data from 4467 participants, aged 21 to 82 years not taking antihypertensive medication and not having type 2 diabetes mellitus or a history of myocardial infarction at baseline and follow-up, from four population-based studies conducted in Germany. Body weight, WC, and blood pressure were measured at baseline and follow-up (median follow-up of the single studies 4 to 7 years). FM and FFM were calculated based on height-weight models derived from bioelectrical impedance studies. Hypertension was defined as systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg. Confounder-adjusted linear and logistic regressions were used to associate changes in anthropometric markers with changes in blood pressure, incident hypertension, and incident normalization of blood pressure. RESULTS: In a pooled dataset including all four studies, increments in body weight, WC, FM, and FFM were statistically significantly associated with incident hypertension and changes in systolic and diastolic blood pressure over time. Decreases in body weight, FM, and FFM were significantly associated with incident normalization of blood pressure. CONCLUSIONS: Our data suggests that the well-established association between obesity and blood pressure levels might be more related to body composition rather than to total body weight per se. Our findings indicate that gaining or losing FFM has substantial impact on the development or reversion of hypertension.

Association of domain-specific physical activity and cardiorespiratory fitness with all-cause and cause-specific mortality in two population-based cohort studies.

Physical activity (PA) reduces the risk for mortality. Whether the beneficial effects of PA are domain specific is unclear. We associated leisure time (LTPA), sports (SPA) and work (WPA) related PA and cardiorespiratory fitness (CRF) with all-cause mortality in two German population-based cohorts. We used data of the Study of Health in Pomerania (SHIP, n = 2,935, median age 53; 48% male) and the Cardiovascular Disease, Living and Ageing in Halle study (CARLA, n = 1,776, median age 64 and 54% male). Mortality was determined after a median follow-up of 8.2 years in SHIP (n = 332) and 11.5 years in CARLA (n = 409). LTPA (SHIP: hazard ratio [HR] per standard deviation [SD] 0.82 95%-CI 0.73 to 0.91 and CARLA: HR per SD 0.70: 95%-CI 0.59 to 0.82) and SPA (SHIP: HR per SD 0.80 95%-CI 0.71 to 0.91 and CARLA: HR per SD 0.70 95%-CI 0.60 to 0.82) but not WPA were inversely associated with all-cause mortality. In a subsample CRF was inversely related to mortality and positively to LTPA and sports SPA. No association was found for WPA. Our results may suggest that the inverse association between PA and mortality are partly influenced by higher CRF.