Associations of occupational and leisure-time physical activity with all-cause mortality: an individual participant data meta-analysis.

OBJECTIVE: Health effects of different physical activity domains (ie, during leisure time, work and transport) are generally considered positive. Using Active Worker consortium data, we assessed independent associations of occupational and leisure-time physical activity (OPA and LTPA) with all-cause mortality. DESIGN: Two-stage individual participant data meta-analysis. DATA SOURCE: Published and unpublished cohort study data. ELIGIBILITY CRITERIA: Working participants aged 18-65 years. METHODS: After data harmonisation, we assessed associations of OPA and LTPA with all-cause mortality. In stage 1, we analysed data from each study separately using Cox survival regression, and in stage 2, we pooled individual study findings with random-effects modelling. RESULTS: In 22 studies with up to 590 497 participants from 11 countries, during a mean follow-up of 23.1 (SD: 6.8) years, 99 743 (16%) participants died. Adjusted for LTPA, body mass index, age, smoking and education level, summary (ie, stage 2) hazard ration (HRs) and 95% confidence interval (95% CI) for low, moderate and high OPA among men (n=2 96 134) were 1.01 (0.99 to 1.03), 1.05 (1.01 to 1.10) and 1.12 (1.03 to 1.23), respectively. For women (n=2 94 364), HRs (95% CI) were 0.98 (0.92 to 1.04), 0.96 (0.92 to 1.00) and 0.97 (0.86 to 1.10), respectively. In contrast, higher levels of LTPA were inversely associated with mortality for both genders. For example, for women HR for low, moderate and high compared with sedentary LTPA were 0.85 (0.81 to 0.89), 0.78 (0.74 to 0.81) and 0.75 (0.65 to 0.88), respectively. Effects were attenuated when adjusting for income (although data on income were available from only 9 and 6 studies, for men and women, respectively). CONCLUSION: Our findings indicate that OPA may not result in the same beneficial health effects as LTPA.

Association of Asymmetric and Symmetric Dimethylarginine with Inflammation in the Population-Based Study of Health in Pomerania.

The amino acids arginine (Arg), asymmetric (ADMA) and symmetric dimethylarginine (SDMA) are related to nitric oxide (NO) metabolism and potential markers of two different disease entities: cardiovascular disease such as atherosclerosis and systemic inflammation in critically ill patients with sepsis. Although very different in their pathophysiological genesis, both entities involve the functional integrity of blood vessels. In this context, large population-based data associating NO metabolites with proinflammatory markers, e.g., white blood cell count (WBC), high-sensitivity C-reactive protein (hsCRP), and fibrinogen, or cytokines are sparse. We investigated the association of Arg, ADMA and SDMA with WBC, hsCRP, and fibrinogen in 3556 participants of the Study of Health in Pomerania (SHIP)-TREND study. Furthermore, in a subcohort of 456 subjects, 31 inflammatory markers and cytokines were analyzed. We identified Arg and SDMA to be positively associated with hsCRP (ß coefficient 0.010, standard error (SE) 0.002 and 0.298, 0.137, respectively) as well as fibrinogen (ß 5.23 × 10-3, SE 4.75 × 10-4 and 0.083, 0.031, respectively). ADMA was not associated with WBC, hsCRP, or fibrinogen. Furthermore, in the subcohort, Arg was inversely related to a proliferation-inducing ligand (APRIL). SDMA was positively associated with osteocalcin, tumor necrosis factor receptor 1 and 2, and soluble cluster of differentiation 30. Our findings provide new insights into the involvement of Arg, ADMA, and SDMA in subclinical inflammation 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.

Proportional Internal Work-a New Parameter of Exercise Testing in Study of Health in Pomerania (SHIP).

PURPOSE: Cardiopulmonary exercise testing usually requires a maximal exhaustive effort by the patient and is time consuming. The purpose of this study was to assess whether the cost to initiate exercise termed "proportional internal work" (PIW) was related to cardiovascular disease (CVD) risk factors, ventilatory parameters, and mortality. METHODS: We used data from population-based Study of Health in Pomerania. A total of 2829 (49.5% female) study participants with a median age of 52 (42-62) yr were included. Standardized questionnaires were used to assess CV risk factors. The cardiopulmonary exercise testing was performed using a modified Jones protocol. Regression models adjusted for sex and age were used to relate PIW with CVD risk factors and ventilatory parameters. The PIW was calculated by the following formula: (Oxygen uptake at rest - Oxygen uptake without load)/V˙ o2peak ) × 100. Cox regression analysis was used to relate PIW and all-cause mortality. RESULTS: We identified a nonlinear association between PIW and percent predicted V˙ o2peak . Women had a 2.96 (95% CI, 2.61-3.32) greater PIW than men. With each year of age and every point in body mass index, the PWI increased by 0.04 (95% CI, 0.03-0.05) and 0.16 (95% CI, 0.12-0.20), respectively. After adjustment for age, sex, smoking, and body mass index, a 1-point greater PIW was associated with a 5% higher risk to die (HR = 1.05; 95% CI, 1.01-1.07). CONCLUSIONS: The PIW is a new cardiopulmonary exercise testing parameter related to CVD risk and all-cause mortality. Future studies should assess the prognostic relevance of PIW for CVD prevention.

Sphingosine-1-phosphate levels are inversely associated with left ventricular and atrial chamber volume and cardiac mass in men : The Study of Health in Pomerania (SHIP).

AIMS: Sphingosine-1-phosphate (S1P) is a signaling lipid, which is involved in several cellular processes including cell growth, proliferation, migration and apoptosis. The associations of serum S1P levels with cardiac geometry and function are still not clear. We investigated the associations of S1P with cardiac structure and systolic function in a population-based sample. METHODS AND RESULTS: We performed cross-sectional analyses of 858 subjects (467 men; 54.4%), aged 22 to 81 years, from a sub-sample of the population-based Study of Health in Pomerania (SHIP-TREND-0). We analyzed the associations of serum S1P with structural and systolic function left ventricular (LV) and left atrial (LA) parameters as determined by magnetic resonance imaging (MRI) using sex-stratified multivariable-adjusted linear regression models. In men, MRI data showed that a 1 µmol/L lower S1P concentration was associated with an 18.1 mL (95% confidence interval [CI] 3.66-32.6; p = 0.014) larger LV end-diastolic volume (LVEDV), a 0.46 mm (95% CI 0.04-0.89; p = 0.034) greater LV wall thickness (LVWT) and a 16.3 g (95% CI 6.55-26.1; p = 0.001) higher LV mass (LVM). S1P was also associated with a 13.3 mL/beat (95% CI 4.49-22.1; p = 0.003) greater LV stroke volume (LVSV), an 18.7 cJ (95% CI 6.43-30.9; p = 0.003) greater LV stroke work (LVSW) and a 12.6 mL (95% CI 1.03-24.3; p = 0.033) larger LA end-diastolic volume (LAEDV). We did not find any significant associations in women. CONCLUSIONS: In this population-based sample, lower levels of S1P were associated with higher LV wall thickness and mass, larger LV and LA chamber sizes and greater stroke volume and work of the LV in men, but not in women. Our results indicate that lower levels of S1P were associated with parameters related with cardiac geometry and systolic function in men, but not in women.

Association of spermidine plasma levels with brain aging in a population-based study.

INTRODUCTION: Supplementation with spermidine may support healthy aging, but elevated spermidine tissue levels were shown to be an indicator of Alzheimer's disease (AD). METHODS: Data from 659 participants (age range: 21-81 years) of the population-based Study of Health in Pomerania TREND were included. We investigated the association between spermidine plasma levels and markers of brain aging (hippocampal volume, AD score, global cortical thickness [CT], and white matter hyperintensities [WMH]). RESULTS: Higher spermidine levels were significantly associated with lower hippocampal volume (ß = -0.076; 95% confidence interval [CI]: -0.13 to -0.02; q = 0.026), higher AD score (ß = 0.118; 95% CI: 0.05 to 0.19; q = 0.006), lower global CT (ß = -0.104; 95% CI: -0.17 to -0.04; q = 0.014), but not WMH volume. Sensitivity analysis revealed no substantial changes after excluding participants with cancer, depression, or hemolysis. DISCUSSION: Elevated spermidine plasma levels are associated with advanced brain aging and might serve as potential early biomarker for AD and vascular brain pathology.

Sex-specific associations of cardiorespiratory fitness and galectin-3 in the general population.

AIMS: Low cardiorespiratory fitness (CRF) is associated with greater mortality and morbidity. Galectin-3 (Gal-3) is a prognostic biomarker for fibrosis and heart failure. Gal-3 is also associated with a greater risk for cardiovascular mortality. Whether CRF is related with Gal-3 is unclear. The objective of this study was to assess the sex-specific associations of CRF and Gal-3 levels in the general population. METHODS: Gal-3 concentrations were determined using a sandwich enzyme immunoassay in the population-based Study of Health in Pomerania (SHIP-TREND-0). Sex-stratified linear regression models adjusted for age, current smoking status, and renal function were used. Individuals with left ventricular ejection fraction (LVEF) <40%, previous myocardial infarction, atrial fibrillation, chronic lung disease, severe renal disease (estimated glomerular filtration rate <30 mL/min/mm2 ), a history of cancer, and extreme values for Gal-3 (<1st percentile; >99th percentile) were excluded. RESULTS: A total of n = 1515 participants with a median age of 49 (IQR: 39-60 years, 48% males) were included. In men, a 1 L/min greater VO2 peak was significantly related to 0.50 ng/mL (95% CI -0.8068 to -0.1938, P < 0.01) less Gal-3. In males, a 1 mL/min/kg higher VO2 peak adjusted for body weight was associated with -0.0286 ng/mL (95% CI -0.0052 to -0.0005, P = 0.02) less Gal-3. When VO2 peak was adjusted for lean mass 1 mL/kg/min more was correlated with a -0.0022 ng/mL (95% CI -0.0043 to -0.0007, P = 0.04) less Gal-3. In women, VO2 peak (ß -0.2046 95% CI -0.6541 to 0.2449, P = 0.37) and VO2 peak adjusted for lean mass (ß -0.0019 95% CI -0.0421 to -0.0050, P = 0.12) were not related with Gal-3, whereas a 1 mL/min/kg higher VO2 peak adjusted for body weight was significantly associated with a -0.0064 ng/mL lower Gal-3 (95% CI -0.0092 to -0.0035, P < 0.01). There were no differences between pre-menopausal and post-menopausal women. CONCLUSIONS: VO2 peak was associated with Gal-3 only in men, but VO2 peak adjusted for body weight in women and men. Our results suggest that the adverse consequences of low CRF may be mediated by Gal-3. Further research is needed to understand the sex-specific association between CRF and Gal-3 and whether they are clinically relevant.

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.

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.

Cardiac MRI shows an association of lower cardiorespiratory fitness with decreased myocardial mass and higher cardiac stiffness in the general population - The Sedentary's Heart.

BACKGROUND: The heart has the capacity to adapt to different demands. The pathophysiological mechanisms involved with sedentarism are not fundamentally the opposite of those related with physical activity and regular exercise. We investigated the impact of lower cardiorespiratory fitness (CRF) on heart's plasticity and function in a population-based setting. METHODS: We used data from 1165 participants (539 women; 46.3%) aged 21-81 years from two independent cohorts of the Study of Health in Pomerania (SHIP-2 and SHIP-TREND-0). We analyzed the cross-sectional associations of peak oxygen uptake (VO2peak), determined by symptom-limited cardiopulmonary exercise testing, with structural and functional left ventricular (LV) and left atrial (LA) parameters determined by magnetic resonance imaging (MRI) using multivariable- adjusted linear regression models. RESULTS: A 1 L/min lower VO2peak was associated with a 10.5 g (95% confidence interval: 8.00 to 12.9; p < 0.001) lower LV mass, a 14.8 mL (10.9 to 18.6; p < 0.001) lower LV end-diastolic volume, a 0.29 mm (0.19 to 0.40; p < 0.001) lower LV wall-thickness, a 8.85 mL/beat (6.53 to 11.2; p < 0.001) lower LV stroke volume, a 0.42 L/min (0.25 to 0.60; p < 0.001) lower LV cardiac output and a 7.51 mL (3.88 to 11.1; p < 0.001) lower LA end-diastolic volume. Moreover, there were no associations with a concentric or eccentric remodeling and LV and LA ejection fraction. CONCLUSIONS: Lower CRF was associated with a smaller heart, LV wall-thickness and mass, LV and LA stroke volume and cardiac output. Conversely, there was no association with LA and LV ejection fraction. Our cross-sectional observations are consistent with cardiac adaptations reflecting reduced volume loading demands of a sedentary lifestyle - "the sedentary's heart".

Lower muscular strength is associated with smaller left and right chambers and lower cardiac mass in the general population - The Sedentary's Heart.

BACKGROUND: The cardiac muscle has the ability to adapt to different loading conditions. We analyzed the associations of the age-related decreasing handgrip strength (HGS), a marker of muscular fitness, on cardiac structure and function in a community-based sample. METHODS: We performed cross-sectional analyses of 4646 subjects (2554 women; 55.0%) aged 20 to 93 years from two independent cohorts of the Study of Health in Pomerania (SHIP-2 and SHIP-TREND-0). We analyzed the associations of HGS with structural and functional left and right ventricular (LV and RV) and left atrial (LA) parameters as determined by echocardiography and magnetic resonance imaging (MRI) as well with log-transformed NT-proBNP values using multivariable-adjusted linear regression models. RESULTS: MRI data showed that a 1 kg lower HGS was associated with a 0.40 mL (95% confidence interval: 0.26 to 0.54; p < 0.001) lower LV end-diastolic volume, a 0.011 mm (0.005 to 0.018; p = 0.001) lower LV wall-thickness, a 0.59 g (0.43 to 0.75; p < 0.001) lower LV mass, a 0.58 mL/beat (0.43 to 0.74; p < 0.001) lower LV stroke volume, a 0.03 L/min (0.02 to 0.04; p < 0.001) lower LV cardiac output, a 0.48 mL (0.27 to 0.68; p < 0.001) lower LA end-diastolic volume, and a 1.02 mL (0.71 to 1.32) lower RV end-diastolic volume. Similar findings were observed for echocardiographic parameters. Moreover, lower HGS was associated with higher echocardiographic LV diastolic stiffness and NT-proBNP levels. CONCLUSIONS: In this large population-based sample, lower muscular fitness as assessed by HGS was associated with lower LV wall thickness and mass as well as with smaller chamber size, stroke volume and cardiac output of the LV, LA and RV. Moreover, HGS was inversely related to LV diastolic stiffness and NT-proBNP values. These outcomes might demonstrate the effects of an aging-related decrease in physical activity and lower muscular fitness on the heart - "the sedentary's heart".

A 10-year follow-up of key gas exchange exercise parameters in a general population: results of the Study of Health in Pomerania.

BACKGROUND: Cardiopulmonary exercise testing (CPET) is a frequently used method for the evaluation of the cardiorespiratory system. The prognostic relevance of the measured parameters is commonly known. Longitudinal data on cardiorespiratory fitness in a large sample of well-characterised healthy volunteers are rare in the literature. METHODS: CPET data of 615 healthy individuals who voluntarily took part in the Study of Health in Pomerania (SHIP) at three different measurement times were analysed. The median observation time was 10.5 years. The age range was 25-85 years. RESULTS: Over the observed timeframe and with increasing age, a decline in maximum power, peak oxygen uptake (V'O2peak) and oxygen uptake at anaerobic threshold (V'O2 @AT) was detectable. This decline was aggravated with increasing age. For the minute ventilation (V'E)/carbon dioxide production (V'CO2 ) slope, an increase was measured in individuals aged ≥50 years only. CONCLUSION: The present study affirms the decrease in aerobic capacity with increasing age in a selected, well-characterised, healthy study sample, which seems to be less pronounced in females.

Physical Activity Does Not Lower the Risk of Lung Cancer.

Observational studies have suggested that physical activity might lower the risk of lung cancer in former and current smokers, but not in never-smokers. Using genetic instruments for self-reported and accelerometer-measured physical activity traits implemented through two-sample Mendelian randomization (MR), we sought to strengthen the evidence for causality. We used 18 genome-wide significant (P < 5 × 10-8) single-nucleotide polymorphisms (SNP) for self-reported moderate-to-vigorous physical activity and seven SNP for accelerometer-measured ("average acceleration") physical activity from up to 377,234 UK Biobank participants and evaluated these in relation to risk using 29,266 lung cancer cases (including 11,273 adenocarcinomas, 7,426 squamous cell carcinoma, and 2,664 small-cell carcinoma cases) and 56,450 controls. MR analysis suggested no effect of self-reported physical activity [OR (95% confidence interval (CI)) = 0.67 (0.42-1.05); P = 0.081; Q-value = 0.243] and accelerometer-measured activity [OR (95% CI) = 0.98 (0.93-1.03); P = 0.372; Q-value = 0.562] on lung cancer. There was no evidence for associations of physical activity with histologic types and lung cancer in ever and never smokers. Replication analysis using genetic instruments from a different genome-wide study and sensitivity analysis to address potential pleiotropic effects led to no substantive change in estimates. Collectively, these findings do not support a protective relationship between physical activity and the risk of lung cancer. SIGNIFICANCE: A new genetic study provides little evidence that recommending physical activity would help prevent lung cancer.

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.

Glucose and insulin levels are associated with arterial stiffness and concentric remodeling of the heart.

BACKGROUND: Mortality attributable to heart failure remains high. The prevalence of heart failure in patients with diabetes mellitus ranges from 19 to 26%. It is estimated that up to 21.1 million adults in the United States have diagnosed diabetes mellitus and around 80.8 million have impaired fasting glucose. We investigated the associations of fasting glucose (FG) and fasting insulin (FI), the homeostasis model assessment-insulin resistance index (HOMA-IR) and 2-h postload glucose (2HG) and insulin (2HI) with parameters of left ventricular geometry and function and arterial stiffness determined by magnetic resonance imaging in individuals without diagnosed type 2 diabetes. METHODS: Cross-sectional analyses of 1001 individuals (453 women, 45.3%), aged 21 to 80 years, from two independent population-based studies, the Study of Health in Pomerania (SHIP-TREND-0) and KORA FF4 Study. FG, FI, HOMA-IR, 2HG and 2HI, as well as glucose tolerance categories, were analyzed for associations with heart and arterial parameters using multivariable-adjusted linear regression models. RESULTS: In total, 390 individuals (39%) had prediabetes (isolated impaired fasting glucose, isolated glucose tolerance or both), and 49 (4.9%) were found to have unknown type 2 diabetes. In the multivariable-adjusted analysis, positive linear associations of FG, FI, HOMA-IR, 2HG and 2HI with arterial stiffness index and left ventricular wall-thickness and concentricity and inverse linear associations with left ventricular end-diastolic volume were observed. A 1 mmol/l higher FG was associated with a 1.18 ml/m2.7 (1.80 to 0.57; p < 0.001) lower left ventricular end-diastolic volume index, a 0.042 mm/m2.7 (0.014 to 0.070) higher left ventricular wall-thickness index, a 0.12 mmHg m2.7/ml (0.06 to 0.17; p < 0.001) greater arterial stiffness index and a 0.037 g/ml (0.018 to 0.056; p < 0.001) higher left ventricular concentricity. CONCLUSIONS: Our findings suggest that higher glucose levels in the prediabetic range and insulin resistance might lead to higher arterial stiffness and concentric remodeling of the heart.

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.

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.

Alcohol consumption and cardiorespiratory fitness in five population-based studies.

Background Poor cardiorespiratory fitness is a risk factor for cardiovascular morbidity. Alcohol consumption contributes substantially to the burden of disease, but its association with cardiorespiratory fitness is not well described. We examined associations between average alcohol consumption, heavy episodic drinking and cardiorespiratory fitness. Design The design of this study was as a cross-sectional population-based random sample. Methods We analysed data from five independent population-based studies (Study of Health in Pomerania (2008-2012); German Health Interview and Examination Survey (2008-2011); US National Health and Nutrition Examination Survey (NHANES) 1999-2000; NHANES 2001-2002; NHANES 2003-2004) including 7358 men and women aged 20-85 years, free of lung disease or asthma. Cardiorespiratory fitness, quantified by peak oxygen uptake, was assessed using exercise testing. Information regarding average alcohol consumption (ethanol in grams per day (g/d)) and heavy episodic drinking (5+ or 6+ drinks/occasion) was obtained from self-reports. Fractional polynomial regression models were used to determine the best-fitting dose-response relationship. Results Average alcohol consumption displayed an inverted U-type relation with peak oxygen uptake ( p-value<0.0001), after adjustment for age, sex, education, smoking and physical activity. Compared to individuals consuming 10 g/d (moderate consumption), current abstainers and individuals consuming 50 and 60 g/d had significantly lower peak oxygen uptake values (ml/kg/min) (ß coefficients = -1.90, ß = -0.06, ß = -0.31, respectively). Heavy episodic drinking was not associated with peak oxygen uptake. Conclusions Across multiple adult population-based samples, moderate drinkers displayed better fitness than current abstainers and individuals with higher average alcohol consumption.

Statins are related to impaired exercise capacity in males but not females.

BACKGROUND: Exercise and statins reduce cardiovascular disease (CVD). Exercise capacity may be assessed using cardiopulmonary exercise testing (CPET). Whether statin medication is associated with CPET parameters is unclear. We investigated if statins are related with exercise capacity during CPET in the general population. METHODS: Cross-sectional data of two independent cohorts of the Study of Health in Pomerania (SHIP) were merged (n = 3,500; 50% males). Oxygen consumption (VO2) at peak exercise (VO2peak) and anaerobic threshold (VO2@AT) was assessed during symptom-limited CPET. Two linear regression models related VO2peak with statin usage were calculated. Model 1 adjusted for age, sex, previous myocardial infarction, and physical inactivity and model 2 additionally for body mass index, smoking, hypertension, diabetes and estimated glomerular filtration rate. Propensity score matching was used for validation. RESULTS: Statin usage was associated with lower VO2peak (no statin: 2336; 95%-confidence interval [CI]: 2287-2,385 vs. statin 2090; 95%-CI: 2,031-2149 ml/min; P < .0001) and VO2@AT (no statin: 1,172; 95%-CI: 1,142-1,202 vs. statin: 1,111; 95%-CI: 1,075-1,147 ml/min; P = .0061) in males but not females (VO2peak: no statin: 1,467; 95%-CI: 1,417-1,517 vs. statin: 1,503; 95%-CI: 1,426-1,579 ml/min; P = 1.00 and VO2@AT: no statin: 854; 95%-CI: 824-885 vs. statin 864; 95%-CI: 817-911 ml/min; P = 1.00). Model 2 revealed similar results. Propensity scores analysis confirmed the results. CONCLUSION: In the general population present statin medication was related with impaired exercise capacity in males but not females. Sex specific effects of statins on cardiopulmonary exercise capacity deserve further research.

Data on subgroup specific baseline characteristics and serum sphingosine-1-phosphate concentrations in the Study of Health in Pomerania.

In this data article, we provide subgroup specific baseline characteristics and serum sphingosine-1-phosphate (S1P) concentrations for healthy individuals within the Study of Health in Pomerania (SHIP)-TREND cohort. After exclusion of subjects with cardiovascular disease, diabetes mellitus, hypertension, metabolic syndrome, elevated liver enzymes and/or chronic kidney disease stadium III or IV, four subgroups were defined according to different limits for body mass index (BMI), alterations in blood lipid levels and smoking status. Tables show respective clinical and laboratory parameters stratified by gender. Serum S1P concentrations are also stratified by age groups. The data presented herein is related to the research article entitled "Reference intervals for serum sphingosine-1-phosphate in the population-based Study of Health in Pomerania" (E. Moritz, D. Wegner, S. Groß, M. Bahls, M. Dörr, S.B. Felix, T. Ittermann, S. Oswald, M. Nauck, N. Friedrich, R.H. Böger, G. Daum, E. Schwedhelm, B.H. Rauch, Clin Chim Acta. 468 (2017) 25-31) [1].