Left ventricular hypertrophy as a risk factor for accelerated brain aging: Results from the Study of Health in Pomerania.

Previous studies provided evidence for the importance of cardiac structure abnormalities, in particular greater left ventricular (LV) mass, for brain aging, but longitudinal studies are lacking to date. We included 926 individuals (median age 48 years; 53% women) from the TREND cohort of the Study of Health in Pomerania (SHIP) without reduced ejection fraction or a history of myocardial infarction. LV mass index (LVMI) was determined by echocardiography at baseline. Brain morphometric measurements were derived from magnetic resonance images at baseline and 7-year follow-up. Direct effects of baseline LVMI on brain morphometry at follow-up were estimated using linear regression models with adjustment for baseline brain morphometry. At baseline, median LVMI was 40 g/m2.7 and 241 individuals (26%) met the criterion of LV hypertrophy. After correction for multiple testing, baseline LVMI was directly associated with reduced global cortical thickness and increased cortical brain age at follow-up independent from hypertension and blood pressure. Exposure-outcome relations were nonlinear and significantly stronger in the upper half of the exposure distribution. Specifically, an increase in baseline LVMI from the 50% quantile to the 95% quantile was associated additional 2.7 years (95% confidence interval = [1.5 years, 3.8 years]) of cortical brain age at follow-up. Additional regional analyses yielded bilateral effects on multiple frontal cortical regions. Our findings highlight the role of cardiac structure in brain aging. LVMI constitutes an easily measurable marker that might help to identify persons at risk for cognitive impairment and dementia.

Deep learning-based NT-proBNP prediction from the ECG for risk assessment in the community.

OBJECTIVES: The biomarker N-terminal pro B-type natriuretic peptide (NT-proBNP) has predictive value for identifying individuals at risk for cardiovascular disease (CVD). However, it is not widely used for screening in the general population, potentially due to financial and operational reasons. This study aims to develop a deep-learning model as an efficient means to reliably identify individuals at risk for CVD by predicting serum levels of NT-proBNP from the ECG. METHODS: A deep convolutional neural network was developed using the population-based cohort study Hamburg City Health Study (HCHS, n=8,253, 50.9 % women). External validation was performed in two independent population-based cohorts (SHIP-START, n=3,002, 52.1 % women, and SHIP-TREND, n=3,819, 51.2 % women). Assessment of model performance was conducted using Pearson correlation (R) and area under the receiver operating characteristics curve (AUROC). RESULTS: NT-proBNP was predictable from the ECG (R, 0.566 [HCHS], 0.642 [SHIP-START-0], 0.655 [SHIP-TREND-0]). Across cohorts, predicted NT-proBNP (pNT-proBNP) showed good discriminatory ability for prevalent and incident heart failure (HF) (baseline: AUROC 0.795 [HCHS], 0.816 [SHIP-START-0], 0.783 [SHIP-TREND-0]; first follow-up: 0.669 [SHIP-START-1, 5 years], 0.689 [SHIP-TREND-1, 7.3 years]), comparable to the discriminatory value of measured NT-proBNP. pNT-proBNP also demonstrated comparable results for other incident CVD, including atrial fibrillation, stroke, myocardial infarction, and cardiovascular death. CONCLUSIONS: Deep learning ECG algorithms can predict NT-proBNP concentrations with high diagnostic and predictive value for HF and other major CVD and may be used in the community to identify individuals at risk. Long-standing experience with NT-proBNP can increase acceptance of such deep learning models in clinical practice.

Body composition markers are associated with changes in inflammatory markers but not vice versa: A bi-directional longitudinal analysis in a population-based sample.

BACKGROUND AND AIM: Growing body of evidence consistently link obesity and inflammation, Although the direction of the association is still unclear. We aimed to investigate longitudinal associations of body anthropometric, composition and fat distribution parameters with inflammatory markers and vice versa. METHOD AND RESULTS: We used data from 2464 individuals of the SHIP-TREND cohort with a median follow-up of 7 years. Linear regression models adjusted for confounders were used to analyze associations of standardized body composition markers derived from classic anthropometry, bioelectrical impedance analysis (BIA) and magnetic resonance imaging (MRI) at baseline with changes in inflammatory markers (C-reactive protein (CRP), white blood cell (WBC), fibrinogen) and vice versa. Higher level of anthropometric markers at baseline were associated with an increase in the change of inflammatory markers. A 13.5 cm higher waist circumference (WC), 16.0 kg body weight and 7.76 % relative fat mass (FM) at baseline was associated with a change in CRP of 0.52 mg/L (95 % confidence interval [CI]: 0.29 to 0.74), 0.51 mg/L (95 % CI: 0.29; 0.74) and 0.58 mg/L (95 % CI: 0.34; 0.82) respectively. Absolute FM showed the strongest association with changes in serum fibrinogen levels (ß for 8.69 kg higher FM: 0.07 g/L; 95 % CI: 0.05; 0.09). Baseline inflammatory markers were only associated with changes in hip circumference. CONCLUSION: Our study indicates the importance of anthropometric, body composition and fat distribution markers as a risk factor for the development of inflammation. To prevent inflammatory-related complications, important is to take measures against the development of obesity.

Body surface scan anthropometrics are associated with grip strength in the general population.

BACKGROUND AND AIM: Body shape and anthropometrics are well-known risk factors for cardiovascular diseases (CVD) and mortality. Hand-grip strength (HGS) is also a meaningful marker of health and a promising predictor of CVD and mortality. There is a lack of studies that have systematically investigated associations between body shape and anthropometrics with HGS. In a population-based study, we investigated if anthropometric markers derived from 3D body scanning are related to HGS. METHODS AND RESULTS: We used the data of 1,599 individuals aged 36 to 93 years, who participated in the Study of Health in Pomerania. A total of 87 anthropometric markers, determined by a 3D body scanner, were included in the analysis. Anthropometric measurements were standardized and used as exposure variables. HGS was measured with a hand dynamometer and used as outcome. Sex-stratified linear regression models adjusted for age and height were used to relate standardized anthropometrics and HGS. Anthropometric markers were ranked according to -log-p-values. In men, left and right forearm circumference, left arm length to neck (C7), left forearm length, and forearm-fingertip length were most strongly related to HGS. In women, right forearm circumference, forearm-fingertip length, shoulder breadth, left forearm circumference, and right wrist circumference showed the most significant associations with HGS. The final prediction models contained 13 anthropometric markers in males (R2=0.54) and eight anthropometric markers in females (R2=0.37). CONCLUSIONS: The identified parameters may help estimate HGS in the clinical setting. However, studies in clinical settings are essential to validating our findings.

Associations between 47 anthropometric markers derived from a body scanner and relative fat-free mass in a population-based study.

BACKGROUND: Low relative fat free mass (FFM) is associated with a greater risk of chronic diseases and mortality. Unfortunately, FFM is currently not being measured regularly to allow for individuals therapy. OBJECTIVE: One reason why FFM is not being used may be related to additional equipment and resources, thus we aimed to identify easily accessible anthropometric markers related with FFM. MATERIALS AND METHODS: We analyzed data of 1,593 individuals (784 women; 49.2%, age range 28-88 years) enrolled in the population-based Study of Health in Pomerania (SHIP-TREND 1). Forty-seven anthropometric markers were derived from a 3D optical body-scanner. FFM was assessed by bioelectrical impedance analysis (FFMBIA) or air displacement plethysmography (FFMADP). In sex-stratified linear regression models, FFM was regressed on anthropometric measurements adjusted for body height and age. Anthropometric markers were ranked according to the coefficient of determination (R2) derived from these regression models. RESULTS: Circumferences of high hip, belly, middle hip, waist and high waist showed the strongest inverse associations with FFM. These relations were stronger in females than in males. Associations of anthropometric markers with FFMAPD were greater compared to FFMBIA. CONCLUSION: Anthropometric measures were more strongly associated with FFMADP compared to FFMBIA. Anthropometric markers like circumferences of the high or middle hip, belly or waist may be appropriate surrogates for FFM to aid in individualized therapy. Given that the identified markers are representative of visceral adipose tissue, the connection between whole body strength as surrogate for FFM and fat mass should be explored in more detail.

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 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.

Identification of candidate metabolite biomarkers for metabolic syndrome and its five components in population-based human cohorts.

BACKGROUND: Metabolic Syndrome (MetS) is characterized by risk factors such as abdominal obesity, hypertriglyceridemia, low high-density lipoprotein cholesterol (HDL-C), hypertension, and hyperglycemia, which contribute to the development of cardiovascular disease and type 2 diabetes. Here, we aim to identify candidate metabolite biomarkers of MetS and its associated risk factors to better understand the complex interplay of underlying signaling pathways. METHODS: We quantified serum samples of the KORA F4 study participants (N = 2815) and analyzed 121 metabolites. Multiple regression models adjusted for clinical and lifestyle covariates were used to identify metabolites that were Bonferroni significantly associated with MetS. These findings were replicated in the SHIP-TREND-0 study (N = 988) and further analyzed for the association of replicated metabolites with the five components of MetS. Database-driven networks of the identified metabolites and their interacting enzymes were also constructed. RESULTS: We identified and replicated 56 MetS-specific metabolites: 13 were positively associated (e.g., Val, Leu/Ile, Phe, and Tyr), and 43 were negatively associated (e.g., Gly, Ser, and 40 lipids). Moreover, the majority (89%) and minority (23%) of MetS-specific metabolites were associated with low HDL-C and hypertension, respectively. One lipid, lysoPC a C18:2, was negatively associated with MetS and all of its five components, indicating that individuals with MetS and each of the risk factors had lower concentrations of lysoPC a C18:2 compared to corresponding controls. Our metabolic networks elucidated these observations by revealing impaired catabolism of branched-chain and aromatic amino acids, as well as accelerated Gly catabolism. CONCLUSION: Our identified candidate metabolite biomarkers are associated with the pathophysiology of MetS and its risk factors. They could facilitate the development of therapeutic strategies to prevent type 2 diabetes and cardiovascular disease. For instance, elevated levels of lysoPC a C18:2 may protect MetS and its five risk components. More in-depth studies are necessary to determine the mechanism of key metabolites in the MetS pathophysiology.

The Preventiometer - reliability of a cardiovascular multi-device measurement platform and its measurement agreement with a cohort study.

BACKGROUND: Multimedia multi-device measurement platforms may make the assessment of prevention-related medical variables with a focus on cardiovascular outcomes more attractive and time-efficient. The aim of the studies was to evaluate the reliability (Study 1) and the measurement agreement with a cohort study (Study 2) of selected measures of such a device, the Preventiometer. METHODS: In Study 1 (N = 75), we conducted repeated measurements in two Preventiometers for four examinations (blood pressure measurement, pulse oximetry, body fat measurement, and spirometry) to analyze their agreement and derive (retest-)reliability estimates. In Study 2 (N = 150), we compared somatometry, blood pressure, pulse oximetry, body fat, and spirometry measurements in the Preventiometer with corresponding measurements used in the population-based Study of Health in Pomerania (SHIP) to evaluate measurement agreement. RESULTS: Intraclass correlations coefficients (ICCs) ranged from .84 to .99 for all examinations in Study 1. Whereas bias was not an issue for most examinations in Study 2, limits of agreement for most examinations were very large compared to results of similar method comparison studies. CONCLUSION: We observed a high retest-reliability of the assessed clinical examinations in the Preventiometer. Some disagreements between Preventiometer and SHIP examinations can be attributed to procedural differences in the examinations. Methodological and technical improvements are recommended before using the Preventiometer in population-based research.

Body composition markers from classic anthropometry, bioelectrical impedance analysis, and magnetic resonance imaging are associated with inflammatory markers in the general population.

BACKGROUND AND AIM: The associations of body composition markers derived from different modalities with inflammatory markers are unclear. The aim of this study was to determine associations of the body composition markers from different modalities with inflammatory markers in a population-based study. METHODS AND RESULTS: We analyzed data from 4048 participants (2081 women, 51.4%) aged 20-84 years. Linear regression models adjusted for confounding were used to analyze the association of classic anthropometry markers, absolute and relative fat mass, absolute fat-free mass (FFM), and body cell mass (BCM) assessed by bioelectrical impedance analysis, subcutaneous, visceral, and liver fat from magnetic resonance imaging (MRI), with markers of inflammation. We found positive associations of classic anthropometry markers, total body fat, subcutaneous, visceral, and liver fat, with all inflammatory markers. Waist circumference (WC) showed the strongest association with high-sensitivity C-reactive protein (hsCRP) (ß: 1.39; 95% confidence interval [CI]: 1.22 to 1.56) and white blood cell (WBC) (0.39; 0.29 to 0.48), whereas visceral fat showed the strongest association with ferritin (41.9; 34.7 to 49.0). Relative body fat was strongly associated with hsCRP (1.39; 1.20 to 1.58), fibrinogen (0.29; 0.27 to 0.32), and WBC (0.35; 0.25 to 0.46). Conversely, we found inverse associations of body height, FFM, and BCM with hsCRP, fibrinogen, and WBC. CONCLUSIONS: Our study indicates the importance of WC as an easily measured marker for early inflammation. MRI-assessed markers of central obesity seem to be most strongly related to ferritin.

Low-grade inflammation is associated with a heterogeneous lipoprotein subclass profile in an apparently healthy population sample.

BACKGROUND AND AIMS: Prevention measures for cardiovascular diseases (CVD) have shifted their focus from lipoproteins to the immune system. However, low-grade inflammation and dyslipidemia are tightly entangled. The objective of this study was to assess the relations between a broad panel of inflammatory biomarkers and lipoprotein subclass parameters. METHODS: We utilized data from the population-based Study of Health in Pomerania (SHIP-TREND, n = 403). Plasma concentrations of 37 inflammatory markers were measured by a bead-based assay. Furthermore, we employed nuclear magnetic resonance spectroscopy to measure total cholesterol, total triglycerides, total phospholipids as well as the fractional concentrations of cholesterol, triglycerides, phospholipids, ApoA1, ApoA2 and ApoB in all major lipoprotein subclasses. Associations between inflammatory biomarkers and lipoprotein subclasses were analyzed by adjusted linear regression models. RESULTS: APRIL, BAFF, TWEAK, sCD30, Pentraxin-3, sTNFR1, sTNFR2, Osteocalcin, Chitinase 3-like 1, IFN-alpha2, IFN-gamma, IL-11, IL-12p40, IL-29, IL-32, IL-35, TSLP, MMP1 and MMP2 were related with lipoprotein subclass components, forming two distinct clusters. APRIL had inverse relations to HDL-C (total and subclasses) and HDL Apo-A1 and Apo-A2 content. MMP-2 was inversely related to VLDL-C (total and subclasses), IDL-C as well as LDL5/6-C and VLDL-TG, IDL-TG, total triglycerides as well as LDL5/5-TG and HDL4-TG. Additionally, we identified a cluster of cytokines linked to the Th1-immune response, which were associated with an atherogenic lipoprotein profile. CONCLUSION: Our findings expand the existing knowledge of inflammation-lipoprotein interactions, many of which are suggested to be involved in the pathogeneses of chronic non-communicable diseases. The results of our study support the use of immunomodulatory substances for the treatment and possibly prevention of CVD.

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.

[Fit for Two - A Study of Sedentary Behavior and Physical Activity During Pregnancy]. / Fit für Zwei ­ Eine Studie zu sitzendem Verhalten und körperlicher Aktivität in der Schwangerschaft.

BACKGROUND: In the pilot study sedentary behavior and physical activity were measured in pregnant women using an accelerometer. METHODS: A total of 32 pregnant women were enrolled in the study; eleven of them were included in the first trimester. The defined wearing periods for the accelerometer in the first, second and third trimester were weeks 9-12, 23-26, and 36-39, respectively. A self-administered survey was carried out after a 7-day measurement. RESULTS: The pregnant women were on average 30 years old, 50% were nulliparous, and 68.8% had a high school diploma. The accelerometer was worn on average of 13 hours per day. Sedentary behavior was recorded more than half of the wearing time for all trimesters. The proportion of time spent in moderate-to-vigorous activity was highest at 4.7% in the second trimester, compared to 2.5% in the first and 3.8% in the third. A proportion of women, ranging from 32% in the first, 54% in the second, and 58% in the third trimester did reach the levels of PA recommended by the guidelines. Nulliparous women in the second and third trimester spent twice as much time in moderate-to-vigorous activities compared to multiparous women. CONCLUSION: Pregnant women spent more than half of the monitored day in sedentary behaviors. Half of them did meet the recommendations for physical activity in the second and third trimester. The results show that sedentary behavior and physical activity should be considered more in clinical practice and research to motivate pregnant women to adopt a physically active lifestyle.

Low cardiopulmonary fitness is associated with higher liver fat content and higher gamma-glutamyltransferase concentrations in the general population - "The Sedentary's Liver".

BACKGROUND: We investigated the association between low cardiorespiratory fitness and liver fat content (LFC) in the general population. MATERIALS AND METHODS: We evaluated data from 2151 adults (51.1% women) from two population-based cohorts of the Study of Health in Pomerania (SHIP-2 and SHIP-TREND-0). We analysed the cross-sectional associations of peak oxygen uptake (VO2peak ) with LFC, assessed by magnetic resonance imaging proton density fat fraction, as well as serum gamma-glutamyltransferase (GGT) and aminotransferase concentrations by multivariable regression models. RESULTS: We observed significant inverse associations of VO2peak with LFC and serum GGT, but not with serum aminotransferase levels. Specifically, a 1 L/min lower VO2peak was associated with a 1.09% (95% confidence interval [CI]: 0.45-1.73; P = .002) higher LFC and a 0.18 µkatal/L (95% CI: 0.09-0.26; P < .001) higher GGT levels. The adjusted odds ratio (OR) for the risk of prevalent hepatic steatosis (HS) by a 1 L/min decrease in VO2peak was 1.61 (95% CI: 1.22-2.13; P = .001). Compared to subjects with high VO2peak , obese and overweight individuals with low VO2peak had 1.78% (95% CI: 0.32-3.25; P = .017) and 0.94% (95% CI: 0.15-1.74; P = .021) higher mean LFC, respectively. Compared to those with high VO2peak , low VO2peak was independently associated with a higher risk of prevalent HS in the obese (adjusted-OR 2.29, 95% CI=1.48-3.56; P < .001) and overweight (adjusted OR 1.57, 95% CI=1.16-2.14; P = .04) groups. CONCLUSIONS: Lower VO2peak was significantly associated with greater LFC and higher serum GGT levels in a population-based cohort of adult individuals. Our results suggest that low VO2peak might be a risk factor for HS.

Association of Cardiopulmonary Exercise Capacity and Adipokines in the General Population.

Adipokines and cardiorespiratory fitness (CRF) are associated with the (patho)physiology of cardiometabolic diseases. Whether CRF and adipokines are related is unclear. We investigated associations of CRF with leptin, adiponectin, chemerin, resistin and vaspin. Data from the population-based Study of Health in Pomerania was used (n=1,479; median age 49 years; 51% women). Cardiopulmonary exercise testing was used to measure CRF. Circulating adipokine concentrations were measured by enzyme-linked immunosorbent assay. The association between CRF and adipokines was assessed using multivariable sex-specific quantile regression models. Higher maximum oxygen uptake was significantly associated with lower leptin (men:-0.11 ng/ml; 95%-confidence interval [CI]:-0.18 to-0.03 ng/ml; p<0.005; women:-0.17 ng/ml; 95%-CI:-0.33 to-0.02 ng/ml; p<0.05) and chemerin (men:-0.26 ng/ml; 95%-CI:-0.52 to-0.01 ng/ml; p<0.05; women:-0.41 ng/ml; 95%-CI:-0.82 to-0.01 ng/ml; p<0.05) as well as higher adiponectin concentrations (men: 0.06 µg/ml; 95%-CI: 0.02 to 0.11 µg/ml; p<0.05; women: 0.03 µg/ml; 95%-CI:-0.05 to 0.10 µg/ml; p=0.48). We found that CRF was inversely associated with leptin and chemerin in both sexes and positively associated with adiponectin only in men.

Association of sex-specific differences in lipoprotein(a) concentrations with cardiovascular mortality in individuals with type 2 diabetes mellitus.

BACKGROUND: Compared to individuals without type 2 diabetes mellitus, the relative increase in cardiovascular mortality is much higher in women than in men in individuals with type 2 diabetes mellitus. METHODS: We evaluated data from 7443 individuals (3792 women, 50.9%), aged 20 to 81 years, from two independent population-based investigations, SHIP-0 and MONICA/KORA S3. We analyzed the longitudinal sex-specific associations of lipoprotein(a) with cardiovascular mortality in individuals with and without type 2 diabetes mellitus using Cox regression. RESULTS: During a median follow-up of 20.5 years (136,802 person-years), 657 participants (404 men and 253 women) died of cardiovascular causes. Among individuals without type 2 diabetes mellitus, men had a significantly higher risk for cardiovascular mortality compared to women in unadjusted model and after adjustment. On the other hand, in participants with type 2 diabetes mellitus, the risk for cardiovascular mortality was not different between men and women in the unadjusted model and after adjustment for age, body mass index, low-density lipoprotein-cholesterol, fasting status and study sample (SHIP-0, MONICA/KORA S3). Further adjustment for lipoprotein(a) concentrations had no impact on the hazard ratio (HR) for cardiovascular mortality comparing men versus women in individuals without type 2 diabetes mellitus [HR: 1.94; 95% confidence interval (CI) 1.63 to 2.32; p < 0.001]. In individuals with type 2 diabetes mellitus, however, further adjustment for lipoprotein(a) led to an increased risk for cardiovascular mortality in men and a decreased risk in women resulting in a statistically significant difference between men and women (HR: 1.53; 95% CI 1.04 to 2.24; p = 0.029). CONCLUSIONS: Women are described to have a stronger relative increase in cardiovascular mortality than men when comparing individuals with and without type 2 diabetes mellitus. Higher lipoprotein(a) concentrations in women with type 2 diabetes mellitus than in men with type 2 diabetes mellitus might partially explain this finding.

Physical activity and cardiorespiratory fitness-A ten-year follow-up.

Physical activity (PA) may influence cardiorespiratory fitness (CRF). Yet, PA takes place in different domains (i.e., sports-related physical activity [SPA], leisure time related physical activity [LTPA], and work-related physical activity [WPA]) and not all domain-specific PA may help to maintain high CRF levels throughout life. We assessed the relationship between changes in domain-specific PA and the age-related decline in CRF. We analyzed data of 353 men (median age 50 years; inter-quartile range [IQR] 40 to 60) and 335 women (median age 50 years; IQR 41 to 59) with data for domain-specific PA as well as CRF testing measured ten years apart. CRF was assessed with cardiorespiratory exercise testing. Domain-specific PA was measured using the Baecke questionnaire. During the 10-year follow-up, CRF decreased in men from 29.3 (IQR 25.0 to 34.7) mL/min/kg to 24.3 (IQR 20.8 to 27.3) mL/min/kg. In women, CRF declined from 26.0 (IQR 21.0 to 30.9) to 21.4 (IQR 18.3 to 25.6) mL/min/kg. A one point higher SPA at baseline was related to a 1.14 (95% confidence interval [CI] -1.50 to -0.53) mL/min/kg greater decrease in VO2peak . A one point greater SPA and LTPA over time was associated with a 1.68 (95% CI 1.06 to 2.29) mL/min/kg and 1.24 (95% CI 0.57 to 1.90) mL/min/kg lower decrease in VO2peak , respectively. Neither baseline values nor changes of WPA were associated with CRF. Sports and leisure time related PA may attenuate the age-related decline in CRF.

Do accelerometer-based physical activity patterns differentially affect cardiorespiratory fitness? A growth mixture modeling approach.

Findings on the association between cardiorespiratory fitness (CRF) and moderate-to-vigorous physical activity (MVPA) may be distorted if patterns of accumulated MVPA over a week exist but are ignored. Our aim was to identify MVPA patterns and to associate them to CRF. Two hundred twenty-four 40-75-year-old adults wore accelerometers for 7 days. CRF was measured by peak oxygen uptake (V'O2,peak) assessed on a cycle ergometer via standardized cardiopulmonary exercise testing. Growth mixture modeling indicated four MVPA patterns: "low/stable" (57%, Mean MVPA time (M) = 21 min day-1), "medium/stable" (20%, M = 46 min day-1), "medium/weekend high" (14%, M = 47 min day-1), and "high/weekend low" (9%, M = 71 min day-1). V'O2,peak was higher for persons with "high/weekend low" and "medium/weekend high" patterns compared to "low/stable" and "medium/stable" (p values < 0.001). The same total amount of MVPA may have greater benefit if performed on fewer days during the week but with a longer duration than if performed every day but with a lower duration.

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.

Metabolomic profiling implicates adiponectin as mediator of a favorable lipoprotein profile associated with NT-proBNP.

BACKGROUND: The N-terminal prohormone of brain natriuretic peptide (NT-proBNP) is an important biomarker for the diagnosis of heart failure. Apart from this and only recently recognized, NT-proBNP levels associate with higher HDL- and lower LDL-cholesterol levels comprising a favorable blood lipid profile. To further examine this observation, the lipoprotein profile in relation to NT-proBNP was examined in-depth by proton nuclear magnetic resonance spectroscopy (1H-NMR). We complemented this investigation with a state-of-the-art untargeted metabolomics approach. METHODS: Lipoprotein particles were determined by 1H-NMR spectroscopy in 872 subjects without self-reported diabetes from the population-based Study of Health in Pomerania (SHIP)-TREND with available NT-proBNP measurements. Comprehensive metabolomics data for plasma and urine samples were obtained. Linear regression models were performed to assess the associations between serum concentrations of NT-proBNP and the metabolites/lipoprotein particles measured in plasma or urine. RESULTS: An increase in serum NT-proBNP was associated with a benefical lipoprotein profile, including a decrease in VLDL, IDL and LDL-particles along with an increase in large HDL particles. These findings were replicated in a second independent cohort. Serum concentrations of NT-proBNP showed significant inverse associations with seven plasma metabolites while associations with 39 urinary metabolites, mostly comprising amino acids and related intermediates, were identified. Mediation analyses revealed adiponection as mediating factor for the associations observed with lipoproteins particles. CONCLUSIONS: Most of the metabolic changes associated with NT-proBNP implicate significant influence on the blood lipid profile besides vasodilatory and the diuretic action of BNP signaling. Our data suggest that the more favorable lipoprotein profile as associated with elevated NT-proBNP concentrations in mainly cardiac healthy individuals might relate to adiponectin signaling indicating even indirect cardio-protective effects for NT-proBNP.