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The benefit of regular physical activity and exercise training for the prevention of cardiovascular and metabolic diseases is undisputed. Many molecular mechanisms mediating exercise effects have been deciphered. Personalised exercise prescription can help patients in achieving their individual greatest benefit from an exercise-based cardiovascular rehabilitation programme. Yet, we still struggle to provide truly personalised exercise prescriptions to our patients. In this position paper, we address novel basic and translational research concepts that can help us understand the principles underlying the inter-individual differences in the response to exercise, and identify early on who would most likely benefit from which exercise intervention. This includes hereditary, non-hereditary and sex-specific concepts. Recent insights have helped us to take on a more holistic view, integrating exercise-mediated molecular mechanisms with those influenced by metabolism and immunity. Unfortunately, while the outline is recognisable, many details are still lacking to turn the understanding of a concept into a roadmap ready to be used in clinical routine. This position paper therefore also investigates perspectives on how the advent of ‘big data’ and the use of animal models could help unravel inter-individual responses to exercise parameters and thus influence hypothesis-building for translational research in exercise-based cardiovascular rehabilitation.
Homoarginine (hArg) is a non-essential cationic amino acid which inhibits hepatic alkaline phosphatases to exert inhibitory effects on bile secretion by targeting intrahepatic biliary epithelium. We analyzed (1) the relationship between hArg and liver biomarkers in two large population-based studies and (2) the impact of hArg supplementation on liver biomarkers. We assessed the relationship between alanine transaminase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase (GGT), alkaline phosphatases (AP), albumin, total bilirubin, cholinesterase, Quick’s value, liver fat, and Model for End-stage Liver Disease (MELD) and hArg in appropriately adjusted linear regression models. We analyzed the effect of L-hArg supplemention (125 mg L-hArg daily for 4 weeks) on these liver biomarkers. We included 7638 individuals (men: 3705; premenopausal women: 1866, postmenopausal women: 2067). We found positive associations for hArg and ALT (β 0.38 µkatal/L 95% confidence interval (CI): 0.29; 0.48), AST (β 0.29 µkatal/L 95% CI 0.17; 0.41), GGT (β 0.033 µkatal/L 95% CI 0.014; 0.053), Fib-4 score (β 0.08 95% CI 0.03; 0.13), liver fat content (β 0.016% 95% CI 0.006; 0.026), albumin (β 0.030 g/L 95% CI 0.019; 0.040), and cholinesterase (β 0.003 µkatal/L 95% CI 0.002; 0.004) in males. In premenopausal women hArg was positively related with liver fat content (β 0.047% 95%CI 0.013; 0.080) and inversely with albumin (β − 0.057 g/L 95% CI − 0.073; − 0.041). In postmenopausal women hARG was positively associated with AST (β 0.26 µkatal/L 95% CI 0.11; 0.42). hArg supplementation did not affect liver biomarkers. We summarize that hArg may be a marker of liver dysfunction and should be explored further.
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.
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.
Small animal models are frequently used to improve our understanding of the molecular and biological signaling pathways underlying the beneficial effects of physical activity and exercise. Unfortunately, when running wheels are employed, mice and rats are often kept single-housed to determine the individual running distance of each animal. However, social isolation can be stressful for rodents, and may alter an individual’s propensity for or response to exercise. For example, increased stress from single housing may significantly affect the results when investigating systemic metabolic responses to exercise. We have combined two already available and well-established systems, a radiotelemetry system and a running wheel, to determine spontaneous cage activity (SCA) as well as voluntary exercise (VE) levels of the individual animal in group-housed rodents. Further, we developed a simple software tool which allows monitoring and analyzing the data. Specifically, the radiotelemetry-system utilizes radio-frequency identification via a small, implanted chip to determine the location of each animal. Since, in addition to the animals’ position, also the location of the running wheel in the cage is known, the conclusion of which animal is exercising can be drawn. The developed software enables a fast and reliable assignment of the VE data to the individual animal and a simple analysis of the data collected. Hence, our combined method may be used to investigate the beneficial effects of physical activity, as well as the impact of therapeutic interventions on animal behavior in group-housed rodents.
Sex-specific associations of cardiorespiratory fitness and galectin-3 in the general population
(2022)
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 VO2peak 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 VO2peak 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 VO2peak 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, VO2peak (β −0.2046 95% CI −0.6541 to 0.2449, P = 0.37) and VO2peak adjusted for lean mass (β −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 VO2peak 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
VO2peak was associated with Gal-3 only in men, but VO2peak 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.
Aims
Averaged measurements, but not the progression based on multiple assessments of carotid intima-media thickness, (cIMT) are predictive of cardiovascular disease (CVD) events in individuals. Whether this is true for conventional risk factors is unclear.
Methods and results
An individual participant meta-analysis was used to associate the annualised progression of systolic blood pressure, total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol with future cardiovascular disease risk in 13 prospective cohort studies of the PROG-IMT collaboration (n = 34,072). Follow-up data included information on a combined cardiovascular disease endpoint of myocardial infarction, stroke, or vascular death. In secondary analyses, annualised progression was replaced with average. Log hazard ratios per standard deviation difference were pooled across studies by a random effects meta-analysis. In primary analysis, the annualised progression of total cholesterol was marginally related to a higher cardiovascular disease risk (hazard ratio (HR) 1.04, 95% confidence interval (CI) 1.00 to 1.07). The annualised progression of systolic blood pressure, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol was not associated with future cardiovascular disease risk. In secondary analysis, average systolic blood pressure (HR 1.20 95% CI 1.11 to 1.29) and low-density lipoprotein cholesterol (HR 1.09, 95% CI 1.02 to 1.16) were related to a greater, while high-density lipoprotein cholesterol (HR 0.92, 95% CI 0.88 to 0.97) was related to a lower risk of future cardiovascular disease events.
Conclusion
Averaged measurements of systolic blood pressure, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol displayed significant linear relationships with the risk of future cardiovascular disease events. However, there was no clear association between the annualised progression of these conventional risk factors in individuals with the risk of future clinical endpoints.
This is the first study to analyze the association of accelerometer-measured patterns of habitual physical activity (PA) and sedentary behavior (SB) with serum BDNF in individuals with coronary heart disease. A total of 30 individuals (M = 69.5 years; 80% men) participated in this pre-post study that aimed to test a multi-behavioral intervention. All participants underwent standardized measurement of anthropometric variables, blood collection, self-administered survey, and accelerometer-based measurement of PA and SB over seven days. Serum BDNF concentrations were measured using enzyme-linked immunosorbent assay kit. We applied separate multiple linear regression analysis to estimate the associations of baseline SB pattern measures, light and moderate-to-vigorous PA with serum BDNF (n = 29). Participants spent 508.7 ± 76.5 min/d in SB, 258.5 ± 71.2 min/d in light PA, and 21.2 ± 15.2 min/d in moderate-to-vigorous PA. Per day, individuals had 15.5 ± 3.2 numbers of 10-to-30 min bouts of SB (average length: 22.2 ± 2.1 min) and 3.4 ± 1.2 numbers of > 30 min bouts of SB (average length: 43.8 ± 2.4 min). Regression analysis revealed no significant associations between any of the accelerometer-based measures and serum BDNF. The findings of this study did not reveal an association of accelerometer-measured PA and SB pattern variables with serum BDNF in individuals with coronary heart disease. In addition, our data revealed a considerable variation of PA and SB which should be considered in future studies.
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.