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Institute
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.
Microbial metabolites measured using NMR may serve as markers for physiological or pathological host–microbe interactions and possibly mediate the beneficial effects of microbiome diversity. Yet, comprehensive analyses of gut microbiome data and the urine NMR metabolome from large general population cohorts are missing. Here, we report the associations between gut microbiota abundances or metrics of alpha diversity, quantified from stool samples using 16S rRNA gene sequencing, with targeted urine NMR metabolites measures from 951 participants of the Study of Health in Pomerania (SHIP). We detected significant genus–metabolite associations for hippurate, succinate, indoxyl sulfate, and formate. Moreover, while replicating the previously reported association between hippurate and measures of alpha diversity, we identified formate and 4-hydroxyphenylacetate as novel markers of gut microbiome alpha diversity. Next, we predicted the urinary concentrations of each metabolite using genus abundances via an elastic net regression methodology. We found profound associations of the microbiome-based hippurate prediction score with markers of liver injury, inflammation, and metabolic health. Moreover, the microbiome-based prediction score for hippurate completely mediated the clinical association pattern of microbial diversity, hinting at a role of benzoate metabolism underlying the positive associations between high alpha diversity and healthy states. In conclusion, large-scale NMR urine metabolomics delivered novel insights into metabolic host–microbiome interactions, identifying pathways of benzoate metabolism as relevant candidates mediating the beneficial health effects of high microbial alpha diversity.
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.