In patients with HFpEF, women had significantly lower plasma concentrations of symmetric dimethylarginine (SDMA) compared to men (β-coefficient -0.11 µmol/L), while overall NO-related metabolite profiles showed substantial overlap.
Cross-Sectional (n=171)
Yes
Do circulating NO-related metabolite concentrations differ between men and women with HFpEF?
Sex-related differences in circulating NO-related metabolites in HFpEF are limited, with SDMA showing the most consistent difference (higher in men), suggesting that sex differences in HFpEF may not be strongly reflected in the circulating NO pathway.
Mean Difference: -0.11 (95% CI -0.2–-0.03)
p-value: p=0.010
Abstract Background Heart failure with preserved ejection fraction (HFpEF) is more prevalent in women, who often present with earlier onset and greater severity of vascular and endothelial dysfunction. Nitric oxide (NO) is a key contributor to vascular health, and several NO-related metabolites are associated with cardiovascular outcomes. However, it remains unknown whether differences in circulating NO-related metabolite concentrations exist between men and women with HFpEF. Methods In this cross-sectional analysis of a multicentre randomized controlled intervention trial (OptimEx-Clin), plasma concentrations of NO-related amino acids (L-arginine, L-homoarginine (hArg), L-ornithine, L-lysine, L-citrulline), asymmetric and symmetric dimethylarginines (ADMA, SDMA), and functional metabolite ratios were assessed in 171 patients with HFpEF. Analyses were stratified by sex and age, and further adjusted for relevant clinical covariates using multivariable regression models. A principal component analysis (PCA) was performed to explore sex-related metabolite patterns. Results The comparison of NO-related metabolites in 58 men and 113 women with HFpEF showed significant sex differences for SDMA (β-coefficient 95% CI; -0.11 -0.20 to -0.03 µmol/L, p = 0.010) and hArg (-0.24 -0.46 to -0.01 µmol/L, p = 0.043) in unadjusted models; both with lower concentrations in women. While the association with hArg was attenuated after multivariable adjustment, higher SDMA concentrations in men were observed in five out of six tested models. No other significant sex differences were observed neither in single metabolites nor in composite metabolite ratios. The PCA of all measured metabolites did not demonstrate a clear separation between women and men in the overall metabolite profile. Conclusions In HFpEF, sex-related differences in circulating NO-related metabolites were limited and metabolite-specific, with SDMA showing the most consistent sex-associated difference with higher concentrations in men. The substantial overlap of metabolic profiles between women and men showed no distinct patterns of circulating metabolites linked to endothelial function in patients with HFpEF. Registry ClinicalTrials.gov, TRN: NCT02078947.
Dinges et al. (Mon,) conducted a cross-sectional in Heart failure with preserved ejection fraction (HFpEF) (n=171). Female sex vs. Male sex was evaluated on Plasma concentration of symmetric dimethylarginine (SDMA) (β-coefficient -0.11, 95% CI -0.20 to -0.03, p=0.010). In patients with HFpEF, women had significantly lower plasma concentrations of symmetric dimethylarginine (SDMA) compared to men (β-coefficient -0.11 µmol/L), while overall NO-related metabolite profiles showed substantial overlap.