Circulating nitric oxide pathway metabolites in heart failure with preserved ejection fraction: a sex-stratified cross-sectional analysis
Abstract
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. 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. 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…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 171 participants or records.
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