Searching for Metabolic Markers for Hypertension in Human Urine

Hypertension is a leading risk factor for the development of cardiovascular diseases and is associated with higher morbidity and mortality rates. However, hypertension screening is not routinely applied to asymptomatic individuals and can be influenced by several factors, such as adequate technique and patient emotional factors, recent exercise, and oral consumptions. Therefore, in this study, we aimed to analyze the urinary metabolomic profiles in normotensive and hypertensive participants by untargeted NMR to identify novel biomarkers for hypertension in a population with a high prevalence of hypertension. Hypertensive participants (when compared with normotensive participants) without cardiovascular or metabolic comorbidities had higher urinary levels of sarcosine and lower levels of acetone, citrate, 4-hydroxyphenylacetate, 3-methylglutaconate, N-isovaleroylglycine, oxaloacetate, phenylalanine and pyridoxate. These metabolites are involved in energy metabolism, amino acid metabolism, gut microbiota-derived metabolism, and vitamin B6 metabolism, reinforcing previous evidence of metabolic changes in hypertension. None of the metabolites were significantly influenced by the presence of cardiovascular or metabolic comorbidities such as dyslipidemia, diabetes, or other cardiovascular diseases, supporting their association with hypertension. To our knowledge, this is the first study to report changes in urinary acetone, oxaloacetate, 3-methylglutaconate, N-isovaleroylglycine and pyridoxate in hypertensive individuals (vs. normotensive individuals). Citrate, methylglutaconate, N-isovaleroylglycine, oxaloacetate, phenylalanine and sarcosine seem to have a higher potential for reliable hypertension biomarkers, since they were also not significantly influenced by any of the anti-hypertensive treatments. Together, these findings expand the current urinary metabolomic profile of hypertension and highlight the potential of these urinary metabolites as a non-invasive approach for earlier hypertension detection.