Urinary protein biomarkers in young adults with prehypertension and hypertension

Abstract

The identification of urinary protein biomarkers associated with early blood pressure (BP) elevation is essential for timely cardiovascular risk detection and intervention, particularly in young adults. The less invasive process of urine sample collection, compared to blood sampling, would alleviate anxiety and enhance compliance among young adults in hypertension screening efforts. Moreover, urinary biomarkers are particularly advantageous in younger cohorts, where confounding factors such as polypharmacy and multiple comorbidities that can influence urinary protein expression are minimal. Previous studies have shown that plasma endothelin-1 (ET-1) and interleukin-6 (IL-6) are implicated in the early development of hypertension; however, the role of these protein markers in the urine sample remains underexplored. This study aimed to compare urinary ET-1 and IL-6 concentrations between normotensive, prehypertensive, and hypertensive young adults and to investigate their role in the early development of elevated BP in this cohort. This was a comparative cross-sectional study recruiting a total of 72 subjects aged 18 to 45 years old, comprising 24 normotensive, 25 prehypertensive, and 23 newly diagnosed hypertensive individuals. Normotension was defined as a systolic blood pressure (SBP) of less than 120 mmHg and a diastolic blood pressure (DBP) of less than 80 mmHg; prehypertension as an SBP of 120–139 mmHg and/or a DBP of 80–89 mmHg; and hypertension as an SBP of 140 mmHg or higher and/or a DBP of 90 mmHg or higher. BP classification was based on the mean of three measurements taken in a sitting position using a validated automatic digital monitor. Fasting blood and urine samples were collected for biochemical profiles analysis, and plasma and urinary ET-1 and IL-6 concentrations were determined using enzyme-linked immunosorbent assay (ELISA). The associations between both biomarkers and BP status were determined using logistic regression analysis. This study found that subjects in hypertensive group had significantly higher body mass index (BMI), BMI category, waist circumference, pulse rate, and uric acid levels, along with significantly lower high-density lipoprotein (HDL) cholesterol levels compared to the normotensive group. Similarly, subjects in prehypertensive group exhibited a significantly higher BMI category and lower HDL levels than the normotensive group. Urinary ET-1 concentrations demonstrated a decreasing trend across the normotensive, prehypertensive, and hypertensive groups (median [interquartile range]: 3.84 [7.05] vs. 2.12 [2.04] vs. 1.37 [5.01] pg/mL), with significantly lower levels in the hypertensive group compared to the normotensive group (p = 0.035). However, logistic regression analysis revealed no significant association between urinary ET-1 and elevated BP after adjusting for other established cardiovascular risk factors. There was also no significant correlation between plasma and urinary ET-1 levels. Meanwhile, there were no significant differences in urinary IL-6 levels among the three groups. The significantly lower urinary ET-1 levels observed in the hypertensive group suggest that reduced renal excretion of ET-1 may play a role in the early pathophysiology of young-onset hypertension and could serve as a promising non-invasive biomarker for early detection and cardiovascular risk stratification. This finding aligns with the known physiological role of renal ET-1 in regulation of sodium and water excretion, which is a key mechanism in BP control. Further research is warranted to validate these findings in larger and more diverse cohorts.