European Journal of Cardiovascular Medicine

Pre-hypertension, defined as SBP 120–139 mmHg and/or DBP 80–89 mmHg, is a subclinical condition that predisposes individuals, including young adults, to hypertension and cardiovascular disease [1]. Its prevalence among adolescents and young adults ranges from 20% to 35%, often going undetected due to the asymptomatic nature and limited blood pressure screening [2].

Arterial stiffness, measured by pulse wave velocity (PWV) and augmentation index (AIx), reflects structural and functional vascular changes and is elevated in pre-hypertension, predicting future cardiovascular events independent of traditional risk factors [3]. Heart rate variability (HRV), a marker of autonomic regulation, is reduced even in pre-hypertensive individuals, indicating sympathetic dominance and early autonomic imbalance [4]. Endothelial dysfunction, assessed via flow-mediated dilation (FMD), represents an early event in atherosclerosis and hypertension, occurring before overt blood pressure elevation [5,6].

Although these parameters have been studied individually, their combined predictive value for early vascular impairment in young adults remains unclear. This study aims to evaluate the interrelationships between arterial stiffness, HRV, and endothelial function in pre-hypertensive young adults, providing insights for early cardiovascular risk stratification and preventive strategies

Pre-hypertension, defined as SBP 120–139 mmHg and/or DBP 80–89 mmHg, is a subclinical condition that predisposes individuals, including young adults, to hypertension and cardiovascular disease [1]. Its prevalence among adolescents and young adults ranges from 20% to 35%, often going undetected due to the asymptomatic nature and limited blood pressure screening [2].

Arterial stiffness, measured by pulse wave velocity (PWV) and augmentation index (AIx), reflects structural and functional vascular changes and is elevated in pre-hypertension, predicting future cardiovascular events independent of traditional risk factors [3]. Heart rate variability (HRV), a marker of autonomic regulation, is reduced even in pre-hypertensive individuals, indicating sympathetic dominance and early autonomic imbalance [4]. Endothelial dysfunction, assessed via flow-mediated dilation (FMD), represents an early event in atherosclerosis and hypertension, occurring before overt blood pressure elevation [5,6].

Although these parameters have been studied individually, their combined predictive value for early vascular impairment in young adults remains unclear. This study aims to evaluate the interrelationships between arterial stiffness, HRV, and endothelial function in pre-hypertensive young adults, providing insights for early cardiovascular risk stratification and preventive strategies

A total of 123 young adults with pre-hypertension were included in the study. The mean age of participants was 26.4 ± 4.3 years, with 68 males (55.3%) and 55 females (44.7%). The mean body mass index (BMI) was 24.7 ± 3.1 kg/m², and the mean waist-to-hip ratio was 0.89 ± 0.05. Family history of hypertension was present in 49 participants (39.8%), and 32 participants (26.0%) were current smokers. Regular physical activity was reported by 75 participants (61.0%) (Table 1).

The mean systolic and diastolic blood pressures were 128.3 ± 5.7 mmHg and 83.5 ± 4.8 mmHg, respectively. Arterial stiffness assessment showed a mean pulse wave velocity (PWV) of 7.1 ± 0.8 m/s and a mean augmentation index (AIx) of 26.5 ± 6.3% (Table 2).

Heart rate variability (HRV) analysis revealed a mean SDNN of 42.8 ± 10.5 ms and RMSSD of 35.6 ± 9.4 ms. Frequency-domain analysis demonstrated a mean low-frequency (LF) component of 510 ± 120 ms², high-frequency (HF) component of 480 ± 110 ms², and LF/HF ratio of 1.07 ± 0.25 (Table 3).

Endothelial function, evaluated by brachial artery flow-mediated dilation (FMD), showed a mean baseline diameter of 4.2 ± 0.5 mm and a post-occlusion diameter of 4.6 ± 0.5 mm. The mean FMD was 9.5 ± 2.4%, with 68 participants (55.3%) demonstrating endothelial dysfunction, defined as FMD <10% (Table 4).

Correlation analysis demonstrated a significant inverse relationship between arterial stiffness and endothelial function. PWV and AIx were negatively correlated with FMD (r = -0.48, p < 0.001 and r = -0.42, p < 0.001, respectively). Conversely, HRV parameters exhibited a positive correlation with FMD. SDNN (r = 0.36, p < 0.001) and RMSSD (r = 0.33, p = 0.002) were positively associated with endothelial function, whereas the LF/HF ratio showed a negative correlation (r = -0.29, p = 0.004) (Table 5).

Multivariate linear regression revealed that higher arterial stiffness, reflected by increased PWV and AIx, was independently associated with lower FMD (β = -0.55, p < 0.001 for PWV; β = -0.31, p = 0.006 for AIx). Among autonomic parameters, higher SDNN and RMSSD were positively associated with FMD (β = 0.21, p = 0.021; β = 0.15, p = 0.034, respectively), whereas a higher LF/HF ratio predicted lower FMD (β = -0.19, p = 0.019). Additionally, older age and higher BMI were modest but significant negative predictors of endothelial function (β = -0.12, p = 0.018; β = -0.08, p = 0.048, respectively). Smoking and family history of hypertension showed trends toward lower FMD but did not reach statistical significance (Table 6).

Table 1: Baseline Characteristics of Study Participants (n = 123)

Table 2: Blood Pressure and Arterial Stiffness Parameters (n = 123)

Table 3: Heart Rate Variability Parameters (n = 123)

Table 4: Endothelial Function Assessment (n = 123)

Table 5: Correlation of Arterial Stiffness and HRV with Endothelial Function (n = 123)

Table 6: Multivariate Linear Regression Analysis to Identify Independent Predictors of Early Endothelial Dysfunction (FMD, n = 123)

This study highlights early cardiovascular changes in young adults with pre-hypertension, emphasizing links between arterial stiffness, heart rate variability (HRV), and endothelial function, and underscores the importance of early recognition and intervention.

We observed a clear inverse relationship between pulse wave velocity (PWV) and flow-mediated dilation (FMD), indicating that increased arterial stiffness is associated with impaired endothelial function. This aligns with prior studies showing PWV as a predictor of worsening blood pressure and cardiovascular risk [9,10]. Stiffer arteries accelerate reflected pressure waves, raising central blood pressure and reducing shear stress, which diminishes nitric oxide-mediated vasodilation.

HRV measures (SDNN and RMSSD) were positively correlated with FMD, suggesting that greater parasympathetic activity supports endothelial health, whereas reduced HRV reflects sympathetic dominance, promoting oxidative stress and inflammation [11,12]. Evaluating arterial stiffness and HRV together provides a comprehensive assessment of early vascular health, facilitating identification of individuals at heightened cardiovascular risk and supporting timely preventive interventions [13].

Multivariate regression analysis in 123 participants identified higher PWV and augmentation index (AIx) as robust negative predictors of FMD, while SDNN, RMSSD, age, and BMI also influenced endothelial function [14,15]. Smoking and family history approached significance but were not independent predictors, reflecting the complex interplay of genetic and environmental factors.

Although informative, the cross-sectional design limits causal inference. Longitudinal and interventional studies are needed to clarify the dynamic interactions between arterial stiffness, autonomic regulation, and endothelial function, and to evaluate the impact of lifestyle modifications on these early cardiovascular markers.

The present study demonstrates that young adults with pre-hypertension exhibit early signs of endothelial dysfunction, which are significantly associated with increased arterial stiffness and altered autonomic function as reflected by reduced heart rate variability. Assessment of pulse wave velocity, augmentation index, and HRV parameters may serve as non-invasive predictive markers for identifying individuals at higher cardiovascular risk, emphasizing the need for early lifestyle and preventive interventions in this population.

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