Prehypertension (PH) is regarded as a precursor to hypertension (HT) and is associated with increased morbidity and mortality from cardiovascular diseases (CVD), which account for approximately 32% of deaths in Brazil (1–4). The classification of prehypertension adopted in this study follows the criteria established by the Seventh Report of the Joint National Committee (JNC 7), which defined systolic blood pressure between 120 and 139 mmHg and/or diastolic pressure between 80 and 89 mmHg as prehypertensive (5).

Although this guideline has historical relevance and was widely used at the time of data collection, more recent recommendations—such as the 2017 ACC/AHA guideline and the 2020 Brazilian Hypertension Guidelines—have redefined blood pressure categories, often incorporating lower thresholds for diagnosis and intervention (3, 4). Despite these updates, the JNC 7 framework remains useful for comparative purposes and continues to be referenced in epidemiological studies (5). Based on this classification, the prevalence of prehypertension was estimated at approximately 38% in earlier reports, although more recent data suggest a modest decline in prevalence over the past decades, particularly in high-income populations (2–6).

The risk of developing CVD, which begins at BP levels of 115/75 mmHg, doubles with every 20 mmHg increase in systolic BP (SBP) and 10 mmHg increase in diastolic BP (DBP) (1–4, 6). Consequently, prehypertension has become the most prevalent risk factor for developing HT and is recognized as a significant risk factor for target organ damage, including myocardial infarction and coronary atherosclerotic disease, resulting in higher mortality (2, 7–15). Data from the Strong Heart Study (SHS) indicate that individuals within this BP category have a 1.8-fold higher risk of CVD than normotensive individuals, corresponding to an absolute increase of six cardiovascular events per 1,000 individuals per year (11–17).

Along with BP, functional and morphological parameters, such as heart rate (HR), pulse pressure (PP), mean arterial pressure (MAP), end-systolic stress, and end-isovolumetric systolic stress, have been shown to be significantly higher in prehypertension compared to normotension (13, 18–21). Other markers, including central blood pressure, augmentation index (AI75%), and pulse wave velocity (PWV), widely used as indicators of arterial stiffness, have been linked to increased cardiovascular mortality and are considered superior predictors of CVD (8, 14, 15, 22–27). Central blood pressure represents a blood pressure measured in the aortic root, and AI75% is estimated as a composite marker of wave reflections and arterial stiffness. On the other hand, PWV represents an index of elastic-type aortic stiffness. Studies also suggest that arterial stiffness correlates with age, triglycerides levels, SBP, 24-h PP, urinary albumin excretion, and carotid artery intima-media thickness (14, 15, 28–32). These factors are prevalent in the prehypertensive population, with 64% of individuals under 60% and 94% over 60 years old exhibiting one or more risk factors for CVD (6, 7, 16, 33–38).

Consequently, early diagnosis and implementation of therapeutic measures in prehypertensive individuals aim to mitigate the risk of HT, CVD, and mortality (1, 7, 16, 17). While the diagnosis of HT typically involves detecting consistently elevated BP levels in clinical settings, ambulatory blood pressure monitoring (ABPM) enables the indirect and continuous recording of BP over 24 h or more (39–42). This method facilitates the identification of circadian BP variations, the development of therapeutic and prognostic strategies, and the evaluation of antihypertensive treatment efficacy (18, 43–47).

Given the clinical relevance of arterial stiffness assessment, it is essential to consider the methodologies available for its measurement. Among these, carotid-femoral pulse wave velocity (cfPWV) is widely regarded as the gold standard due to its direct evaluation of aortic stiffness and robust predictive value for cardiovascular outcomes (14, 15, 19, 24, 25). However, cfPWV requires specialized equipment and trained personnel, which may limit its feasibility in routine clinical practice and large-scale epidemiological studies. As an alternative, oscillometric devices such as the Mobil-O-Graph® estimate central hemodynamic parameters and PWV through mathematical modeling of brachial pressure waveforms (24). These methods offer practical advantages—including ease of use, noninvasiveness, and suitability for 24-h ambulatory monitoring—but rely on indirect calculations and single-segment assessments that may not fully reflect central arterial stiffness. Consequently, interpretation of results obtained via such devices should be approached with consideration of these methodological constraints (15, 19, 24, 25).

Among the variables derived from ABPM, sleep SBP, 24-h SBP, and wake SBP have demonstrated the strongest associations with cardiovascular events and target organ damage (18, 19). In particular, nocturnal blood pressure dipping—characterized by a physiological decline in BP during sleep—has emerged as a key prognostic marker, with reduced or absent dipping linked to increased cardiovascular risk and end-organ injury (20). Building on this evidence, the present study aimed to comprehensively evaluate peripheral hemodynamic parameters (BP, MAP, HR, and PP) and central indices (cSBP, cDBP, and PWV) in prehypertensive individuals, comparing them to normotensive and controlled hypertensive subjects. This approach seeks to elucidate early vascular and metabolic alterations across distinct blood pressure categories under real-life conditions.

Therefore, the objective of this study was to compare peripheral and central hemodynamic parameters—including blood pressure, pulse wave velocity, and nocturnal dipping—as well as biochemical variables such as glycemia, lipid profile, renal function markers, and uric acid levels across normotensive, prehypertensive, and controlled hypertensive individuals. The originality of this work lies in its integration of 24-h ABPM monitoring with central arterial stiffness indices using a validated oscillometric method, allowing for real-life assessment of vascular function. Unlike previous studies that focused solely on prehypertension, this design enables a broader understanding of cardiovascular remodeling across the blood pressure spectrum, while emphasizing the prognostic relevance of nocturnal dipping—a parameter often overlooked in conventional evaluations.

A total of 224 subjects (104 male, 46.4%) participated in the study, comprising 47 NT individuals (9 male, 19.1%), 39 PH subjects (34 male, 85.0%), and 138 CHT individuals (61 male, 43.5%). Gender, mean age, BMI, and biochemical variables, as well as comparisons between groups, are shown in Table 1.

To support the classification and comparison between groups, mean office blood pressure values were recorded and statistically analyzed. The NT group presented an average systolic/diastolic BP of 116.5 ± 13.9/72.4 ± 10.6 mmHg, the PH group 130.2 ± 5.6/84.1 ± 4.8 mmHg, and the CHT group 128.7 ± 6.3/82.9 ± 5.1 mmHg (Table 1). These findings confirm that, although under antihypertensive treatment, the CHT group maintained BP levels within the controlled range, which may overlap with prehypertensive thresholds. Therefore, the inclusion of both office BP and ABPM values reinforces the validity of between-group comparisons.

Significant differences were observed in the PH group compared to the NT and CHT groups concerning gender (p = 0.000 for both) and triglycerides levels (p = 0.000 and p = 0.02, respectively). Compared to the NT group, the PH group also exhibited significant differences in creatinine levels (p = 0.000), uric acid (p = 0.000), and HDL-c (p = 0.000). When compared to the CHT group, the PH group differed significantly in age (p = 0.000), history of diabetes (p = 0.000), glucose levels (p = 0.000), eGFR (p = 0.01 for both MDRD and Cockroft-Gault models), total cholesterol (p = 0.000), and LDL-c (p = 0.002). Given the lack of differences between MDRD and Cockroft-Gault calculations, only MDRD results are presented (Table 1).

No significant differences were noted between groups for race, smoking status, or serum potassium levels. Although albuminuria levels increased across groups, no statistical significance was observed (Table 1).

This study revealed biochemical-metabolic differences among the groups in terms of glycemia, creatinine, uric acid, eGFR, total cholesterol, HDL-c, LDL-c, and triglycerides. Through ABPM, differences were observed in all three periods (24-hour, wakefulness, and sleep) for both peripheral (SBP, DBP, and MAP) and central parameters (cSBP, cDBP, and PWV) among the groups.

The observed differences in gender proportions among NT, PH, and CHT groups are consistent with prior findings, often attributed to biological and behavioral factors (27). Studies have shown that men typically present higher BP levels than premenopausal women; however, after menopause, BP increases in women, diminishing or nullifying this difference (28, 29). Hormone replacement therapy has not demonstrated significant reductions in BP for most postmenopausal women, suggesting that estrogen loss alone does not fully explain elevated BP in this population (28, 29).

The inclusion of the CHT group, despite ongoing antihypertensive therapy, was intended to provide a broader clinical perspective on the progression of vascular changes across different blood pressure categories. This comparison enables the assessment of whether early alterations in arterial stiffness and central hemodynamics observed in PH individuals resemble those found in treated hypertensive patients. Pharmacological treatment may influence biochemical and hemodynamic parameters in the CHT group—particularly lipid profiles due to statin use and PWV values due to age and blood pressure levels. Nevertheless, contrasting untreated PH with clinically controlled hypertension offers relevant insight into the continuum of cardiovascular remodeling and the potential impact of therapeutic interventions.

Regarding biochemical parameters, uric acid, creatinine, and HDL-c levels were significantly different in prehypertensive individuals compared to normotensive individuals, while glycemia, total cholesterol, LDL-c, and eGFR levels differed when comparing PH to CHT individuals. Triglycerides levels were distinct between the PH group and both the NT and CHT groups. Elevated uric acid levels, a byproduct of purine metabolism, have been associated with increased prehypertension risk (30–33), a finding found in the PH group compared to the NT group. Our study aligns with studies of Liu et al. (32, 33). The first reported a positive correlation between uric acid levels and PH incidence in a 6-year prospective cohort study (32), while the second showed that elevated levels of uric acid may be associated with increased risk of PH in the meta-analysis of 17 observational studies of approximately 79,358 participants (33). The authors demonstrated that the risk of PH increased 46% for highest levels compared with lowest levels of uric acid (33). Moreover, PH and high uric acid levels significantly increase the risk of arterial stiffness (34).

Prehypertensive individuals also exhibited higher levels of triglycerides, total cholesterol, and LDL-c, and lower HDL-c compared to both NT and CHT groups. While this finding aligns with previous research regarding normotensive individuals (35), the differences relative to the CHT group may be attributable to statin use. Statins effectively reduce cholesterol and LDL-c levels, lower CVD risk, stabilize atherosclerotic plaques, and possess anti-inflammatory properties, thus reducing cardiovascular complications and mortality (36, 37). Anyway, Vucak et al. found association between hyperuricemia and prehypertension in individuals with elevated BMI and triglycerides, suggesting an interplay between metabolic factors and PH (38), fact that corroborates with our results.

Renal function, evaluated via MDRD and Cockcroft-Gault equations, showed statistical differences between PH and CHT groups. This aligns with studies highlighting the close relationship between HT and kidney disease (39, 40). Notably, although not statistically significant, eGFR was lower in PH compared to NT individuals, suggesting a potential trend of reduced renal function in prehypertensive individuals. Spite of microalbuminuria have not showed a statistically significant difference between the groups, it is interesting to note that the PH group showed greater loss of urinary albumin than the NT group, a fact previously observed by Tenekecioglu et al. Thus, the urinary albumin leakage may be a manifestation of generalized vascular lesion already present in prehypertensive individuals (41).

The 24-h ABPM comparison of PH and NT groups revealed significant differences in SBP, DBP, MAP, cSBP, and cDBP, an underscoring the importance of early follow-up and, where necessary, pharmacological intervention to prevent HT onset (42). These differences, particularly in cSBP and cDBP, support prior studies linking higher central pressures with carotid intima-media thickness (43) and atherosclerotic plaque risk (44), as well as increased left ventricular mass (45) in prehypertensive individuals.

As expected, PWV was significantly higher in hypertensive individuals than in prehypertensive and normotensive individuals. PWV measured by Mobil-O-Graph is highly dependent on age and blood pressure, which were higher in hypertensive individuals in this sample, and this fact may have influenced this finding. Likewise, PWV in prehypertensive individuals was higher than in normotensive individuals, with a difference of 0.3 m/s, but this did not reach significance due to the sample size.

Moreover, differences in PP and PWV between PH and CHT groups across all periods (24-h, wakefulness, sleep) corroborate studies suggesting an acceleration of arterial stiffness from prehypertension to hypertension (46, 47). As PWV is a known predictor of cardiovascular events and mortality, its use in prehypertensive patients may aid in preventing sustained hypertension development (14).

The use of the Mobil-O-Graph® system for central blood pressure and arterial stiffness assessment was chosen due to its validated oscillometric method, which applies a transfer function to brachial waveforms to estimate central hemodynamic parameters. This technique offers a noninvasive, reproducible, and clinically applicable alternative to applanation tonometry, with demonstrated consistency across diverse populations. Furthermore, the decision to employ 24-h ABPM instead of the simpler triple office measurement was based on its superior ability to capture circadian blood pressure variations, detect masked or white-coat hypertension, and provide more reliable prognostic information. ABPM also enables the evaluation of nocturnal dipping and PWV under real-life conditions, which are critical for understanding early vascular changes in prehypertensive individuals.

In summary, differences in ABPM parameters were observed across the groups during all three periods (24-h, wakefulness, and sleep) for both peripheral (SBP, DBP, MAP) and central (cSBP, cDBP, and PWV) hemodynamic variables. The PH group displayed higher peripheral and central pressure values compared to the NT group but lower values than the CHT group across all periods. This study demonstrates that prehypertensive patients present some biochemical-metabolic and in central hemodynamic parameters alterations, which may be suggestive of functional and structural alterations that predispose individuals to the development of hypertension.