Hypertension is a major public health concern and a leading risk factor for cardiovascular morbidity and mortality worldwide. While the majority of clinical focus has traditionally been on systolic hypertension, isolated diastolic hypertension (IDH)—characterized by elevated diastolic blood pressure (DBP) with normal systolic blood pressure (SBP)—has emerged as a clinically relevant subtype, particularly among younger adults and prehypertensive individuals (1). Prehypertension, defined by the Joint National Committee (JNC-7) as systolic BP of 120–139 mmHg and/or diastolic BP of 80–89 mmHg, is recognized as a precursor to established hypertension and is associated with increased cardiovascular risk (2).

Serum uric acid (SUA), the final metabolic product of purine degradation, has garnered attention as a potential mediator and marker of cardiovascular diseases, including hypertension. Elevated SUA levels are frequently observed in individuals with high blood pressure and may contribute to vascular dysfunction through endothelial impairment, oxidative stress, and activation of the renin-angiotensin system (3,4). Furthermore, experimental studies have demonstrated that uric acid can induce arteriolopathy and renal microvascular changes, potentially initiating or exacerbating hypertensive states (5).

Several epidemiological studies have shown an association between hyperuricemia and the incidence of hypertension in general populations (6,7). However, the specific relationship between SUA levels and the progression from prehypertension to isolated diastolic hypertension remains inadequately understood. Given the rising prevalence of prehypertension and the relative under-recognition of IDH, there is a critical need to identify early biomarkers that can predict progression to overt diastolic hypertension.

This study aims to evaluate serum uric acid as a predictive marker for the development of IDH in prehypertensive adults over a two-year follow-up period. By identifying high-risk individuals based on biochemical profiles, early intervention strategies may be effectively targeted to delay or prevent the onset of hypertension.

A total of 320 prehypertensive adults aged between 25 and 45 years were included in the study. Prehypertension was defined according to JNC-7 guidelines as systolic blood pressure between 120–139 mmHg and/or diastolic blood pressure between 80–89 mmHg, recorded on two separate occasions at least one week apart. Individuals with existing hypertension, diabetes mellitus, renal disorders, gout, cardiovascular disease, or those on medications affecting uric acid levels (e.g., diuretics, allopurinol) were excluded from the study.

Data Collection and Clinical Assessment:

At baseline, demographic data including age, gender, BMI, smoking status, alcohol intake, physical activity, and dietary habits were recorded using a structured questionnaire. Blood pressure was measured using a calibrated sphygmomanometer after the participant had rested for at least five minutes in a seated position. The average of two readings taken five minutes apart was recorded.

Laboratory Investigations:

Fasting blood samples were collected for the estimation of serum uric acid, fasting glucose, lipid profile, and renal function. Serum uric acid was measured using an enzymatic colorimetric method. All laboratory tests were performed in the hospital's central laboratory using standard protocols.

Follow-up:
Participants were followed up at 6-month intervals for a total duration of 24 months. At each follow-up visit, blood pressure was recorded using the same standardized method. The development of isolated diastolic hypertension was defined as a diastolic blood pressure ≥ 90 mmHg with systolic blood pressure < 140 mmHg on two consecutive visits.

Statistical Analysis:

Data were analyzed using SPSS version 25.0. Continuous variables were expressed as mean ± standard deviation, while categorical variables were presented as frequencies and percentages. Differences between groups were assessed using independent t-tests or chi-square tests, as appropriate. Cox proportional hazards regression was used to identify independent predictors of progression to IDH. Receiver operating characteristic (ROC) analysis was performed to determine the predictive value of serum uric acid levels. A p-value of <0.05 was considered statistically significant

A total of 320 prehypertensive individuals were enrolled in the study, with a mean age of 36.2 ± 5.4 years. Of these, 184 (57.5%) were male and 136 (42.5%) were female. Over the 24-month follow-up period, 68 participants (21.3%) progressed to isolated diastolic hypertension (IDH), while the remaining 252 (78.7%) maintained prehypertensive status or regressed to normotension.

Baseline Characteristics

Table 1 presents the baseline demographic and clinical variables of the participants categorized into two groups—those who developed IDH and those who did not. Individuals who developed IDH had significantly higher baseline serum uric acid levels (6.4 ± 1.1 mg/dL) compared to those who did not (5.3 ± 0.9 mg/dL, p < 0.001). BMI was also slightly elevated in the IDH group (p = 0.041), whereas age and gender distribution did not show significant differences between the groups (Table 1).

Table 1: Baseline Characteristics of Study Participants

*Statistically significant at p < 0.05; ***Highly significant at p < 0.001

Predictive Ability of Serum Uric Acid

Receiver Operating Characteristic (ROC) analysis demonstrated that a serum uric acid threshold of >5.8 mg/dL had the best discriminatory value in predicting progression to IDH. The area under the curve (AUC) was 0.78 (95% CI: 0.72–0.83), with a sensitivity of 76.5% and specificity of 70.2% (Table 2).

Table 2: ROC Curve Analysis for Serum Uric Acid as Predictor of IDH

Multivariate Cox Regression Analysis

Multivariate analysis showed that elevated SUA remained a significant independent predictor for the development of IDH after adjusting for confounding variables such as age, BMI, and lifestyle factors. Participants with SUA >5.8 mg/dL had a 2.15-fold increased risk of developing IDH (HR: 2.15; 95% CI: 1.41–3.27; p = 0.002) (Table 3).

Table 3: Multivariate Cox Regression for Risk of Developing IDH

Significant at p < 0.01

These findings underscore the strong association between elevated serum uric acid and the risk of progression to isolated diastolic hypertension in prehypertensive individuals (Table 1–3).

This study aimed to assess the predictive role of serum uric acid (SUA) in the development of isolated diastolic hypertension (IDH) among prehypertensive adults over a two-year period. The results revealed a significant association between elevated baseline SUA levels and the subsequent progression to IDH. Participants with higher SUA at baseline were more likely to develop IDH, even after adjusting for traditional cardiovascular risk factors such as age, BMI, and gender.

Our findings are consistent with earlier studies indicating that hyperuricemia plays a pathogenic role in the development of hypertension, particularly in younger individuals (1,2). Uric acid has been shown to impair endothelial function, promote smooth muscle cell proliferation, and induce oxidative stress—mechanisms that contribute to increased vascular resistance and elevated diastolic pressure (3,4). These vascular changes may precede structural arterial stiffness typically associated with systolic hypertension, supporting the relevance of SUA as a marker in the early hypertensive continuum (5).

Previous prospective cohort studies have demonstrated that individuals with higher SUA levels are at increased risk for incident hypertension (6,7). Notably, Sundström et al. reported that higher SUA was independently associated with longitudinal blood pressure tracking and new-onset hypertension in a community-based population (8). However, only a few studies have specifically addressed the role of SUA in isolated diastolic hypertension. Our study bridges this gap by focusing on a younger prehypertensive population, where IDH is more commonly observed and may have different pathophysiological implications compared to isolated systolic or combined hypertension (9).

The use of ROC curve analysis in our study identified a SUA threshold of >5.8 mg/dL as predictive of IDH, with acceptable sensitivity and specificity. This finding supports the utility of SUA as a screening tool in risk stratification of prehypertensive individuals (10). Given the non-invasive and cost-effective nature of uric acid testing, incorporating SUA measurement in routine clinical assessments could aid in early identification of at-risk individuals and timely implementation of lifestyle or pharmacological interventions (11).

Moreover, the multivariate analysis confirmed that the relationship between SUA and IDH persisted independent of confounders, highlighting the potential of SUA as an independent risk factor rather than merely a surrogate for other metabolic disturbances (12). Several interventional trials have suggested that uric acid-lowering therapies, such as allopurinol or febuxostat, may reduce blood pressure in adolescents and young adults with hyperuricemia and early hypertension, further supporting the causal link between elevated SUA and increased blood pressure (13,14).

However, the study is not without limitations. It was conducted at a single center with a relatively homogeneous population, limiting the generalizability of results. Dietary purine intake and genetic polymorphisms affecting uric acid metabolism were not evaluated. Future multicenter studies with larger, diverse populations and interventional arms are warranted to validate these findings and explore whether lowering SUA can delay or prevent the onset of IDH (15).

In conclusion, this study reinforces the association between elevated serum uric acid and the risk of developing isolated diastolic hypertension in prehypertensive adults. Monitoring SUA may offer a practical approach to identify individuals at higher risk of hypertension progression and facilitate early preventive strategies.

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