Hypertension remains one of the foremost modifiable risk factors for cardiovascular and renal morbidity and mortality worldwide. Chronic elevated blood pressure promotes structural and functional changes in multiple organs even before clinical disease becomes evident; these so-called preclinical or subclinical target organ damage (TOD) include left ventricular hypertrophy (LVH), microalbuminuria, increased carotid intima-media thickness, arterial stiffness, and reduced renal function. Early detection of TOD helps stratify cardiovascular risk, guide therapy and delay progression to overt organ failure. Serum uric acid (SUA) has drawn increasing attention as a potential biomarker and even a contributory factor in hypertension and its complications. Uric acid arises endogenously from purine metabolism, and under conditions of reduced renal excretion or increased production it may accumulate, triggering endothelial dysfunction, oxidative stress, vascular smooth muscle proliferation, and low-grade inflammation. These mechanisms provide biological plausibility that elevated SUA could be linked with TOD in hypertensive individuals [1,2]. Several cross-sectional studies have reported an association between SUA and preclinical TOD. For instance, in untreated patients with essential hypertension, higher SUA was found in those with LVH and microalbuminuria, compared to those without these complications. In that study, nearly half of the hypertensive subjects had hyperuricemia, which correlated with increased prevalence of both LVH and microalbuminuria [3]. Another large cohort of middle-aged, untreated hypertensive patients reported that increasing tertiles of SUA were associated with higher prevalence and severity of TOD involving heart, arteries and kidney; after adjusting for confounders such as age, BMI, creatinine clearance, and lipid profile, each standard deviation increment in SUA was associated with significantly greater odds of LVH and carotid abnormalities [4]. Longitudinal data extend these observations. In the STANISLAS cohort, initially healthy middle-aged adults followed over about 20 years demonstrated that higher baseline SUA and greater increase in SUA over time were predictive of incident hypertension and of vascular and renal forms of TOD, especially decline in glomerular filtration rate and higher pulse wave velocity (a measure of arterial stiffness) [5]. Similarly, meta-analyses have linked elevated SUA with increased risk of cardiovascular mortality, coronary artery disease and major adverse cardiovascular events in hypertensive populations, though results are not entirely consistent across studies [6]. However, the literature also shows discordant findings. Some studies find that SUA associates more strongly with renal TOD (e.g. reduced estimated glomerular filtration rate or albuminuria), whereas its links with cardiac TOD (such as LVH) or arterial TOD are weaker or attenuated after controlling for traditional risk factors [7]. Others suggest that the association might differ by sex: in some reports, hypertensive women show a more linear and robust relationship between SUA and multiple TODs than men [8]. There are also reports indicating that in treated hypertensive populations, especially when accounting for blood pressure control, obesity, metabolic syndrome components, lipid levels, the independent predictive power of SUA diminishes [9]. Despite growing evidence, several gaps remain. Many studies are cross-sectional, limiting causal inference; thresholds of SUA that confer clinically significant risk of TOD are not well defined; there is heterogeneity in populations (ethnic, genetic, dietary) and in methods of assessing TOD (echocardiography, ECG, imaging, albumin/proteinuria, carotid ultrasound, arterial stiffness etc.), so generalisability is constrained. Moreover, evidence from Indian populations is relatively scarce, and whether SUA has similar correlations with TOD in hypertensive populations in South Asia, with their unique risk factor profiles, remains under-studied. Therefore, this study aims to evaluate the correlation between serum uric acid levels and preclinical target organ damage in a hypertensive population, examining multiple TOD indices (cardiac, renal, vascular), and to assess whether SUA can serve as an early marker to stratify risk in this context. By including both untreated and treated hypertensive subjects (or focusing on untreated cases), controlling for common confounders, and using standardized measures of TOD, we hope to clarify the strength, consistency, and possible sex differences of the SUA-TOD relationship in our setting

Study Design: Cross-sectional observational study.

Place Of Study: Department of General Medicine in St. Stephen’s Hospital Delhi.

Study Duration: The study will be conducted over a period of one and a half years from February 2023 to July 2024.

Study Population:

Sample Size: The proposed sample size for the study is 159.

Study Variables: Age in Group and Sex, Chief Complaint, Uric Acid (Mg/Dl), Microalbuminuria, UACR, Age, SBP (MMHG) and DBP (MMHG), TG, LDL,HDL and Cholesterol, Microalbuminuria, and  Retinopathy.

Inclusion Criteria: Patients above 18 years of age with hypertension.

Exclusion Criteria:

1. Patients on Anti-tubercular drugs, Anti-retroviral drugs, Thiazide diuretics, and cytotoxic drugs
2. Cardiac failure
3. Chronic kidney disease
4. Coronary artery disease
5. Diabetes mellitus
6. Alcohol use.
7. Obesity
8. Lipid-lowering agents
9. Smoking
10. Stroke
11. Hypothyroidism
12. Pregnancy

Statistical Analysis: Statistical analysis was performed using descriptive statistics for demographic and clinical data. Continuous variables were expressed as mean ± SD, while categorical variables were presented as frequencies and percentages. Comparisons between groups (normal vs. elevated uric acid) were made using Chi-square test for categorical variables and independent t-test for continuous variables. A p-value <0.05 was considered statistically significant.

Table 1: Distribution of Age in Group and Sex

Table 2: Distribution of Chief Complaint, Uric Acid (Mg/Dl), Microalbuminuria, UACR, ECG, 2D ECHO and Retinopathy

Table 3: Distribution of mean of Age, SBP (MMHG) and DBP (MMHG)

Table 4: Distribution of mean TG, LDL, HDL and Cholesterol

Table 5: Association between Micro albuminuria, ECG, 2D ECHO and Retinopathy

Figure 1: Distribution of Age in Group and Sex

Figure 4: Distribution of mean TG, LDL,HDL and Cholesterol

In our study, a total of 159 patients were included. Among them, 13 patients (8.2%) were in the 21–30 years age group, 24 patients (15.1%) in 31–40 years, 41 patients (25.8%) in 41–50 years, 32 patients (20.1%) in 51–60 years, 29 patients (18.2%) in 61–70 years, 13 patients (8.2%) in 71–80 years, and 7 patients (4.2%) in 81–90 years. With respect to sex distribution, 85 patients (53.5%) were male and 74 patients (46.5%) were female.

In our study, a total of 159 patients were evaluated. Regarding chief complaints, 1 patient (0.6%) was asymptomatic, 1 patient (0.6%) had bilateral lower limb swelling, 2 patients (1.3%) had blurring of vision, 32 patients (20.1%) presented with chest pain, 11 patients (6.9%) with dizziness, 2 patients (1.2%) with fatigability, 22 patients (13.8%) with ghabrahat, 38 patients (23.9%) with headache, 2 patients (1.3%) with nasal bleed, 1 patient (0.6%) with pain abdomen, 12 patients (7.5%) with palpitation, 1 patient (0.6%) with pedal edema, 2 patients (1.3%) with restlessness, 1 patient (0.6%) with severe headache, 23 patients (14.5%) with shortness of breath, 2 patients (1.3%) with sweating, 1 patient (0.6%) with syncope, 3 patients (1.9%) with uneasiness, and 2 patients (1.3%) with vomiting. Biochemical parameters showed that 107 patients (67.3%) had normal uric acid levels, while 52 patients (32.7%) had abnormal levels. Microalbuminuria was absent in 129 patients (79.87%) and present in 32 patients (20.13%). Based on UACR, 127 patients (79.87%) had <30 mg/g, 20 patients (12.58%) had values between 30–300 mg/g, and 12 patients (7.55%) had >300 mg/g. On ECG findings, 74 patients (46.5%) showed LVH, while 85 patients (53.5%) had no LVH. On 2D ECHO, 72 patients (45.3%) had LVH and 87 patients (54.7%) were normal.Regarding retinopathy, 128 patients (80.5%) had no retinopathy, 20 patients (12.6%) had Grade 1, 10 patients (6.3%) had Grade 2, and 1 patient (0.6%) had Grade 4 retinopathy.

In our study, a total of 159 patients were included with a mean age of 52.28 ± 15.49 years. The mean systolic blood pressure (SBP) of 159 patients was 169.18 ± 19.62 mmHg, while the mean diastolic blood pressure (DBP) measured in 158 patients was 95.94 ± 14.93 mmHg.

In our study, a total of 159 patients were analyzed, out of which 107 had normal lipid levels and 52 had abnormal lipid levels. The mean triglyceride (TG) level was 139.08 ± 74.19 mg/dl in the normal group and 141.54 ± 51.22 mg/dl in the abnormal group, with no statistically significant difference (p = 0.8302,not significant). The mean LDL was 101.14 ± 31.39 mg/dl in the normal group and 103.57 ± 38.68 mg/dl in the abnormal group (p = 0.6743, not significant). The mean HDL was 49.62 ± 11.14 mg/dl in the normal group and 50.04 ± 12.19 mg/dl in the abnormal group (p = 0.8285, not significant). The mean cholesterol level was 172.76 ± 69.21 mg/dl in the normal group and 170.40 ± 70.62 mg/dl in the abnormal group, which was also not statistically significant (p = 0.8419, not significant).

In our study, a total of 159 patients were included, of whom 107 had normal uric acid levels and 52 had abnormal uric acid levels. For microalbuminuria, among the 127 patients without microalbuminuria, 94 (87.9%) had normal uric acid and 33 (63.5%) had abnormal uric acid, while among the 32 patients with microalbuminuria, 13 (12.1%) had normal uric acid and 19 (36.5%) had abnormal uric acid. On ECG, of the 74 patients with LVH, 40 (37.4%) had normal uric acid and 34 (65.4%) had abnormal uric acid, whereas among the 85 patients without LVH, 67 (62.6%) had normal uric acid and 18 (34.6%) had abnormal uric acid. On 2D ECHO, of the 72 patients with LVH, 38 (35.5%) had normal uric acid and 34 (65.4%) had abnormal uric acid, while of the 87 patients with normal findings, 69 (64.5%) had normal uric acid and 18 (34.6%) had abnormal uric acid.Regarding retinopathy, of the 128 patients without retinopathy, 91 (85.0%) had normal uric acid and 37 (71.2%) had abnormal uric acid. Among the 20 patients with Grade 1 retinopathy, 11 (10.3%) had normal uric acid and 9 (17.3%) had abnormal uric acid. In Grade 2 retinopathy (10 patients), 5 (4.7%) had normal uric acid and 5 (9.6%) had abnormal uric acid, while in Grade 4 retinopathy (1 patient), none had normal uric acid and 1 (1.9%) had abnormal uric acid

In our study, the prevalence of abnormal uric acid levels was 32.7%, and its association with preclinical target organ damage was evident across cardiac, renal, and retinal parameters. Microalbuminuria was more frequently present in patients with abnormal uric acid (36.5%) compared to those with normal uric acid (12.1%). Similarly, ECG and 2D ECHO findings revealed that LVH was more common in the abnormal uric acid group (65.4% and 65.4% respectively) than in the normal group (37.4% and 35.5%). Retinopathy was also observed more frequently among patients with abnormal uric acid levels (28.8%) than in those with normal levels (15%), with a trend towards higher grades of retinopathy in the hyperuricemic group. These results indicate that serum uric acid may serve as an important biomarker for early identification of target organ involvement in hypertensive patients.Our findings are in line with the observations of Ofori and Odia, who reported that serum uric acid correlated significantly with microalbuminuria and LVH in essential hypertensive patients, suggesting its role in renal and cardiac structural damage [10]. Similarly, Muiesan et al. demonstrated in a large cohort that increased uric acid levels were independently associated with LVH and carotid atherosclerosis, thereby supporting the relationship between hyperuricemia and cardiovascular TOD [11]. Kanbay et al., in a 20-year follow-up of the STANISLAS cohort, highlighted that elevated uric acid levels were predictive not only of hypertension but also of subsequent vascular and renal TOD, underscoring its prognostic value [12].In contrast, Tsioufis et al. noted that while uric acid correlated with renal parameters such as microalbuminuria, its association with cardiac TOD was weaker after adjusting for confounders, indicating that renal involvement might be a more sensitive marker of hyperuricemia-related damage [13]. A meta-analysis by Li et al. further supported that hyperuricemia is associated with increased risk of renal dysfunction and cardiovascular morbidity in hypertensive patients, although heterogeneity in study designs was acknowledged [14].Interestingly, sex-specific differences have also been reported. A study by Bombelli et al. found that the correlation between uric acid and TOD was stronger in women, particularly with respect to renal impairment and LVH, whereas men showed weaker associations [15]. This highlights the potential role of hormonal and metabolic factors influencing uric acid metabolism and its vascular effects. In an Indian context, Agarwal et al. also documented that hyperuricemia was more prevalent among hypertensive patients with LVH and microalbuminuria compared to those without TOD, which supports the applicability of our findings in similar populations [16].Another prospective study by Kuwabara et al. demonstrated that elevated serum uric acid was a predictor of hypertension development and progression to TOD, emphasizing the need for early recognition and management of hyperuricemia [17]. Similarly, Fang and Alderman reported that higher uric acid levels were associated with increased cardiovascular mortality among hypertensive patients, thus reflecting long-term adverse outcomes [18]. On the other hand, Feig et al. emphasized that lowering uric acid levels in hypertensive adolescents improved blood pressure control and reduced TOD risk, indicating potential therapeutic implications [19].Taken together, these findings suggest that hyperuricemia is not merely an epiphenomenon but a potential causal factor in hypertensive TOD. Our results, showing higher prevalence of microalbuminuria, LVH, and retinopathy in patients with abnormal uric acid levels, are consistent with prior studies and strengthen the argument for incorporating uric acid estimation into routine evaluation of hypertensive patients. Further prospective interventional studies are needed to confirm whether uric acid lowering can reduce TOD progression and improve cardiovascular outcomes

In our study, elevated serum uric acid was found to be associated with the presence of preclinical target organ damage in hypertensive patients. Patients with higher uric acid levels demonstrated a greater prevalence of renal involvement, as evidenced by microalbuminuria, as well as cardiac structural changes, including left ventricular hypertrophy on both ECG and 2D echocardiography. Additionally, retinal involvement was more frequent among those with elevated uric acid levels, suggesting a link between hyperuricemia and microvascular complications. Lipid parameters did not show a significant correlation with uric acid, indicating that the observed associations with target organ damage were independent of dyslipidemia. Overall, the findings of this study highlight the potential role of serum uric acid as a biomarker for early detection of target organ damage in hypertension, underscoring the importance of monitoring and managing uric acid levels to mitigate cardiovascular and renal risk in this population.

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