European Journal of Cardiovascular Medicine

Hypertension remains a critical global health concern, affecting nearly one billion individuals worldwide and contributing to an estimated 7.1 million deaths annually ^[1]. The JNC 7 report identifies high blood pressure as the leading modifiable risk factor for mortality globally ^[2]. Poorly controlled hypertension leads to progressive end-organ damage, including coronary artery disease (CAD), congestive heart failure (CHF), left ventricular hypertrophy (LVH), stroke, and peripheral vascular disease ^[3].

Hypertension approximately doubles the risk of symptomatic CAD, such as acute myocardial infarction and sudden death, and increases the likelihood of CHF more than threefold ^[4]. Chronic elevation of blood pressure increases left ventricular wall stress, resulting in myocardial stiffness and hypertrophy, and accelerates atherosclerosis within the coronary vasculature. LVH is the most frequent structural cardiac abnormality in hypertension and serves as a robust marker of subclinical cardiovascular disease ^{[5, 6]}. This combination of increased myocardial oxygen demand and reduced coronary perfusion predisposes to ischemia, thereby heightening the incidence of myocardial infarction, sudden cardiac death, arrhythmias, and CHF. Endothelial dysfunction and chronic low-grade inflammation have been proposed as biological links between microalbuminuria (MA) and cardiovascular disease.

The American Diabetes Association (ADA) and National Kidney Foundation (NKF) define MA as an albumin–creatinine ratio of 30–300 µg/mg in both sexes, or equivalently: urinary albumin excretion (UAE) of 30–300 mg/24 h, 20–200 mg/L in a first morning sample, 20–200 µg/min in an overnight collection, or a urinary albumin–creatinine ratio of 30–300 mg/g in a first morning midstream specimen ^[7].

MA is frequently observed in essential hypertension and is recognized as an early predictor of cardiovascular and renal events ^[8]. Even albumin levels within the low range of microalbuminuria are associated with increased risks of myocardial infarction, stroke, cardiovascular death, heart failure, and peripheral vascular disease ^[9]. UAE measurement is thus regarded as a valuable index of global cardiovascular risk ^[10].

The pathophysiology of MA in essential hypertension is multifactorial and incompletely understood. Proposed mechanisms include increased glomerular hydrostatic pressure due to impaired autoregulation, increased glomerular basement membrane permeability, endothelial dysfunction, and inflammation. The predictive relationship between left ventricular mass index (LVMI) and MA may reflect common pathophysiological drivers such as hemodynamic overload, sympathetic and renin–angiotensin system activation ^[11], subclinical inflammation, and oxidative stress ^{[12, 13]}, all of which contribute to fibrotic remodelling in both the heart and kidneys ^[14]. Furthermore, LVH-related diastolic dysfunction may exacerbate central venous congestion, impairing renal perfusion and promoting MA^.[15]

LVM by body surface area (BSA) and expressed in g/m². LVH was defined as LVMI ≥131 g/m² in men and ≥100 g/m² in women ^[16].

Given the strong prognostic implications, early detection of MA in hypertensive patients may guide timely initiation of multifactorial interventions to reduce cardiovascular risk and prevent renal decline. This study was designed to determine the prevalence of MA in non-diabetic essential hypertension and evaluate its correlation with LVH.

Objectives:

1. To determine the frequency of microalbuminuria in non-diabetic, essential hypertensive individuals.
2. To assess the relationship between microalbuminuria and Left Ventricular Mass Index.
3. To determine the correlation between microalbuminuria and Left Ventricular Mass Index with the duration of hypertension.

A cross-sectional descriptive study was conducted in the Department of General Medicine, MIMS, Mandya, from July 2021 to June 2022, involving outpatient and inpatient cases meeting predefined eligibility criteria. The sample size was calculated from a reported microalbuminuria prevalence of 51.88% [25] using the formula n=Z²pq/d² with Z = 1.96, p = 0.5188, q = 0.4812, and d = 0.10, yielding 99.8, rounded to 100. Participants were recruited through purposive sampling.

Inclusion criteria were age 18–60 years, essential hypertension (any grade per JNC 8), and no current or prior ACE inhibitor use.

Exclusion criteria included secondary hypertension; diabetes mellitus or impaired glucose tolerance; renal disease; urinary tract infection; pregnancy; regular tobacco use; serum creatinine >1.5 mg/dL; BMI >25 kg/m²; major cardiovascular or cerebrovascular events in the preceding six months (coronary artery disease, congestive heart failure NYHA class III/IV, valvular heart disease, atrial fibrillation, cerebrovascular accident, myocardial infarction); and ongoing ACE inhibitor therapy.

After informed consent, detailed history, examination, and laboratory investigations were performed. Urine samples (spot, first morning void, or 24-hour collection) were analyzed for microalbuminuria or urine albumin-to-creatinine ratio. Echocardiography assessed left ventricular hypertrophy via left ventricular mass index (LVMI), measuring interventricular septal thickness, posterior wall thickness, and left ventricular internal diameter during diastole. Venous blood was collected for routine tests. Urine microalbumin levels were correlated with LVMI, and associations with clinical variables, including hypertension duration, were evaluated.

Data were entered into Microsoft Excel 2021 and analyzed in IBM SPSS Statistics v26. Normality was tested using the Kolmogorov–Smirnov test. Categorical variables were expressed as frequency and percentage, continuous variables as mean ± standard deviation (parametric) or median with interquartile range (non-parametric). Associations between categorical variables were assessed with Chi-square or Fisher’s exact test; mean differences for parametric data with Student’s t-test; and non-parametric data with the Mann–Whitney U test. Statistical significance was set at p < 0.05.

Table 1: Profile of subjects in the study with respect to Microalbuminuria

In the present study, the majority of subjects in both groups were in the 51–55 years age group (30.0%), followed by the 41–45 years group (21.0%). The mean age was 53 ± 8 years in those without microalbuminuria and 51 ± 6 years in those with microalbuminuria, with no statistically significant difference (p = 0.384). There was no significant association between age distribution and microalbuminuria (p = 0.574). A significant gender difference was observed, with females comprising 53.1% of the microalbuminuria group compared to 23.5% in the non-microalbuminuria group (p = 0.003). Smoking history showed a significant association, with non-smokers being more common in the microalbuminuria group (68.8%) compared to the non-microalbuminuria group (44.1%) (p = 0.021). LVH was present in 90.6% of subjects with microalbuminuria compared to only 7.4% in those without, and this association was highly significant (p = 0.001).

Table 2: Vitals and Anthropometry distribution with respect to Microalbuminuria

The mean systolic blood pressure (SBP) was 165 ± 12 mmHg in both groups, while the mean diastolic blood pressure (DBP) was 113 ± 16 mmHg in the non-microalbuminuria group and 110 ± 19 mmHg in the microalbuminuria group, with no significant differences (p = 0.849 and p = 0.438, respectively). Mean height was 166.6 ± 6.5 cm in the non-microalbuminuria group and 167.1 ± 4.9 cm in the microalbuminuria group (p = 0.652). Mean weight was 78.2 ± 61.1 kg in the non-microalbuminuria group and 71.5 ± 10 kg in the microalbuminuria group (p = 0.540). The mean BMI was similar in both groups (25 ± 3 kg/m²), with no significant association with microalbuminuria (p = 0.914).

Table 3: Laboratory parameters with respect to Microalbuminuria

Subjects with microalbuminuria had significantly higher mean urinary creatinine levels (106 ± 58 mg/dL) compared to those without microalbuminuria (84 ± 26 mg/dL) (p = 0.001). The mean albumin-to-creatinine ratio (ACR) was also significantly elevated in the microalbuminuria group (12.02 ± 11.5 mg/mmol) compared to the non-microalbuminuria group (2.11 ± 0.58 mg/mmol) (p = 0.001). The mean duration of hypertension was slightly longer in subjects with microalbuminuria (7.6 ± 2.9 years) than in those without (7.4 ± 2.9 years), and this difference was statistically significant (p = 0.001).

Table 4: Correlation between MA with different parameters

Figure 1: Scatter plot showing Significant positive correlation between MA and LV Mass

Figure 2: Scatter plot showing Significant positive correlation between MA and Urinary Creatinine

Figure 3: Scatter plot showing Significant positive correlation between MA and ACR

In the present study, microalbuminuria (MA) showed a strong positive correlation with left ventricular mass (r = 0.639, p = 0.017), urinary creatinine (r = 0.339, p = 0.001), and albumin-to-creatinine ratio (ACR) (r = 0.718, p < 0.001). There was no statistically significant correlation between MA and age (r = –0.09, p = 0.374), systolic blood pressure (SBP) (r = 0.073, p = 0.470), diastolic blood pressure (DBP) (r = 0.018, p = 0.858), height (r = 0.051, p = 0.611), weight (r = –0.074, p = 0.464), or body mass index (BMI) (r = –0.135, p = 0.181). These findings indicate that higher left ventricular mass, urinary creatinine levels, and ACR are significantly associated with higher microalbuminuria values, whereas demographic and anthropometric parameters did not show any significant association.

Our study findings align with previously published data in several respects. The majority of participants were middle-aged, with the mean age being 52 ± 7 years, reaffirming the continued high prevalence of essential hypertension in this age group, despite emerging evidence of increasing hypertension among younger populations in other regions of India. Age distribution did not show a significant association with microalbuminuria (p = 0.574), consistent with reports that age alone is not a determinant of urinary albumin excretion in essential hypertension.

In contrast to some earlier studies, our results demonstrated a significant gender association, with females showing a higher prevalence of microalbuminuria (53.1%) compared to males (46.9%) (p = 0.003). This differs from previous reports that found no gender-related difference in microalbuminuria prevalence. Interestingly, smoking history showed an inverse association, with non-smokers having a higher prevalence of microalbuminuria (p = 0.021), a finding that warrants further exploration given the known endothelial effects of tobacco use.

In our cohort, microalbuminuria was present in 32% of patients. This is lower than the incidence reported by Poudyal et al. (62.5%) ^[17] and Rameez et al. (69%) ^[18], but higher than in the studies by Stalin et al. (24.3%) ^[19] and Hitha et al. (26.67%) ^[20]. Comparable prevalence was observed in the Nigerian study by Busari et al. (32.2%) ^[21], whereas Hemmati et al. in an Iranian population reported a markedly lower prevalence of 5.6% ^[22]. These variations are likely due to differences in study design, inclusion criteria (inpatients vs. outpatients), methods for microalbuminuria detection, severity and duration of hypertension, demographic differences, and the presence of comorbidities.

Analysis of vital parameters showed no significant association between microalbuminuria and systolic or diastolic blood pressure (p = 0.849 and p = 0.438, respectively), suggesting that single-point BP measurements may not reflect cumulative vascular damage as accurately as other indices. Similarly, no association was seen with anthropometric parameters, including height, weight, and BMI (p > 0.05 for all). This indicates that, within our study population, body size did not directly influence urinary albumin excretion.

Our findings confirmed that longer duration of hypertension was significantly associated with higher prevalence of microalbuminuria (p = 0.001). This is consistent with studies by Kartik et al. ^[23] (Chi-square = 27.38, p < 0.001) and Stalin et al. ^[19], both of which demonstrated higher microalbuminuria rates in long-standing hypertensives. In our study, the mean duration of hypertension was 7.6 ± 2.9 years in the microalbuminuria group versus 7.4 ± 2.9 years in those without, supporting the association between chronic hypertension and early renal involvement.

Biochemical parameters further reinforced this relationship. Patients with microalbuminuria had significantly higher mean urinary creatinine levels (p = 0.001) and markedly elevated albumin-to-creatinine ratios (p = 0.001), indicating early renal microvascular damage. Correlation analysis showed that microalbuminuria had a strong positive correlation with ACR (r = 0.718, p < 0.001) and urinary creatinine (r = 0.339, p = 0.001), suggesting that these measures may be sensitive indicators of hypertensive nephropathy progression.

A highly significant association between microalbuminuria and LVH was observed, with LVH present in 90.6% of those with microalbuminuria compared to only 7.4% in those without (p = 0.001). The correlation analysis further supported this relationship, showing a strong positive correlation between MA and LV mass (r = 0.639, p = 0.017). These findings reinforce existing literature indicating that LVH, like microalbuminuria, appears early in hypertension and that both share common pathophysiological pathways ^[24–27].

The prevalence of LVH in our study (92%) was markedly higher than that reported by Kartik et al. ^[23] and Stalin et al. ^[19], and substantially greater than the 29.33% reported by Hitha et al. in a South Indian cohort ^[20]. This higher prevalence could be attributable to differences in echocardiographic criteria, population characteristics, and the severity of hypertension in our sample.

Overall, our findings emphasize that microalbuminuria is a frequent finding in essential hypertension and correlates strongly with LVH and biochemical markers of renal function, even in the absence of overt renal disease. These results suggest that routine screening for microalbuminuria, alongside echocardiographic evaluation, could serve as an effective strategy for early detection of target organ damage in hypertensive patients.

Microalbuminuria was significantly associated with left ventricular hypertrophy, longer hypertension duration, and elevated urinary creatinine and albumin-to-creatinine ratio. Its higher prevalence in females and strong correlation with cardiac and renal parameters underscore its value as an early marker of hypertensive target organ damage, warranting routine screening in clinical practice.

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