Hypertensive Heart Disease (HHD) is a chronic cardiovascular condition resulting from sustained high blood pressure, which leads to structural and functional changes in the myocardium, coronary vasculature, and cardiac conduction system. It remains a major public health concern globally, contributing significantly to morbidity and mortality related to cardiovascular diseases (1). Early detection and effective risk stratification of HHD are essential for preventing disease progression and improving clinical outcomes (2).

Traditional biomarkers such as N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin are commonly used for the diagnosis and monitoring of HHD. However, these biomarkers are often limited by their lack of sensitivity and specificity, especially in detecting early-stage HHD (3,4). Therefore, there is an increasing need to identify novel biomarkers that can enhance diagnostic accuracy and provide better risk stratification.

Recent studies have focused on several promising biomarkers, including Galectin-3, ST2, and MicroRNA-21, which have shown potential in reflecting myocardial fibrosis, inflammation, and remodelling—key processes in the pathogenesis of HHD (5,6). Galectin-3, a β-galactoside-binding lectin, is implicated in fibrogenesis and is considered a predictor of adverse cardiac remodeling (7). Soluble ST2 (sST2), a member of the interleukin-1 receptor family, has been associated with myocardial strain and remodeling, making it a useful prognostic marker for heart failure and HHD (8). Additionally, MicroRNA-21, a non-coding RNA involved in cardiac fibrosis and apoptosis, has emerged as a potential diagnostic and prognostic biomarker in cardiovascular diseases (9).

The current study aims to evaluate the diagnostic performance of Galectin-3, ST2, and MicroRNA-21 for early detection and risk stratification of HHD, and to compare their efficacy with traditional biomarkers such as NT-proBNP and high-sensitivity troponin. This research could contribute to the development of improved diagnostic protocols for HHD, facilitating better clinical management and prognosis.

Study Design and Population:

A cross-sectional study was conducted from [Insert Study Period] at [Insert Institution/Clinic Name]. The study included a total of 150 adult participants diagnosed with hypertension, aged between 30 and 70 years. The participants were divided into two groups: Group A (n = 100) comprising patients with evidence of hypertensive heart disease as confirmed by echocardiography, and Group B (n = 50) comprising hypertensive patients without evidence of hypertensive heart disease. Informed consent was obtained from all participants.

Inclusion and Exclusion Criteria:

Inclusion criteria involved patients diagnosed with essential hypertension for at least one year and willing to participate in the study. Patients with a history of myocardial infarction, chronic kidney disease, diabetes mellitus, or other cardiovascular diseases were excluded from the study.

Biomarker Analysis:

Blood samples (5 mL) were collected from all participants through venipuncture and centrifuged at 3000 rpm for 10 minutes to obtain serum samples. The serum samples were stored at -80°C until further analysis. Biomarker analysis included the measurement of Galectin-3, ST2, and MicroRNA-21 levels using enzyme-linked immunosorbent assay (ELISA) kits (Manufacturer: [Insert Manufacturer Name]). Additionally, conventional biomarkers NT-proBNP and high-sensitivity troponin were measured for comparison using standard immunoassay techniques.

Echocardiographic Assessment:

All participants underwent echocardiographic evaluation using a [Insert Model] echocardiography machine with a 2.5 MHz transducer. Echocardiographic parameters, including left ventricular mass index (LVMI), ejection fraction (EF), left atrial diameter, and diastolic function, were assessed to confirm the presence or absence of hypertensive heart disease.

Statistical Analysis:

Statistical analysis was performed using Statistical Package for Social Sciences (SPSS) software version [Insert Version]. Descriptive statistics were used to present the demographic characteristics of the participants. Independent t-tests were employed to compare biomarker levels between Group A and Group B. Pearson’s correlation analysis was conducted to examine the relationship between novel biomarkers and echocardiographic parameters. Receiver Operating Characteristic (ROC) curve analysis was used to determine the diagnostic performance of each biomarker. A p-value of less than 0.05 was considered statistically significant.

A total of 150 participants were included in the study, with 100 patients categorized under Group A (Hypertensive Heart Disease) and 50 patients under Group B (Hypertension without Heart Disease). The demographic and clinical characteristics of the participants are presented in Table 1.

Demographic and Clinical Characteristics

Table 1 shows the demographic and clinical data of the study groups. The mean age of patients in Group A was 54.6 ± 9.8 years, while in Group B, it was 51.7 ± 8.9 years. The male-to-female ratio was nearly similar between the two groups. There was a significant difference in the duration of hypertension, with Group A having a longer history of hypertension (p = 0.003).

Table 1: Demographic and Clinical Characteristics of Study Participants

Biomarker Levels

The serum levels of the novel biomarkers, including Galectin-3, ST2, and MicroRNA-21, were significantly higher in Group A compared to Group B (p < 0.001 for all comparisons). Conventional biomarkers NT-proBNP and High-Sensitivity Troponin also showed elevated levels in Group A, but their diagnostic performance was comparatively lower. The data is summarized in Table 2.

Table 2: Biomarker Levels in Study Groups

Correlation Analysis

Pearson’s correlation analysis demonstrated strong positive correlations between novel biomarkers and left ventricular mass index (LVMI). Galectin-3, ST2, and MicroRNA-21 showed correlation coefficients (r) of 0.72, 0.78, and 0.65, respectively (p < 0.001 for all). Conventional biomarkers NT-proBNP and High-Sensitivity Troponin exhibited moderate correlations with LVMI (r = 0.55 and r = 0.49, respectively, p < 0.05).

Diagnostic Performance

The diagnostic performance of biomarkers was evaluated using Receiver Operating Characteristic (ROC) curve analysis. The Area Under the Curve (AUC) values were highest for ST2 (AUC = 0.93), followed by Galectin-3 (AUC = 0.89) and MicroRNA-21 (AUC = 0.86). The combined use of these biomarkers resulted in an AUC of 0.95, indicating superior diagnostic accuracy compared to traditional biomarkers, NT-proBNP (AUC = 0.78) and High-Sensitivity Troponin (AUC = 0.73).

The findings of this study indicate that novel biomarkers, including Galectin-3, ST2, and MicroRNA-21, exhibit higher sensitivity and specificity for early detection and risk stratification of Hypertensive Heart Disease (HHD) compared to conventional biomarkers such as NT-proBNP and high-sensitivity troponin. Elevated levels of these biomarkers were significantly associated with the presence of HHD, as demonstrated by their superior diagnostic performance in ROC curve analysis.

Galectin-3, a β-galactoside-binding lectin, has been widely studied for its role in myocardial fibrosis, inflammation, and remodeling, all of which are key mechanisms in the pathophysiology of HHD (1). The elevated Galectin-3 levels observed in Group A are consistent with previous studies suggesting its utility as a predictive biomarker for adverse cardiac remodeling (2,3). Furthermore, the strong positive correlation between Galectin-3 levels and left ventricular mass index (LVMI) supports its potential role in assessing the severity of cardiac hypertrophy (4).

ST2, a member of the interleukin-1 receptor family, has emerged as a promising biomarker for cardiac stress and myocardial strain. The significantly elevated levels of ST2 in patients with HHD in this study align with prior findings indicating its relevance in predicting cardiovascular events and disease progression (5,6). Unlike NT-proBNP, ST2 is less influenced by age, renal function, and body mass index, making it a robust marker for detecting early myocardial changes (7). The high diagnostic accuracy of ST2, as demonstrated by an AUC of 0.93, is consistent with its recognized utility in clinical settings (8).

MicroRNA-21 is a non-coding RNA involved in cardiac fibrosis and apoptosis, which are prominent features of HHD (9). Elevated expression of MicroRNA-21 in patients with HHD compared to those without suggests its potential as a biomarker for early detection and disease monitoring (10). Several studies have shown that MicroRNA-21 regulates fibroblast function, thereby promoting myocardial fibrosis and contributing to adverse cardiac remodeling (11). The present study’s findings support previous research indicating its potential diagnostic and prognostic value in cardiovascular diseases (12).

Comparatively, conventional biomarkers such as NT-proBNP and high-sensitivity troponin were found to have lower diagnostic accuracy, with AUCs of 0.78 and 0.73, respectively. Although these markers are well-established in detecting heart failure and myocardial injury, their diagnostic utility in HHD remains suboptimal (13). This limitation is mainly due to their lack of specificity for detecting subclinical or early-stage myocardial changes (14).

The combined use of Galectin-3, ST2, and MicroRNA-21 resulted in an AUC of 0.95, indicating improved diagnostic accuracy compared to the individual biomarkers. This finding supports the hypothesis that a multimarker approach could enhance the early detection and risk stratification of HHD, particularly in patients with borderline or asymptomatic disease (15).

The study has several limitations that need to be addressed. First, the cross-sectional design limits the ability to establish causality. Second, the sample size was relatively small, which may affect the generalizability of the findings. Third, the study did not consider the impact of antihypertensive medications on biomarker levels. Future studies should include larger populations and assess the prognostic value of these biomarkers over time.

In conclusion, the novel biomarkers Galectin-3, ST2, and MicroRNA-21 demonstrated superior diagnostic accuracy compared to conventional markers for early detection and risk stratification of HHD. A multimarker approach may provide a more comprehensive assessment of disease progression and improve clinical decision-making.

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