Degenerative Aortic Valve Disease (DAVD) is one of the most common valvular heart conditions, particularly prevalent among elderly individuals, and is characterized by progressive calcification and thickening of the aortic valve leaflets (1). Traditionally considered a passive, age-related process, recent evidence has established inflammation as a central player in its pathogenesis, akin to atherosclerosis (2,3). The initial stages of valve degeneration involve lipid infiltration, inflammatory cell recruitment, and cytokine release, which promote fibrosis and calcific remodeling of the valve tissue (4).

Biomarkers such as high-sensitivity C-reactive protein (hs-CRP), Interleukin-6 (IL-6), and Tumor Necrosis Factor-alpha (TNF-α) have been identified as key indicators of systemic inflammation and may reflect early pathological changes in the aortic valve before significant hemodynamic impairment occurs (5–7). Elevated levels of these markers have been associated with increased cardiovascular risk and structural heart disease (8). Despite advances in imaging modalities, the identification of accessible, cost-effective blood-based markers could enhance early detection and monitoring of DAVD progression.

This study aims to assess the serum levels of hs-CRP, IL-6, and TNF-α in patients with early-stage DAVD and compare them with healthy individuals to evaluate their potential as non-invasive tools for early diagnosis.

Study Design and Setting

A cross-sectional observational study was conducted over a period of six months at a tertiary care cardiology center. The study protocol was approved by the Institutional Ethics Committee, and informed consent was obtained from all participants.

Study Population

A total of 60 individuals aged between 50 and 75 years were enrolled and divided into two groups. Group A included 30 patients with early-stage Degenerative Aortic Valve Disease diagnosed based on echocardiographic criteria, including aortic valve thickening and mild calcification without significant stenosis. Group B comprised 30 age- and gender-matched healthy individuals with no known cardiac or inflammatory diseases, serving as the control group.

Inclusion and Exclusion Criteria

Inclusion criteria for Group A were patients with echocardiographically confirmed early DAVD, while individuals with a history of rheumatic heart disease, autoimmune disorders, chronic kidney disease, or acute infections were excluded. Similar exclusion criteria were applied to the control group to ensure valid comparisons.

Sample Collection and Biomarker Analysis

Venous blood samples (5 mL) were collected from all participants under sterile conditions. The blood was centrifuged at 3000 rpm for 10 minutes to separate serum, which was stored at -80°C until analysis. Serum concentrations of high-sensitivity C-reactive protein (hs-CRP), Interleukin-6 (IL-6), and Tumor Necrosis Factor-alpha (TNF-α) were measured using commercially available enzyme-linked immunosorbent assay (ELISA) kits, following the manufacturer’s instructions.

Echocardiographic Assessment

All participants underwent transthoracic echocardiography performed by an experienced cardiologist. Parameters such as aortic valve thickness, mobility, and degree of calcification were evaluated to confirm the diagnosis and stage of valve degeneration.

Statistical Analysis

Data were entered into Microsoft Excel and analyzed using SPSS version 25.0 (IBM Corp., Armonk, NY). Continuous variables were expressed as mean ± standard deviation (SD). Intergroup comparisons were performed using independent sample t-tests. A p-value of less than 0.05 was considered statistically significant.

A total of 60 participants were enrolled, with 30 individuals in each group. The mean age of participants in Group A (DAVD patients) was 64.3 ± 5.8 years, while in Group B (controls), it was 63.7 ± 6.2 years (p = 0.68). Both groups were comparable in terms of gender distribution (p = 0.74), as shown in Table 1.

Table 1. Demographic characteristics of study participants

The mean hs-CRP level in Group A was significantly higher at 4.18 ± 0.76 mg/L compared to 1.27 ± 0.54 mg/L in Group B (p < 0.001). Similarly, IL-6 and TNF-α levels were elevated in the DAVD group (IL-6: 12.4 ± 2.3 pg/mL; TNF-α: 18.9 ± 3.6 pg/mL) in contrast to the control group (IL-6: 5.1 ± 1.6 pg/mL; TNF-α: 9.1 ± 2.1 pg/mL), with both differences being statistically significant (p < 0.001). These findings are summarized in Table 2.

Table 2. Comparison of inflammatory biomarker levels between study groups

A positive correlation was observed between hs-CRP levels and aortic valve thickness measured on echocardiography (r = 0.68, p < 0.01). IL-6 and TNF-α also showed significant correlations with valve echogenicity scores (r = 0.61 and r = 0.65, respectively). These correlations are presented in Table 3.

Table 3. Correlation between inflammatory markers and echocardiographic parameters

These findings support the hypothesis that systemic inflammation is closely linked with early structural changes in the aortic valve.

This study evaluated the role of inflammatory biomarkers—hs-CRP, IL-6, and TNF-α—in the early detection of Degenerative Aortic Valve Disease (DAVD). Our findings demonstrated significantly elevated levels of these markers in patients with early-stage DAVD compared to healthy controls. These results support the hypothesis that inflammatory processes play a key role in the pathogenesis of aortic valve degeneration, even before significant hemodynamic compromise occurs.

Several earlier studies have described DAVD not as a passive consequence of aging but as an active cellular process involving lipid accumulation, oxidative stress, and chronic inflammation (1,2). Inflammation initiates endothelial dysfunction, recruitment of mononuclear cells, and upregulation of osteogenic pathways within the valve tissue (3,4). Elevated hs-CRP levels, as observed in our study, have previously been associated with cardiovascular events and valvular calcification (5,6). High hs-CRP levels may reflect both systemic and local inflammatory activity within the aortic valve (7).

IL-6 and TNF-α are pro-inflammatory cytokines implicated in various cardiovascular pathologies, including atherosclerosis and heart failure (8,9). Their elevated levels in DAVD patients, as demonstrated in our study, suggest a potential mechanistic link to valvular remodeling. IL-6 promotes the expression of adhesion molecules and matrix metalloproteinases, facilitating tissue degeneration and calcification (10). TNF-α has been shown to induce apoptotic changes in valvular interstitial cells and stimulate osteoblastic differentiation, accelerating calcific deposition (11,12).

The significant correlations observed between these biomarkers and echocardiographic markers of valve degeneration highlight their potential clinical utility. As non-invasive serum markers, they could aid in identifying at-risk individuals before irreversible structural changes occur, potentially allowing for earlier therapeutic interventions (13).

However, some studies argue that the elevation of inflammatory biomarkers may reflect systemic vascular inflammation rather than localized valvular pathology (14). Therefore, while these markers are promising, their specificity for DAVD remains to be fully established. Future longitudinal studies are warranted to assess their predictive value in disease progression and to differentiate DAVD-related inflammation from other cardiovascular conditions (15).

Our study is limited by its cross-sectional design and relatively small sample size. Additionally, histopathological correlation was not performed, which could have further validated the biomarker findings. Nevertheless, the consistency of our results with existing literature supports the growing recognition of inflammation as a therapeutic and diagnostic target in DAVD.

The study highlights that elevated levels of hs-CRP, IL-6, and TNF-α are significantly associated with early-stage Degenerative Aortic Valve Disease. These inflammatory markers may serve as useful non-invasive tools for early detection and monitoring of disease progression, enabling timely clinical interventions.

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