A Multidisciplinary Evaluation of Endothelial Dysfunction, Gut Dysbiosis, Inflammatory Biomarkers, and Their Association with Essential Hypertension: A Case–Control Study

Background: Essential hypertension remains one of the most prevalent non-communicable diseases worldwide and is a major contributor to cardiovascular morbidity and premature mortality. While sustained elevation of arterial blood pressure has traditionally been attributed to neurohormonal activation, renal sodium handling, and vascular remodeling, accumulating evidence suggests that endothelial dysfunction, chronic low-grade systemic inflammation, and alterations in gut microbial ecology collectively contribute to disease initiation and progression. The interaction between vascular endothelial integrity, immune activation, and the gut microbiome has emerged as an important mechanistic pathway linking environmental and metabolic risk factors with persistent hypertension. However, multidisciplinary evaluation integrating these biological domains within a single clinical population remains limited, particularly in hospital-based settings. Objectives: The present analytical case–control study was undertaken to comprehensively evaluate endothelial dysfunction, gut dysbiosis, and inflammatory biomarkers among patients with essential hypertension and to determine their independent and combined associations with disease severity. Methods: A hospital-based analytical case–control study was conducted over an 18-month period in a tertiary care teaching hospital. A total of 320 participants were enrolled, comprising 160 clinically diagnosed patients with essential hypertension (cases) and 160 age- and sex-matched normotensive healthy individuals (controls). All participants underwent detailed clinical examination, anthropometric assessment, blood pressure profiling, biochemical investigations, endothelial function analysis, inflammatory biomarker estimation, and gut microbiome evaluation. Endothelial function was assessed by serum nitric oxide (NO), endothelin-1 (ET-1), vascular cell adhesion molecule-1 (VCAM-1), intracellular adhesion molecule-1 (ICAM-1), and brachial artery flow-mediated dilatation (FMD). Inflammatory status was evaluated using high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and monocyte chemoattractant protein-1 (MCP-1). Gut microbial alterations were assessed through quantitative polymerase chain reaction (qPCR)-based estimation of dominant bacterial taxa, Firmicutes/Bacteroidetes ratio, relative abundance of Lactobacillus spp. and Bifidobacterium spp., serum lipopolysaccharide (LPS), and fecal calprotectin. Multivariate logistic regression, Pearson's correlation analysis, receiver operating characteristic (ROC) curve analysis, and multiple linear regression models were employed for statistical evaluation. Results: Compared with healthy controls, hypertensive patients demonstrated significantly reduced endothelial function, evidenced by lower serum nitric oxide levels and impaired flow-mediated dilatation, accompanied by significantly elevated endothelin-1, VCAM-1, and ICAM-1 concentrations (p < 0.001). Inflammatory biomarkers including hs-CRP, IL-6, TNF-α, and MCP-1 were markedly increased among hypertensive individuals, indicating persistent systemic inflammatory activation. Gut microbiome analysis revealed significant dysbiosis characterized by: • Reduced abundance of beneficial Lactobacillus and Bifidobacterium species • Increased Firmicutes/Bacteroidetes ratio • Elevated serum lipopolysaccharide concentrations • Higher fecal calprotectin levels Serum lipopolysaccharide demonstrated strong positive correlations with hs-CRP, IL-6, endothelin-1, and systolic blood pressure while showing an inverse relationship with nitric oxide bioavailability and flowmediated dilatation. Multivariate regression identified endothelial dysfunction markers, serum lipopolysaccharide, IL-6, and reduced nitric oxide levels as independent predictors of essential hypertension after adjustment for age, sex, body mass index, diabetes, smoking, and dyslipidemia. Receiver operating characteristic analysis demonstrated that combined assessment of nitric oxide, endothelin-1, IL-6, and serum lipopolysaccharide significantly improved discrimination between hypertensive and normotensive individuals compared with individual biomarkers alone. Conclusion: The study showed that endothelial dysfunction, gut microbial dysbiosis, and chronic systemic inflammation coexist in patients with essential hypertension and exhibit strong interdependent associations. These findings support the concept of a gut–vascular–immune axis contributing to hypertension pathogenesis and suggest that integrated biomarker profiling may facilitate improved risk stratification and early identification of vascular dysfunction. Therapeutic strategies targeting restoration of endothelial homeostasis and modulation of gut microbial composition may represent promising adjunctive approaches for the prevention and management of essential hypertension.