A New Perspective in Hypertensive Heart Disease: From Epidemiology to Molecular and Metabolic Inflammation Insights

Background: Hypertensive heart disease (HHD), a progressive condition with significant morbidity and mortality, remains poorly understood at the molecular and mechanistic level. Methods: We first analyzed the latest trends in HHD using data from the Global Burden of Disease Study 2021. Correlations between HHD and immune-inflammatory indices were explored using the continuous National Health and Nutrition Examination Survey (NHANES) datasets 2015–2018. Transcriptomic analyses of cardiac tissue from healthy individuals and patients with HHD were conducted using high-throughput sequencing, while Mendelian Randomization (MR) analysis utilized data from the expression quantitative trait loci (eQTL) database. Functional enrichment analyses were performed to identify relevant biological pathways. CIBERSORT was used to assess the subtypes of immune cell infiltration and validate the associations between target genes and the immune-inflammatory response. Finally, we validated the results obtained from the Gene Expression Omnibus (GEO) for the target genes. Results: Our analyses revealed a continued increase in the global age-standardized prevalence and death rates of HHD, underscoring the urgent need for effective public health interventions. Using data from the NHANES, we observed significant differences in differential leukocyte percentages and several novel composite inflammatory indices used to assess systemic inflammation between hypertensive and normotensive individuals. A total of 1,299 differentially expressed genes (DEGs) were identified in HHD. MR analysis highlighted six co-expression key genes, which were mainly implicated in the following biological processes, including macrophage activation and various metabolic pathways. CIBERSORT analysis further revealed distinct immune cell infiltration patterns across HHD, emphasizing the pivotal role of immune processes in disease progression. More importantly, we also confirmed the strong correlation in mice and patients with HHD using the GEO database. Conclusion: This study provided novel insights into the molecular and immune-inflammatory mechanisms underlying HHD. These findings established a foundation for future research and clinical applications aimed at improving long-term clinical outcomes in HHD patients.