Cardiovascular disease remains the leading cause of mortality worldwide despite substantial advances in lipid-lowering therapies. Although achieving recommended low-density lipoprotein cholesterol (LDL-C) targets significantly reduces cardiovascular risk, many patients continue to experience recurrent cardiovascular events, a phenomenon known as residual cardiovascular risk. Increasing evidence indicates that chronic low-grade inflammation is a major contributor to this persistent risk. This review analyzes current scientific evidence regarding the biological mechanisms, inflammatory biomarkers, and emerging therapeutic strategies associated with residual inflammatory risk beyond LDL cholesterol. The literature demonstrates that activation of the NLRP3 inflammasome and the interleukin-1β/interleukin-6 pathway plays a central role in endothelial dysfunction, plaque progression, and atherosclerotic instability. High-sensitivity C-reactive protein (hs-CRP) remains the most widely validated biomarker for identifying persistent inflammatory activity in clinical practice. Landmark clinical trials, including CANTOS, COLCOT, and LoDoCo2, have demonstrated that selective anti-inflammatory therapies reduce recurrent cardiovascular events independently of additional LDL-C lowering, whereas nonspecific anti-inflammatory approaches have shown limited benefit. Furthermore, obesity, type 2 diabetes mellitus, metabolic syndrome, and chronic kidney disease substantially amplify residual inflammatory risk through shared pathophysiological mechanisms. Current evidence supports a transition toward comprehensive cardiometabolic prevention integrating lipid management, lifestyle modification, metabolic optimization, and targeted anti-inflammatory therapy. Future precision medicine strategies incorporating inflammatory biomarkers and individualized risk assessment may further improve cardiovascular outcomes and reduce the global burden of atherosclerotic disease.
Santiago Alberto Avila Ak, Ana Clemente, Rafaela Denisse Zambrano Mendieta et al.· IECCMEXICO· 0 citations
Immune senescence has emerged as one of the principal biological mechanisms linking aging with the development and progression of autoimmune rheumatic diseases. Rather than representing a simple decline in immune function, aging induces profound remodeling of both innate and adaptive immunity, characterized by chronic low-grade inflammation, loss of immune tolerance, impaired cellular regeneration, mitochondrial dysfunction, telomere shortening, epigenetic alterations, and expansion of senescent immune-cell populations. The objective of this review was to analyze current evidence regarding the mechanisms through which immune senescence reshapes autoimmune rheumatic diseases and to examine its clinical implications, biomarkers, and emerging therapeutic strategies. A narrative literature review was conducted using the scientific method and included publications retrieved from PubMed/MEDLINE, Scopus, Web of Science, ScienceDirect, SpringerLink, Nature, Frontiers, and Wiley. The evidence consistently demonstrated that inflammaging, adaptive immune remodeling, and cellular senescence contribute to disease progression, increased susceptibility to infections, reduced vaccine responsiveness, cardiovascular complications, frailty, osteoporosis, sarcopenia, and diminished functional capacity. Conventional inflammatory biomarkers remain widely used; however, increasing attention has been directed toward multi-omics technologies, epigenetic clocks, mitochondrial biomarkers, proteomics, metabolomics, and immune-cell phenotyping for more accurate assessment of biological immune aging. Current therapeutic approaches continue to rely on disease-modifying antirheumatic drugs and biologic agents, while emerging interventions—including JAK inhibitors, mTOR modulation, senolytic therapies, microbiome-targeted strategies, and precision medicine—offer promising opportunities for future individualized management. Overall, immune senescence should be recognized as a fundamental component of autoimmune rheumatic diseases, providing important opportunities for improving diagnosis, risk stratification, therapeutic decision-making, and long-term clinical outcomes in aging populations.
