Inflammaging in Cardiovascular Disease: Emerging Mechanisms and Therapeutic Perspectives

Background: The majority of deaths from cardiovascular diseases occur within older adult populations; cardiovascular disease is also the major source of morbidity for all ages. Inflammation with an age-related increase in chronic low-grade inflammation called inflammaging(definition) is a hallmark of aging. This includes continuous activation of inflammatory signaling, increased production of reactive oxygen species (oxidative stress), dysfunction in mitochondria, and dysregulation of the immune system. Together these contribute to significant amounts of dysfunction at the level of the endothelium, vascular remodeling, myocardial fibrosis, and worsening cardiovascular conditions including but limited to atherosclerosis, coronary artery disease, heart failure and atrial fibrillation. The elevation of systemic levels of inflammatory cytokine mediators such as IL-6, TNF-alpha, and CRP has been associated with increased cardiovascular risk and poor clinical outcome. As well there are now increasing data which suggest that blocking inflammatory pathways may be a viable new therapeutic target for cardiovascular disease Aim:To present the current body of evidence demonstrating that the underlying process of inflammaging has significant effects upon both the initiation and progression of all forms of cardiovascular disease by identifying molecular and cellular mechanisms of inflammation, cardiovascular manifestations, biomarkers for inflammation and new and emerging therapeutic options addressing chronic inflammation as it relates to aging. Methods:A qualitative, narrative systematic review of research articles from 2010-2025 were identified through searches of PubMed, Scopus and Google Scholar. Articles included in this systematic review examined inflammaging-related molecular mechanisms (e.g. pro-inflammatory cytokines), cardiovascular aging (e.g. changes in blood vessels), inflammatory biomarkers (e.g. C-reactive protein) and anti-inflammatory therapeutic strategies in cardiovascular diseases. All relevant review articles, clinical trials and observational studies were evaluated. Results:The association of inflammaging with increased oxidative stress, endothelial dysfunction, vascular inflammation and a multitude of other cardiovascular disorders was clearly established. Activation of pathways involved in atherosclerosis (i.e. NLRP3 inflammasome), myocardial remodeling, arrhythmias and decreased vascular compliance (stiffness) were also found to be mediated by elevated levels of inflammatory cytokines. The utility of several inflammatory biomarkers (including CRP and IL-6) was also supported as predictive of future cardiovascular events. Lifestyle interventions, statins, colchicine and some novel targeted anti-inflammatory therapeutics have shown promise in decreasing inflammatory responses within the cardiovascular system. Despite these results, considerable variability exists due to differences in inflammatory pathway activation among individuals; lack of specificity for most biomarkers; and a general paucity of long-term clinical outcome data assessing efficacy. Conclusions:While inflammaging is an essential link connecting the processes of aging and cardiovascular disease, the findings presented here indicate that chronic low-grade inflammation plays a substantial role in the progression of many types of cardiovascular disease. Therefore, anti-inflammatory-based strategies or those employing a "precision" approach could represent viable methods for preventing or treating cardiovascular disease. Further prospective studies will be needed to identify the most effective therapeutic targets for implementing the use of inflammation-focused treatments in clinical practice.