Residual Traditional Risk in Non-Traditional Atherosclerotic Diseases

Individuals with chronic inflammatory and immune disorders are at an increased risk of atherosclerotic events and premature cardiovascular (CV) disease. Despite extensive literature exploring the relationship between "non-traditional" atherosclerotic conditions and CV risk, many aspects remain unresolved, including the underlying mechanisms promoting the "non-traditional CV risk", the development of an innovative and comprehensive CV risk assessment tool, and recommendations for tailored interventions. This review aims to evaluate the available evidence on key "non-traditional" CV risk-enhancer conditions, with a focus on assessing and managing CV risk factors. We conducted a comprehensive review of 412 original articles, narrative and systematic reviews, and meta-analyses addressing the CV risk associated with "non-traditional" atherosclerotic conditions. The analysis examined the underlying mechanisms of these relationships and identified strategies for assessing and mitigating elevated risk. A major challenge highlighted is the difficulty in quantifying the contribution of individual risk factors and disease-specific elements to CV risk. While evidence supports the cardiovascular benefits of statins beyond lipid lowering, such as pleiotropic and endothelial effects, current guidelines lack specific recommendations for the use of statins or other therapies targeting non-traditional CV risk factors. Additionally, the absence of validated cardiovascular risk scores that incorporate non-traditional risk factors hinders accurate CV risk evaluation and management. The growing prevalence of "non-traditional CV risk-enhancer conditions" underscores the need for improved awareness of CV risk assessment and management. A thorough understanding of all contributing factors, including disease-specific elements, is crucial for accurate prediction of cardiovascular disease (CVD) risk. This represents an essential foundation for informed decision-making in primary and secondary prevention. We advocate for future research to focus on developing innovative, disease-specific CV risk assessment tools that incorporate non-traditional risk factors, recognizing this as a promising avenue for translational and clinical outcome research.