Targeting Systemic Immune Dysregulation in Cardiovascular Disease: From Mechanisms to Precision Therapeutic Strategies

Cardiovascular diseases remain a leading cause of morbidity and mortality despite advances in conventional pharmacological therapy. Persistent inflammation and immune dysregulation contribute to residual cardiovascular risk, disease heterogeneity, and variable therapeutic responses. Increasing evidence links cardiovascular injury to systemic immune and immunometabolic disturbances arising from the kidney, liver, brain, hematopoietic and lymphoid organs, gut, and adipose tissue. This review summarizes how systemic immune disturbances contribute to cardiovascular remodeling through altered immune-cell activation, impaired inflammatory resolution, metabolic stress, and pathological immune memory. We discuss the contributions of kidney-, liver-, neuroimmune-, gut-adipose-, and hematopoietic-associated abnormalities to major cardiovascular phenotypes, including heart failure with preserved ejection fraction, atherosclerotic cardiovascular disease, cardiorenal syndrome, metabolic cardiomyopathy, and aging-associated cardiovascular disease. These systemic abnormalities converge on common cardiovascular effector mechanisms, including endothelial dysfunction, inflammatory-cell recruitment, macrophage activation, fibroblast remodeling, extracellular matrix deposition, and cardiomyocyte dysfunction. We further examine emerging pharmacological strategies targeting systemic immune dysregulation, including cytokine inhibition, inflammasome modulation, metabolic interventions, and therapies targeting maladaptive immune memory. Although several approaches have demonstrated clinical benefit, effective translation requires identification of biologically defined patient subgroups, reliable biomarkers, and appropriate assessment of therapeutic response and safety. Integrating immune profiling with cardiovascular pharmacotherapy may facilitate a transition from nonspecific anti-inflammatory approaches toward precision modulation of pathological immune networks.