Coronary atherosclerosis is increasingly recognized as a chronic, maladaptive inflammatory disease initiated by arterial retention of apolipoprotein B (apoB)–containing lipoproteins and amplified by innate and adaptive immune responses. Although low-density lipoprotein cholesterol (LDL-C) remains a central causal factor, substantial residual risk persists despite intensive LDL-C lowering, emphasizing the clinical relevance of residual inflammatory risk and additional atherogenic lipid metrics such as apolipoprotein B (apoB), remnant cholesterol, small dense LDL, and lipoprotein(a) Lp(a). Landmark outcome trials validate both paradigms: potent lipid-lowering therapies reduce major adverse cardiovascular events, and targeted anti-inflammatory therapies such as IL-1β inhibition and low-dose colchicine reduce recurrent events without altering LDL-C, establishing inflammation as a modifiable driver of coronary risk. This review integrates mechanistic evidence linking lipids and inflammation across the atherosclerotic continuum—from endothelial activation and leukocyte recruitment to plaque destabilization and thrombosis—while critically appraising biomarkers, imaging approaches, and therapeutic strategies. We propose a practical dual-axis framework integrating residual cholesterol and inflammatory risks to guide combined therapy and highlight future directions including genetics-informed lipid management notably Lp(a), inflammation-resolution biology, and precision targeting of upstream inflammatory pathways such as IL-6 signaling.
Zhang et al. (2026) studied this question.