Bidirectional Crosstalk Between Vulnerable Coronary Plaque and Coronary Microvascular Dysfunction: A Narrative Review.

Coronary microvascular dysfunction (CMD) is a major contributor to myocardial ischaemia and angina, both in the presence and absence of obstructive coronary artery disease, yet it remains underdiagnosed and therapeutically challenging. The mechanistic links between CMD, myocardial ischaemia, and major adverse cardiovascular events (MACE) are incompletely understood. Emerging mechanistic, imaging, and clinical evidence suggests that CMD and vulnerable plaque (VP) could be connected through shared inflammatory, metabolic, and haemodynamic pathways. This review synthesises data across these domains to propose a bidirectional plaque-microcirculatory crosstalk framework, whereby each process may amplify the other. Evidence indicates that plaque-derived inflammatory mediators and haemodynamic disturbances can impair microvascular function, while CMD-related flow abnormalities may, in turn, accelerate plaque inflammation, progression, and destabilisation. Furthermore, distinct CMD endotypes (e.g., structural or functional) have different underlying pathophysiology and present with different phenotypes. Identifying mediators of coronary-microvascular crosstalk presents an opportunity to refine cardiovascular risk stratification and uncover novel therapeutic targets. Current anti-inflammatory therapies have shown variable effects, and CMD-directed vasomodulatory interventions have produced mixed results, partly due to limited endotype stratification. Emerging approaches, including coronary sinus reducer therapy and precision anti-inflammatory strategies, may offer dual benefits by improving CMD and stabilising vulnerable plaques. This review examines the bidirectional crosstalk hypothesis, aiming to provide an integrative framework linking epicardial atherosclerosis and microvascular pathology and may guide future phenotype-specific mechanistic and interventional studies aimed at reducing residual cardiovascular risk.