Epidemiology and pathogenesis of diffuse obstructive coronary artery disease: the role of arterial stiffness, shear stress, monocyte subsets and circulating microparticles

Despite falling age-adjusted mortality rates coronary artery disease (CAD) remains the leading cause of death worldwide. Advanced diffuse CAD is becoming an important entity of modern cardiology as more patients with historical revascularisation no longer have suitable anatomy for additional procedures. Advances in the treatment of diffuse obstructive CAD are hampered by a poor understanding of its development. Although the likelihood of developing clinically significant (obstructive) CAD is linked to traditional risk factors, the morphology of obstructive CAD among individuals is highly variable - some patients have diffuse stenotic disease, while others have a focal stenosis. This is challenging to explain in mechanistic terms as vascular endothelium is equally exposed to injury stimulants. Patients with diffuse disease are at high risk of adverse outcomes, particularly if unsuitable for revascularisation. We searched multiple electronic databases (MEDLINE, EMBASE and the Cochrane Database) and reviewed the epidemiology, pathogenesis and prognosis relating to advanced diffuse CAD with particular focus on the role of endothelial shear stress, large artery stiffness, monocyte subsets and circulating microparticles.Key messagesAlthough traditional CAD risk factors correlate strongly with disease severity, significant individual variation in disease morphology exists.Advanced, diffuse CAD is difficult to treat effectively and can significantly impair quality of life and increases mortality.The pathophysiology associated with the progression of CAD is the result of complex maladaptive interaction between the endothelium, cells of the immune system and patterns of blood flow.