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

Abstract

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 messages Although 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.

NCF2, MYO1F, S1PR4, and FCN1 as potential noninvasive diagnostic biomarkers in patients with obstructive coronary artery: A weighted gene co‐expression network analysis

“…*P < .05; **P < .01; ***P < .005 (Student t test). WGCNA, weighted gene co-expression network analysis activation, and cytokine secretion, indicative of leukocyte stimulation and migration in patients of obstructive CAD.KEGG and GO pathway analyses of the genes in the blue module showed similar findings as those by the total significant genes, which indicated that genes in the blue module played critical roles in the development of obstructive CAD by involving enhanced leukocyte activation and migration (Figure 4B) 21. Enrichment analysis of different modules identified by WGCNA in…”

“…Totally, these results suggested that these genes could play pivotal roles in the pathogenesis of obstructive CAD. 21…”

Outcomes of Surgical Patch Angioplasty of the Coronary Artery for Diffuse Coronary Artery Disease

“…Diffuse coronary artery disease (CAD) is generally considered in the presence of a narrowing ≥70%) of a coronary artery ≥20 mm or in the presence of multiple stenoses encompassing the whole length of the coronary artery [ 1 , 2 ] . Nevertheless, diffuse CAD can lead to severe myocardial ischemia and thereby angina, myocardial infarction (MI), and even heart failure, especially when the left anterior descending artery (LAD) is extensively involved [ 1 , 3 - 5 ] . The prognosis of diffuse CAD after stenting or coronary artery bypass grafting (CABG) is unknown.…”

Impact of Mon2 monocyte‐platelet aggregates on human coronary artery disease

“…1 Increased monocyte-platelet aggregates (MPAs) are early markers of cardiovascular disease and are associated with coronary endothelial dysfunction in patients with CAD. The atherosclerotic process itself is highly variable such that, on an individual level, the severity and morphology of coronary artery disease (CAD) do not always reflect the presence of traditional risk factors.…”

“…The atherosclerotic process itself is highly variable such that, on an individual level, the severity and morphology of coronary artery disease (CAD) do not always reflect the presence of traditional risk factors. 1 Increased monocyte-platelet aggregates (MPAs) are early markers of cardiovascular disease and are associated with coronary endothelial dysfunction in patients with CAD. 2 Monocyte subsets are heterogeneous and include 3 biologically distinct subsets, known in the contemporary literature as Mon1 (monocyte subset 1), Mon2 (monocyte subset 2) and Mon3 (monocyte subset 3).…”