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The consequences of atherosclerotic vascular disease are the leading cause of morbidity and mortality in the developed countries of the world and are rapidly approaching that status in the developing world. This chapter reviews the pathologic mechanisms of atherosclerotic disease development and progression and details the interaction of these processes with the coagulation system. The earliest morphologically visible lesion of arterial atherosclerosis, the fatty streak, already is an advanced metabolic and immunologic locus that manifests as abnormalities of vascular tone, inflammation, cellular growth, and endothelial cell dysfunction. After years to decades, the lesions advance to form plaques that grow and eventually either impinge on the arterial lumen or rupture. Rupture of a vulnerable plaque is a catastrophic event that, through activation of both platelets and the coagulation cascade, triggers thrombosis, which leads to complete occlusion, and unless collateral circulation has already been established, results in tissue ischemia. Based on an increased understanding of the pathogenesis and consequences of atheromatous plaque development and progression, medical management of atherothrombotic syndromes has improved and is reviewed for the coronary, cerebrovascular, and peripheral arteries.

Acronyms and Abbreviations:

ACC, American College of Cardiology; ACCF, American College of Cardiology Foundation; ACCP, American College of Chest Physicians; ACS, acute coronary syndrome; AHA, American Heart Association; apo, apolipoprotein; aPTT, activated partial thromboplastin time; CABG, coronary artery bypass graft; CAD, coronary artery disease; CAPRIE, Clopidogrel Versus Aspirin in Patients at Risk of Ischaemic Events; CCL, CC chemokine ligand; CK, creatine kinase; CVD, cardiovascular disease; DAPT, dual antiplatelet therapy; ECG, electrocardiogram; eNOS, endothelial nitric oxide synthase; EPC, endothelial progenitor cell; EV, extracellular vesicle; GP, glycoprotein; HAART, highly active antiretroviral therapy; HDL, high-density lipoprotein; hsCRP, high-sensitivity C-reactive protein; IFN, interferon; Ig, immunoglobulin; IL, interleukin; LDL, low-density lipoprotein; Lp-PLA2, lipoprotein phospholipase A2; MCP, monocyte chemoattractant protein; MHC, major histocompatibility complex; MI, myocardial infarction; NO, nitric oxide; NOX, nicotinamide adenine dinucleotide phosphate oxidase; NSTEMI, non–ST-segment elevation myocardial infarction; PAD, peripheral arterial disease; PAI, plasminogen-activator inhibitor; PCI, percutaneous coronary intervention; RBC, red blood cell; SLE, systemic lupus erythematosus; SNP, single nucleotide polymorphisms; STEMI, ST-segment elevation myocardial infarction; TF, tissue factor; TFPI, tissue factor pathway inhibitor; TGF, transforming growth factor; Th, T helper; t-PA, tissue-type plasminogen activator; VCAM, vascular cell adhesion molecule; VLDL, very-low-density lipoprotein; VWF, von Willebrand factor.


Atherothrombosis describes a disease process that begins with atherosclerosis and predisposes to thrombosis in the artery. In the 1850s, Virchow1 described atherosclerosis as an inflammatory and prothrombotic process. Rokitansky, and later Duguid, posited that atherosclerotic lesions are initiated by incorporation of platelet lipids into the vessel wall (“encrustation”) following thrombosis. It was subsequently demonstrated that insudation of plasma lipoproteins is responsible for most of the lipid content of the atherosclerotic lesions. In 1913, Anitschkow noted atherosclerosis developing in rabbits fed a relatively high cholesterol diet. Although the involvement of inflammation in atherosclerosis has been known for more than 100 ...

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