Coronary artery disease pathophysiology

Zambon A, Hokanson JE, Brown BG, Brunzell JD. Evidence for a new pathophysiological mechanism for coronary artery disease regression hepatic lipase-mediated changes in LDL density. Circulation 1999 99 1959-1964. 

P. Libby, P. Theroux, Pathophysiology of coronary artery disease. Circulation 111 (2005) 3481-3488. 

The early clinical benefits observed in statin trials of acute coronary syndrome patients (MIRACL and PROVE-IT TIM 1-22) where coronary vascular inflammation, thrombosis, and unstable plaque are critical pathophysiologic elements that may be positively modified by statins compared to the more delayed benefits observed in statin trials of patients with stable coronary artery disease. 

This review summarizes the available morphological evidence for coronary microembolization in patients who died from coronary artery disease, most notably from sudden death. Then the experimental pathophysiology of coronary microembolization in animal models of acute coronary syndromes is detailed. Finally, the review presents the available clinical evidence for coronary microembolization in patients, highlights its key features - arrhythmias, contractile dysfunction, microinfarcts and reduced coronary reserve -, compares these features to those of the experimental model and addresses its prevention by mechanical protection devices and glycoprotein Ilb/IIIa antagonism. 

There is epidemiologic evidence to suggest an increased prevalence of duodenal ulcers in patients with certain chronic diseases, but the pathophysiologic mechanisms of these associations are uncertain. A strong association exists in patients with systemic mastocytosis, multiple endocrine neoplasia type 1, chronic pulmonary diseases, chronic renal failure, kidney stones, hepatic cirrhosis, and ai-antitrypsin deficiency. An association may exist in patients with cystic fibrosis, chronic pancreatitis, Crohn s disease, coronary artery disease, polycythemia vera, and hyperparathyroidism. 

The PPARs constitute a family of three nuclear receptors that have important roles in physiological lipid and glucose metabolism. Converse, dysregulation of the PPARs has been associated with pathophysiological conditions such as hyperlipidemia, insulin resistance and coronary artery disease. There are three PPAR isoforms -PPARa, PPARy and PPARS (also termed PPARP). All PPARs are expressed in cardiovascular tissues and in addition to their known metabolic actions they exhibit distinct functions. While the expression of PPARa and PPARP/8 is surprisingly high in the heart, PPARy expression is very low and does not appear to play an important role in the heart. Since Chapter 11 in this book is dedicated to the well-established role of the PPARs in metabolic diseases, we will focus in this chapter on the role of P PA Ra in cardiac diseases. 

Mast cells are found in the human heart [31, 52], around coronary arteries [53], and in the coronary intima [54], Human heart mast cells have been implicated in the pathophysiology of myocarditis [55, 56], coronary artery diseases [53] and dilated cardiomyopathy [57], Finally, mast cells, through the release of vasoactive mediators, are also involved in systemic vasculitis [39],... 

FIGURE 4-2. Coronary artery anatomy with sternocostal and diaphragmatic views. (Reproduced from Talbert RL. Ischemic heart disease. In DiPiro JT, Talbert RL, Yee GC, et al, (eds.) Pharmacotherapy A Pathophysiologic Approach. 6th ed. New York McGraw-Hill 2005 263, with permission.)... 

Peripheral arterial occlusion can be the initial manifestation of cardiac or systemic disease. At times, patients with chronic stable claudication may experience abrupt shortening of the distance at which claudication occurs, and this may be the only symptomatic evidence of an acute arterial occlusion either by embolization of by thrombus formation on a pre-existing arterial stenosis. The situation is not chronic and stable any more, but acute and unstable. As ischemia becomes more severe, the patient with chronic peripheral arterial disease develops ischemic pain at rest. The pathophysiologic mechanisms and the clinical presentation parallel the evolution of chronic stable angina pectoris to unstable angina and acute coronary syndromes. 

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