CHD Is an Inflammatory Disease

Most investigators agree that atherosclerosis is a chronic low-grade inflammatory disease.26 Proinflammatory factors (free radicals produced by cigarette smoking, hyperhomocysteinemia, diabetes, peroxidized lipids, hypertension, elevated and modified blood lipids) contribute to the injury to the vascular endothelium, which results in alterations of its antiatherosclerotic and anti-thrombotic properties. This is thought to be a major step in the initiation and formation of arterial fibrostenotic lesions. From a clinical point of view, however, an essential distinction should be made between unstable, lipid-rich and leukocyte-rich lesions and stable, acellular fibrotic lesions poor in lipids, as the propensity of these two types of lesion to rupture into the lumen of the artery, whatever the degree of stenosis and lumen obstruction, is totally different.

In 1987, we proposed that inflammation and leukocytes play a role in the onset of acute CHD events.27 This has recently been confirmed. It is now accepted that one of the main mechanisms underlying the sudden onset of acute CHD syndromes, including unstable angina, myocardial infarction, and SCD, is the erosion or rupture of an atherosclerotic lesion, which triggers thrombotic complications and considerably enhances the risk of malignant ventricular arrhythmias. Leukocytes have been also implicated in the occurrence of ventricular arrhythmias in clinical and experimental settings, and they contribute to myocardial damage during both ischemia and reperfusion. Clinical and pathological studies showed the importance of inflammatory cells and immune mediators in the occurrence of acute CHD events and prospective epidemiological studies showed a strong and consistent association between acute CHD and systemic inflammation markers. A major challenge is to understand why there are macrophages and activated lymphocytes in atherosclerotic lesions and how they get there. Issues such as local inflammation, plaque rupture, and attendant acute CHD complications follow.

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