The thrombus then travels downstream to other blood vessels, where the blood clot may partially or completely block blood flow. If the blood flow is completely blocked, cell deaths occur due to the lack of oxygen supply to nearby cells, resulting in necrosis. The narrowing or obstruction of blood flow can occur in any artery within the body. Obstruction of arteries supplying the heart muscle results in a heart attack, while the obstruction of arteries supplying the brain results in an ischaemic stroke. Lumen stenosis that is greater than 75% was considered the hallmark of clinically significant disease in the past because recurring episodes of angina and abnormalities in stress tests are only detectable at that particular severity of stenosis. However, clinical trials have shown that only about 14% of clinically debilitating events occur at sites with more than 75% stenosis. The majority of cardiovascular events that involve sudden rupture of the atheroma plaque do not display any evident narrowing of the lumen. Thus, greater attention has been focused on "vulnerable plaque" from the late 1990s onwards.Besides the traditional diagnostic methods such as angiography and stress-testing, other detection techniques have been developed in the past decades for earlier detection of atherosclerotic disease. Some of the detection approaches include anatomical detection and physiologic measurement.Examples of anatomical detection methods include coronary calcium scoring by CT, carotid IMT (intimal media thickness) measurement by ultrasound, and intravascular ultrasound (IVUS). Examples of physiologic measurement methods include lipoprotein subclass analysis, HbA1c, hs-CRP, and homocysteine.
The bulk of these lesions is made of excess fat, collagen, and elastin. At first, as the plaques grow, only wall thickening occurs without any narrowing. Stenosis is a late event, which may never occur and is often the result of repeated plaque rupture and healing responses, not just the atherosclerotic process by itself. Cellular
Early atherogenesis is characterized by the adherence of blood circulating monocytes (a type of white blood cell) to the vascular bed lining, the endothelium, then by their migration to the sub-endothelial space, and further activation into monocyte-derived macrophages. The primary documented driver of this process is oxidized lipoprotein particles within the wall, beneath the endothelial cells, though upper normal or elevated concentrations of blood glucose also plays a major role and not all factors are fully understood. Fatty streaks may appear and disappear.Low-density lipoprotein (LDL) particles in blood plasma invade the endothelium and become oxidized, creating risk of cardiovascular disease. A complex set of biochemical reactions regulates the oxidation of LDL, involving enzymes (such as Lp-LpA2) and free radicals in the endothelium.Initial damage to the endothelium results in an inflammatory response. Monocytes enter the artery wall from the bloodstream, with platelets adhering to the area of insult. This may be promoted by redox signaling induction of factors such as VCAM-1, which recruit circulating monocytes, and M-CSF, which is selectively required for the differentiation of monocytes to macrophages.