Lessons From Sudden Coronary Death

Abstract

T his review will reconsider the current paradigm for understanding the critical, final steps in the progression of atherosclerotic lesions. That scheme, largely an outgrowth of observations of autopsy tissues by Davies and colleagues, 1,2 asserts that the cause of death in atherosclerotic coronary artery disease is rupture of an advanced atherosclerotic lesion. Although this assumption may be partially true, recent autopsy studies suggest that it is incomplete. See p 1177To reconsider this paradigm, we reexamined the morphological classification scheme for lesions proposed by the American Heart Association (AHA). 3,4 This scheme is difficult to use for 2 reasons. First, it uses a very long list of roman numerals modified by letter codes that are difficult to remember. Second, it implies an orderly, linear pattern of lesion progression. This tends to be ambiguous, because it is not clear whether there is a single sequence of events during the progression of all lesions. We have therefore tried to devise a simpler classification scheme that is consistent with the AHA categories but is easier to use, able to deal with a wide array of morphological variations, and not overly burdened by mechanistic implications. The Current ParadigmThe current paradigm is based on the belief that type IV lesions, or "atheromas," described by the AHA are stable because the fatty, necrotic core is contained by a smooth muscle cell-rich fibrous cap. Virchow's analysis 5 in 1858 pointed out that historically, the term "atheroma" refers to a dermal cyst ("Grützbalg"), a fatty mass encapsulated within a cap. Extending Virchow's argument, the fibrous cap over the lipid mass of an atherosclerotic plaque is analogous to the capsule containing an abscess, and like an abscess, the plaque can be ruptured. Rupture of the fibrous cap exposes thrombogenic material, initiating platelet aggregation and coagulation in the infiltrating and overlying blood. These thrombotic changes result from activation of the clotting cascade by tissue factor, and further propagation of the thrombosis results from the interaction of platelets with the active thrombogenic matrix. 6 Platelet activation and thrombin formation combined with the evulsion of thrombogenic plaque contents into the lumen then result in sudden occlusion. 7 This widely held concept of atherosclerotic death is based on morphological data from autopsies as well as clinical angiographic studies, in which the presence of surface irregularities has been interpreted as plaque rupture. 8 -10 Previous pathological studies of sudden coronary death have demonstrated evidence of plaque rupture associated with thrombosis in 73% of cases. 2 Of the remaining cases, 8% consist of plaque fissure with intraplaque fibrin deposition and hemorrhage, while 19% show no evidence of thrombi. 2 Consequently, recent reviews of atherosclerosis have uniformly accepted plaque rupture as the critical event leading to coronary artery death. 6

Detection of thrombus size and protein content by ex vivo magnetization transfer and diffusion weighted MRI

“…350) was used. Disrupted rabbit aortic plaques contained an overlying thrombus similarly to what has been observed for human coronary plaques [42]. …”

Clinical Predictors for Lack of Favorable Vascular Response to Statin Therapy in Patients With Coronary Artery Disease: A Serial Optical Coherence Tomography Study

“…Plaque rupture is a major cause of ACS and sudden coronary death,1, 24 and a thin fibrous cap appears to be a marked precursor to plaque rupture 2, 3. Yet, the continuously changing nature of fibrous cap morphological features weakens its predictive and prognostic values 25.…”

“…Fibrous‐cap thickness (FCT) is one of the major determinants of coronary plaque vulnerability 1, 2, 3. Thinning of the cap is a result of the degradation of collagen tissue by excessive release of matrix metalloproteinases from the accumulated macrophages 4, 5.…”

Atherosclerotic Calcification: Wnt Is the Hint

“…During minimal vascular injury, whereby the short‐lived inflammatory response can effectively remove or solve the problem, vessel remodeling is less likely to occur 1. In contrast, sustained exposure to the above mentioned risk factors increases vascular adhesiveness, leakage, and accumulation of extracellular lipid within the vessel wall, thereby inducing foam cell formation and inflammatory response propagated by sustained release of growth factors and cytokines 3, 28, 29…”

“…Apoptosis of VSMCs and macrophages, along with loss of extracellular matrix, contributes to plaque instability and may lead to eventual rupture, which accounts for ≈50% of MIs and acute coronary syndromes attributable to occlusion of the artery 1, 28. A plaque burden of 70% or greater has significantly increased the risk of rupture 32.…”