How is ruptured plaque differentiated from vulnerable plaque?

Updated: Dec 30, 2019
  • Author: Elena R Ladich, MD; Chief Editor: Allen Patrick Burke, MD  more...
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Morphologic studies have identified coronary lesions that share many histologic similarities with plaque rupture and are therefore hypothesized to be the precursor lesion of plaque rupture. Those precursor plaques that closely resemble ruptures but lack a luminal thrombus have been characterized as thin-cap fibroatheromas (TCFAs), or vulnerable plaques.

As previously described, plaque ruptures are characterized by a necrotic core with an overlying thin-ruptured fibrous cap infiltrated by macrophages and lymphocytes. The thickness of the cap near the rupture site measures 23 ± 19 µm, with 95% of the caps measuring < 65 µm. The TCFA, like the rupture, demonstrates a necrotic core with an overlying fibrous cap (measuring less than 65 µm in thickness) but lacks a thrombus (see the following image).

Vulnerable plaque pathology. A nonhemodynamically Vulnerable plaque pathology. A nonhemodynamically limiting thin-cap fibroatheroma (TCFA). A TCFA having a necrotic core (NC) and an overlying thin fibrous cap (< 65 µm) is shown in A and B, with a high-power view of the boxed area in A. Note that an advanced necrotic core with a large number of cholesterol clefts with surrounding loss of matrix and no cellular infiltration is seen. The fibrous cap is infiltrated by macrophages, better seen in C when stained by hematoxylin and eosin (H&E). D and E show macrophage infiltration (CD68+) and rare actin positive staining in the fibrous cap. (Kolodgie-Alpha staining of smooth muscle cells). Kolodgie et al. Heart. 2004; 90:1385-91, with permission).

Despite many similarities, several morphologic features distinguish the TCFA from the ruptured plaque. For example, TCFAs demonstrate a smaller necrotic core, fewer macrophages infiltrating the fibrous cap, and significantly less calcification. Other plaque features have been analyzed and compared for these 2 lesions as well as erosions and stable plaques. Overall, cross-sectional luminal narrowing is greater in ruptures than TCFAs, with occlusive thrombi having greater underlying stenosis than nonocclusive thrombi. The number of cholesterol clefts in the necrotic core, vasa vasorum, and macrophages are significantly greater in ruptures than erosions or stenotic stable lesions.

The necrotic core and its enlargement are critical for plaque rupture. It has been shown that macrophage infiltration is the first step toward the eventual formation of an atherosclerotic plaque. In vitro studies have shown that low-density lipoprotein (LDL) oxidation facilitates its uptake by macrophages. This 2-step process begins with oxidation of lipid, followed by apolipoprotein B oxidation. Foamy macrophages contain cholesterol esters and free cholesterol. However, as the plaque progresses, the free cholesterol content of the lesion increases, whereas the cholesterol esters decrease.

A study by Niccoli et al found that among patients with acute coronary syndrome, raised lipoprotein levels are associated with an increased atherosclerotic burden and it identifies a subset of patients with features of high risk coronary atherosclerosis. [12]

Intraplaque hemorrhage may also be an important contributor to expansion of the necrotic core. [13, 14] Hemorrhage into the atheroma may occur through leaky vasa vasorum and the subsequent accumulation of free cholesterol derived from erythrocyte membranes. Interestingly, the cholesterol content of erythrocyte membranes exceeds that of all other cells in the body, with lipid constituting 40% of the weight.

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