Atherosclerosis Pathology
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The term atherosclerosis is derived from the Greek “athero,” meaning gruel, or wax, corresponding to the necrotic core area at the base of the atherosclerotic plaque, and “sclerosis” for hardening, or induration, referring to the fibrous cap of the plaque’s luminal edge.
The earliest pathologic descriptions of atherosclerotic lesions focused on morphologies of fatty streaks to fibroatheromas (FAs) and advanced plaques complicated by hemorrhage, calcification, ulceration, and thrombosis. In the mid 1990s the terminology used to define atheromatous plaques was refined by the American Heart Association (AHA) Consensus Group headed by Dr. Stary.
The classification consists of 6 different numeric categories to include early lesions of initial type I, adaptive intimal thickening; type II, fatty streak; and type III, transitional or intermediate lesions; and advanced plaques characterized as type IV, atheroma; type V, fibroatheroma or atheroma with thick fibrous cap; and type VI, complicated plaques with surface defects, and/or hematoma-hemorrhage, and/or thrombosis.
A modified version of the AHA classification was developed by our laboratory to include important pathologic lesions responsible for luminal thrombosis other than plaque rupture, such as plaque erosion and calcified nodule. [1] In this modified classification, numeric AHA lesions types I to IV are replaced by descriptive terminology to include adaptive intimal thickening, intimal xanthoma, pathologic intimal thickening (PIT), and fibroatheroma, as shown in the table below.
Table 1. Modified AHA Consensus Classification Based on Morphologic Descriptions* (Open Table in a new window)
Description
Thrombosis
Nonatherosclerotic intimal lesions
Intimal thickening
Normal accumulation of smooth muscle cells (SMCs) in the intima in the absence of lipid or macrophage foam cells
Absent
Intimal xanthoma
Superficial accumulation of foam cells without a necrotic core or fibrous cap; based on animal and human data, such lesions usually regress
Absent
Progressive atherosclerotic lesions
Pathologic intimal thickening
SMC-rich plaque with proteoglycan matrix and focal accumulation of extracellular lipid
Absent
Fibrous cap atheroma
Early necrosis: focal macrophage infiltration into areas of lipid pools with an overlying fibrous cap
Late necrosis: loss of matrix and extensive cellular debris with an overlying fibrous cap
Absent
Thin cap fibroatheroma
A thin, fibrous cap (< 65 µm) infiltrated by macrophages and lymphocytes with rare or absence of SMCs and a relatively large underlying necrotic core; intraplaque hemorrhage/fibrin may be present
Absent
Lesions with acute thrombi
Plaque rupture
Fibroatheroma with fibrous cap disruption; the luminal thrombus communicates with the underlying necrotic core
Occlusive or nonocclusive
Plaque erosion
Plaque composition, as above; no communication of the thrombus with the necrotic core; can occur on a plaque substrate of pathologic intimal thickening or fibroatheroma
Usually nonocclusive
Calcified nodule
Eruptive (shedding) of calcified nodules with an underlying fibrocalcific plaque with minimal or absence of necrosis
Usually nonocclusive
Lesions with healed thrombi
Fibrotic (without calcification)
Fibrocalcific (+/- necrotic core)
Collagen-rich plaque with significant luminal stenosis; lesions may contain large areas of calcification with few inflammatory cells and minimal or absence of necrosis; these lesions may represent healed erosions or ruptures
Absent
* Modified from Virmani et al. [1]
Lesion reference to AHA types V and VI was discarded, because it failed to account for the 3 different morphologies (rupture, erosion, and calcified nodule) that give rise to acute coronary thrombosis.
Despite advances in medical, interventional, and surgical treatment, atherosclerotic disease remains the most important cause of death in developed and underprivileged nations. [2, 3] In the United States alone, coronary artery disease causes approximately 1 of every 6 deaths, accounting for more than 400,000 deaths annually. [2] Each year, an estimated 785,000 Americans have an initial myocardial infarction, and 470,000 Americans have a recurrent attack. [2]
Coronary artery disease remains the leading cause of death in the Western world. A new or recurrent myocardial infarction afflicts approximately 1.1 million people in the USA per year, of which 40% are fatal. Sudden cardiac death as a first manifestation of the atherosclerotic process occurs in >450,000 individuals annually. The vast majority of acute myocardial infarctions (approximately 75%) occur from plaque rupture; other causes of coronary thrombosis include erosion and calcified nodules. [4]
Although lesions with rupture occur in men of all ages (this is consistent for all plaque morphologies with thrombi), the frequency of sudden coronary death decreases with advancing age. The incidence of rupture varies with each decade, and the highest incidence of plaque rupture is seen in the 40s in men, whereas in women the incidence increases beyond age 50 years. Approximately 80% of coronary thrombi in women older than 50 years occur from plaque rupture, and there is a strong association with circulating cholesterol. In acute myocardial infarction or sudden coronary death, plaque erosion occurs primarily in patients younger than 50 years and represents the majority of acute coronary thrombi in premenopausal women. Furthermore, 20-25% of acute myocardial infarcts occurring in hospitalized patients are due to plaque erosion.
The etiology of atherosclerosis is unknown, but there are multiple factors that contribute to atherosclerotic plaque progression. These include genetic and acquired factors. Processes involved in atherosclerosis include coagulation, inflammation, lipid metabolism, intimal injury, and smooth muscle cell proliferation (see the image below).
Factors that affect these processes may inhibit or accelerate atherosclerosis. The most common risk factors are family history, hyperlipidemia, diabetes mellitus, cigarette smoking, hypertension, and dietary deficiencies of antioxidants. [5] Early lesion development is marked by lipid retention with activation of endothelial adhesion molecules. Inflammatory macrophages play a significant role throughout all phases of atherosclerotic progression; hyperlipidemia-induced macrophage infiltration of the arterial intima is one of the earliest pathologic changes.
A major event in atherosclerotic plaque progression is thrombosis, which may occur in any arterial bed (coronary, aorta, carotid, etc.) Three different morphologies (rupture, erosion and calcified nodule) may give rise to acute coronary thrombosis. Plaque rupture is defined by fibrous cap disruption or fracture, whereby the overlying thrombus is in continuity with the underlying necrotic core. Plaque erosion is identified when serial sectioning through a thrombus fails to show communication with a necrotic core or deep intima; the endothelium is absent, and the thrombus is superimposed on a plaque substrate primarily composed of smooth muscle cells and proteoglycans. Calcified nodules are characterized by eruptive dense calcified bodies protruding into the luminal space and represent the least frequent morphology associated with luminal thrombosis. See the following diagram.
A long term study that began in 1980 to investigate if low vitamin D levels in childhood are related with increased carotid artery intima-media thickness (IMT) in adulthood reported that vitamin D deficiency in childhood may be linked to hardening of the arteries in middle age. [6, 7]
Atherosclerosis occurs in elastic and muscular arteries and may occur iatrogenically in vein grafts interposed in the arterial circulation. The aorta is affected earliest, followed by the carotid arteries, coronary arteries, and iliofemoral arteries. Sawabe et al have shown that disease progression occurred more rapidly in the aorta, followed by coronary and femoral, and occurred least in the carotid and intracerebral arteries. [8] Initially, lesions are most common at branch points, at sites of low shear, where a predilection to plaque formation has been observed. Coronary lesions, including thrombi occuring at atherosclerotic sites, are most prevalent in the proximal coronary arteries: the proximal left anterior descending coronary artery, followed by the right and left circumflex coronary arteries.
Atherosclerosis causes symptoms by arterial obstruction, embolization of plaque material, and weakening with rupture of the arterial wall. Obstruction with or without embolization causes ischemia of the circulation supplied by the vessel. Ischemic strokes result from atherosclerosis of the carotid arteries and aortic arch, which embolize thrombi and atherosclerotic material, as well as local atherosclerosis of the cerebral vessels.
Obstruction of coronary arteries causes myocardial ischemia. Myocardial ischemia may present as acute coronary syndromes (acute ST elevation infarct, non-ST elevation infarct, and unstable angina), sudden death, or chronic congestive heart failure. Obstruction of iliac vessels results in ischemia of the lower extremities (claudication). Atherosclerotic aneurysms show a predilection for the aorta, especially the abdominal aorta. Aortic aneurysms may rupture and cause death by hemorrhage into the retroperitoneal space or pleural cavities, depending on the location.
The criterion standard for imaging atherosclerotic lesions of the coronary circulation is angiography, whereas CT angiography is emerging as a promising approach for the noninvasive assessment of coronary artery stenosis and plaque characteristics. [9, 10] Motoyama et al has reported that the presence of low attenuated plaque and positive remodeling by CT angiography are predictive of future acute coronary events. [11] Newer imaging modalities, such as cardiac MRI, are being developed that may provide less invasive methods of determining sites of stenosis. Imaging of atherosclerotic lesions of the carotid circulation include carotid ultrasonography, a noninvasive technique.
Focal calcification in atherosclerotic plaques is common and increases with age. Although calcification is a good marker for plaque burden, absolute calcium scores do not indicate plaques that are unstable or prone to clinical events but are predictors of future events. An autopsy study has demonstrated a good correlation between plaque size and morphometric analysis of calcification, but no correlation between residual lumen and calcification was identified. [12]
A study comparing the 10-year Framingham risk index, histologic coronary calcification, and culprit plaque morphology in 79 consecutive adults with sudden coronary death demonstrated a modest relationship between the Framingham risk index and the extent of histologic coronary calcification (r = 0.35, p = 0.002). [13] The addition of coronary artery calcium score of more than 400 (as assessed by CT scanning) to the Framingham Risk Score has resulted in a higher reclassification rate in the intermediate-risk cohort, thus showing the benefit of imaging. [14]
In the aorta, atherosclerotic lesions have been classified largely on gross findings. Fatty streaks are yellow, minimally raised lesions that demonstrate abundant lipid when stained with oil red O. Fibrous plaques are raised, white, firmer areas that are relatively well demarcated. Ulcerated plaques demonstrate surface thrombosis and represent ruptured fibroatheromas.
Coronary lesions, when cut on cross-section, show bright yellow cores when there is abundant extracellular lipid, as in fibroatheromas. Ruptured or eroded plaques demonstrate a luminal thrombus, which is pale red or tan in the unfixed state, depending on the proportion of fibrin, platelets, and entrapped red blood cells. Calcified plaques are hard and brittle, are difficult to cute with a scalpel blade, and must be decalcified during or after fixation so that sections for microscopy may be performed.
The gross findings of carotid plaques are similar to those of the coronary arteries. There is often calcification, which can be seen and felt as mineral deposits. Atheromas are bright yellow on cross-section, and atheromas with intraplaque hemorrhage show a more variegated yellow-red cut surface. Fibrous plaques are homogeneous, firm and white, and often show areas of calcification.
The early lesions consist of 2 nonatherosclerotic intimal lesions referred to as adaptive intimal thickening and intimal xanthoma (“fatty streak” in the AHA classification) (see the image below). Intimal xanthoma denotes a lesion rich in foamy macrophages without extracelullar lipid pools. Adaptive intimal thickening is present from birth and grow in areas of low shear stress, and are consist mainly of smooth muscle cells in a proteoglycan rich matrix.
Observations from experimental models and autopsy studies in young human subjects suggest that monocyte adherence to the endothelial surface and transmigration into the intima occur as the earliest events in the development of atherosclerotic lesions. Adaptive intimal thickening is characterized by retention of modified lipoproteins within the proteoglycan rich matrix in the intima. The initiation of adhesion increases the expression of selectins, which facilitates the rolling of monocytes, followed by firm attachment by endothelial integrins. Low density lipoprotein (LDL) oxidation, a critical step in atherosclerosis development, has been shown to occur through induction of lipoxoygenases, myeloperoxidases, inducible nitric oxide synthase and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. (See the image below.)
Pathologic intimal thickening (PIT) or type III lesions in the AHA classification are thought to represent the earliest of the progressive plaques. This lesion is primarily composed of smooth muscle cells near the lumen and matrix consisting chiefly of proteoglycan and type III collagen. Focal areas of accumulated lipid (“lipid pools”) are found localized toward the abluminal medial wall as areas devoid of smooth muscle cells but rich in proteoglycans.
It is thought that lesions of PIT that show the presence of macrophages are at a more advanced stage, as demonstrated by Nakashima et al in their study of early coronary lesions progression near branch points. [15] This study demonstrated that PIT and intimal xanthoma occur simultaneously and are not truly separable lesions. A variable number of T lymphocytes are also observed at this stage, but a true necrotic core is absent. Areas of lipid pools may also contain free cholesterol appearing as cholesterol clefts on paraffin stained sections.
Although the precise origin of the “lipid pool” is debatable, studies suggest that the loss of smooth muscle cells (death by apoptosis) may be involved, as their remnant basement membranes can be visualized by periodic acid Schiff (PAS) staining and show microcalcification. In addition, the confirmation of lipids by oil red O staining is highly suggestive of a lipid retention process facilitated by select proteoglycans and oxidation, which may lead to activation of factors responsible for apoptosis.
The following generally describes the progression of atherosclerotic lesions. Also, see the image below.
Fibroatheroma
Thin cap fibroatheroma (“vulnerable plaque”) and plaque rupture
Necrotic core expansion and risk for plaque rupture
Intraplaque hemorrhage and necrotic core expansion
Healed plaque rupture (HPR)
Erosion
The fibrous cap atheroma is the first of the advanced lesions of coronary atherosclerosis by the AHA classification scheme. Its defining feature is the presence of a lipid-rich necrotic core encapsulated by collagen rich fibrous tissue. The fibrous cap atheroma may result in significant luminal narrowing and is also prone to complications of surface disruption, thrombosis, and calcification. The origin and development of the core is fundamental to understanding the progression of coronary artery disease. The fibrous cap consists of collagen, smooth muscle cells, and proteoglycan with varying degrees of inflammatory cells—mostly macrophages and lymphocytes. The thickness of the fibrous cap distinguishes the fibroatheroma (relatively thick) from the thin fibrous cap atheroma (classic “vulnerable” plaque).
Recognition of early necrosis is identified by macrophage infiltration within lipid pools associated with a substantial increase in free cholesterol and breakdown of extracellular matrix, presumably by matrix metalloproteinase (MMP) activity. This, together with the death of macrophages in the setting of defective phagocytic clearance of apoptotic cells, is thought to contribute to the development of late plaque necrosis. Ultimately, the size of the necrotic core is a strong predictor of lesion vulnerability. [15, 16]
The thin cap atheroma is thought to be a precursor lesion to plaque rupture and is characterized by a necrotic core overlaid by a thin, fibrous cap (65 µm or less), which is heavily infiltrated by macrophages and T lymphocytes. The density of macrophages at the site of rupture is typically very high, although in some cases macrophages may be sparse. However, because plaque rupture is responsible for 76% of fatal coronary events associated with thrombi in sudden coronary death patients, identification of the thin cap atheroma is critical. A common mechanism of disruption of the fibrous cap atheroma occurs via the thinning or weakening of the fibrous cap, resulting in fissures and ruptures.
Plaque rupture is defined as an area of fibrous cap disruption in which the overlying thrombus is in contact with the underlying necrotic core. The fibrous cap is composed of type I collagen with varying degrees of macrophages and lymphocytes and very few, if any, alpha-actin positive smooth muscle cells. The luminal thrombus is platelet rich at the rupture site. Plaque ruptures are most prevalent in the proximal coronary artery near branch points and are frequently found in the proximal left anterior descending coronary artery, followed by the right and left circumflex coronary arteries.
The causes of plaque rupture are poorly understood, but responsible factors include expression of factors that weaken the fibrous cap, such as MMPs, enzymes (eg, myeloperoxidases) produced by inflammatory cells, high shear regions, stress points, macrophage calcification, and iron deposition. Data are also beginning to emerge that demonstrate critical differences in gene expression between stable and unstable atherosclerotic plaques. [17] In one of these studies, differential expression of 18 genes associated with lesion instability included the metalloproteinase ADAMDEC1, retinoic acid receptor responser-1, cysteine protease legumain (a potential activator of MMPs) and cathepsins. [17]
Expansion of the necrotic core is an important pathogenic process contributing to plaque vulnerability. The presenting inflammatory stimuli for macrophage recruitment into lipid pools are poorly understood along with the respective signaling pathways for subsequent apoptotic cell death and necrosis. Recent studies point toward the involvement of the endoplasmic reticulum (ER) stress pathway, or so-called unfolded protein response (UPR), as the primary mechanisms of macrophage cell death in plaques. This pathway promotes the death of macrophages—the resultant accumulation of dead macrophages coupled with defective phagocytic clearance has been cited as one of the principal factors causing necrotic core expansion.
Data from the authors’ laboratory provide evidence that repeat intraplaque hemorrhage is a contributing factor to necrotic core expansion, as red blood cells are a rich source of free cholesterol, which is an important constituent of ruptured plaques. [18] The red blood cells are enriched with lipids constituting 40% of their weight and free cholesterol content within membranes exceeding all other cell types. The expression of glycophorin-A (a protein exclusive to red blood cell membranes) within the necrotic cores of advanced coronary atheroma is strongly positive, whereas its presence in plaques with early necrosis or pathologic intimal thickening remains absence or low.
Intraplaque hemorrhage likely occurs from leaky vasa vasorum that infiltrate the plaque as the lesion thickness increases. The authors have reported that microvessel density is increased in advanced plaques compared with early plaques. Microvessels in normal and atherosclerotic arteries are thin-walled, with compromised structural integrity characterized by poor endothelial junctions. [19] Therefore, intraplaque hemorrhage together with the death of macrophages in the setting of defective phagocytic clearance of apoptotic cells is thought to contribute to the development of necrotic core in advance stage plaques.
Morphologic studies suggest that plaque progression beyond 40-50% cross-sectional luminal narrowing occurs secondary to repeated ruptures. Ruptured lesions with healed repair sites, namely, healed plaque ruptures (HPRs) as shown by Mann and Davies, are easily detected microscopically by the identification of breaks in the fibrous cap with an overlying repair reaction consisting of proteoglycans and/or collagen, depending on the phase of healing. [20] Early-healed lesions are rich in proteoglycan, which are eventually replaced by type I collagen.
The prevalence of silent ruptures in the clinical population is unknown. Few angiographic studies have demonstrated plaque progression, and short-term studies have suggested that thrombosis is the likely cause. Mann and Davies showed that the frequency of healed plaque ruptures increases along with lumen narrowing. [20] In plaques with 0-20% diameter stenosis, the incidence of healed plaque ruptures was 16%; in lesions with 21-50% stenosis, the incidence was 19%; and in plaques with >50% narrowing, the incidence was 73%. [20]
The authors have shown a high frequency of healed plaque ruptures in the coronary arteries from patients dying suddenly with severe coronary disease. [21] The percentage of cross-sectional luminal narrowing was dependent on the number of healed repair sites.
Although plaque rupture is the most common cause of coronary thrombosis, acute coronary syndromes may occur in the absence of rupture. As mentioned earlier, thrombi may occur as a result of 3 different events: plaque rupture, plaque erosion, or, rarely, a calcified nodule (see Etiology). Plaque erosion is characterized by absence of the endothelium at the site of erosion, with exposed intima composed of smooth muscle cells and proteoglycans, as well as typically minimal inflammation.
In a series of 20 patients who died with acute myocardial infarction, van der Wal et al found plaque ruptures in 60% of lesions with thrombi, whereas the remaining 40% showed “superficial erosion.” [22] The term “erosion” was chosen because the luminal surface beneath the thrombus lacked endothelial cells. In these lesions, the thrombus was confined to the most luminal portion of the plaque, and there was an absence of ruptures following serial sectioning of these lesions.
In addition, the authors’ laboratory studied nearly 100 cases of sudden coronary death and found that 60% of all thrombi could be attributed to plaque rupture and 40% to erosions. Morphologically, major differences exist in the cellular composition of ruptured versus erosion lesions. Unlike the prominent fibrous cap inflammation described in ruptures, eroded surfaces contain few macrophages (rupture 100% vs erosion 50%, P< 0.0001) and T lymphocytes (rupture 75% vs erosion 32%, P< 0.004). Cell activation, indicated by human lymphocyte antigen (HLA)-DR staining, was identified in macrophages and T cells in 89% of plaque ruptures and in 36% of plaque erosions (P = 0.0002). [23] The smooth muscle cells near the erosion site appeared “activated,” often displaying bizarre shapes with hyperchromatic nuclei and prominent nucleoli. The incidence of calcification was also less common in erosion than in ruptures.
The authors have also shown that more than 85% of thrombi in erosions exhibited late stages of healing characterized by acute inflammatory cell lysis, invasion by smooth muscle cells and/or endothelial cells, or organized layers of smooth muscle cells and proteoglycans with varying degrees of platelet/fibrin layering, whereas in ruptures only one half of thrombi showed healing. [24] Postmortem coronary thrombi superimposed on eroded plaques have been shown to contain a higher density of myeloperoxidase-positive cells than those superimposed on ruptured plaques. [25] Also, circulation blood myeloperoxidase levels are elevated in patients with acute coronary sinus with erosion compared with those with rupture, suggesting that elevations in selective inflammatory biomarkers may reflect specific acute coronary events.
Both clinical and morphologic differences are widely apparent between plaque rupture and erosion. Beginning with age, patients with plaque rupture tend to be significantly older (53 ± 10 y) than those with erosion (44 ± 7 y) (P< 0.02). Survival is also a critical factor, because an estimation of fatal ruptures in the fifth decade of life is 17 per 100,000 per year compared with 6 per 100,000 for plaque erosion.
Although the relationship between risk factors and culprit plaques is similar between women and men, the proportion of women younger than the age of 50 years dying suddenly with plaque erosion is remarkably higher. Plaque burden expressed as the percentage of cross-sectional area stenosis excluding the thrombus is greater in plaque ruptures (78 ± 12%) than erosions (70 ± 11%) (P< 0.03), whereas eccentric plaques are more common in erosions. Unlike the prominent fibrous cap inflammation described in ruptures, eroded surfaces contain fewer macrophages and T lymphocytes. Taken together, eroded plaques tend to be eccentric lesions rich in smooth muscle cells and proteoglycans with very little inflammation or calcification.
Immunohistochemistry (IHC) is not necessary for the diagnosis or classification of atherosclerotic plaques. However, immunolocalization of both cellular and acellular elements within human and animal lesions has contributed greatly to the understanding of atheroslcerotic plaque progression. Immunohistochemical stains for smooth muscle cell antigens (eg, smooth muscle actin), inflammatory cells (especially macrophages and T lymphocytes), blood-derived antigens (eg, fibrin and platelet surface antigens), and enzymes (eg, elastases and collagenases) have all been used to characterize the components of atherosclerotic plaques, and these represent only a sample.
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Description
Thrombosis
Nonatherosclerotic intimal lesions
Intimal thickening
Normal accumulation of smooth muscle cells (SMCs) in the intima in the absence of lipid or macrophage foam cells
Absent
Intimal xanthoma
Superficial accumulation of foam cells without a necrotic core or fibrous cap; based on animal and human data, such lesions usually regress
Absent
Progressive atherosclerotic lesions
Pathologic intimal thickening
SMC-rich plaque with proteoglycan matrix and focal accumulation of extracellular lipid
Absent
Fibrous cap atheroma
Early necrosis: focal macrophage infiltration into areas of lipid pools with an overlying fibrous cap
Late necrosis: loss of matrix and extensive cellular debris with an overlying fibrous cap
Absent
Thin cap fibroatheroma
A thin, fibrous cap (< 65 µm) infiltrated by macrophages and lymphocytes with rare or absence of SMCs and a relatively large underlying necrotic core; intraplaque hemorrhage/fibrin may be present
Absent
Lesions with acute thrombi
Plaque rupture
Fibroatheroma with fibrous cap disruption; the luminal thrombus communicates with the underlying necrotic core
Occlusive or nonocclusive
Plaque erosion
Plaque composition, as above; no communication of the thrombus with the necrotic core; can occur on a plaque substrate of pathologic intimal thickening or fibroatheroma
Usually nonocclusive
Calcified nodule
Eruptive (shedding) of calcified nodules with an underlying fibrocalcific plaque with minimal or absence of necrosis
Usually nonocclusive
Lesions with healed thrombi
Fibrotic (without calcification)
Fibrocalcific (+/- necrotic core)
Collagen-rich plaque with significant luminal stenosis; lesions may contain large areas of calcification with few inflammatory cells and minimal or absence of necrosis; these lesions may represent healed erosions or ruptures
Absent
* Modified from Virmani et al. [1]
Lesion reference to AHA types V and VI was discarded, because it failed to account for the 3 different morphologies (rupture, erosion, and calcified nodule) that give rise to acute coronary thrombosis.
Elena R Ladich, MD Medical Director of Cardiovascular Pathology, Memorial Regional Hospital
Elena R Ladich, MD is a member of the following medical societies: College of American Pathologists, Society for Cardiovascular Pathology, United States and Canadian Academy of Pathology
Disclosure: Nothing to disclose.
Renu Virmani, MBBS, MD President and Medical Director, CVPath Institute, Inc
Renu Virmani, MBBS, MD is a member of the following medical societies: American College of Cardiology, American Heart Association, United States and Canadian Academy of Pathology
Disclosure: Received consulting fee from Abbott Vascular, 480 Biomedical, Lutonix, Medtronic, W.L. Gore for consulting; Received none from Merck, Abbott Vascular, Biosensors International, Boston Scientific, CeloNova, Cordis J&J, Lutonix, Medtronic, Terumo, 480 Biomedical, W.L. Gore for speaking and teaching; Received grant/research funds from Abbott Vascular, Atrium, Biosensors International, Biotronik, Boston Scientific, CeloNova, Cordis J&J, GlaxoSmithKline, Medtronic, MicroPort Medical, OrbusNiech, ReCo.
Frank Kolodgie, PhD Adjunct Assistant Professor, Department of Pathology, University of Maryland at Baltimore; Associate Director, CVPath Institute
Frank Kolodgie, PhD is a member of the following medical societies: American Heart Association
Disclosure: Nothing to disclose.
Fumiyuki Otsuka, MD, PhD Cardiovascular Research Fellow, CVPath Institute, Inc
Fumiyuki Otsuka, MD, PhD is a member of the following medical societies: Japanese Society of Internal Medicine, Japanese College of Cardiology, Japanese Society of Interventional Cardiology, Japanese Circulation Society
Disclosure: Nothing to disclose.
Allen Patrick Burke, MD Associate Professor, Department of Pathology, University of Maryland School of Medicine; Chairman, Department of Cardiovascular Pathology, Armed Forces Institute of Pathology
Allen Patrick Burke, MD is a member of the following medical societies: American Academy of Forensic Sciences, American College of Cardiology, American College of Gastroenterology, American Medical Association, Society for Cardiovascular Pathology, United States and Canadian Academy of Pathology
Disclosure: Nothing to disclose.
Atherosclerosis Pathology
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