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ORIGINAL ARTICLE Table of Contents   
Year : 2009  |  Volume : 52  |  Issue : 4  |  Page : 486-489
Coronary atherosclerosis in sudden cardiac death: An autopsy study


1 Department of Pathology, Sri Ramachandra Medical College and Research Institute, Sri Ramachandra Universiy, Porur, Chennai-600 116, India
2 Zena and Wiener Cardiovascular Institute, The Mount Sinai School of Medicine, New York, USA
3 Department of Forensic Medicine, Sri Ramachandra Medical College and Research Institute, Sri Ramachandra Universiy, Porur, Chennai-600 116, India

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Date of Web Publication1-Oct-2009
 

   Abstract 

Background: The incidence of ischemic heart disease (IHD) has markedly increased in India over the past few years. Considering the variations in racial, dietary and lifestyle patterns in our population, it is essential to study the biology of coronary atherosclerosis in our patients. Vulnerable plaques have a large number of foam cells, extracellular lipid, thin fibrous caps and clusters of inflammatory cells and are more prone to rupture. These plaques are nourished by the microvessels arising from the vasa vasorum of the blood vessels and by lumen-derived microvessels through the fibrous cap. This autopsy study was designed to analyse the coronary arterial tree in cases of sudden cardiac death, classify coronary atherosclerotic plaques and to assess the factors contributing to vulnerability of the plaques including inflammation, calcification and microvascular density. Materials and Methods: Seven cases of sudden cardiac death were included in the study. The hearts were perfusion-fixed and the coronary arteries along with their main branches were dissected and studied. The location of the plaques, type of plaques, presence of inflammation and calcification were assessed. The cap thickness and microvessel density per 1000um 2 were assessed. The statistical significance was estimated. Results and Conclusions: Extensive high-grade coronary atherosclerotic disease was seen in all sudden cardiac death cases. Majority of the plaques were vulnerable. High-grade inflammation was seen in most of the vulnerable and ruptured plaques. All the ruptured plaques were uncalcified indicating that calcification probably stabilizes the plaques and protects against rupture. Increased microvessel density was noted in ruptured plaques compared to vulnerable plaques. However, it was not statistically significant.

Keywords: Atherosclerosis, autopsy, microvessel density, sudden cardiac death

How to cite this article:
Sudha M L, Sundaram S, Purushothaman K R, Kumar P S, Prathiba D. Coronary atherosclerosis in sudden cardiac death: An autopsy study. Indian J Pathol Microbiol 2009;52:486-9

How to cite this URL:
Sudha M L, Sundaram S, Purushothaman K R, Kumar P S, Prathiba D. Coronary atherosclerosis in sudden cardiac death: An autopsy study. Indian J Pathol Microbiol [serial online] 2009 [cited 2014 Dec 19];52:486-9. Available from: http://www.ijpmonline.org/text.asp?2009/52/4/486/56130



   Introduction Top


The incidence of coronary artery disease has doubled in Indians during the past three to four decades. It will soon emerge as the single largest disease accounting for nearly one-third of all deaths in India. The number of deaths due to coronary artery disease in India is projected to increase from 1.591 million in year 2000 to 2.034 million by year 2010 (World Health Organisation report; 1999). [1] Considering the variations in racial, dietary and lifestyle patterns in our population it is essential to study the morphology and evolution of coronary atherosclerosis in our patients.

It is widely accepted that rupture of vulnerable atherosclerotic plaque leads to acute coronary syndromes. [2] The important characteristics of an unstable or vulnerable plaque are a large lipid core, a thin fibrous cap and many inflammatory cells including macrophages. The fibrous cap is the only structure separating the blood compartment containing coagulation factors from the thrombogenic material in the lipid core. When such a fibrous cap ruptures, it allows contact of these coagulation factors with tissue factors and promotes thrombosis. [3]

Virmani et al., [3],[4] used specific criteria to define thin fibrous cap. In their study they classified plaques with cap thickness of 65 um or less as vulnerable. They also observed that all thin fibrous cap atheromas need not necessarily rupture. The factors in the fibrous cap which predispose to rupture include the extent of inflammation in the cap, fissuring, calcification, intra-plaque vasa vasorum or intra-plaque hemorrhage.

This autopsy study was designed to analyze the coronary arterial tree in cases diagnosed as sudden cardiac death in the casualty department of our hospital, classify coronary atherosclerotic plaques and to assess the factors contributing to vulnerability of the plaques including inflammation, calcification, and microvascular density (MVD).


   Materials and Methods Top


Seven heart specimens from adult autopsies conducted on cases of sudden cardiac deaths were analysed. Cases were selected on the basis of the history of chest pain followed by death within one hour. All these cases were brought dead to our hospital.

After autopsy, the hearts were perfusion-fixed [4] for 30 min and subsequently immersed in formalin and allowed to fix.

The entire coronary tree was dissected along with its major branches. These vessels were decalcified for a period of 15-20 min. Following decalcification, the entire left coronary, left anterior descending and left circumflex artery were sectioned at 3-mm intervals. The right coronary artery and right circumflex artery were identified and sectioned at 3-mm intervals.

After routine processing and paraffin embedding, 4-um sections were taken. Hematoxylin and eosin staining of all the sections was done and the atherosclerotic plaques were identified. Modified elastic trichrome stain was performed on all sections with atheromatous plaques. The plaque morphology was studied in these sections under the following headings.

  • location of the plaque.
  • type of atheromatous plaque based on modified American heart association (AHA) classification.
  • grade of inflammation (>25 cells/hpf)
  • presence of calcification.
  • measurement of cap thickness by morphometry. Plaques with cap thickness <65 um were classified as vulnerable plaques.


Forty plaques whose morphology was studied by modified trichrome stain were selected of which 88% were vulnerable plaques and immunohistochemical (IHC) staining for CD31 was done on them. These slides were studied using the image analysis system Image Pro-Plus Analysis software (Media Cybernetics Corporation, USA), Microsoft Excel data storage and analysis software (Microsoft Corporation, USA) to assess,

  • The number of microvessels in three different areas of the plaques.
  • The density of microvessels per 1000 um 2 of the plaque.


Microvessels are defined as vascular spaces with CD31 positivity on immunostaining. The microvessel density (MVD) per 1000 um 2 was calculated.


   Results Top


The mean age of the seven cases of sudden cardiac death was 54 years.

Total number of plaques identified was 100.

Left anterior descending artery was the most common site for plaques (47%). Next common site was the right coronary artery.

Vulnerable plaques with cap thickness less than 65 um were found to be predominant (87%) [Figure 1] and [Figure 2].

Non-vulnerable plaques were only two in number.

Eleven plaques were ruptured [Figure 3].

Thirty-one per cent of the plaques were calcified [Figure 4].

Fifty-eight of the vulnerable plaques were uncalcified plaques.

Plaque rupture was more common in uncalcified plaques compared to calcified vulnerable plaques. This difference was statistically significant (P=0.040 i.e. P<0.05). Twenty-one per cent of the vulnerable plaques had Grade 1 inflammation and 66% had Grade 2. Both the non-vulnerable plaques in our study had Grade 2 inflammation. Though the grade of inflammation is higher in the majority of the vulnerable and ruptured plaques, this was not statistically significant when these two categories were compared (P=0.45, P>0.05). Ninety-one per cent of the ruptured plaques showed Grade 2 inflammation.

Grade 2 inflammation was more common in both calcified and uncalcified vulnerable plaques. One non-vulnerable calcified plaque had Grade 2 inflammation and the other non-vulnerable uncalcified plaque also had Grade 2 inflammation.

Mean MVD for vulnerable plaques and ruptured plaques was 0.6 and 0.9 respectively [Figure 5].Though the mean MVD is higher in ruptured plaques when compared to the vulnerable plaques, this is not statistically significant (P=0.165, P>0.05).

Mean MVD in calcified plaques was 1.05, and 0.52 in uncalcified plaques. Mean MVD in vulnerable plaques with Grade 1 inflammation was 0.40, and 0.8 in plaques with Grade 2 inflammation. However, the comparison of mean MVD in vulnerable and ruptured plaques with Grade 1 and Grade 2 inflammation was not statistically significant (P=0.39, P>0.05).


   Discussion Top


There is an alarming increase in the number of deaths due to coronary atherosclerosis in India and this number is expected to escalate rapidly in the next decade. It is essential to analyze the effect of these factors in our patients considering the difference in racial, dietary and lifestyle patterns.

The American Heart Association characterized and classified atherosclerotic lesions from Type I to Type VI. [5] It was proposed that these lesions progressed from one type to the next. Now plaque vulnerability is established to be the most significant determinant of thrombus-mediated acute coronary syndromes.

In concordance with this view, Renu Virmani et al., [3] found that cross-sectional luminal narrowing of more than 75% is not a prerequisite for luminal thrombosis. They felt that the relationship between luminal narrowing and plaque progression is not addressed in the AHA classification. They proposed the modified AHA scheme which focused more on advanced lesions which lead to sudden death. [3] This classification provided a descriptive terminology based on the pathological characteristics of atherosclerotic lesions, like thin cap fibroatheroma, eroded plaques and calcified nodules. [3],[6]

All the plaques from main coronaries and their major branches in sudden cardiac death patients were analyzed. We chose to classify the plaques by modified AHA scheme which has more clinical implications. Thin cap fibroatheroma, was the most common type in our study.

Next in frequency was ruptured plaque. Only a negligible number of plaques were non-vulnerable and these plaques also had a cap thickness very close to the cutoff point of 65 um. This indicates that these patients not only had extensive involvement but also the majority were high-grade lesions. This was in concordance with the findings of Virmani et al., [3] who found 95% of the plaques to be vulnerable in sudden cardiac death patients.

The frequency of ruptured plaques was found to be 11% in our study. This was found to be much lower than that reported in the earlier two studies where 37.5% and 33% were ruptured plaques. [3],[7] The lower frequency of ruptured plaques noticed in our study despite all being sudden cardiac death cases, could be explained by the presence of extensive atherosclerotic lesions leading to overall coronary insufficiency. Plaque rupture was not found in three cases. However, these cases showed extensive calcified plaques. In contrast, none of the ruptured plaques identified in our study showed calcification. This supports the view that calcification stablilizes the plaques reducing the incidence of rupture. [8]

Higher grade of inflammation was noticed in majority of the ruptured and vulnerable plaques. This indicates that inflammation plays a major role in plaque vulnerability.

Higher MVD was found in ruptured plaques compared to vulnerable plaques. This was in concordance with the study by Moreno et al., [9],[10] who suggested that microvessels facilitate blood-derived inflammatory cells to penetrate through the vessel wall and contribute to plaque rupture.

The mean MVD was higher in calcified plaques in our study. This finding contradicts those mentioned by Moreno et al., [9] which state that microvessel density is increased in lipid-rich and ruptured plaques when compared to fibrocalcific lesion. This study was done on aortic plaques. [9] Further study in this area on coronary plaques is necessary to substantiate this finding.

The morphological features of coronary atherosclerosis in random autopsy cases studied earlier by us [11] were compared with those of sudden cardiac death cases. The vulnerable plaques were more in number in the sudden death category (87%) compared to the random cases (55%). There was a higher grade of inflammation in sudden death (66% with Grade 2) cases compared to random cases (24.5%).


   Conclusion Top


Extensive high-grade coronary atherosclerotic disease is seen in all sudden cardiac death cases. The majority of the plaques are vulnerable. High-grade inflammation is associated with plaque vulnerability and rupture. Calcification probably stabilizes the plaques and prevents rupture.



 
   References Top

1.WHO report. Park's Textbook of Social and Preventive Medicine. 17thed. Banarasi Bhanot; 1999. p. 273-6.  Back to cited text no. 1      
2.Rioufol G, Finet G, Ginon I, Andrι-Fouλt X, Rossi R, Vialle E, et al. A Multiple atherosclerotic plaque rupture in acute coronary syndrome: a three-vessel IVUS examination. Circulation 2002;106:804-8.  Back to cited text no. 2      
3.Virmani R, Kolodgie FD, Burke AP, Farb A, Schwartz SM. Lessons from sudden coronary death - A comprehensive morphological classification scheme for atherosclerotic lesions. Arterioscler Thromb Vasc Biol 2000;20:1262-75.   Back to cited text no. 3      
4.Virmani R, Burke AP, Farb A, Kolodgie FD. Pathology of the Unstable plaque. Prog Cardiovasc Dis 2002;44:349-56.  Back to cited text no. 4      
5.Stary HC, Chandler AB, Glagov S, Guyton JR, Insull W Jr, Rosenfeld ME, et al. A definition of Initial fatty streak and intermediate lesions of atherosclerosis - a report from the committee on vascular lesions of the council on arteriosclerosis, AHA. Arteriosclerosis Thromb 1994;14:840-56.  Back to cited text no. 5      
6.Galis ZS. Vulnerable plaque -The devil is in the details. Circulation 2004;110:244-6.  Back to cited text no. 6      
7.Farb A, Tang AL, Burke AP, Sessums L, Liang Y, Virmani R. Sudden coronary death - frequency of active coronary lesions, inactive coronary lesions and myocardial infarction. Circulation 1995;92:1701-9.  Back to cited text no. 7      
8.Moreno PR, Purushothaman KR, William N O'Connor. Microvessel sprouting, Red blood cell extravasation, and perivascular inflammation is increased in plaques from patients with Diabetes Mellitus. J Am Coll Cardiol 2005;45:1140-56.  Back to cited text no. 8      
9.Moreno PR, Purushothaman KR, Fuster V, Echeverri D, Truszczynska H, Sharma SK et al. Plaque neovascularization is increased in ruptured atherosclerotic lesions of Human aorta. Circulation 2004;110:2032-8.  Back to cited text no. 9      
10.Moreno PR, Purushothaman KR, Fuster V, O'Connor WN. Intimomedial interface damage and adventitial inflammation is increased beneath disrupted atherosclerosis in the aorta: implications for plaque vulnerability. Circulation 2002;105:2504-11.  Back to cited text no. 10  [PUBMED]  [FULLTEXT]  
11.Amel E, Prathiba D, Kumar S. Morphological and morphometric analysis of coronary atherosclerosis - an autopsy study. Indian J Pathol Microbiol 2006;49:239-42.  Back to cited text no. 11  [PUBMED]    

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Correspondence Address:
D Prathiba
Department of Pathology, Sri Ramachandra Medical College and Research Institute, Sri Ramachandra University, Porur, Chennai - 600 116
India
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DOI: 10.4103/0377-4929.56130

PMID: 19805952

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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]

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