A histopathological analysis of the epidemiology of coronary atherosclerosis: an autopsy study

Diagnostic Pathology

Aram Mokarizadeh²  Mahsa Darvish¹  Maryam Gilasgar¹  Seyed Mohamad Hossein Tabatabaei Nodushan¹  Yasan Sadeghian¹  Behnam Pedram⁴  Negin Abedinzadeh³ 

[1] Graduate, Faculty of Medicine, Shahid Beheshti University of Medical Sciences and Health Services, Tehran, Iran;Cellular & Molecular Research Center, and Department of Immunology, Kurdistan University of Medical Sciences, Sanandaj, Iran;Graduate, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran;Department of Pathobiology, Susangerd Branch Islamic Azad University, Susangerd, Iran

关键词: Plaque;    Inflammation;    Autopsy;    Coronary artery;    Atherosclerosis;   

Others  :  1219359
DOI  :  10.1186/s13000-015-0324-y

 received in 2015-05-12, accepted in 2015-06-12,  发布年份 2015

【 摘 要 】

Background

Atherosclerosis accounts for a large proportion of cardiovascular system associated morbidity and mortality. We studied the possible association between the histopathological changes of the coronary atherosclerotic lesions and the risk of sudden cardiac death (SCD) using autopsy cases.

Methods

We performed an autopsy analysis (n = 13, 4 women, 9 men mean age 67.5 years; age range 56–93 years) of SCD which occurred in patients aged over 50 years during March 2010 to December 2013. The following variables were considered: sex, age, medical history, autopsy findings to macroscopic and histological evaluation of the heart. The autopsies were performed according to standard techniques. In all subjects, the heart was dissected following standard autopsy protocol and a 5 cm section of the right coronary artery (RCA) in the atrio-ventricular groove from its origin, a 5 cm segment of the left anterior descending artery (LADA) distal to the origin of the circumflex artery, but including the region of origin of the circumflex branch and left coronary artery (LCA) from its origin till the circumflex branch were excised, dissected out, fixed in 10 % formalin, marked for identification and sent for histopathological analysis.

Results

Atherosclerotic plaques were identified in 6.5 % of specimens, 69.34 % of males and 30.66 % of female. Such plaques were typically concentric and more represented with necrosis, calcification, cholesterol crystals, and giant cells, as well as had a higher inflammatory cell count. Furthermore, intima and media thickness of coronary arteries were significantly higher in studied specimens with visualize the connective tissue layers of the adventitia and the fatty acid containing adipose cells in the periadventitial tissue. Furthermore, the degree of microscopic lesion of atherosclerosis increased proportionally with the increase in the intensity of lipid deposition and with the percentage of collagen in the atherosclerotic plaques.

Conclusion

In this study, age estimate to be a risk factor for coronary atherosclerosis in individuals more than 50 years old and may be used to predict SCD. Altogether, an enhanced understanding of the pathobiologic processes responsible for atherosclerotic changes might allow for early identification of a high-risk coronary plaque and thereby provide a rationale for innovative diagnostic and/or therapeutic strategies for the management of coronary patients and prevention of acute coronary syndromes.

【 授权许可】

   
2015 Abedinzadeh et al.

【 图 表 】

Fig. 1.

Fig. 2.

Fig. 3.

【 参考文献 】

• [1]Bairey NCB, Merz BD, Johnson BL, Sharaf WISE. Hypoestrogenemia of hypothalamic origin and coronary artery disease in premenopausal women: a report from the NHLBI-sponsored WISE study. J Am Coll Cardiol. 2003; 41:413-419.
• [2]Chirinos JA, Segers P, Duprez DA, Brumback L, Bluemke DA, Zamani P, Kronmal R, Vaidya D. Late systolic central hypertension as a predictor of incident heart failure: the Multi-ethnic Study of Atherosclerosis. J Am Heart Assoc. 2015; 4(3):e001335.
• [3]Bertomeu A, García-Vidal O, Farré X. Preclinical coronary atherosclerosis in a population with low incidence of myocardial infarction: cross sectional autopsy study. British Med J. 2003; 327(7415):591-592.
• [4]Sharma K, Gulati M. Coronary artery disease in women: a 2013 update. Glob Heart. 2013; 8(2):105-12.
• [5]Koopal C, Retterstøl K, Sjouke B, Hovingh GK, Ros E, de Graaf J, Dullaart RP. Vascular risk factors, vascular disease, lipids and lipid targets in patients with familial dysbetalipoproteinemia: a European cross-sectional study. Atherosclerosis. 2015; 240(1):90-7.
• [6]Tintut Y, Patel J, Territo M. Calcification of human vascular cells in vitro is correlated with high levels of matrix Gla protein and low levels of osteopontin expression. Circulation. 2002; 105:650-5.
• [7]Rodríguez-Saldaña J, Rodriguez-Flores M, Cantú-Brito C, Aguirre-Garcia J. A pathological study of the epidemiology of atherosclerosis in Mexico city. Cardiol Res Pract. 2014; doi:10.1155/2014/264205.
• [8]Campbell LA, Rosenfeld ME. Infection and Atherosclerosis Development. Arch Med Res. 2015 May 21
• [9]Rodrigues AN, Perez AJ, Carletti L, Bissoli NS, Abreu GR. The association between cardiorespiratory fitness and cardiovascular risk in adolescents. J Pediatr (Rio J). 2007; 83(5):429-35.
• [10]Knuiman MW, Folsom AR, Chambless LE, Liao D, Wu KK. Association of hemostatic variables with MRI-detected cerebral abnormalities: the atherosclerosis risk in communities study. Neuroepidemiology. 2001; 20(2):96-104.
• [11]Jefferis BJ, Whincup PH, Lennon LT, Papacosta O, Goya WS. Physical activity in older men: longitudinal associations with inflammatory and hemostatic biomarkers, N-terminal pro-brain natriuretic peptide, and onset of coronary heart disease and mortality. J Am Geriatr Soc. 2014; 62(4):599-606.
• [12]Wong TY, Klein R, Sharrett AR. Retinal arteriolar narrowing and risk of coronary heart disease in men and women. The Atherosclerosis Risk in Communities Study. JAMA. 2002; 287:1153-1159.
• [13]Huber SA, Sakkinen P, David C. T helper-cell phenotype regulates atherosclerosis in mice under conditions of mild hypercholesterolemia. Circulation. 2001; 103:2610-16.
• [14]Gauss S, Klinghammer L, Steinhoff A, Raaz-Schrauder D, Marwan M, Achenbach S, Garlichs CD. Association of systemic inflammation with epicardial fat and coronary artery calcification. Inflamm Res. 2015; 64(5):313-9.
• [15]Lakoski SG, Greenland P, Wong ND. Coronary artery calcium scores and risk for cardiovascular events in women classified as “low risk” based on Framingham risk score: the Multi-Ethnic Study of Atherosclerosis (MESA). Arch Intern Med. 2007; 167:2437-2442.
• [16]de Oliveira Otto MC, Wu JH, Baylin A, Vaidya D, Rich SS, Tsai MY, Jacobs DR, Mozaffarian D. Circulating and dietary omega-3 and omega-6 polyunsaturated fatty acids and incidence of CVD in the Multi-Ethnic Study of Atherosclerosis. J Am Heart Assoc. 2013; 2(6):e000506.
• [17]Karakas M, Baumert J, Herder C, Rottbauer W, Meisinger C, Koenig W, Thorand B. Soluble thrombomodulin in coronary heart disease: lack of an association in the MONICA/KORA case-cohort study. J Thromb Haemost. 2011; 9(5):1078-80.
• [18]Mosca L, Benjamin EJ, Berra K, Bezanson JL, Dolor RJ, Lloyd-Jones DM, Newby LK. Effectiveness-based guidelines for the prevention of cardiovascular disease in women–2011 update: a guideline from the American Heart Association. Circulation. 2011; 123(11):1243-1262.
• [19]Bielak LF, Yu P, Ryan KA, Rumberger JA, Sheedy PF, Turner ST, Post W, Shuldiner AR, Mitchell BD, Peyser PA. Differences in prevalence and severity of coronary artery calcification between two non-Hispanic white populations with diverse lifestyles. Atherosclerosis. 2008; 196(2):888-95.
• [20]Newman AB, Naydeck BL, Whittle J. Racial differences in coronary calcification in older adults. Arterioscl Thromb Vasc Biol. 2002; 22:424-30.
• [21]Budoff MJ. Atherosclerosis imaging in calcified plaque: coronary artery risk assessment. Prog Cardiovasc Dis. 2003; 46:135-148.
• [22]Anaka A, Shimada K, Namba M. Relationship between longitudinal morphology of ruptured plaques and TIMI flow grade in acute coronary syndrome: a three-dimensional intravascular ultrasound imaging study. Eur Heart J. 2008; 29:38-44.
• [23]Virmani R, Burke AP, Farb A, Gold HK, Finn AV, Kolodgie F. Plaque rupture.Virmani R. The Vulnerable Atherosclerotic Plaque 2007. Blackwell Futura Valley Stream, NY; 2007.
• [24]He ZX, Hedrick TD, Pratt CM. Severity of coronary artery calcification by electron beam computed tomography predicts silent myocardial ischemia. Circulation. 2000; 101:244-251.
• [25]Mollet N, Maffei E, Martini C, Weustink A, van Mieghem C, Baks T, McFadden E, de Feyter P. Coronary plaque burden in patients with stable and unstable coronary artery disease using multislice CT coronary angiography. Radiol Med. 2011; 116(8):1174-87.
• [26]Bavelaar FJ, Beynen AC. Atherosclerosis in parrots: a review. Vet Q. 2004; 26:50-60.
• [27]Brunkwall J, Mattsson E, Bergqvist D. Diet-induced atherosclerosis in rabbits alters vascular prostacyclin release. Eicosanoids. 1992; 5:197-202.
• [28]Fricke C, Schmidt V, Cramer K. Characterization of atherosclerosis by histochemical and immunohistochemical methods in African grey parrots (Psittacus erithacus) and Amazon parrots (Amazona spp.). Avian Dis. 2009; 53:466-472.
• [29]Racial/ethnic and socioeconomic disparities in multiple risk factors for heart disease and stroke. MMWR Morb Mortal Wkly Rep. 2005; 54:113-7.
• [30]Galkina E, Ley K. Immune and inflammatory mechanisms of atherosclerosis. Annu Rev Immunol. 2009; 27:165-197.
• [31]Hansson GK, Libby P. The immune response in atherosclerosis: a double-edged sword. Nat Rev Immunol. 2006; 6:508-519.
• [32]Kensey KR, Cho YI. The Origin of Atherosclerosis: An Introduction to Hemodynamics. EPP Medica, Haddonfield; 2001.
• [33]Greenland P, Alpert JS, Beller GA, Benjamin EJ, Budoff MJ, Fayad ZA, Foster E, Hlatky MA. ACCF/AHA guideline for assessment of cardiovascular risk in asymptomatic adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2010; 56:50-103.
• [34]Silverman S. Diagnostic Imaging. In: Reptile Medicine and Surgery. 2nd ed. Mader DR, editor. Saunders Elsevier, St. Louis; 2006: p.471489.
• [35]Willecke F, Yuan C, Oka K, Chan L, Hu Y, Barnhart S, Bornfeldt KE, Goldberg IJ, Fisher EA. Effects of High Fat Feeding and Diabetes on Regression of Atherosclerosis Induced by Low-Density Lipoprotein Receptor Gene Therapy in LDL Receptor-Deficient Mice. PLoS One. 2015; 10(6):e0128996.
• [36]Smith SC, Smith EC, Taylor RL. Susceptibility to spontaneous atherosclerosis in pigeons: an autosomal recessive trait.J. Heredity. 2001; 92:439-442.
• [37]Stetter MD. Ultrasonography. In: Reptile Medicine and Surgery. 2nd ed. Mader DR, editor. Saunders Elsevier, St. Louis; 2006: p.665674.
• [38]Pearson TA, Blair SN, Daniels SR, Eckel RH, Fair JM, Fortmann SP. AHA guidelines for primary prevention of cardiovascular disease and stroke: 2002 update: Consensus panel guide t comprehensive risk reduction for adult patients without coronary or other atherosclerotic vascular diseases. American Heart Association Science Advisory and Coordinating Committee. Circulation. 2002; 106:388-91.
• [39]Yusuf S, Reddy S, Ôunpuu S, Anand S. Global Burden of Cardiovascular Diseases Part II: Variations in Cardiovascular Disease by Specific Ethnic Groups and Geographic Regions and Prevention Strategies. Circulation. 2001; 104:2855-64.
• [40]Ford ES. C-reactive protein concentration and cardiovascular disease risk factors in children: findings from the National Health and Nutrition Examination Survey 1999–2000. Circulation. 2003; 108:1053-8.
• [41]Thomas AC, Knapman PA, Kirkler DA, Davies MJ. Community study of the causes of ‘natural’ sudden death. Br Med J. 1988; 297:1453-1456.
• [42]Alioglu E, Turk UO, Engin C, Tengiz I, Tuzun N, Posacioglu H. Left main coronary artery aneurysm in young patient with acute myocardial infarction. J Cardiovasc Med (Hagerstown). 2009; 10(6):494-6.
• [43]Hassantash SA, Bikdeli B, Kalantarian S, Sadeghian M, Afshar H. Pathophysiology of aortocoronary saphenous vein bypass graft disease. Asian Cardiovasc Thorac Ann. 2008; 16:331-336.
• [44]Van der Wal AC, Becker AE, Elbers JRJ, Das PK. An immunocytochemical analysis of rapidly progressive atherosclerosis in human vein grafts. Eur J Cardiothorac Surg. 1992; 6:469-474.
• [45]Leonard S. Lilly MD Pathophysiology of Heart Disease. A Collaborative Project of Medical Students and Faculty (Pathophysiology of heart disease (lilly)). Fifth Edition, North American Edition, ISBN-13: 978-1605477237
• [46]Packard RR, Lichtman AH, Libby P. Innate and adaptive immunity in atherosclerosis. Semin Immunopathol. 2009; 31:5-22.
• [47]Cherian SM, Bobryshev YV, Inder SJ, Wang AY, Lord RS, Farnsworth AE. Dendritic cells in aortocoronary saphenous vein bypass grafts. Heart Lung Circ. 2000; 9:39-42.
• [48]Thej MJ, Kalyani R, Kiran J. Atherosclerosis in coronary artery and aorta in a semi-urban population by applying modified American Heart Association classification of atherosclerosis: An autopsy study. J Cardiovasc Dis Res. 2012; 3(4):265-71.
• [49]Yazdi SAT, Rezaei A, Azari JB, Hejazi A. Prevalence of Atherosclerotic Plaques in Autopsy Cases with Noncardiac Death. Iranian J Pathol. 2009; 4(3):101-104.
• [50]Singh H, Oberoi SS, Gorea RK, Bal MS. Atherosclerosis in coronaries in Malwa region of Punjab. JIAFM. 2005; 27:236-9.
• [51]Hassantash SA, Bikdeli B, Kalantarian S, Sadeghian M, Afshar H. Pathophysiology of aortocoronary saphenous vein bypasses graft disease. Asian Cardiovasc Thorac Ann. 2008; 16(4):331-6.
• [52]Wong ND. Epidemiological studies of CHD and the evolution of preventive cardiology. Nature reviews Cardiology. 2014; 11(5):276-89.
• [53]Rumberger JA, Brundage BH, Rader DJ, Kondos G. Electron beam computed tomographic coronary calcium scanning: a review and guidelines for use in asymptomatic persons. Mayo Clin Proc. 1999; 74:243-252.
• [54]Deb S, Wijeysundera HC, Ko DT, Tsubota H, Hill S, Fremes SE. Coronary artery bypass graft surgery vs percutaneous interventions in coronary revascularization: a systematic review. JAMA. 2013; 310(19):2086-95.
• [55]Taylor AJ, Burke AP, O’Malley PG. A comparison of the Framingham risk index, coronary artery calcification, and culprit plaque morphology in sudden cardiac death. Circulation. 2000; 101:1243-8.
• [56]Assemat P, Siu KK, Armitage JA, Hokke SN, Dart A, Chin-Dusting J, Hourigan K. Haemodynamical stress in mouse aortic arch with atherosclerotic plaques: preliminary study of plaque progression. Comput Struct Biotechnol J. 2014; 10(17):98-106.
• [57]Soraya H, Rameshrad M, Mokarizadeh A, Garjani A. Metformin attenuates myocardial remodeling and neutrophil recruitment after myocardial infarction in rat. Bioimpacts. 2015; 5(1):3-8.
• [58]Mokarizadeh A, Hassanzadeh K, Abdi M, Soraya H, Faryabi MR, Mohammadi E, et. al. Trasnsdermal delivery of bovine milk vesicles in patients with multiple sclerosis: A novel strategy to induce MOG-specific tolerance. Med Hypotheses. 2015 Apr 24
• [59]Mokarizadeh A, Delirezh N, Morshedi A, Mosayebi G, Farshid AA, Mardani K. Microvesicles derived from mesenchymal stem cells: potent organelles for induction of tolerogenic signaling. Immunol Lett. 2012; 147(1-2):47-54.