Correlation of coronary artery atherosclerosis typing and luminal narrowing with ischemic myocardial lesions in post mortem heart specimens: a four year retrospective study

Introduction: Atherosclerosis accounts for a large proportion of cardiovascular system associated morbidity and mortality. Coronary artery disease (CAD) is the leading cause of global deaths with about 80% of burden occurring in developing countries. Material & Methods: In order to assess the magnitude of the problem, a retrospective study of autopsy cases for the presence of atherosclerotic lesions of coronary arteries and associated ischemic cardiac lesionswas under taken from January 2013 to December 2017. Also, correlation of the atherosclerosis with ischemic heart diseases was studied. Result: Total number of heart specimens received in department of Pathology during four years were 272. Out of these 57 were autolyzed and were excluded from the study. Significant atherosclerotic lesions were seen in 54(25.11%) and 64(29.76%) cases in right and left coronary arteries respectively and were statistically significantly higher among age group > 41 years as compared to those with age <41 years, overall atherosclerotic lesions were significantly higher in age groups >41 years as compared to <41 years. Conclusion: Maximum number of significant cardiac lesion were associated with atherosclerotic type VIII lesions (75%) followed by type VII (66.66%) and type VI (33.33%). Maximum number of significant myocardial lesions were associated with grade IV (66.66%) coronary luminal narrowing followed by grade III (45.71) and grade II (38.46). The study also showed significant correlation between the higher grade of the coronary atherosclerotic lesions and the ischemic heart disease.


Introduction
In India, CAD has emerged as the single largest disease accounting for nearly one third of all deaths. The incidence of coronary artery disease has doubled during past three to four decades. A total of nearly 6.4 crore cases of coronary artery disease were likely to occur in the year 2015; nearly 96% would be coronary heart disease cases [1]. An estimated 1.3 million Indian died from this in 2000. The projected deaths from coronary artery disease by 2015 were 2.95 million, of which 14% will be under 30 years and 31% will be under 40 years [2]. CAD is the leading cause of global deaths with about 80% of burden occurring in developing countries [3,4]. There is an alarming increase in the morbidity and mortality due to coronary atherosclerosis in India. There is no valid method for sampling of living population. The exact global incidence of atherosclerosis is not possible to calculate because it can exist without producing any signs & symptoms. The autopsy study provides a means of understanding the basic process which sets a stage for clinically significant atherosclerotic cardiovascular disease [1].
In order to assess the magnitude of the problem, a retrospective study of autopsy cases for the presence of atherosclerotic lesions of coronary arteries and associated ischemic cardiac lesions like acute myocardial infarction (MI) /chronic ischemic heart disease (CIHD)/myocardial fibrosis (MF) / left ventricular hypertrophy (LVH) was under taken for a Micro sections from representative areas of heart were examined for the presence & extent of coronary atherosclerosis and evidence of acute myocardial infarction / myocardial fibrosis / left ventricular hypertrophy. Detailed medical history and clinical diagnosis before death in review of the cases were not available.
Typing of atherosclerotic plaque was done as per the criteria of American Heart Association [5,6].

Results
Total number of heart specimens received in department of Pathology during four years was 272. Out of these 57 were autolysed and were excluded from the study.
All the deceased were grouped into specific age groups according to the age mentioned in the postmortem documents. In present study males (73.02%) out numbered the female (26.98%). Most of the specimens of heart were from age group 21-30 years (Table No.1).  1). Thirty-four specimens did not show any atherosclerotic lesion in either of the coronary arteries.
Commonest prevalent atherosclerotic lesion in present study was of type I (32.59%). Significant coronary artery disease (type IV to type VIII) in right and left coronary arteries was seen in 54 (29.83%) and 64 specimens (35.35%) respectively.
Type V was the most common significant atherosclerotic lesion in right coronary artery and type VII as most common significant atherosclerotic lesion in left coronary artery. Least common was type VI (3.86%) in right and type VIII in left coronary artery (2.76%) (Table no 2). Significant CAD lesions were seen in 54 (25.11%) and 64 (29.76%) cases in right and left coronary arteries respectively and were statistically significantly higher among age group > 41 years as compared to those with age <41 years (p value=0.000) in both right and left coronary arteries.

Figure-1: Left coronary artery with atherosclerotic plaque type VIII (H & E, 4x).
In this study the overall atherosclerotic lesions were significantly higher age groups >41 years as compared to <41years (p value=0.000) and also significant CAD lesions were statistically significant higher among age group > 41 years as compared to those with age <41 years (p value=0.000) in both right and left coronary arteries (Table III) Original Research Article

R= Right Coronary Artery L= Left Coronary Artery
Different grades of coronary artery luminal narrowing were observed in total 74(34.41%) and 69(32.09%) cases in right and left side respectively out of total 215 specimens (figure 2). Grade I (12.55%) was most common in right coronary artery and Grade III(15.81%) was the most common among left coronary artery. Coronary artery luminal narrowing was statistically significantly higher among age group > 41 years as compared to those with age <41 years (p value=0.000) in both right and left coronary arteries (Table no 4).

Discussion
Atherosclerosis is a disease of large and medium sized muscular arteries, characterized by inflammation of smooth muscle cells and formation of atherosclerotic plaques composed of necrotic cores; calcium deposits and an accumulation of modified lipids, endothelial cells, leukocytes, and foam cells [8][9][10][11][12][13]. Buildup of material and infiltrates leads to vascular remodeling, acute and chronic luminal obstruction, abnormalities of blood flow and diminished oxygen supply to target organs [9,10,14]. In human beings, atherosclerosis is the most common pathologic process leading to cardiovascular disease [14][15][16].
Coronary artery disease (CAD) is a leading cause of death of women and men worldwide. An estimated 17.5 million people died from this cause in 2005, representing 30% of all deaths in the world; of these, 7.6 million were caused by coronary heart disease [17]. Coronary artery disease due to atherosclerosis is an epidemic in India. The incidence of coronary artery disease has doubled during past three to four decades. It will soon emerge as the single largest diseaseaccounting for nearly one-third of all deaths in India. A total of nearly 6.4 crore cases of coronary vascular disease are likely in the year 2015; nearly 96% would be coronary heart disease cases. Deaths from this group of diseases are likely to amount to be a staggering 34 lakh. An estimated 1.3 million Indians diedfrom this in 2000. The projected death from coronary artery disease by 2015 is 2.95 million, of which 14% will be <30 years, 31% will be <40 years [2].
Ischemic heart disease (IHD) is defined as acute or chronic form of cardiac disability due to imbalance between supply and demand of oxygenated blood. In more than 90% cases the cause of myocardial ischemia is reduced blood flow due to coronary atherosclerosis. Thus, IHD is often termed coronary artery disease (CAD) or coronary heart disease (CHD) [18]. The autopsy study provides a means of understanding the basic process which sets a stage for clinically significant atherosclerotic cardiovascular disease. There is no valid method of sampling of living population. It was; therefore, considered that death suspected due to any reason, probably provide the best sample of the living population for studying atherosclerosis and their correlation with ischemic heart diseases. In this study total number of heart specimens received in department All the deceased were grouped into specific age groups according to the age mentioned in the postmortem documents. In our study, most of the specimens of heart specimens were from age group 21-30 years. All the micro sections were examined microscopically for the presence of different types of atherosclerosis and myocardial infarction / fibrosis/hypertrophy. According to American Heart Association, typing of atherosclerotic plaques was done from type I to type VIII [5,6].
Aging is associated with structural and functional changes of the vessel wall, which result indecreased vascular dispensability and elevated arterial stiffness [17,24]. As a consequence of arterial stiffness, systolic blood pressure increases, causing a rise in left ventricular workload and subsequent hypertrophy, and diastolic blood pressure decreases, leading to an impairedcoronary perfusion [24,25].
In this study the overall atherosclerotic lesions (type I to type VIII) were significantly higher amongage groups>41 years as compared to <41 years and also significant atherosclerotic lesions (type IV to type VIII) were statistically significantly higher among age group > 41 years as compared to those with age <41 years (p value=0.000) in both right and left coronary arteries. Dhruv et al [26], Garg M et al [1]also reported increased frequency of atherosclerosis from 3rd decade onwards. Stressful, sedentary lifestyle, lack of exercise and poor dietary habits are the important factors for early initiation and development of atherosclerosis in young generation.
Age is a powerful risk factor for coronary heart disease. The development of atherosclerosis increases markedly with age up to an age of about 65, regardless of sex and ethnic background [27,28]. Major advances in medical, interventional and surgical therapy, together witheffective secondary prevention, has resulted inextended life expectancy and an improvement inthe quality of life of most patients with clinicalcoronary artery disease. Despite these achievements, the prevalence of coronary artery disease seems toremain high. However, the exact data on theprevalence of coronary atherosclerosis or clinicalcoronary artery disease are extremely diverse [29]. Overall incidence of atherosclerosis was foundto be 84.18% (181/215) in both the right and left coronary arteries our present study, however frequency given by Garg M et al [1]was (46%),Yazdi (40%) [30] and Golshahi et al (28.9%) [31].
Significant atherosclerotic lesions (type IV to type VIII) appearedin seconddecade onwards and there after there is a gradual increase both in its severity and frequency from third decade onwards. Maximum incidence was in fourth decade (88.9%) followed by in fifth decade.
Overall incidence of significant atherosclerotic lesions was 25.11% in right and 29.76% in left coronary artery. Earlier studies also in India by Wiget al [32] found significant atheroma in two-third of cases above the age of 20 years while Tandon [22] found atherosclerosis in second and thirddecade. Singh et al [20] found atherosclerosis atthe age of 17 years. Thereafter, there was steep rise in all the studies. Although we cannot explain the reason for sudden increaseafter the third decade but it deserves to attract enough attention. In present studyalso significant CAD lesions were statistically significantly higher among age group > 41 years as compared to those with age <41 years (p value=0.000) in both right and left coronary arteries.  [7], the overall incidence of significant atherosclerosis was found to be 55.33%, by Shirani et al [36]was (65%) and by McGill et al [37] it was (58%) in their studies.
Ischemic heart disease due to CAD is mainly caused by atherosclerosis. In general slowly developing coronary atherosclerosis of high grade (fibroatheroma) may not cause acute lesions but complications in atherosclerotic plaque in the form of superimposed coronary thrombosis due to plaque rupture or thrombosis may lead to acute attack. Those patients who survived attack showed changes of chronic myocardial ischemia in the form of focal or diffuse myocardial fibrosis, so small areas of fibrous scarring are found in elderly patients who have history of attacks of MI years back. Hearts from patients with chronic IHD are usually enlarged and heavy, due to left ventricular hypertrophy and dilation. Myocardial hypertrophy represents compensatory mechanism to meet the cardiac demand as hypoxia is produced by significant coronary atherosclerosis. In our study, 41 (19.06%) specimens showed different types significant myocardial lesions, acute MI was seen in 2 case (0.93%). In study by Garg M et al [1], acute MI was seen in 3 cases (3%), by Maru (6.5%) [38] and however Bharti Jha et al [39]12.3%, Porwal Vet al [7] 18.44% and Shiladaria P et al [40] in 22.5% of cases.
Present study shows that maximum number of significant cardiac lesion were associated with atherosclerotic type VIII lesions followed by type VII and type VI correlating with findings of Garg Met al [1] who observed that Maximum cases of significant cardiac lesions were associated with advanced atherosclerotic lesions i.e.type VI & type VII lesions.
In our study maximum cases of ischemic heart diseases were seen between 5 th -6 th decade of life. In study by Porwal Vet al [7], the maximum cases of ischemic heart diseases were seen between 4 th -5 th decade of life.

Conclusions
The study of human atherosclerotic lesion is an extremely difficult task in a living subject and an autopsy study is the best possible way to work on it. Our study aids valuable data to the literature regarding the morphology of atherosclerotic lesion and its relation to the significant cardiac lesion. Significant atherosclerotic lesions were seen in 54(25.11%) and 64(29.76%) cases in right and left coronary arteries respectively and were statistically significant higher among age group > 41 years as compared to those with age <41 years. The study also showed significant correlation between the higher grade of the coronary atherosclerotic lesions and the ischemic heart disease.

What is new in this study?
This study brings attention to the burden of the atherosclerosis in mewat region of Haryana. To the best of our knowledge no such study has been conducted in our institute, it also highlights a need of life style changes in general public and also calls for screening programmes and prevention and control measures against atherosclerosis from early age.