Morphological Changes of Coronary Arteries in Cases of Sudden Death due to Cardiac Causes - An Autopsy-Based 10-Year Retrospective Study.

INTRODUCTION: Ischemic heart disease (IHD) is the most common cause of cardiac deaths worldwide, mainly due to atherosclerosis. Prevalence of atherosclerosis evaluation, in an autopsy-based study, can be a valuable tool on subjects who died of cardiac causes. With this hypothesis, we conducted this 10-year retrospective study on the hearts of subjects who died due to cardiac causes.
MATERIALS AND METHODS: This study was conducted from January 2010 to May 2020 at Department of Pathology, Hassan Institute of Medical Sciences, Hassan, Karnataka. Autopsy was conducted at our hospital in the deceased patients who died of suddenly due to cardiac causes. Standard procedures were followed for the removal of intact heart. Heart specimens were sent to our department for histopathological analysis. After fixation in 10% formalin, specimens of the heart were examined in detail. Heart specimens were weighed and measured. The three main coronary arteries were identified and dissected out according to the standard guidelines. These arteries were carefully examined for any histological evidence of atherosclerosis and associated pathological lesions. After detailed study, the lesions were graded according to the classification given by the American Heart Association from Grade I to Grade VI and coronary luminal narrowing by White and Edwards method.
RESULTS: Evaluation of a total of 682 autopsy cases was done. In the evaluation, 574 cases were due to sudden cardiac caused deaths. 436 (76.03%) subjects had evidence of atherosclerosis in coronary arteries. In our study, 468 (81.53%) were male and remaining 106 (18.46%) were female. The most commonly involved coronary artery was left anterior descending coronary artery (LADA, 412 cases, 71.74%). Triple-vessel disease was found in 118 cases (20.55%) of subjects.
CONCLUSION: In Indian population, atherosclerosis of the coronary arteries begins at a younger age. Therefore, thorough screening for the same should begin at an early age. Our study showed alarmingly high prevalence of atherosclerosis in coronary arteries, especially in the LADA. Coronary atherosclerosis is an important risk factor for IHDs in both sexes, even though the incidence of atherosclerosis is more common in males when compared to females. Copyright:

INTRODUCTION

Atherosclerosis is a chronic degenerative condition of the arteries. Significant cardiovascular morbidity and mortality worldwide are mainly due to atherosclerosis. This condition is reported to be responsible for more than 25% of deaths in the Indian subcontinent.[1] In our country (India), atherosclerosis of the coronary artery has emerged as a major social epidemic. The increasing incidence of coronary artery atherosclerosis has touched alarming proportions. During the past 3–4 decades, this condition has almost doubled. It will soon emerge as the main etiology for nearly one-third of all deaths due to single largest disease in India. According to estimates, about 6.4 crore cases of coronary vascular disease occurred in 2015. About 1.3 million Indians died from this in 2000. It is projected that, in subsequent years, coronary artery disease would cause more and more sudden deaths, of which 14% of the mortality will be in population under 30 years of age and 31% deaths will occur in subjects below the age of 40 years.[2]

Development of atherosclerotic lesions starts at an earlier age. In the Indian population, lesions are found to be in more advanced stages when compared to the patients in western countries. The major concern of atherosclerosis is that it can lead to various complications such as myocardial infarction (MI), stroke, embolization, ulceration, thrombosis, and aneurysm. These complications can cause significant morbidity and mortality, which will affect the lifespan and the quality of life of a large segment of the population. Most of the time, those affected are the sole earners of a family.[12]

In living subjects, assessment of atherosclerotic lesions is very difficult due to its invasive nature and can be a highly expensive enterprise. Hence, in deceased subjects, autopsy-based study of the coronary vessels and the aorta has emerged as an invaluable tool for studying these atherosclerotic lesions. If an autopsy study is conducted on deceased patients without any prior history of coronary artery disease and who died suddenly due to cardiac causes (as compared to the deaths caused by noncardiac causes), it shall be a true representation of distribution and prevalence of atherosclerotic lesions present in the population. With this hypothesis, we conducted this retrospective study in 682 cardiac deceased patients.

MATERIALS AND METHODS

This study was conducted from January 2010 to May 2020 at the Department of Pathology, Hassan Institute of Medical Sciences, Hassan, Karnataka, in India.

The deceased patient's prior/past medical histories were recorded in detail. Autopsy was done on the deceased patients at our hospital. Heart samples were also received from the peripheral referring hospital related to medicolegal cases. Deceased hearts were subjected for histopathological analysis. Written informed consent was taken from the relative/guardian of the deceased patient. The study was ethically approved by the institute's ethical committee.

During this 10-year retrospective study, we received the hearts of 682 successive autopsies in our department, ranging in age from 18 to 78 years. Among these, 574 deceased individuals had no prior history of cardiac disease, that is, sudden deaths due to cardiac causes. According to the standard autopsy protocol and guidelines by Virchow's method, the hearts were dissected. The hearts were fixed in 10% formalin, weighed, measured, and the three main coronary arteries were dissected out. All the representative suspected pathological lesions from left common coronary artery, right coronary artery (RCA), left anterior descending coronary artery (LADA) and left coronary artery (LCX) were subjected for tissue processing.

Each coronary artery was then sectioned transversely and if needed longitudinally with a new scalpel blade. The exposed artery was carefully examined for any thickening, yellow streaks, frank plaque, or calcification. From these representative grossly appreciable areas, multiple sections were taken and proper identification number was given. 4 μm thickness sections were taken, after routine tissue processing and paraffin embedding, and stained with routine hematoxylin and eosin.

All the histological sections were examined microscopically for the presence of atherosclerotic changes and also studied for the features of areas of MI present if any in representative anatomical areas supplied by these arteries. Atherosclerotic changes were graded according to the American Heart Association guidelines as below:

Grade 0: Sections showing normal histology or adaptive thickening without macrophages or foam cells

Grade 1: Presence of isolated macrophages and foam cells

Grade 2: Mainly intracellular lipid accumulation [Figure 1]

Figure 1

Left anterior descending coronary artery showing atherosclerotic changes with luminal stenosis of Grade II

Grade 3: Grade 2 lesions along with focal amount of small extracellular lipid pools [Figure 2]

Figure 2

Atherosclerotic lesion in the wall showing plenty of cholesterol clefts

Grade 4: Grade 2 changes along with a core of extracellular lipid [Figure 3]

Figure 3

Left anterior descending coronary artery showing atherosclerotic changes with luminal stenosis of Grade III

Grade 5: Lipid core and fibrotic layer or multiple lipid cores and fibrotic lipid layers; mainly calcific or fibrotic

Grade 6: Surface defect [Figure 4], hematoma, hemorrhages, or thrombus formation.

Figure 4

Left circumflex coronary artery showing surface ulceration of fibroatheromatous plaque

After thorough evaluation, the degree of luminal narrowing of all these main coronary arteries was graded from I to IV [Figure 5] by the guidelines of White and Edwards method [Table 1].

Figure 5

Left anterior descending coronary artery showing atherosclerotic changes with luminal stenosis of Grade IV

Table 1

Grades of stenosis of lumen due to coronary atherosclerosis (White and Edwards method)

Grade	Percentage of coronary artery luminal stenosis
I	Up to 25
II	26 to 50
III	51 to 75
IV	76 to 100

RESULTS

In our retrospective study period from January 2010 to May 2020, 682 consecutive autopsied hearts were submitted to the department of pathology, of which 574 deceased subjects had no prior history of coronary vessel disease and had a history of sudden cardiac cause of death. The age group ranged from 18 to 78 years.

Out of these 682 deceased heart specimens due to sudden death, 574 (84.16%) subjects had histopathological evidence of coronary atherosclerosis. In our study, 468 (81.53%) were male and remaining 106 (18.46%) were female. The average heart weight for all 574 cardiac death subjects in males and females was found to be 282.21 g and 221.74 g, respectively.

All the subjects were grouped into specific age groups based on the age at the time of death. The age-wise distribution of all 574 cases showing evidence of atherosclerosis is given in Table 2. Our study revealed that the maximum number of atherosclerosis (139) cases was seen in the age group of 51–60 years. Similarly, the distribution of types of coronary atherosclerosis in the LADA of the present study in relation to age and sex according to the American Heart Association is shown in Table 3 in which Type IV lesions were commonly seen in male heart specimens and Type III lesions were commonly seen in female heart specimens. When compared with that of female heart coronary arteries, severe Type V and VI of lesions with complications such as severe critical stenosis [Figure 6] rupture, hemorrhage, obstruction, and organized and recanalized thrombus [Figure 7] were more common in male coronary arteries.

Table 2

Age - wise distribution of coronary atherosclerosis in this present study

Age (In years)	Number of Atherosclerosis cases	Involvement in percentage
18-30	74	12.89
31-40	108	18.81
41-50	131	22.82
51-60	139	24.21
61-70	84	14.63
71-80	38	6.62

Table 3

Distribution of types of coronary atherosclerosis in LADA of present study in relation to age and sex according to American Heart Association (M=Male, F=Female)

Age	Type of lesion												Total
	I		II		III		IV		V		VI
	M	F	M	F	M	F	M	F	M	F	M	F
18-30	12	5	15	4	17	5	15	1	-	-	-	-	74
31-40	16	6	18	5	25	4	27	3	4	-	-	-	108
41-50	10	5	17	6	31	5	32	2	21	2	-	-	131
51-60	-	-	13	2	28	8	33	7	35	2	9	2	139
61-70	-	-	-	-	-	-	25	10	32	7	6	4	84
71-80	-	-	-	-	-	5	12	2	13	2	2	2	38
Total	38	16	63	17	101	27	144	25	105	13	17	8	574

(Deceased Female: 106, Deceased Male: 468)

Figure 6

Fibroatheromatous plaque with critical stenosis of lumen of left anterior descending coronary artery

Figure 7

Complicated atherosclerosis showing organized thrombus, recanalization, and associated pathologic calcification

Out study results revealed that watershed line in the pathogenesis of coronary vascular atherosclerosis appears to be the third decade of life. The severity of atherosclerosis and number of coronary vessels involved will be from the third decade onward. A steady increase in overall frequency of atherosclerosis from mild (Type I and II) to moderate (Type III and IV) to severe (Type V and VI) was observed in our study. The degree of coronary artery luminal stenosis was graded by White and Edwards method [Table 4]. Severe grade of atherosclerosis with secondary complications were more so observed commonly after 40 years of age, especially in male, and there was a gradual decline in severity after 70 years.

Table 4

Grade of coronary artery luminal stenosis in LADA of present study in relation to age and sex according to White and Edward method

Age	I		II		III		IV		Total
	M	F	M	F	M	F	M	F
18-30	38	2	28	-	6	-	-	-	74
31-40	37	7	21	1	20	3	18	1	108
41-50	22	5	33	8	41	3	17	2	131
51-60	7	2	21	14	45	11	31	8	139
61-70	-	-	11	15	22	8	23	5	84
71-80	-	-	5	6	11	4	11	1	38
Total	104	16	119	44	145	29	100	17	574

(Female patients – 106, Male patients: 468)

Among the 574 cases, all the three coronary arteries were severely involved (triple-vessel disease) in 242 cases (42.16%). Involvement of two-coronary vessel and single-coronary vessel disease was seen in 211 (36.75%) and 121 (21.08%) cases, respectively.

Evidence of acute MI was found in 69 (12.02%) cases. Old healed scars [Figure 8] were found in 87 (15.15%) cases, and evidence of congestion was found in 262 (45.64%) cases as associated histopathological findings on histopathological examination of deceased heart.

Figure 8

Microscopy showing associated features of old healed myocardial infarction

DISCUSSION

In India, alarming proportions of morbidity and mortality have reached due to coronary atherosclerosis. In the next decades, maintenance of upward trend in the numbers is expected. The onset of atherosclerosis starts early in life from childhood and gradually progresses through young adulthood to form the lesions that cause coronary heart disease later in life. Atherosclerosis is a commonly observed pathological finding in almost all ethnicities and societies worldwide, with variable prevalence in different races.

In our study, the overall incidence of atherosclerosis was found to be 84.16% caused by sudden death due to cardiac causes. The incidence rates were compared to the earlier study findings by Garg et al. (46.4%),[3] Yazdi et al. (40%),[4] Golshahi et al. (28.9%),[5] and Dhruva et al. (23.3%).[6]

The Indian population is more vulnerable to coronary vascular disease with earlier onset of this condition. Coronary vascular disease is mainly caused due to atherosclerosis which can result in ischemic heart disease. In our study, we found that in individuals from the third decade of life onward, there is a progressive steady increase in atherosclerosis of coronary vessels. Our present study result findings corroborate well with the data from earlier studies in India by Singh et al.[7] and Wig et al.[8]

According to Singh et al.,[7] significant atherosclerotic lesions start developing from the second decade of life onward. Atherosclerotic lesions from the second and third decades of life onward show a progressive increase in the number and severity in Tandon et al.'s study.[9] Dhruva et al.[6] also reported similar findings with increasing frequency of atherosclerosis from the third decade onward and with a peak of 76.6% in the sixth decade, followed by a decline to 66.7% in the eighth decade. A progressive increase in atherosclerotic lesions from the third decade onward was noted in Garg et al.'s[3] observations.

Human life style has become more and more complex and challenging in this modern globalized era. Etiological factors, pathogenesis, clinical course and complications of atherosclerotic lesions in Indian subset of population may be due to anxiety, depression, etc. along with a sedentary lifestyle, lack of exercise, intake of junk food and increased use of refined and processed food items instead of consuming whole grains and fresh fruits and vegetables.

A multitude of national and international studies conducted in the past have shown that coronary heart disease has a relative preponderance in males. Garg et al.[3] have shown that coronary atherosclerotic lesions were 80.9% (93) in males as compared to 19.1% (22) in females. In the study done by Murthy et al.,[10] of 150 cases of coronary atherosclerotic lesions, 123 (82%) were male and 27 (18%) were female. Coronary atherosclerotic lesions were more prevalent in 74.8% of males in comparison to 24.2% of females in the study by Bhargava and Bhargava.[11] Singh et al.[7] also reported coronary atherosclerotic lesions in 200 cases and found that these lesions were more frequently found in 85% of males as compared to 15% in females. 66.5% of males and 33.5% of females were affected by coronary atherosclerotic lesions in the study by Padmavati and Sandhu.[12] Priti Vyas et al.[13] found a male (82%) preponderance of coronary atherosclerosis as compared to 18% in females.

In our present study too, we found a male (80.43%) preponderance of coronary atherosclerosis as compared to 19.56% in females, especially in sudden death due to cardiac cause. The findings of our study corroborate well with the findings of previous studies. Possible explanation in male preponderance toward the development of more severe and progressive atherosclerosis is greater indulgence of males in smoking and alcoholism as compared to females. Moreover, there may be a protective role of female hormones like estrogen against atherosclerosis.

In our present study, compared to 108 individuals of nonatherosclerotic cases, the average weight of the heart was greater in these 574 individuals with atherosclerosis. This may be due to increased cardiac workload and compensatory hypertrophy. Frequency and degree of severity of atherosclerotic lesions were more in males as compared to females. It was also evident as the average hearts of males were heavier than those of age group-matched female patients. Our findings are comparable to the similar findings of Dhruva et al.,[6] Garg et al.,[3] and Priti Vyas et al.,[13] who too found that the average heart weight in males was higher as compared to females.

In our study, atherosclerotic lesions with triple-, double-, and single-vessel disease were found in 42.16%, 36.75%, and 21.08% of cases, respectively. In the study done by Priti Vyas et al.,[13] the involvement of triple-, double-, and single-vessel was 22%, 12, and 13% of cases, respectively. Dhruva et al.[6] found that single-vessel was involved in 31%, while two- and three-vessel involvements were seen in 17 and 36% cases, respectively. Triple-vessel involvement (44.4%) was the most common, followed by double- and single-vessel involvement seen in 42.2 and 13.3% cases, respectively, in the study by Garg et al.[3] Our study reports correlated well with that of Garg et al.'s[3] findings.

In our study, coronary atherosclerosis with severe grade and luminal narrowing was noted in the LADA (38%), followed by RCA (29%) and left circumflex coronary artery (14%). The findings were in concordance with the data by Priti Vyas et al.,[13] wherein the incidence of coronary involvement in LADA was 40%, RCA 32%, and left circumflex artery 30%.

LADA was the most common site for fibroatheromatous plaque (47%) in the data given by Sudha et al.[14] Yazdi et al.[4] showed LADA as the most commonly involved artery (60%), followed by RCA (50%) and left circumflex artery (42.5%). Garg et al.[3] too found that LADA (38.1%) was the most common involved vessel followed by RCA (35.1%) and left circumflex artery (34%).

Our study data showed 69 cases (12.02%) of acute MI. Similar results were seen in Priti Vyas et al.,[13] study of acute MI of 10.8% cases. Observations of 9.72%, 6.5%, and 3% acute MI cases were revealed by Dhruva et al.,[6] Maru,[15] and Garg et al.,[3] respectively, in their study. In our study, even though subjects did not have any prior history of a coronary vascular event or history of cardiac cause of death, the percentage of acute MI was slightly on the higher side. The rising cardiac death rate definitely indicates that it is the price being paid for the industrialization and rising socioeconomic status which are linked to increased tobacco smoking, alcoholism, fat-rich diet, and sedentary life style. These are common preventable risk factors.[16]

CONCLUSION

Autopsy study is the best possible way to work on human atherosclerotic lesions. Results of our study highlight the early onset with increasing prevalence and severity of atherosclerotic lesions (in India). Our study involved only large number of cases with 10-year retrospective study causing sudden cardiac death.

In this study, findings revealed unexpectedly high prevalence of atherosclerotic lesions, especially in the relatively young population with no prior history of cardiovascular disease and where the diagnosis of coronary vascular disease was least suspected. Hence, screening programs along with preventive and control measures against atherosclerosis from an early age may be adopted to prevent complications of this disease.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.