Coronary Artery Disease: Risk Promoters, Pathophysiology and Prevention Gundu HR Rao, S Thanikachalam
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Epidemic of Coronary Heart Disease in the Migrant South-African Indian Population1

YK Seedat
 
SUMMARY
Coronary heart disease (CHD) is the most common cause of morbidity and mortality in the South-African Indians. Cardiovascular diseases are just as much an “epidemic” among the Indians of South Africa as among the Whites, and the “epidemic” of ischemic heart disease, cerebrovascular disease and heart disease is of more serious proportions than in Whites. Ischemic heart disease was also more common in Indians in South Africa than those in India. It appears that emigrant Indians have a higher incidence of vascular disease than Indians in India. This is because of the combination of hyperlipidemia, hypertension and diabetes mellitus. The high incidence of ischemia in Indians and the low incidence in Blacks in South Africa suggests that there may be different thresholds beyond which the risk factors begin to operate. This paper reviews the historical aspects, risk factors and clinical pattern of CHD in this population group.
 
INTRODUCTION
South Africa is a large country with a surface area of just over 1.2 million square kilometers, situated on the southern tip of Africa. Its population is about 40 million and is growing at the rate of 2.5 percent per year.1 Census data (1998) showed that the population of South Africa is 40.5 million (Blacks 31.5 million, Whites 4.4 million, “mixed” group 3.6 million and Indians 1 million).2 South-African Indians probably constitute the largest migrant Indian population in the world.
Coronary heart disease (CHD) is by far the most important cause of death among Whites and Asians in the category of diseases of the circulatory system and, in fact, the most important of all causes of death. The total rates (males and females) of 165.3 / 100,000 for Whites and 101.2 for Asians surpass by far that of the ‘mixed’ group (55.1/100,000). Blacks have a minimal rate of CHD, at 5.3/100,000.3 However, from 1978 to 1989 the total death rate for White males 2(per 100 000 population) fell from 1 002 to 631 (37%), and the CHD mortality rate from 312 to 139 (a 56% decrease). Rates for Asians fell from 1,306 to 1,130 (14%) and from 355 to 226 (36%), respectively, and those for ‘mixed’ group from 1,691 to 1,392 (18%) and from 171 to 110 (36%). For Blacks, the total mortality rate remained unchanged. Local falls are none the less in line with those in Western countries.4 Cerebrovascular disease has the highest death rate in the ‘mixed’ group (80.6/100,000) followed by Whites, Asians and then Blacks with decreasing rates of 73.6, 62.5 and 36.5.3 These data are unreliable. Understandably the accuracy of the data, as with such data overseas, is questionable.4
 
Historical Background
The majority of Indian South Africans are the descendants of indentured workers brought to Natal between 1860 and 1911 to develop the country's sugar belt. Free or passenger Indians followed the indentured workers, but White colonists became alarmed by the competition offered by these merchants and by those whose labor contracts had expired. By 1913 Indian immigration was generally prohibited by law. The result is that, with few exceptions, Indian South Africans are South-African citizens by birth.5 The Indian population of South Africa is composed of two so-called races, Dravidian and Aryan, the two having distinct cultural and anthropological characteristics.
The major Indian languages spoken in South Africa are Tamil, Telegu, Hindi, Gujarati and Urdu. The three main religions are Hinduism, Islam and Christianity. These groups of people differ from one another considerably as regards dietary habits, body build, degree of pigmentation of skin in the majority of cases, marriage and social customs, cultural activities, home dress and place of origin in India. The Tamil and Telegu-speaking people came to South Africa from the South Indian states of Tamil Nadu and Andhra Pradesh. All Indians who do not belong to the Dravidian race are said to belong to the Aryan race and culture. Aryans speak mainly Hindi, Gujarati, Memon and Konkani. Those who have migrated to South Africa from the Northern and Northeastern parts of India, mainly the states of Uttar Pradesh, Bihar and Orissa, speak Hindi or Urdu. Both Muslims and Hindus who migrated from the state of Gujarat speak Gujarati.6
 
Cardiovascular Mortality Rates
The data issued by the Central Statistical Services show that because of the high mortality rates for CHD and hypertensive disease in older Indians, in Indians over the age of 45 years approximately 50 percent of deaths from all causes were due to disease of the circulatory system. The mortality rate for diabetes is extremely high in both male and female Indians.7 In a mortality rate analysis Wyndham concluded that “Cardiovascular diseases are as much an ‘epidemic’ among Asians as in Whites.8 Walker9 considered that from the age of 50 years onwards the South-African Indian population, which enjoys much better economic circumstances than the indigent rural 3population in India, had very little life-expectancy advantage; the main cause of death had changed from infectious to degenerative diseases. South-African Indians were worse off than Indians in India beyond middle age.9 The high incidence of CHD in the metropolitan hospitals of Durban has been recorded.1014
 
Risk Factors for CHD in the Community
The Department of Medicine, University of Natal, did a field survey in 1984 to 1985 to document the prevalence of known risk factors for CHD in the community.15,16 This was done in the Indian population living in the metropolitan area of Durban, Natal. The majority of South-African Indians live in Natal and most of them live in Durban, a city on the sea coast of Natal. Durban, like the rest of South Africa when the Group Areas Act was in existence, was divided into zones set-aside specifically for different ethnic groups. The Indian group areas were scattered throughout metropolitan Durban. A representative random sample of the population, residing in these various geographical areas specifically set aside for Indians, was selected for the survey. The sample size was determined on the grounds of practicality. The 1980 population census figures were used to ascertain the total Indian population of metropolitan Durban (499–520) and that for each residential area.17 The latter information, together with the number of dwellings in each area, was obtained from the various municipalities included in metropolitan Durban. Using this information together with the number of dwellings and the population in each group area, a fixed percentage of 0.24 percent per area was selected for the study. The sampling was by random selection. Eligible respondents had to be within the age range of 15 to 69 years and permanent residents within the geographical area of metropolitan Durban. The exclusion criteria were pregnancy and lactation, being bedridden, mental retardation, carcinoma and antituberculosis therapy. Household addresses were randomly selected from the latest ratepayers' and electricity consumers' records. At each address one member of the family was selected randomly for participation in the study.16 The overall response rate was 95 percent. Crude prevalences for each sex were age-adjusted using the 1985 census population figures.
A summary of the salient risk factors leading to CHD is as follows. In a study of 778 subjects aged 15 to 69 years (408 men), a positive history of CHD as based on the Rose Questionnaire18 was obtained from 12 percent of the men and 18.9 percent of the women, i.e. 15.3 percent of the total sample. Resting ECG tracings were analyzed on 741 subjects (389 men and 352 women). Abnormalities that could be coded according to the revised Minnesota Code Manual19 were detected in 49.6 percent (age-adjusted 49.4%) of men and 45.5 percent (age-adjusted 47.1%) of women. Table 1.1 shows the prevalence of ECG findings possibly denoting the presence of CHD.4
Table 1.1   Relevant ECG findings denoting coronary artery disease
Minnesota code19
ECG Abnormalities
Men (%)
Women (%)
1.1
Large Q waves
1.80
0.85
1.2
Medium Q waves
8.48
5.11
3.1
Left ventricular hypertrophy
6.68
2.27
4.1
Large ST depression
0.77
1.99
5.1
Large T waves
0.26
5.2
Medium T waves
1.54
3.41
7.1
Left bundle-branch block
7.2
Right bundle-branch block
0.26
0.28
The prevalences of hypercholesterolemia, smoking and hypertension were examined at two levels of risk: level A (≥ 6,5 mmol/l), which is the conventional cutoff point and is regarded as the higher level of risk, and level B (≥ 5.7 mmol/l) at which the risk of CHD is higher than average according to the Pooling Project Data.20 Fasting serum cholesterol levels of ≥ 6.5 mmol/l were detected in 22.3 percent (age-adjusted 20.2%) of males and 20.0 percent (age-adjusted 13.8%) of females. Smoking was regarded as a risk factor (≥ 10 cigarettes per day), and 41.9 percent (age-adjusted 40.8%) of males and 5.7 percent (age-adjusted 5.3%) of females were smokers. It was observed that when the figures were age-adjusted, 55.8 percent of males and 33.0 percent of females smoked 1 cigarette per day or more. Hypertension (according to the definition of systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 95 mmHg) was more prevalent in women (20.0%) than in men (17.4%). On the basis of the modified glucose tolerance test21 and the presence of a positive history of diabetes, 15.3 percent (age-adjusted 12.8%) of men and 16.2 percent (age-adjusted 12.0%) of women were diabetic. In the total sample, therefore, at the higher level of risk, 20 percent were hypercholesterolemic, 25 percent were at risk from smoking, 19 percent were hypertensive and 16 percent were diabetic. An analysis of the major reversible risk factors showed that when considering hypercholesteremia, hypertension, smoking and diabetes 52 percent had at least one major risk factor at level A and 68 percent at level B. Looking at the combination of risk factors, it was found that 17 percent and 25.1 percent had two major risk factors at levels A and B respectively. With regard to combinations of risk factors, hypertension and smoking (≥ 10 cigarettes a day) was the most frequent combination in men, while in women hypertension and diabetes frequently occurred together. The high-density lipoprotein (HDL)/total cholesterol (TC) ratio was regarded as being protective when the HDL level was 20 percent or more of the TC level. This ratio was found to be favorable (‘protective”) in 58.6 percent of the respondents—an extremely high level in a population group known to have a high prevalence of CHD (57.1% in males and 68.2% in females).5
Investigation of minor risk factors such as the body mass index showed that 58.4 percent of women were overweight and 21.8 percent obese (BMI ≥ 30). Hyperuricemia (males ≥ 0.42 mmol/l, females ≥ 0.34 mmol/l) was found in 10.4 percent of males and 11.8 percent of females. A positive history of CHD in immediate family members, viz. grandparents, parents and/or siblings, was obtained in 41 percent of the respondents.
A fair proportion of subjects—30.6 percent of males and 21.7 percent of females—were involved in sedentary work activity. Using the Bortner scale for detection of type A behavior, 19.8 percent of males and 17.9 percent of females fell into this coronary-prone category. A history of alcohol intake was obtained from 56 percent males and 5 percent of females and found not be significantly related to the presence of CHD.
 
Association between Hypercholesterolemia and Other Risk Factors
In our study 22.3 percent of the men and 20 percent of the women were hypercholesteremic (level A), but this difference was not significant (P = 0.110; chi-square test). Unpublished data have shown that in a fair proportion of our population hypercholesteremia is likely to be familial in origin and that diet also possibly plays a role. There was a highly significant association between age and high serum cholesterol levels. When stratifying for age, it was found that in the group aged under 45 years, 14.8 percent of a total of 540 subjects were hypercholesteremic. In the group aged 45 years and over 32.6 percent of respondents had high levels of cholesterol. Hypercholesteremia was significantly associated with high triglyceride levels (Cochran-Mantel-Haenszel: P = 0.001) and a non-protective HDL/TC ratio (Cochran-Mantel-Haenszel: P = 0.001). In the younger age group there was a significant association with smoking of 10 or more cigarettes per day. Similarly, there was a significant association with hypertension in the younger age group (P = 0.001' chi-square test), but not in the older group (P = 0.499).
 
Association of Risk Factors with Presence of CHD (Table 1.2)
This association was tested after stratifying for age (< 45 years, ≤ 45 years) and sex. For the analysis the presence of CHD was based on a positive Rose questionnaire or relevant ECG changes (Table 1.1). A highly significant association was found between diabetes and a history of CHD (CMH: P < 0.001). Similarly, there was a highly significant association between a raised serum triglyceride level and CHD. It was also observed that 30 percent of the subjects who had hypertriglyceridemia were diabetics. Since the prevalence of diabetes was high in this population group, the association between a history of CHD and other risk factors was assessed by controlling for age and sex as well as diabetes, and indicated that high triglyceride levels (CMH: P = 0.001), hypercholesterolemia (CMH: P = 0.023) and low levels of education (< Standard 5) (CMH: P = 0.042) were significantly associated with CHD.
6
Table 1.2   Prevalence (%) of risk factors in subjects with history of coronary artery disease
History of CAD
No history of CAD
Men
Women
Total
Men
Women
Total
No of subjects
49
70
119
359
300
659
Mean age (years)
44.3 ± 15.9
44.1 ± 7
35.5 ± 13.5
37.5 ± 13
Hypercholesterolemia
33.3
29.4
31.0
20.9
15.1
18.2
Hypertension
40.8
25.7
31.9
14.2
18.7
16.2
Overweight
20.4
67.1
47.9
22.0
56.3
37.6
Obesity
4.1
27.1
17.7
3.1
20.3
10.9
Hyperuricemia
12.5
16.2
14.7
10.1
15.4
12.5
Smoking > 10/d
44.9
11.4
25.2
41.5
4.3
24.6
Diabetes
21.6
21.5
21.6
11.1
9.9
10.6
Family history of CAD
42.9
50.0
47.1
39.0
41.7
40.2
 
Insulin Resistance
The syndrome of insulin resistance consists of glucose intolerance, hyperinsulinemia, hypertension, low plasma HDL cholesterol and high serum triglyceride.22 We have found that important factors denoting insulin resistance were associated with hypertension, viz. hypercholesterolemia, low plasma HDL cholesterol, obesity, diabetes and hypertriglyceridemia.23 Our Indian population has been shown to have high plasma insulin levels in pregnancy24 and in impaired glucose tolerance states.25 Young Indian medical students develop metabolic risk factors for CHD at an early age compared with young Black medical students.26 It has been suggested that insulin resistance in the South Asians of London leads to the high incidence of CHD.27 We consider that this interesting concept could explain the high incidence of CHD in migrant Indians throughout the world.
 
Dietary Pattern of Durban Indians
We did a cross-sectional study,28 which formed part of a CHD survey on the dietary pattern of Indians in Durban. Results showed a low energy intake, and the percentage of energy derived from total fat varied from 21.3 to 34.9 percent in males and from 33.1 to 36.1 percent in females. A salient characteristic of the diet was the high intake of polyunsaturated fatty acids, which comprised more than 10 percent of energy, with a median polyunsaturated/saturated fatty acid ratio (P/S ratio) varying between 1.38 and 1.96 for the various age and sex groups. Dietary cholesterol ranged from 66 to 117 mg/4.2 MJ in males and from 76 to 109 mg/4.2 MJ in females. Dietary fibre intake was also low. Although the energy distribution for total fat and dietary fibre intakes of the study population did not meet prudent dietary guidelines, the dietary P/S ratios were high and the effect of such a high P/S ratio on the oxidation of low-density lipoprotein 7in this population, which has a high prevalence of CHD, should be investigated as a possible factor for CHD.
Indian and Black patients admitted to hospitals in Durban with a diagnosis of cardiac infarction and diabetes mellitus were studied. The mean cholesterol was higher in the Indian group compared with the Black group. A negative correlation was found between the leucocyte ascorbic acid and serum cholesterol in Indians, especially in patients with infarction. This, however, did not preclude an effect of latent ascorbic acid deficiency on the vessel wall.29
 
Other Dietary Studies in South Africa
Dietary risk factors for CHD include high intakes of saturated fatty acids and cholesterol, with low intakes of mono and polyunsaturated fatty acids. In a characterization study, plasma fatty acid profiles have been determined in seven groups of high school pupils aged 16 to 18 years, namely, White, rural Black, urban Black and middle-class and lower socioeconomic class ‘mixed’ group and Indians. Plasma fatty acids were measured by gas liquid chromatography in 20 subjects from each group. Contrary to expectation, urban and rural Black pupils had the highest mean molar composition of saturated fatty acids, largely myristic (14:0) and palmitic (16:0) acids. Rural Blacks and middle-class ‘mixed’ group had the highest molar percentage composition of mono-unsaturated fatty acids, primarily oleic acid (18:1). Again unexpectedly, White, colored and Indian groups had the highest level of polyunsaturated fatty acids, due entirely to linoleic acid (18:2). As the findings are unrelated to proneness to CHD mortality in the particular communities studied, plasma fatty acid levels are not predictive of the disease. Epidemiologically, there are many examples of lack of correlation in serum lipid levels and proneness to CHD.30
 
Other Clinical Studies in South Africa
Studies in a coronary care unit in Durban between 1966 and 1999 in 245 patients showed that there was a strong familial link: 54 percent of the patients had a family background of CHD, whilst 42 percent and 41 percent had family members who suffered from diabetes mellitus and hypertension respectively. The authors felt that a strong familial link was observed not only for CHD, but also for hypertension and diabetes mellitus, supporting a genetic basis for the development of premature CHD.31
Coronary artery disease (CAD) was investigated by selective coronary cine angiography in 94 White, 59 Indian and 17 Black patients and correlated with plasma cholesterol and triglyceride levels and glucose tolerance. CAD was found in 94 percent, 97 percent and 82 percent and hypercholesterolemia in 68 percent, 61 percent and 50 percent of the Whites, Indians and Blacks respectively. In the White group, cholesterol levels correlated with both frequency and severity of CAD. Hypertriglyceridemia occurred in 44 percent of the White, 47 percent of the Indian and 23 percent of the Black group, but did not correlate with the extent of CAD in any. Diabetes was 8detected in 56 percent of the Whites and 47 percent of the Indians, but was absent in all the Blacks tested. Hypercholesterolemia appeared to be the only risk factor common to all racial groups.32
A number of risk factors for CHD in 7 groups of South-African male scholars aged between 15 and 20 years were surveyed. Selection of the groups was based on socioeconomic status and comprised urban and rural Blacks, Indians of higher and lower socioeconomic status, ‘mixed’ group of higher and lower socioeconomic status and middle-class Whites. Both Indian groups, both ‘mixed’ groups and the Whites had a much greater prevalence and severity of CHD risk factors than the two Black groups. This held for total cholesterol, low-density lipoprotein cholesterol (LDLC), high-density lipoprotein cholesterol (HDLC), the HDLC/LDLC ratio, apolipoprotein B, apolipoprotein A-I, insulin, fibrinogen and mass. One exception was lipoprotein a, levels of which were higher in both Black groups. In general, the CHD risk factor profile was worse in the higher socioeconomic groups and it also tended to be worse in urban than in rural Blacks.33
 
Comparison of CHD Data in India and in Indians in the UK
CHD and coronary risk factors were two or three times higher among urban compared to rural subjects of India, which may be due to more sedentary behavior and greater alcohol intake among urban people. In both sexes central obesity was four times more common in the urban than in the rural population. In both sexes, there was a significant association between CHD and age, hypercholesterolemia, hypertension and central obesity.34 Fasting plasma insulin and HDL cholesterol levels in urban subjects were comparable with rural subjects. Underlying these differences in risk factors, urban subjects had three times better socioeconomic status than rural subjects and were eating more total and saturated fat, cholesterol and refined carbohydrate and less total and complex carbohydrates than rural men and women. Energy expenditure during routine and spare-time physical activity was significantly higher in rural than in urban subjects.35 Risk factors for CHD were higher in social classes 1, 2 and 3 compared with lower social classes.36
A West London cohort study comparing migrants from the Indian subcontinent of Punjabi origin with their siblings in Punjab found that the West London cohort had a greater mean body mass index and higher serum cholesterol and apolipoprotein B levels, lower HDL cholesterol levels and higher fasting blood glucose levels than their counterparts in India. Insulin sensitivity was lower in men in West London and beta-cell function was lower in Indians in West London compared with their siblings in the Punjab. Serum lipoprotein (a) concentrations were similar in the two populations, but were significantly higher than those of White populations in the UK. Increases in serum cholesterol after migration from India led to increased coronary risk conferred by high serum lipoprotein (a) concentrations and greater insulin resistance. Such between-country comparisons are an important means of establishing the importance of coronary risk factors.37 Patients originating from the Indian subcontinent are at 9substantially higher risk of death and of further coronary events after a first myocardial infarction than are Europeans.38 This is probably due to their higher prevalence of diffuse coronary atheroma. Their need for investigation with a view to coronary revascularization is therefore greater. A history of diabetes is an inadequate surrogate of ethnic origin as a prognostic indicator.39 In a review of CHD in India, Bhatia39 stated that estimates of the prevalence are similar to those of many developed countries. In his analysis, Bhatia found that in some studies in India the data were inadequate and the available information cannot be used for national data projection. He felt that there was an urgent need for well-designed studies in all parts of India in view of the differences in race, culture, ways of life, diet, stress and strain, and the myriad other factors likely to affect the occurrence of cardiovascular diseases.39
 
CONCLUSION
CHD is a major cause of morbidity and mortality in the Indian population of South Africa. A study of the major risk factors leading to CHD showed that 52 percent (age-adjusted 45.5%) had at least one major risk factor at level A (high level of risk) and 68 percent (age-adjusted 61.9%) at least one factor to level B. Diabetes mellitus was strongly associated with a positive history of CHD. Because of the severe nature of the ‘epidemic’ of CHD in the Indian population, an immediate and intensive program of primary prevention of CHD risk factors should be instituted.
While knowledge of the reasons for the rises and falls in CHD rates remains incomplete, Whites have none the less taken some preventive actions, while Indians and ‘mixed’ group have apparently taken little.3 It is probable that Indians will benefit from reducing serum cholesterol by dietary changes and then drug therapy, controlling blood pressure, blood sugar and central obesity, stopping cigarette smoking (particularly in males), and increasing physical activity. Success has been achieved in countries such as Finland, which have adopted this regime of prevention.4041 This includes all avenues of public health education, primary prevention, early diagnosis, effective treatment and secondary prevention.42
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