Trends in coronary artery disease and associated risk factors ... - Nature

Journal of Human Hypertension (2003) 17, 381–387 & 2003 Nature Publishing Group All rights reserved 0950-9240/03 $25.00 www.nature.com/jhh

ORIGINAL ARTICLE

Trends in coronary artery disease and associated risk factors in sub-Saharan Africans O Akinboboye1, O Idris2, O Akinboboye3 and O Akinkugbe4 1

Saint Francis Hospital, State University of New York at Stony Brook, NY, USA; 2Lagos State Ministry of Health, Lagos, Nigeria; 3Rohi Medical Clinic, Akure, Nigeria; 4University of Ibadan, Ibadan, Nigeria

It has been suggested that the prevalence of coronary artery disease (CAD) is steadily increasing in subSaharan Africa. To address this issue, we conducted a Medline search of English language articles on cardiovascular diseasesFand specifically CAD in AfricaF from 1966 to 1997. The prevalence of CAD and related complications is relatively low in most regions in Africa compared to that obtained in the economically developed countries, although the situation is rapidly changing due to trends in urbanization, changes in lifestyle,

acquisition of technology and the increasing numbers of tertiary care institutions. There are variations in reported prevalence rates within the different regions, but there is an upward trend in all the regions of the sub-Saharan Africa. This trend is believed to be related to the increasing frequencies of CAD risk factors in the subcontinent. Journal of Human Hypertension (2003) 17, 381–387. doi:10.1038/sj.jhh.1001562

Keywords: coronary artery disease; sub-Saharan Africa; cardiovascular disease; racial differences

Introduction

Results

With recent improvement in the control of malnutrition and infectious diseases, cardiovascular diseases (CVDs) have emerged as major causes of morbidity and mortality in many African countries. Hypertension is by far the most common CVD followed by rheumatic heart disease and cardiomyopathy.1 Nonrheumatic valvular heart diseases, coronary artery disease (CAD), pericardial diseases, congenital heart diseases, peripheral vascular disease and pulmonary heart disease are either underreported or rare (Figure 1).

Most of these studies were hospital-based series clustered in a few urban centres predominantly in western and southern parts of Africa. This poses a limitation, given the fact that the sub-Saharan region of Africa is home to approximately 500 million people with very diverse ethnic, physical and cultural make-ups living predominantly in rural communities. These include the true and forest Negroes who largely inhabit most of West Africa, the Bantus in Central and Southern Africa, the Tuareg Nilo-Hamites in the East horn of Africa, the pygmies of the Congo basin and the Hottentots in rural Namibia.3

Methods It is widely believed that the prevalence of CVDs in sub-Saharan Africa is increasing. 2 To address this issue, we conducted a Medline search of English language articles (including reference sections of literature) on CVDsFand specifically CAD in AfricaFfrom 1966 to 1999. Correspondence: Dr OO Akinboboye, Non-invasive Laboratory, St Francis Hospital, 100 Port Washington Blvd, Roslyn, NY 11576, USA. E-mail: [email protected] Received 1 May 2002; revised 1 October 2002; accepted 17 October 2002

Prevalence of CVDs in general

Most of the studies spanning the early part of the 20th century reported that CVDs were very rare and were predominantly infection related. Cooke4 in 1901 reported on the first 1500 in-patients that he saw in his hospital in Uganda in East Africa. He noted that 6% of all medical admissions were because of cardiac diseases. He wrote further ‘valvular diseases of the heart are common and high-tension pulses are not often met with’. Donnison5 in 1929 also noted the rarity of hypertension in a hospital-based survey of 1800 subjects in

Trends in CAD in sub-Saharan Africans O Akinboboye et al 382

50 Deve lope d Worl d Developin g World

45 40 35

IHD Ischaemic Heart Disease

30

HHD Hypertensive Heart Disease

25

CM Cardiomyopathy (incl. EMF)

RHD Rheumatic

PHD Pulmonary Heart Disease

20

CHD Congenital Heart Disease PER Pericarditis.

15 10 5 0 IHD

HHD

RHD

CM

PHD

CHD

PER

Figure 1 Distribution of specific cardiovascular diseases in developed (black bars) and developing (white bars) nations expressed as a percentage of total burden of cardiovascular diseases. IHD ¼ ischemic heart disease, HHD ¼ hypertensive heart disease, RHD ¼ rheumatic heart disease, CM ¼ cardiomyopathy, PHD ¼ pulmonary heart disease, CHD ¼ congenital heart disease, PER ¼ pericardial disease.

Kavirondo district of Kenya, East Africa. The annual medical and sanitary reports of Nigeria and Ghana in West Africa from the early 20th century to the 1940s did not include hypertension in their lists of common CVDs;6 they identified infection-related cardiac diseases such as rheumatic heart disease, endocarditis, myocarditis and pericarditis as the most common CVDs in these countries. The prevalence of CVDs increased slightly by the middle of the century as reported by other series based on percentage of medical admissions because of CVDs. These include studies by Nhonoli7 in Tanzania, East Africa, 1968 (8.8%), Edginton8 in Seklukhuneland, South Africa, 1972 (8.6%) and Lauckner et al9 in Ibadan, Nigeria, West Africa, 1958 (11.2%). The spectrum of diseases also began to change, with hypertension becoming the most prevalent CVD in the region. Later studies conducted in the 1960s and beyond reported a higher overall prevalence of CVDs in general and hypertension in particular. The profile of CVDs in Ibadan, Nigeria in West Africa as reported by Akinkugbe et al3 showed that hypertension is the most prevalent CVD in adults. Another review by Vaughan10 reported the following spectrum of CVDs in sub-Saharan Africa: hypertension 16.3–44.5%, rheumatic heart disease 9.7–38.3%, endomyocardial fibrosis 4–12.1%, idiopathic cardiomyopathy 5–37.55%, syphilitic heart disease 1.1–16.8% and CAD 0.4–2.2%.

Prevalence of CAD

CAD is generally considered as an insignificant cause of morbidity and mortality in sub-Saharan Africa. Frequencies and related complications are relatively low in most regions in Africa, although Journal of Human Hypertension

the situation is rapidly changing owing to trends in urbanization, changes in lifestyle, acquisition of technology and the increasing numbers of tertiary care institutions. There are variations in reported prevalence rates within the different regions. South AfricaFA recent survey that was carried out at the King George V Hospital in Durban in 198611 found a prevalence rate of CAD (elicited by a questionnaire) of 2.4%. However, on an average, 40% of the subjects had ECG abnormalities based on the Minnesota Coding System.12 The wide disparity between the prevalence of CAD based on history and on ECG abnormalities in this survey11 underscores the limitations of using clinical history and ECG abnormalities to elicit the presence of CAD in black subjects. Schwartz et al13 reported a prevalence rate of CAD of 0.01% in their analysis of patients admitted to Barangwanath Hospital in the period 1951–1961. A later study at the Johannesburg Hospital in 1970 reported a prevalence rate of CAD of 0.6%.14 Also using electrocardiographic criteria, Schrire15 in Cape Town in 1970 reported a CAD prevalence rate of 1.4% in black subjects. These reports suggest an increasing trend over the years. East AfricaFVery low CAD prevalence rates were reported from Kenya and Uganda. In an autopsy study at the Coast Province General Hospital in Kenya in 1960, only one case out of 2000 admitted cases was confirmed as myocardial infarction.16 In Uganda, 449 out of the 15 176 admissions in a 1-year period had CVD and, of these, only three were considered to be CAD.17 Similarly, in Kampala, electrocardiographic evidence of possible CAD was found in only one of 412 villagers over the age of 45 years.18 West AfricaFA comparable prevalence was observed in West Africa, specifically in Ghana and

Trends in CAD in sub-Saharan Africans O Akinboboye et al

Nigeria. Autopsy procedures in Ghana over a 33year period reported 30 cases of CAD out of 3645 autopsies.8 An 8-year retrospective review of 6817 autopsies at the University College Hospital in Ibadan, Nigeria found only eight cases of CAD and a 1/20 000 admission rate for myocardial infarction (MI) in the same institution between 1961 and 1970.19 In a survey that was conducted in Ghana in 1976, 2% of 978 subjects aged 35–69 years had electrocardiographic evidence of infarction.20 In Cote d’Ivoire, 2.2% of patients admitted to a medical unit in 1965 with CVD had CAD.20 Central AfricaFIn a prospective review at the University Hospital, Butare, Rwanda, 17.2% of the elderly patients reviewed had CVD and only 1% had confirmed MI.21 In general, reports from West, East and South Africa have similar prevalence rates for CAD as shown above. However, it appears that CAD may be more common in the northern African countries than in the sub-Saharan regions.2 It has also been shown that CAD is more prevalent in urban than rural dwellers.2

Demographic trends in CAD

Age-related trends: As observed in developed countries, the prevalence of and mortality from CAD increases with age in sub-Saharan Africa. Data from South Africa suggest a gradual increase in death from CAD with age.22 In this analysis, mortality rates for CAD were found to be highest among older south African Asians. Some authors have attributed this trend to the increasing prevalence of most of the cardiovascular risk factors (hypertension, body mass index, alcohol consumption, etc) with age. A study of these risk factors was conducted in Tanzania in 1993 to determine their prevalence in adolescents.23 This study reported that, although the levels of these risk factors were generally low, most of them were established before the age of 15 years, thus highlighting the need for early primary prevention of CAD. Race-related trends: Of the different racial groups in South Africa, mortality rates for CAD were found to be highest in the Asians followed by white people.13 The mortality rates for CAD were found to be significantly lower in black people and coloreds compared to white people and Asians. The rates of CAD among Asians in South Africa are as high as seen in Western countries. Gender-related trends: Unlike the pattern in Western countries, gender-related differences in the prevalence of CAD have not been clearly shown in sub-Saharan Africa. The International Atherosclerosis Project found very little gender-related difference in advanced coronary lesions in a study on black South Africans.24 Some investigators have reported marked variations in the prevalence of CVD between different

races in sub-Saharan Africa. Studies in black and white South Africans showed that hypertension is the most common cause of CVD in black people, while CAD is the most common cause in white people.2 The study, which was conducted in Cape Town, South Africa in 1970, reported a CAD prevalence rate of 3% for white and 1.4% for black people.2 The study of deaths from CVD in various populations in South Africa also revealed some interesting trends.22 Mortality rates for CAD in Asian men and women were higher than those of white men with the exception of men in the 15 to 24-year age group and women in the 25 to 35-year age group. The rates for white people were also higher than for coloreds at all ages. The rates for black people were low compared to those for white people and coloreds.

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Effects of Trends in the Risk Factors for CAD

The upward trend, albeit small, in the prevalence of CAD in sub-Saharan Africa is believed to be mainly because of the increasing prevalence of CAD risk factors. A community-based cross-sectional study by Steyn et al25 that was conducted in 986 black subjects in Cape Peninsula, South Africa, showed that the prevalence of high blood pressure (4140/95 mmHg) was 14.4% in men and 13.7% in women. A total of 52% of men and 8.4% of women were smokers, and 17% of men and 26% of women had hyperlipidaemia. The most common risk factors for CAD were smoking in men and hyperlipidaemia in women. The known modifiable risk factors for CAD include hypertension, hypercholesterolaemia, low levels of HDL, cigarette smoking, diabetes mellitus, obesity, physical inactivity, hypertriglyceridemia and coagulopathy. (1) Hypertension: Hypertension is widely prevalent in most black African communities. The overwhelming majority of the patients have primary (essential) hypertension. Secondary forms are quite rare in Africans. In a recent national survey, the prevalence of hypertension in the general adult population in Nigeria was found to be between 10 and 12%. Furthermore, an increased prevalence of hypertension was noted at both extremes of socioeconomic strata (Figure 2). In an urban hospital survey in Zaire,26 hypertension constituted 70.7% of all CVDs seen, and was more frequent in the higher socioeconomic classes. In a survey of 2000 adults in the Cameroon, hypertension was present in 14.7% of the entire population and 8% of subjects under 30 years.27 A higher prevalence of hypertension in the lower socioeconomic groups and rural dwellers was noted in this latter study. Overall, the disease is found in both rural and urban black African communities, with slightly higher frequency in the latter, and does not appear to have any gender preference. Journal of Human Hypertension


60

% With Hypertension

50

40

30

20

10

0 1

3

5

7

9

11

13

15

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Socio-ecoomic Status Figure 2 Percentage of patients with hypertension in a Nigerian population by socioeconomic status (ranked from 1 (low) to 17 (high)) and sex (black bars ¼ women, white bars ¼ men).

Investigators have looked into the heterogeneity within and between African populations to detect clues to the prevalence of hypertension in subSaharan Africa. The high prevalence has been attributed to a biological adaptation to low salt supply in ancient West Africa, causing a tendency to salt retention.28 These investigators cited the relatively lower prevalence of hypertension in Gambia and SenegalFcountries with extensive salt production since ancient timesFas supporting evidence. This theory was challenged by Curtin29 in his review of the slavery hypothesis for hypertension among African Americans. He noted that although some areas in the sub-Sahara were deficient in salt in the 18th and 19th centuries, they made up for it through an elaborate set of trade networks. He also emphasized that tropical regions near the sea coast had ready access to salt through the practice of collection and evaporation of sea water. In addition, the fact that studies conducted in the early part of the century in the region reported a low prevalence of hypertension contradicts this theory. A more credible explanation for the high prevalence of hypertension is the influence of changes in lifestyle. In support of this theory is the fact that hypertension is generally more prevalent in the urban than rural areas. In addition, there are still some communities in Africa with a low prevalence of hypertension and without the customary rise in blood pressure with age.1 The common characteristics of such communities are their remoteness from Western lifestyle and the absence of risk factors Journal of Human Hypertension

associated with hypertension. These communities include the Pygmies of the Ituri forest in northeastern Zaire, the Xhosa of Namibia, the Samburu, Turkana and rural Luo of Kenya, and the Koma people of northeastern Nigeria. (2) Obesity: Obesity is a well-known risk factor for hypertension. Most studies on obesity in the black African population suggest that it is generally more common in women than in men.2 In the Durban study, a prevalence of 3.7% in men and 22.6% in women was observed.11 Rates of 8.3% for men and 35.7% for women have also been reported from Nigeria.2 The Tanzanian adolescent study reported a mean body mass index (BMI) of 20.8 kg/m2 for women and 18.5 kg/m2 for men.22 In the study, 0.4% of men as against 4.6% of women were found to be overweight. (3) Smoking: Cigarette smoking in Africa has increased by over 40% over the past two decades.30 This trend is generally believed to be because of rapid urbanization, acculturation and the heavy export of tobacco products to Africa. The Durban study by Seedat and Mayet31 reported that smoking was common in black men, with 28.1% of the male subjects having smoked 10 or more cigarettes per day compared to 3.4% in women. The Rwandan study of disease patterns of elderly patients reported that the average age at the inception of smoking is 20 years, and 22% of the population started smoking before the age of 18 years.21 Another study reported a per capita cigarette consumption in developing countries as 300 per year compared to 2500 elsewhere. The mean cigarette consumption rates were 10.8/day and 7.6/day for men and women, respectively.32 A study in 1976 on secondary school students in Nigeria reported that 13.6% of men aged 16–18 years and 10.3% of women of the same age were current smokers.33 Similar figures were obtained from the Accra Civil Servant Study with 32.5% of adult men and 4.9% of women being active smokers. In the same study, it was observed that over 90% of the smokers smoke less than 15 cigarettes a day.34 (4) Hyperlipidaemia: High serum cholesterol is undoubtedly a major risk factor for CAD in adults. Cholesterol levels have been found to be relatively lower in Africans than in Caucasians. In Uganda, the mean total cholesterol (TC) level was found to be in the range of 145–166 mg/dl.35 In Nigeria, Ghana and Cote d’Ivoire, the levels in all the age groups range from 116 to 166 mg/dl.36,37 A slightly higher level was found in Zimbabwe among 238 urban black men in an occupationally stratified sample, with higher levels being observed in the upper socioeconomic groups.38 Akinkugbe3 from Nigeria also reported that TC levels in the general population have steadily remained around 140 mg/dl in the period from 1958 to the 1980s with higher values in the upper socioeconomic class in Nigeria. The Tanzanian adolescent study revealed mean serum TC levels of 134 mg/dl in young men and 144 mg/dl


in women.23 One explanation for these low rates may be the occurrence of relatively high levels of HDL cholesterol. HDL cholesterol is thought to have an independent and inverse influence on CAD risk. A high HDL/TC ratio is thus considered by many to be protective. In Nigeria, mean levels of 69–79 mg/dl of HDL cholesterol were detected.39 In the Transvaal, South Africa, the levels in a sample of black adolescents were 60–66 mg/dl, constituting 45– 54% of TC.40 A similarly high ratio was reported by Seedat and Mayet31 in the Durban study on black people. The protective effect of HDL cholesterol becomes more obvious in settings in which CAD prevalence and LDL cholesterol values are high. Higher values of TC and TC/HDL ratios are observed in highincome groups as found in many professionals living in urban centres in developing countries. These values tend to approximate those found in industrialized communities. This trend was clearly demonstrated in studies on lipoprotein patterns in Lagos and Ibadan, Nigeria.3 The diet, which includes little animal fat and relatively higher physical activity, has been suggested as reasons for the low risk of CAD. The Rwandan study clearly demonstrated this point. The diet for most of the study subjects was mainly vegetarian with very little fat. (5) Diabetes and impaired glucose tolerance: The prevalence of diabetes (NIDDM) is probably less than 1% of the rural adult population in most of Africa.2 Reported frequencies are generally less than 5% for the sub-Saharan population.2 On the other hand, the frequency of impaired glucose tolerance (IGT), considered a stage in the evolution of this disease in some individuals, may be as high as 9% in this region.2 The prevalence of diabetes mellitus and IGT was determined in 479 urban South African black people (141 men and 338 women) of Zulu descent selected by cluster sampling in a suburb of Durban.40 The overall prevalence of diabetes was 4.2% and of IGT 6.9%; the age- and sex-adjusted prevalences were 5.3 and 7.7%, respectively. Diabetes mellitus was more common in women (5.2 vs 2.3%), while the reverse was true of IGT (5.5 vs 11.5%). In another study,41 the prevalence of diabetes in urban subjects aged 65 years or greater, of mixed ancestry in Capetown, South Africa was 29% in men and 30% in women. Thus, compared to earlier reports,1,2 there is an increasing prevalence of diabetes, particularly in urban black people that is most likely attributable to the increasing prevalence of obesity. Although diabetes is a well-established risk factor for CAD in Western countries, there are very little data confirming or suggesting that IGT or diabetes is a risk factor for CAD in Africans. Physical inactivity: High levels of regular physical activity presumably exert a protective effect against CAD, perhaps through its effects on other risk factors such as HDL cholesterol and blood fibrino-

lytic activity. The higher physical activity among black Africans is related to occupation, which largely involves high physical activity such as farming, and limited access to transportation. A study on South African children reported that children who walked 10 km daily to and from school have minimally higher HDL cholesterol levels than those who lived near the school.42 (6) Coagulation and fibrinolysis: Physiologic imbalance between the haemostatic and fibrinolytic systems have been shown to contribute to the development of CAD.43,44 Fibrinogen: Prospective studies in Europe and North America demonstrated that elevated plasma fibrinogen levels are an independent risk factor for CVD, particularly CAD and stroke.45,46 Fibrinogen levels are positively correlated with age, smoking, body mass, serum insulin levels and, LDL cholesterol, and negatively correlated with alcohol intake, physical activity, HDL cholesterol and female sex hormone use.47 Previous studies have yielded conflicting results about whether or not Africans have higher fibrinogen levels than white people. In 1960, Carrington48 reported higher levels in Gambian women and children compared to European controls. A similar trend was described in 1986 in rural compared to urban Gambians.49 Shaper and Summerscales,50 however, demonstrated no significant difference between black East Africans compared to a British group. A South African study also reported no difference.51 Factor VIIc: There is also a positive correlation between factor VIIc and both plasma cholesterol and triglyceride concentrations. The Northwick Park Heart Study first demonstrated this association.46 In the Gambia, both rural and urban populations were shown to have significantly lower levels of this factor.52 Similarly low levels have been demonstrated from other parts of Africa.53 Factor VIIIc: Unlike factor VIIc whose activity is determined by dietary fat, factor VIIIc levels are more influenced by ethnicity and ABO status and less by any environmental influence.50 The implications of this to the development of CAD are unclear. Merskey et al51 demonstrated higher levels of factor VIIIc in black people compared to white people in South Africa. The levels were also found to be higher in Gambians than in European groups.49 Platelets: Platelet aggregability tends to increase in patients with ischaemic heart disease and hypertension. Reports from Uganda,53 Nigeria,54 and Zimbabwe55 have demonstrated higher platelet counts in both white people and Asians than in black people. Fibrinolysis: Extensive studies have been conducted to determine the effects of the fibrinolytic system and CVD. Most of these studies, especially those in African black people, white people and Asians, have demonstrated enhanced fibrinolytic activity in black men as against their white counterparts. Higher activity was initially reported in

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African compared to European men.51,56 The comparative study on a group of Nigerian and European men confirmed these findings.57,58 Similar trends have been reported in Gambia and Uganda. Studies from South Africa and the Evans County Investigations have also suggested that higher fibrinolytic activity may contribute to lower CAD incidence in black people than in white people. It has also been suggested that habitual physical activity may exert a protective effect against CAD, perhaps through its effect on risk factors such as HDL cholesterol and blood fibrinolytic activity.59

Clinical manifestations

The clinical manifestations of CAD are well documented especially in the developed countries. Very few studies on manifestations in Africa are available. These suggest that physical signs are rather few, and in a large proportion of the patients seen, a past history of angina or chest pain is often lacking.3 Questionnaire surveys on past attacks of chest pain are generally less useful in African countries. In general, diagnosis of CAD in Africa is usually based on a clinical picture and electrocardiographic findings. Definitive diagnosis is hampered by a lack of investigative facilities, which unfortunately are high technology-based. Thus, very few centres carry out enzyme and/or angiographic studies. Rather, most of the confirmations are made from necropsy studies.

Conclusions In conclusion, there appears to be an upward trend in the prevalence of CVDs in sub-Saharan Africa. Over the past 5 decades, hypertension has emerged as the most prevalent CVD. Although there are increasing reports of CAD, it is unclear whether this is because of improved diagnostic ability or a true increase in the prevalence of CAD. The influences of Western lifestyle and technology are believed to play major roles in the observed trend.

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