7

Cardiovascular Diseases, Cancers, and Chronic Obstructive Pulmonary Diseases

An increasing number of studies suggest that noncommunicable diseases will soon be the most important cause of morbidity and mortality in developing countries (Commission on Health Research for Development, 1990; Dodu, 1988; Feachem et al., 1992; Ghali, 1991; Manton, 1988; World Bank, 1993). The reasons for this are several, and include the changing demographic profile of Sub-Saharan Africa (see the Appendix to this volume), as well as changes in environmental, economic, and other sociocultural variables (Commission on Health Research for Development, 1990; Feachem and Jamison, 1991; Ghali, 1991; Manton, 1988). Issues such as increased access to health care, population aging patterns, and modifications in lifestyle patterns—especially in connection with established risk factors such as smoking—are also equally pertinent considerations in any discussions of these disease transitions.

The historic dominance of the communicable diseases and the emphasis to date on their treatment and control partially explain the lack of information and reliable data on the noncommunicable diseases. Lack of interest and appropriately trained medical personnel, especially in epidemiology, and the absence of coherent policies concerning data collection, information management, and research in general, however, are more critical in explaining the present dearth of understanding concerning the large and important category of noncommunicable and chronic diseases (Commission on Health Research for Development, 1990; Feachem and Jamison, 1991).

This chapter begins with a discussion of cardiovascular diseases (CVD), which as a group are rapidly becoming a major cause of mortality and morbidity in Sub-Saharan Africans. The discussion is structured in two parts: (1) emerging problems, including coronary artery disease and stroke and their risk factors, such as smoking, hypertension, dyslipidemias, obesity, and diabetes; and (2) continuing problems, including rheumatic heart disease and the cardiomyopathies. An overview of selected cancers in women follows, and this section is also divided into two parts: (1) emerging problems, including breast cancer; cancers of the uterus, ovary, and choriocarcinoma; colorectal and lung cancers; and liver cancer; and (2) continuing problems, including cancer of the cervix; the leukemias and lymphomas; skin cancers; and cancer of the bladder. The evidence on chronic obstructive pulmonary diseases is then reviewed, and the chapter ends with a presentation of conclusions and a summary of research needs. Where specific information and data are not available for Sub-Saharan populations, the chapter offers analogies (or extrapolations) from current trends in other populations and their implications.

Table 7-1 identifies the chronic diseases reviewed in this chapter that appear to show a disproportionately high burden in African females compared with males. Of the eight listed, four—including rheumatic heart disease and cancers of the breast, skin, and possibly bladder associated with Schistosoma haematobium infection—occur both



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IN HER LIFETIME: Female Morbidity and Mortality in Sub-Saharan Africa 7 Cardiovascular Diseases, Cancers, and Chronic Obstructive Pulmonary Diseases An increasing number of studies suggest that noncommunicable diseases will soon be the most important cause of morbidity and mortality in developing countries (Commission on Health Research for Development, 1990; Dodu, 1988; Feachem et al., 1992; Ghali, 1991; Manton, 1988; World Bank, 1993). The reasons for this are several, and include the changing demographic profile of Sub-Saharan Africa (see the Appendix to this volume), as well as changes in environmental, economic, and other sociocultural variables (Commission on Health Research for Development, 1990; Feachem and Jamison, 1991; Ghali, 1991; Manton, 1988). Issues such as increased access to health care, population aging patterns, and modifications in lifestyle patterns—especially in connection with established risk factors such as smoking—are also equally pertinent considerations in any discussions of these disease transitions. The historic dominance of the communicable diseases and the emphasis to date on their treatment and control partially explain the lack of information and reliable data on the noncommunicable diseases. Lack of interest and appropriately trained medical personnel, especially in epidemiology, and the absence of coherent policies concerning data collection, information management, and research in general, however, are more critical in explaining the present dearth of understanding concerning the large and important category of noncommunicable and chronic diseases (Commission on Health Research for Development, 1990; Feachem and Jamison, 1991). This chapter begins with a discussion of cardiovascular diseases (CVD), which as a group are rapidly becoming a major cause of mortality and morbidity in Sub-Saharan Africans. The discussion is structured in two parts: (1) emerging problems, including coronary artery disease and stroke and their risk factors, such as smoking, hypertension, dyslipidemias, obesity, and diabetes; and (2) continuing problems, including rheumatic heart disease and the cardiomyopathies. An overview of selected cancers in women follows, and this section is also divided into two parts: (1) emerging problems, including breast cancer; cancers of the uterus, ovary, and choriocarcinoma; colorectal and lung cancers; and liver cancer; and (2) continuing problems, including cancer of the cervix; the leukemias and lymphomas; skin cancers; and cancer of the bladder. The evidence on chronic obstructive pulmonary diseases is then reviewed, and the chapter ends with a presentation of conclusions and a summary of research needs. Where specific information and data are not available for Sub-Saharan populations, the chapter offers analogies (or extrapolations) from current trends in other populations and their implications. Table 7-1 identifies the chronic diseases reviewed in this chapter that appear to show a disproportionately high burden in African females compared with males. Of the eight listed, four—including rheumatic heart disease and cancers of the breast, skin, and possibly bladder associated with Schistosoma haematobium infection—occur both

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IN HER LIFETIME: Female Morbidity and Mortality in Sub-Saharan Africa TABLE 7-1 Noncommunicable Diseases in Sub-Saharan Africa: Gender-Related Burden Disorder Exclusive to Females Greater for Females than for Males Burdens for Females and Males Comparable, but of Particular Significance for Females Cancer       Breast   X   Uterus, ovary, choriocarcinoma X     Cervix X     Skin   X   Bladder   X?   Cardiomyopathies associated with pregnancy X     Gestational diabetes mellitus X     Rheumatic heart disease   X   NOTE: Significance is defined here as having an impact on health that, for any reason—biological, reproductive, sociocultural, or economic—is different in its implications for females than for males. in males and females, but show a disproportionate burden in females. The other four disorders—including gestational diabetes mellitus; the cardiomyopathies associated with pregnancy; and cancers of the uterus, ovary, and cervix and chriocarcinoma—are unique to females. The other major chronic diseases covered in this chapter currently show no differences in occurrence or outcome by gender; this may reflect inadequacies in the evidentiary base, as well as a possible true lack of gender-specific burden. CARDIOVASCULAR DISEASES Emerging Problems Coronary Artery Disease The frequency of coronary artery disease (CAD) and related complications in the Sub-Saharan region is much lower than that in developed countries, and CAD is only infrequently the reason an individual is hospitalized for cardiovascular problems (Bertrand et al., 1991; Hutt, 1991; Ticolat et al., 1991) (see Tables 7-2 and 7-3). Nevertheless, recent trends in urbanization, lifestyle changes, and acquisition of appropriate technology are thought to be responsible for what seems to be an increasing number of reports and hospitalizations for this condition (Hutt, 1991; Ticolat et al., 1991). Approximately 6 percent of all admissions into a cardiovascular unit in Côte d'Ivoire between 1988 and 1990 were for CAD; the frequency about a decade ago was less than 3 percent in that same unit (Bertrand, 1991; Bertrand et al., 1991). In all the studies cited above, myocardial infarction, and CAD in general, are more common in men than in women. Although a direct extrapolation to Sub-Saharan African women cannot be made, it has been shown in some populations that while survival rates with CAD are similar in black men and women, the prognosis is considerably worse in black women for reasons that are not well understood (Liao et al., 1992; Tofler, et al., 1987; Willerson et al., 1987). Because Sub-Saharan women tend to live longer than men (see Appendix), studies will be needed to determine if this added longevity produces a selective effect.

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IN HER LIFETIME: Female Morbidity and Mortality in Sub-Saharan Africa TABLE 7-2 Hospitalizations in a Cardiovascular Unit: Five Most Common Cardiovascular Disorders Disorder Number of Admissions Percentage Hypertension Rheumatic heart Congenital heart Cerebrovascular Cardiomyopathies 574 212 182 159 135 39.3 14.5 12.5 10.9 9.1 NOTE: Based on 1,458 admissions over a two-year period. SOURCE: Bertrand et al., 1991. TABLE 7-3 Common Disorders in a Population of Hospitalized Patients of a General Internal Medicine Service   Number of Admissions Percentage Disorders Men Women Total Men Women Total Hypertension 634 366 1,000 9.8 5.6 15.4 Diabetes 523 262 785 8.0 4.0 12.0 Nonhypertensive cardiac disorders 402 305 707 6.2 4.7 10.9 Hepatitis 326 74 400 5.0 1.1 6.1 Renal 296 85 381 4.5 1.3 5.8 Respiratory 178 151 329 2.7 2.3 5.0 NOTE: Based on 6,515 admissions over a three-year period. SOURCE: Data supplied by the National Epidemiology Board of Cameroon,1993. Stroke As shown in Table 7-2, cerebrovascular disease—or stroke—is the fourth leading cause of hospitalization in a large reference cardiovascular unit of this region (Bertrand, 1991; Bertrand et al., 1991). As in the case of cardiovascular disease, the incidence of stroke increases with age, and this may again place older Sub-Saharan women at increased risk (Bam and Yako, 1984). Factors Influencing Coronary Artery Disease and Stroke Risk Smoking In addition to its implications in CVD, smoking is a pivotal risk factor in a large number of chronic disorders, with significant impact on burdens of morbidity and mortality. While the frequency of tobacco use and the absolute number of smokers are generally on the decrease in many developed countries, the reverse is true in much

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IN HER LIFETIME: Female Morbidity and Mortality in Sub-Saharan Africa TABLE 7-4 Cardiovascular Risk Factors: Frequency of Hypertensiona and Smokingb in Selected Age Groups in Cameroon   Hypertension (%c) Smokers (%c) Age Range Total Females Males Total Females Males 0–1 3.6 2.0 1.0 — — — 3–15 7.3 3.4 7.8 4.5 1.5 3.0 10–20 5.5 6.0 5.1 14.6 3.3 11.3 18–30 5.0 5.9 4.5 15.5 2.0 13.5 25–64d 12.3 7.7 13.5 16.5 3.5 13.0 a For the 0–1-year age group, systolic blood pressure only was used, and values greater than the mean plus 2 standard deviations were considered to be in the hypertensive range. For the age groups younger than 15 years, both systolic and diastolic readings were used, with the values higher than the mean plus two standard deviations considered to be in the hypertensive range. For the age groups older than 15 years, WHO criteria were used to define hypertension. b Have smoked cigarettes daily or weekly for at least six months. c All percentages shown are pooled averages from one or more studies, using the same or a similar protocol on the same or similar population groups. d This age group concerns studies involving the general population. All other age groups shown are from studies involving institutions such as hospitals, schools, and universities in urban or semi-urban areas. Total number of subjects involved in the studies from which the data above were generated = 11,200. (See text for further discussion.) of Sub-Saharan Africa (WHO, 1992). The present estimate is that the prevalence of smoking increases at a rate of about 3.4 percent a year in developing countries overall, while a reduction of about 0.2 percent a year is recorded for the developed countries (WHO, 1992). As for the behavior of specific subpopulations, a group of great size and particular risk—and, obviously, a primary matter of concern for this report—is the world's population of girls and women. About 10 percent of African women report that they smoke cigarettes daily (WHO, 1992). Although earlier data from Cameroon suggested a figure of less than 3.5 percent across all age groups (see Table 7-4), it is unlikely that this figure will hold. Recent, unpublished results from that country suggest that a significant number of girls under age 12 may already have established smoking habits. A study involving female university students in Nigeria showed an increase in smoking prevalence from 3 to 24 percent between 1973 and 1982 (Elegboleye and Femi-Perse, 1976; WHO, 1992), with an even more alarming increase among student teachers, among whom a prevalence of 50 percent was encountered. Similar trends have been noted in Ghana (Report from Ghana, 1984). The major culprits identified in these changes, in Africa and elsewhere in the developing world, are rapid urbanization and acculturation, associated changes in lifestyle, and the dumping of tobacco products into these countries (WHO, 1992). Our current understanding of the effects of environment smoke (and passive smoking in general) also suggests that young people who live around adult smokers run significant smoking-related health risks. Consequently, all children may be exposed to the ill-effects of environmental tobacco smoke at practically all ages (Taylor et al., 1992). Hypertension Hypertension is commonly defined as sustained elevated arterial blood pressure, measured indirectly by an inflatable cuff and pressure manometer. Hypertension is the most common cardiovascular disorder in Sub-Saharan Africa. It results in more hospital admissions than any other disorder in almost all cardiovascular hospital

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IN HER LIFETIME: Female Morbidity and Mortality in Sub-Saharan Africa units (see Table 7-2) and in general internal medicine units (see Table 7-3). Hypertension has been shown to increase the risk of developing stroke, coronary heart disease, congestive heart failure, peripheral vascular disease, and nephrosclerosis (NRC, 1989; Philips and Whisnant, 1992). It can also directly affect many organ systems, including the heart, endocrine organs, kidneys, and central and autonomic nervous systems (NRC, 1989). Thus, hypertension can be considered both a risk factor for CVD and a cardiovascular disorder in its own right. The classification of hypertension most commonly used for adults in the studies cited below is that of the World Health Organization Expert Committee published in 1978 (WHO, 1978): systolic blood pressure 160 mmHg, or diastolic blood pressure 95 mmHg. Risk factors for hypertension include a positive family history of the disorder, increased body mass, obesity, and elevated salt intake (Dyer et al., 1994; NRC, 1989; Stamler et al., 1991). Race has also been shown to be an important risk factor; many studies demonstrate that blood pressure is higher and hypertension more prevalent among blacks of African origin than in Caucasians living in similar environments (DHHS, 1986; Stamler et al., 1975). Now that acceptable blood pressure levels for different age groups have been defined, we are also able to recognize hypertension in childhood. Table 7-4 summarizes the results of several cross-sectional studies from Cameroon that included screening for hypertension across various age groups. These studies show prevalence rates of hypertension of less than 8 percent among subjects between 0 and 30 years of age, and of less than 14 percent among subjects aged 25–64. A greater percentage of females aged 0–30 years were labeled hypertensive than males of the same age. Beyond the 18-to-30-year-old group, males predominate, but it is unclear when this transition occurs. While most hospital-based and screening studies in the adult general population suggest that hypertension rates are much higher in men (see Table 7-3), some studies suggest that the prevalence of hypertension hypertension rates are much higher in men (see Table 7-3), some studies is much higher in women than in men, with higher rates among Sub-Saharan Africans in general (Bam and Yako, 1984; M'Buyamba-Kabangu et al., 1987; Seedat and Seedat, 1982). These seemingly contradictory observations again highlight the problems of differential access and utilization of health care and reporting bias in the attempt to achieve a clear picture of regional mortality and morbidity by gender. Additional data from Cameroon and other Sub-Saharan countries may raise more questions than they answer. Table 7-5 presents population-based rates of hypertension derived from several comparable studies in six countries of the region. Hypertension rates in the rural populations of those countries vary between about 5 percent and 15 percent, while rates for urban population groups vary between 7 and 24 percent. Rates for women are generally one-third to one-half the rates for men; rarely are both rates the same. Table 7-5 also shows higher rates of hypertension in the urban than the rural population of Ghana and the South African Zulu population, but higher rates in rural than in urban areas of Cameroon and the Congo (M'Buyamba-Kabangu et al., 1987; Seedat and Seedat, 1982). Age may play a role in those differences, because migration of large numbers of young people into urban areas will affect distributions, although other factors may be involved (M'Buyamba-Kabangu et al., 1987; Seedat and Seedat, 1982). The relevance of hypertension to the health of Sub-Saharan Africa's female population is far from trivial. TABLE 7-5 Rates of Hypertensiona in Selected Countries of Sub-Saharan Africa   Population   Country Rural Rates (%) Urban Rates (%) Ghana Nigeria South Africa (Zulu) Côte d'Ivoire Cameroon Congo, The 5.9 10.2 5–6.6 — 14.8 12.4 11.3 — 23.8 13.8 10.2 6.8 a WHO criteria used for definition. Composite data derived from published reports (see text for further details).

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IN HER LIFETIME: Female Morbidity and Mortality in Sub-Saharan Africa Women are especially vulnerable from hypertension associated with pregnancy; among its consequences are elevated risk for eclampsia and preeclampsia, with potentially fatal implications (Dulay, 1990; Merz et al., 1992; Schoon et al., 1990). Hypertension may also produce excess morbidity and mortality in black African women in older age groups because of a documented contribution to increased frequency of stroke (Bertrand, 1991; Hutt, 1991; Seedat and Seedat, 1982; Bam and Yako, 1984; Philips and Whisnant, 1992), although reporting bias and other issues related to access to care will need to be taken into account in future studies of this association. Dyslipidemias There are relatively few reports on lipid levels in Sub-Saharan populations (Bensadoun et al., 1984; Hutt, 1991; Ngongang and Titanji, 1985; Raisonnier et al., 1988; Shaper, 1974). Both women and men in these populations have relatively higher HDL cholesterol levels than their counterparts in other developing countries, which may explain the ''relative protection" of black Africans against CVD. Obese women may, however, have atherogenic levels—that is, lipid levels that initiate, increase, or accelerate the process leading to atherosclerosis (Ngongang et al., 1988). Studies have shown that some East African tribes appear to have cholesterol and lipid levels indistinguishable from those found in a number of Western societies (Barnicot et al., 1972; Shaper et al., 1969). Studies involving other important lipid fractions that also control for potential confounding variables will be required, however, before firm conclusions can be drawn about similarities and differences between such populations and those in the West. Obesity Obesity (see also Chapter 3, Nutritional Status) is an important risk factor for a number of disorders: cardiovascular disorders, a variety of conditions related to women's reproductive health, and a number of cancers. There is a strong association between obesity and other cardiovascular risk factors, including hypertension and metabolic disorders such as diabetes (Bonham and Brock, 1985; Gillum and Grant, 1982; Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure, 1986; Sims and Berchtold, 1982). Although relatively few studies have involved Sub-Saharan population groups (Alade and Ezeokeke, 1990), most studies conclude that obesity —generally defined in these studies as a body mass index (BMI) greater than 27km/m2—is more common in women than in men, and there is presently no reason to think that Sub-Saharan Africa diverges from this pattern (Johnson, 1970; Kumanyika and Adams-Campbell, 1991; Njitoyap et al., 1991; Sloan, 1960). Obesity rates of 8.3 percent for men and 35.7 percent for women have been reported in nigeria, and rates in the neighborhood of 50 percent have been recorded for the Bantus of South Africa (Johnson, 1970; Sloan, 1960). Akintewe and Adetuyibi (1986) report a significant association between obesity and hypertension in diabetics in the Sub-Saharan region, particularly in females. All in all, the prevalence of obesity in Sub-Saharan female populations would seem to constitute a real health problem for those populations. A determination of which of these populations, where, and under what circumstances obesity reaches problematic levels is a matter of future study, as are the varying cultural perceptions of the condition—that is, its acceptability, and even desirability. Diabetes Mellitus While the frequencies of degenerative and metabolic diseases in Sub-Saharan populations remain unknown, increasing clinical awareness of disorders such as diabetes mellitus (DM) suggests that they are either more common than initially thought, or that their prevalence is increasing (King and Rewers, 1991) (see Table 7-3). Like hypertension, diabetes mellitus is considered both a disease and an independent risk factor for CVD. There is also a suggestion that diabetes mellitus is associated with poorer CVD prognosis in women. Reported prevalence rates for diabetes (See Table 7-6) are generally under 5 percent for Sub-Saharan populations (King and Rewers, 1991), and there seems to be a general impression among clinicians in the region that the DM subclass, insulin-dependent diabetes mellitus (IDDM), may be less common in Sub-Saharan African populations

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IN HER LIFETIME: Female Morbidity and Mortality in Sub-Saharan Africa TABLE 7-6 Percentage Prevalence Rates for Diabetes and Impaired Glucose Tolerance for Selected Populations of Sub-Saharan Africa   Diabetes Mellitus Impaired Glucose Tolerance Country and Population Group General Population Men Women Men Women Tanzania   3 1 9 16 Kenya (Wachaga/Masai)   1 1 8 10 Ghana (civil servants)   0.5 0.6     Nigeria (urban) 1.7         Cameroon 0.5–3         Mali 1         SOURCE: King and Rewers, 1991. than in populations of developed countries, but the basis for this impression is probably compromised by biases in access, utilization, and reporting and issues of cost. The prevalence of impaired glucose tolerance, however, considered a stage in the progression to diabetes in some individuals, may be almost double the 5 percent figure in some Sub-Saharan populations, and it is invariably higher among women (King and Rewers, 1991). In Tanzania, which has the highest prevalence rates of six countries studied, prevalence of impaired glucose tolerance was 9 percent in men and 16 percent in women (see Table 7-6). At the same time, a study of three years of hospital admissions in a general internal medicine service in Cameroon found that, of over 500 admissions for diabetes during that period, 8 percent were males and 4 percent were females (information from the National Epidemiology Board of Cameroon, 1991). Since male admissions overall ran at almost 2:1 compared with female admissions for six common disorders, it would be unwise to draw a conclusion from these figures, which may only reflect differential utilization of tertiary facilities by gender. Diabetes is especially compromising for females. For already diabetic women, the complex metabolic alterations that accompany pregnancy may complicate disease control and place both mother and fetus in jeopardy, with particularly grave risks for the fetus. Gestational diabetes mellitus (GDM), a special category for pregnant women, is defined as carbohydrate intolerance of variable severity, with onset or first recognition during the present pregnancy. There is considerable demographic and phenotypic heterogeneity in the prevalence of gestational diabetes mellitus (Dooley et al., 1991), and optimum case management includes screening for GDM in any pregnant woman, because the consequences of unrecognized or untreated GDM include increased fetal and neonatal loss and higher neonatal and maternal morbidity. Oral Contraceptive Use The use of contraceptive pills has increased substantially among Sub-Saharan African females, especially in the middle and upper socioeconomic groups who can afford their cost. Since the mid-1960s a considerable amount of epidemiological clinical and laboratory evidence has linked current use of combined oral contraceptives with certain types of CVD, especially venous thromboembolism, thrombotic stroke, myocardial infarction, subarachnoid hemorrhage, and hypertension (Irey et al., 1978; Lancet, 1979; Stadel, 1981; Thorgood et al., 1981). The risk of CVD from oral contraceptive use is independent of smoking, although, except for venous thromboembolism, that risk is increased by smoking. There may also be some residual excess risk of myocardial infarction in women

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IN HER LIFETIME: Female Morbidity and Mortality in Sub-Saharan Africa aged 40 or over with 5 or more years of pill use in the past (Mishell, 1989). Still, there is also evidence that current users of low-dose estrogen oral contraceptives showed no increase in risk (relative risk of 0.87) of myocardial infarction (Mant et al., 1987), and that use of oral contraceptive formulations containing less than 50 micrograms of estrogen by healthy, nonsmoking women up to age 45 is not associated with increased risk of serious CVD (Mishell, 1989). Whether these findings from developed countries can be extrapolated to Africa is debatable. So far, there are no valid epidemiologic data to link the use of oral contraceptives by black Africans with an increased risk factor of CVD. The risk factors discussed above do not constitute an exhaustive listing of all the factors implicated in the general picture of all risks for cardiovascular disorders. They were addressed because of current estimates and projections of their relative prevalence in Sub-Saharan populations. It is unfortunate that there is still a considerable void in our understanding of the magnitude and implications of these factors in the region, a void that has negative implications for regional capability for prevention and control, for containing the elevated costs of managing most cardiovascular disorders in the situation of limited resources faced by the countries of Sub-Saharan Africa, and for long-term health care planning in general. Continuing Problems Rheumatic Heart Disease Rheumatic heart disease (RHD) is second only to hypertension and its complications among cardiovascular disorders resulting in hospital admissions in Sub-Saharan Africa (Bertrand, 1991; Ekra and Bertrand, 1992; Hutt, 1991) (see Table 7-2). Screening studies among schoolchildren suggest a prevalence for RHD that may range from less than 1 per 1,000 to over 15 per 1,000 (WHO, 1988). A history of rheumatic fever, generally considered a prelude to the subsequent development of RHD, is present in less than 50 percent of the cases (Hutt, 1991). RHD accounts for over 14 percent of hospital admissions for cardiovascular disease (see Table 7-2) (Bertrand, 1991; Hutt, 1991; Serme, 1992), and it appears to be more common and associated with higher rates of morbidity and mortality in Sub-Saharan African women than in men (Cole, 1980; Sankale and Koate, 1970; Serme, 1992). The prevalence of RHD is highest among the young, and consequently morbidity and mortality are particularly high in this age group. Cardiomyopathies The cardiomyopathies comprise a group of heart muscle disorders of obscure etiology and, in some cases, pathophysiology as well. Cardiomyopathies invariably lead to intractable heart failure and are the fifth leading cause of hospitalization in cardiovascular or related units in the Sub-Saharan region (Bertrand et al., 1991) (see Table 7-2). Although some infectious and parasitic agents are known to attack the heart muscle directly—or indirectly, through immunological mechanisms —the Sub-Saharan African region is endemic for idiopathic cardiomyopathies characterized by cardiac dilatation, with or without muscle hypertrophy (Hutt, 1991; WHO, 1984). There is no evidence that women are particularly prone to heart failure, with the exception of some forms of cardiomyopathy —for example, peripartum and postpartum cardiomyopathy—that are intimately related to pregnancy and childbirth, and consequently exclusive to women (Bertrand et al., 1985; Talabi et al., 1985). Although excessive salt consumption and undiagnosed hypertension have been suggested as possible mechanisms operative in the cardiomyopathies observed during pregnancy and childbirth, or shortly afterward, their etiology remains obscure. They are suspected to have a nonnegligible impact on maternal morbidity and mortality, but the frequency and the amplitude of this impact requires carefully designed, controlled studies. CANCERS Neoplastic disorders are another increasingly prominent cause of morbidity and mortality in Sub-Saharan African countries (Bassett et al., 1992; Hutt, 1991; Mbakop et al., 1992; Parkin et al., 1988; Sobo, 1982; Tuyns and

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IN HER LIFETIME: Female Morbidity and Mortality in Sub-Saharan Africa Ravisse, 1970). This increase, similar to that observed for cardiovascular disorders, is probably the result of a combination of factors, including decreasing childhood mortality and increasing longevity, availability of trained manpower, improved health care and related diagnostic technology, changes in lifestyle and diet, and other environmental factors (WHO, 1990). In a seminal study in 1981, Doll and Peto estimated that approximately 35 percent (range, 10 to 70 percent) of all cancer mortality in the United States was related to diet. In 1977, Wynder and Gori estimated that 40 percent of cancer incidence among men and nearly 60 percent among women was related to diet. In 1989, the National Research Council commented that, because few of the relationships between specific dietary components and cancer risk are well established, the contribution of diet to individual cancers, and thus to total cancer rates, cannot be quantified precisely (NRC, 1989). Nevertheless, these now fundamental estimates emphasize the importance of diet in the etiology and prevention of cancer in the United States and, by extension, its importance worldwide. Dietary influence aside, females are at risks of cancer that differ from male risk profiles simply because of differences in their basic physiologies. Neoplasms affecting the breast, cervix, and uterus belong exclusively to the female domain, with the exception of rare cases of breast cancer in males. According to studies to date, the most common neoplasms in African women are cancers of the cervix, followed by breast cancer, with cancer of the lymphatic system in third position (see Bassett et al., 1992, Zimbabwe; Mbakop et al., 1992, Cameroon; Parkin et al., 1988, worldwide frequencies of 16 major cancers; Sobo, 1982, Liberia; Stanley et al., 1987, worldwide statistics; Tuyns and Ravisse, 1970, the Congo). Estimated annual incidence rates for these neoplasms are 37, 27, and 12 per 100,000, respectively. Emerging Problems Cancer of the Breast There are no reliable studies on the true frequency of breast cancer in Sub-Saharan Africa, because routine breast examinations, either by individuals or health professionals, are not commonly practiced. Clinical experience suggests, however, as indicated above, that breast cancers may be the second most common neoplasm in women of this region (Bassett et al., 1992; Mbakop et al., 1992; Parkin et al., 1988; Sobo, 1982; Stanley et al., 1987). As for etiology, it is possible that changes in hormonal profiles brought by greater longevity, as well as shifts in patterns of childbearing in response to such socioeconomic factors as urbanization, will affect the frequency of cases of breast cancer, if they have not done so already. Dietary factors have been implicated as a possible contributor to breast cancer, and socioeconomic factors may also be producing dietary modifications that could be meaningful (Howe et al., 1990; Lubin et al., 1986; WHO, 1990) It may also be, as conditions improve and screening programs are developed, that the combination of all these changes with improvements in case-finding will generate higher frequencies, so that breast cancer may be found to be more common than cervical cancer (Miller, 1992). As with the other forms of gynecologic cancer in Sub-Saharan Africa, diagnosis in most cases of breast cancer is made relatively late in the course of the disease, significantly reducing survival. Thus, unlike so many other cancers, a thorough clinical examination and patient education in self-examination can have a crucial impact on early identification of breast cancer; its diagnosis; and, ultimately, enhanced survival (Koroltchouk, 1990). Cancers of the Uterus and Ovary and Choriocarcinoma The exact frequency of these three cancers in the Sub-Saharan region is a subject of considerable debate, despite the low rates currently reported—generally less than 5 per 100,000 (Bassett, et al., 1992; Doll and Peto, 1981; Hutt, 1991; Mbakop et al., 1992; Mmiro, 1987; Omigbodun, and Akanmu, 1991; Parkin et al., 1988; Sobo, 1982; Stanley et al., 1987). Some risk factors for endometrial and ovarian cancer —such as early menarche, late menopause, and obesity (for cancer of the uterus)—are characteristic of many female populations in this region. And, as in the case of the etiology of breast cancer, dietary factors have been implicated (Howe et al., 1990; Lubin

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IN HER LIFETIME: Female Morbidity and Mortality in Sub-Saharan Africa et al., 1986; WHO, 1990). The debate results largely from ignorance of the facts, which are obscured by the lack of clinical and laboratory skills necessary for accurate diagnosis, as well as by cultural resistance to autopsy. In countries that have acquired the appropriate diagnostic technology and trained manpower, reports of cases of these cancers are becoming more common, so there is reason to suspect that this will occur more generally in the Sub-Saharan region as diagnostic capabilities improve. Colorectal and Lung Cancers Colorectal cancer appears to be relatively uncommon in the Sub-Saharan region. As in the case of breast cancer and some gynecologic cancers, changes in diet and lifestyle have been implicated as etiologic factors (Bassett et al., 1992; Hutt, 1991; Mbakop et al., 1992; Parkin et al., 1988; Sobo, 1982; WHO, 1990). The risk levels of the various populations and whether women are at any special risk are unknown (Soubeyrand et al., 1984). Similarly, while lung cancers rarely have been found in women in Sub-Saharan Africa, this profile may change with time, given the increased smoking at earlier ages observed among women in the region. In addition, improvements in diagnostic capabilities can be expected in themselves to increase cases of lung cancer in women. Continuing Problems Cancer of the Cervix Cancer of the cervix is the most common form of malignancy in Sub-Saharan African women, and it may be the most common of all malignancies in the population as a whole (Doll and Peto, 1981; Hutt, 1991; Mbakop et al., 1992; Mmiro, 1987; Omigbodun and Akanmu, 1991; Sobo, 1982; Stanley et al., 1987; Tuyns and Ravisse, 1970; WHO, 1990). In some Sub-Saharan regions, cervical cancer may constitute as much 35 percent of all malignancies in women, and reported incidence rates range between 20 and 28 per 100,000. Cervical cancer is generally considered a sexually transmitted disease that is intimately linked to the presence of human papillomavirus (HPV; see also Chapter 11). The disease may remain undetected until a relatively advanced stage. Sadly, the critical diagnostic techniques that would catch the disease at an earlier stage, when it is curable—ideally, in its premalignant phase—are not readily available in most countries of the region. Leukemias and Lymphomas Leukemias and some lymphomas (e.g., Burkitt's) are also relatively common in some Sub-Saharan countries and have been reported to be the third most common cancer in African women (Bassett et al., 1992; Feldmeier and Kranz, 1992; Stanley et al., 1987). Further studies will be required to determine with more accuracy how these frequencies compare with those in males in the region (Hutt, 1991). Skin Cancers Cancers of the skin are of special concern in Sub-Saharan African women (Bassett et al., 1992; Doll and Peto, 1981; Hutt, 1991; Mbakop et al., 1992; Mmiro, 1987; Omigbodun and Akanmu, 1991; Parkin et al., 1988; Sobo, 1982; Stanley et al., 1987). They have been reported as the fourth leading cancer among women in Zimbabwe (Bassett et al., 1992), and it has been suggested that certain skin and other systemic disorders may be related to use of skin-lightening creams and ointments containing steroids and known toxic chemicals (Gwet-Bell, 1990). In addition, chronic tropical ulcers have a tendency to degenerate into malignant skin-based lesions (Hutt, 1991). By virtue of their daily agricultural and other domestic duties, Sub-Saharan African women can be expected to be prone to such ulcers, and they are consequently at risk for this particular lesion. Whether they differ from males in this respect is unknown.

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IN HER LIFETIME: Female Morbidity and Mortality in Sub-Saharan Africa Liver Cancer Cancer of the liver has been described in some populations of Sub-Saharan women (Bassett et al., 1992; Doll and Peto, 1981; Hutt, 1991; Mbakop et al., 1992; Mmiro, 1987; Omigbodun and Akanmu, 1991; Parkin et al., 1988; Sobo, 1982; Stanley et al., 1987), although the extent and magnitude of the disease remain unknown. Environmental factors associated with increased risk of liver cancer include infection with Hepatitis B virus, exposure to aflatoxin, and alcohol consumption (Barnum and Greenberg, 1993). That these factors are common to many Sub-Saharan African populations would suggest that liver cancer has been, and continues to be, an important malignancy in the region. The degree to which the disease affects African females disproportionately compared with males remains unknown. Bladder Cancer Bladder cancers are also relatively common in the Sub-Saharan region and have been intimately linked to chronic infection by Schistosoma haematobium. Where the nature of women's agricultural work enhances their chances of infection, in contrast to the chances of males, or where gender-linked limitations on access to appropriate health care are at issue, females may be at higher risk not only for infection and reinfection, but also for receiving inadequate therapy. Whether this differential is real remains to be resolved (Bassett et al., 1992; Feldmeier and Kranz, 1992; Parkin et al., 1988). CHRONIC OBSTRUCTIVE PULMONARY DISEASES Chronic obstructive pulmonary (lung) disease (COPD) refers to several disease entities, including asthma, emphysema, chronic bronchitis, peripheral airways disease, right-sided heart disease, and cor pulmonale (heart disease with an underlying pulmonary deficiency). These conditions are ill-defined and rarely characterized separately in descriptive epidemiologic studies of COPD. Risk factors for COPD include cigarette smoking, childhood respiratory tract infections, occupational dust exposure, and both indoor and outdoor air pollution (Bumgarner and Speizer, 1993; Elo and Preston, 1992; Hutt, 1991; Malik et al., 1983). Data on COPD mortality and morbidity are scarce in Sub-Saharan Africa and elsewhere in the developing world. This scarcity reflects both a relative lack of attention and a lack of consistency in classification and reporting of COPD internationally. Evidence from industrialized countries indicates an inverse association of COPD rates with socioeconomic status, a factor that may act as a surrogate for other influences, such as cigarette smoking, poor nutrition, and higher levels of ambient pollution, including indoor air pollution. Data also demonstrate consistently higher mortality rates in males than females, most probably because of the longer and heavier smoking experience among men. It is believed, however, that COPD is a more important cause of mortality and morbidity in the developing than in the developed world, and that the burden of COPD may be growing disproportionately in Sub-Saharan African females, particularly the poor, for reasons noted below (Bumgarner and Speizer, 1993). Cigarette Smoking The relative increase in smoking prevalence in Sub-Saharan African females described earlier heralds increasing COPD incidence in this group. Prospective studies in other regions of the world have demonstrated higher COPD mortality and earlier disease onset in cigarette smokers (Peters and Ferris, 1967), and there is no reason to believe that African females will be immune to these effects. Indoor Air Pollution Outdoor air pollution has long been recognized to exacerbate COPD. While many studies in industrialized countries have failed to establish a conclusive link between COPD risk and air pollution levels, smoking behavior

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IN HER LIFETIME: Female Morbidity and Mortality in Sub-Saharan Africa alone has not been sufficient to explain geographic variations in the prevalence of symptoms. Similarly, in studies in developing countries outside of the Sub-Saharan region, prevalence rates of cigarette smoking cannot explain all the variation seen in COPD rates, because mortality and prevalence rates often appear to be higher than in industrialized countries, and the sex ratios more equal (Bumgarner and Speizer 1993; Chen et al., 1990; Saha and Jain, 1970). This last point is significant, because the relative increase in COPD rates in females in these studies may be indicative of other gender-specific exposures, such as indoor air pollution. In one study in the Kenyan highlands, Clifford (1972) estimated the exposure to (mainly indoor) airborn total suspended particles at 25,000 milligrams annually. In another study in India, women in kitchens were found to be inhaling levels of benzopyrene, a known carcinogen present in cigarette smoke, at levels equivalent to smoking 20 cigarettes a day (Smith et al., 1983). Although benzopyrene exposure has not been linked to COPD risk, its presence clearly indicates that the microenvironment in the kitchens studied contained significant amounts of smoke. Although the materials used for cooking can be expected to vary in Sub-Saharan African households, there are no reasons to suggest that kitchens and indoor spaces in the region are necessarily better-ventilated or "cleaner" than those in the Indian study. These findings suggest that COPD may have a greater effect on females, particularly poor women and girls, in Sub-Saharan Africa than might otherwise be expected. In summary, the etiology of most COPD remains obscure, although environmental factors, including cigarette smoking, appear to play a major role in causation, as well as in disease management and prognosis. Current trends in cigarette smoking indicate that COPD rates can be expected to rise disproportionately in Sub-Saharan females in the coming years. Prolonged exposure to smoke and its various component substances in poorly ventilated kitchens, homes, and related structures and pollen and dust particle exposure in settings where farming and field work are principal activities for Sub-Saharan women (see Chapter 9) may place females at increased risk for this disorder. CONCLUSIONS Chronic disorders—especially cardiovascular and neoplastic diseases—are important emerging health issues for Sub-Saharan populations, although descriptive data on demographic trends in chronic disease incidence and mortality, especially for females, are limited. It is currently projected that these maladies will rapidly become leading causes of morbidity and mortality. In addition, current and past experience in developed countries suggest that health care resources and planning to manage chronic diseases will be a major challenge for Sub-Saharan African countries in the near future. Table 7-7 indicates the approximate ages at which chronic diseases and their sequelae occur in Sub-Saharan African females. The following conclusions can be drawn on the basis of existing data: Because of their relatively early age of onset and persistence across the life span, the cardiovascular disorders—hypertension, rheumatic heart disease, and cardiomyopathies associated with pregnancy—appear to be among the chronic disorders that may most adversely affect female health status in the region. Metabolic disorders such as diabetes mellitus constitute a major source of added morbidity and mortality for Sub-Saharan African women. This entity presents specific problems for women during pregnancy, for the fetus, and for both mother and child during delivery. Among the neoplastic disorders, clinical experience suggests that breast and cervical cancers are increasingly important causes of morbidity and mortality. While the screening and diagnosis of cervical cancer will continue to represent a major technological challenge for Sub-Saharan countries in general, opportunities for early screening for breast cancer do exist, but their potential is far from being realized. Leukemias and lymphomas and cancers of the skin and bladder may also represent important causes of female mortality and morbidity in the region. Gender-related environmental or occupational exposures—for example, cooking fires in enclosed spaces—may place Sub-Saharan African women at particular risk for COPD.

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IN HER LIFETIME: Female Morbidity and Mortality in Sub-Saharan Africa TABLE 7-7 Ages of Occurrence of Noncommunicable Diseases and their Sequelae in Sub-Saharan African Females In Utero Infancy Early Childhood (birth through age 4) Childhood (ages 5–14) Adolescence (ages 15–19) Adulthood (ages 20–44) Postmenopause (age 45+)       Hypertension Hypertension Hypertension       Rheumatic heart disease Rheumatic heart disease Rheumatic heart disease       Cardiomyopathies associated with pregnancy Cardiomyopathies associated with pregnancy         Gestational diabetes mellitus Gestational diabetes mellitus           Breast cancer Breast cancer         Cancer of the cervix Cancer of the cervix       Leukemias and lymphomas Leukemias and lymphomas Leukemias and lymphomas         Skin cancer Skin cancer         Bladder cancer Bladder cancer           Chronic obstructive pulmonary diseases RESEARCH NEEDS There is an urgent need to create or support existing units concerned with data collection, evaluation, and surveillance of the major chronic disorders in Sub-Saharan Africa. Gender disaggregation in the collection and analysis of such data will be required in order to discover and understand specific issues related to women's health. The chronic disorders that should be surveyed include, in particular, rheumatic heart disease; hypertension and stroke; cardiomyopathies; coronary artery disease; leukemias and lymphomas and cancers of the cervix, breast, uterus, ovary, skin, and bladder and choriocarcinoma; diabetes mellitus; and COPD. In collecting and interpreting these data, special attention must be given to reporting bias and other issues related to access of care. Because strokes may be an increasingly important cause of morbidity and mortality in Sub-Saharan African women, future controlled studies should be conducted to determine to what extent factors such as obesity, smoking, alcohol use, and age contribute to stroke-related morbidity and mortality in women. The results of such studies could have useful implications for treatment and, especially, prevention. Comparative surveys to determine the distribution of, and trends in, major risk factors for the other chronic diseases described in this chapter are also needed. These surveys should build on the methods and data of current comparative studies in other regions of the world such as the MONICA study, which provides for efficient assessment of disease severity across different countries and identification of putative risk factors. Special attention should be paid to the strengths and limitations of past longitudinal studies of specific populations in the region—for example, the six African studies described in Feachem and Jamison (1991; pp. 24$1$2$347). (For

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IN HER LIFETIME: Female Morbidity and Mortality in Sub-Saharan Africa additional description of these studies, see the Appendix to this volume). Specific risk factors that should be assessed in these comparative studies include hypertension, serum cholesterol and lipid fractions, obesity, and nutritional status. Better knowledge of the prevalence of these risk factors—and identification of other risk factors for chronic diseases in women—are crucial to prevention and control, as well as to long-term health care planning, given the elevated costs for managing most chronic diseases that are the norm in much of the Western world. Because of evidence of growing rates of cigarette smoking in Sub-Saharan females and the role of smoking as a risk factor for multiple chronic diseases, research in this area is urgent and essential. There are currently no reliable studies surveying the prevalence of, and trends in, smoking in Sub-Saharan females. Experience in Cameroon suggests that a significant number of girls already have established smoking habits at age 12. Special attention should be directed to identification of risk factors for smoking initiation in adolescent females and to the development of intervention programs appropriate to the target audience. The higher prevalence and mortality rates for rheumatic heart disease in Sub-Saharan African females observed in hospital case series is striking and needs to be confirmed. The presence of a history of rheumatic fever, generally considered a prelude to the subsequent development of RHD, in less than 50 percent of those cases requires investigation. Women of African descent with coronary artery disease have been shown in some studies to have a poorer prognosis than males. The reasons for this gender disparity and their implications for Sub-Saharan African women need to be clarified. Skin cancer has been reported to be the fourth leading cause of cancer in some groups of women of the region. The relation of daily agricultural and other female household duties to risk of chronic tropical ulcers and associated malignant skin-based lesions needs to be investigated. The suggestion of a greater frequency of skin and other systemic disorders related to use of skin-lightening creams and ointments containing steroids and other toxic chemicals requires evaluation. The higher rates of glucose intolerance in Sub-Saharan women compared with men that has been observed in a few studies should be confirmed, particularly given the relation of diabetes to complications during pregnancy and childbirth. Attention should be given to identification of environmental and occupational risk factors for cancers and COPD that are particular to the domestic and work environments of Sub-Saharan African females. REFERENCES Akintewe, T. A., and A. Adetuyibi. 1986. 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