Pregnancy-related risk

In Africa there is persistent high fertility and women are under social pressure to conceive. In some communities women opting to practice contraception must do so at considerable risk of social ostracism or familial conflict, because women and children are the property of the corporate family-kin and the community militates against reproductive control.11 Another important factor is that, although children are highly valued for a variety of economic, social and cultural reasons, mortality risks remain extremely high; low fertility imposes the unacceptable risk that a woman will have no surviving children at the end of her reproductive life. In addition, access to contraceptive methods is insufficient and teenage pregnancy remains a major problem. These young women are at higher risk in case of concomitant heart disease as they have so-called ‘hidden’ pregnancies and tend to delay enrolling for antenatal care.12 Pregnancy with heart disease is of high risk and is the leading non-obstetric cause of maternal death, both in developed and developing countries.13

Despite the gradual dissemination of maternal health clinics, they provide very limited preconception counselling and are not equipped to deal with the potential problems of women who have heart disease or develop it during pregnancy. Therefore, despite the high prevalence of diseases such as rheumatic heart valve disease, peripartum cardiomyopathy and untreated CHDs, few pregnant women are identified as having heart disease and therefore do not benefit from adequate management. Moreover, there is a lack of awareness of the risks related to pregnancy, even among women with high-risk conditions such as pulmonary hypertension, cyanotic heart disease, hypertensive disease and severe rheumatic aortic or mitral stenosis. This has a serious impact on maternal and fetal outcome, as shown in a study from Cameroon reporting on 46 pregnant women with valvular heart disease.14

Congenital heart disease (CHD)

The prevalence of CHD, at around 5–8 per 1000 live births in western countries, does not seem to vary according to geographical location. A survey conducted in Mozambique in schoolchildren has shown that CHD is at least as common as in Caucasians.15 However, while prenatal diagnosis is currently used to detect CHD before birth in developed countries,16 in developing countries only a minority of children with CHD are detected in infancy and, among these, few benefit from surgical treatment because of delayed diagnosis, lack of skilled personnel and absence of facilities for surgery. Hospital-based data from Africa indicate that CHD remains an important cause of heart failure in Africa.17

Few countries in Africa have local teams performing permanent open heart surgery, and only a small number of centres perform neonatal surgery for correction of congenital heart defects. Advanced pulmonary vascular disease secondary to left-to-right shunt and cyanotic congenital heart defects with increased pulmonary flow therefore remain a major problem in Africa. In a series of 534 patients with CHD from Mozambique, of which 296 (55.4%) were women, fixed pulmonary hypertension was present in 45 (8.4%) at presentation.18 Although the natural history of patients with Eisenmenger syndrome is considerably better than that of idiopathic pulmonary hypertension, and over half of patients survive for >50 years in some cases, pregnancy may adversely affect the course of the disease19 and, for that reason, women with Eisenmenger syndrome are at higher risk of complications and mortality than men.

Rheumatic heart disease (RHD)

Whereas Africa has 10% of the world's population, approximately half of the 2.4 million children with rheumatic heart disease (RHD) live on the continent.20 The prevalence of RHD in Africa, at least in the low socioeconomic groups, is among the highest in the world.21 Although primary and secondary prevention of RHD may be highly effective,20 22 this condition remains a major cause of morbidity and admission to hospital in African countries.23–25

The spectrum and presentation of valvular disease in Africa is different from elsewhere in that severe forms are seen at earlier ages,24 26 posing serious problems for women when they enter their reproductive life. This was confirmed in the Heart of Soweto study where rheumatic heart disease (RHD) was found in younger women compared to men, >68% of cases with RHD were female and women were also more likely to present with valvular dysfunction associated with idiopathic cardiomyopathy or hypertensive heart disease.25 Of all the rheumatic valvular lesions, mitral stenosis is most likely to lead to a potentially serious outcome because of the interaction between its haemodynamics and the physiological cardiovascular adjustments to pregnancy.26 Data from Ethiopia show higher mortality in women, with female deaths accounting for 57.4% of the 115 cases studied.27 Diao et al14 recently reported 17 maternal deaths in a series of 46 women (34%) from Cameroon with rheumatic heart valve disease, of which 32 had mitral stenosis. Maternal death was associated with mitral stenosis, severe tricuspid regurgitation and New York Heart Association functional class III/IV.

The management of rheumatic heart valve disease in women remains a major challenge. Even when surgery is available, the choice between repair or replacement can be difficult. In a small series from Cameroon, women with prior surgical valve replacement had a better prognosis.14 However, mitral repair and aortic valve replacement with pulmonary autograft (Ross procedure) are the preferred procedures to manage left heart valve disease in young girls because they allow continued growth of the aortic valve and avoid long-term anticoagulation. The results of this approach need to be evaluated as suboptimal results have been reported in patients who are young at time of surgery28 and inadequate secondary prophylaxis after surgery is not rare.26 In women of childbearing age, percutaneous valvotomy could be the treatment of choice for pure mitral stenosis in Africa, but facilities for cardiac catheterisation are unavailable in most countries.

Patients with RHD need anticoagulation in the setting of atrial fibrillation or mechanical valve replacement. A considerable number of women come to medical attention after the first trimester of pregnancy without having stopped warfarin, but no systematic data have been collected to explore the rate of warfarin-related malformations or other adverse pregnancy outcomes in these patients. A study of maternal and perinatal outcome in women with prosthetic heart valves on different anticoagulant regimens in India showed that no regimen can be said to be entirely safe for use during pregnancy as there is a degree of risk associated with all of them.29 Overall, in Africa, monitoring of oral anticoagulation is difficult, low molecular weight heparin is still relatively expensive and unfractionated heparins are difficult to administer in rural settings and non-specialised hospitals.

Cardiac manifestations of HIV/AIDS

As in developing countries in general, there is a trend towards higher rates of HIV infection in women in Africa. The prevalence of HIV in women is six times higher than in men among sexually active 15–19-year-olds, and three times higher than in men among 20–24-year-olds.3 The disparity in HIV prevalence is seen in both married and unmarried individuals and cannot be fully explained by behavioural factors. Adolescent girls are at higher risk because of accelerated sexual maturation processes and because incest, rape and other forms of sexual abuse are commonplace in African settings. This is exacerbated by the inability of young girls to negotiate condom use during intercourse and because the female reproductive anatomy makes female tissue more conducive to penetration by HIV.30

Cardiovascular manifestations of HIV/AIDS and highly active antiretroviral therapy are an increasing concern in sub-Saharan Africa. In a series of 518 HIV-positive de novo cases of heart disease, of whom around half were on highly active antiretroviral therapy, women represented 62% of the total cases and were significantly younger than men (38±13 vs 42±13 years; p=0.002).31 The most common primary diagnosis attributable to HIV/AIDS was HIV-related cardiomyopathy (n=196, 38%), followed by pericarditis/pericardial effusion (n=65, 13%), valve disease (n=58, 11%), arterial hypertension (n=42, 8.1%) and right heart failure (RHF) (n=34, 6.6%). There was no sex difference in the frequency of these conditions except for valve disease where women had a higher frequency (13% vs 7.5%; p=0.045). Of all the 581 cases, 42 (8.1%) had HIV-related PAH.

Peripartum/postpartum cardiomyopathy (PPCM)

PPCM is a serious, potentially life-threatening heart disease of uncertain aetiology in previously healthy women, with a higher prevalence in African women compared with other ethnic groups. The incidence varies with individual studies and has been estimated to range from one in 2300 to one in 4000 pregnancies in western countries. In Africa the incidence has been reported from one case per 100 deliveries in a small region of Nigeria to one case per 1000 deliveries in South Africa.32 As there are no extended prospective studies of PPCM to date, the current epidemiological profile of the condition is unknown.

While previous clinical and experimental data suggest inflammation, autoimmune processes, apoptosis and impaired cardiac (systemic) microvasculature as typical features in the pathophysiology of PPCM,33 34 recent data have shown that unbalanced peri/postpartum oxidative stress is linked to proteolytic cleavage of the nursing hormone prolactin into a potent anti-angiogenic, pro-apoptotic and pro-inflammatory 16-kDa subform.35 These observations strongly suggest that prolactin cleavage may operate as a specific pathomechanism for the development of PPCM. Consistent with these findings, inhibition of prolactin secretion by bromocriptine, a dopamine D2 receptor agonist, prevented the onset of disease in an animal model of PPCM and first clinical experiences with bromocriptine are promising with respect to prevention or treatment of PPCM in patients.36 Thus, inhibition of prolactin release may represent a novel disease-specific therapeutic approach to prevent the onset of PPCM in patients at risk or to treat patients with acute PPCM. Studies in Germany and Africa to confirm this promising finding in larger cohorts are ongoing.

Familial dilated cardiomyopathy affects at least one-quarter of African patients with dilated cardiomyopathy, including peripartum cardiomyopathy.37 The pattern is that of an autosomal dominant pattern of inheritance in the majority of families. This recent finding supports family screening in all cases of unexplained dilated cardiomyopathy, including women with peripartum cardiomyopathy.

Pulmonary hypertension and right heart failure (RHF)

In recent years it has increasingly been recognised that the prevalence of pulmonary arterial hypertension (PAH) in its various forms is far higher than first imagined.38 There has been increased focus on screening for PAH and other pathways to RHF in the past decade. As reported from the international BOLD study, urban areas in Africa such as Cape Town have a particularly high level of chronic obstructive airways disease for a number of reasons,39 including direct and passive smoking, urban pollution and indoor pollution from domestic heaters (wood, solid fuel), as well as occupations such as mining. Africa also has a broad range of antecedent diseases (most notably, tuberculosis and HIV/AIDS) that remain poorly controlled. The lack of adequate paediatric services to deal with CHD leads to pulmonary hypertension, commonly seen in children and young adults.18 RHD commonly contributes to pulmonary hypertension and RHF.25 RHF and pulmonary hypertension are relatively common in an urban centre of South Africa, with women being almost twice as likely to present with PAH. In women the three most common forms of PAH were idiopathic, related to concurrent HIV infection and related to connective tissue disorder (figure 1).8 With the support of the Pulmonary Vascular Research Institute Sub-Saharan Taskforce (led by Professors Karen Sliwa and Ana Mocumbi), the Pan African Pulmonary Hypertension Cohort study (PAPUCO) has recently been launched to collect information on 500 African patients with pulmonary hypertension.

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Figure 1

Diagnostic profile of women with right heart failure (RHF, red) and pulmonary arterial hypertension (PAH, blue) in the ‘Heart of Soweto’ population. Adapted from Stewart et al.42

Hypertension and hypertensive heart disease

Contemporary studies demonstrate high levels of non-communicable antecedents of heart disease (except dyslipidaemia) in sub-Saharan Africa, particularly in urban communities,40 41 with women being particularly vulnerable. A contemporary study from Soweto investigating the effects of migration and socioeconomic factors and its effect on heart disease found that >60% of the 5328 cases were women. In the historically prevalent heart disease groups (eg, RHD), women made up 60% of the cohort whereas, even in the ‘new’ forms of heart disease (eg, coronary artery disease and hypertensive heart failure), women represented >50% of the cases.42 Although more men smoked tobacco, their mean body mass index was markedly lower than that of women (25.7±6.0 kg/m² vs 29.8±7.6 kg/m²; p<0.0001).

The predominance of women presenting with atrial fibrillation in studies from Cameroon and South Africa43 44 compared with reports from high income countries and, indeed, China45 where more men develop atrial fibrillation requires comment. In African studies atrial fibrillation in general presented at a relatively young age, explained by the presence of valve disease in 44% of cases.44 Recent attention has focused on the independent risk of developing atrial fibrillation with increase in weight, with a consistent 2–3-fold increase in the likelihood of atrial fibrillation in obese individuals being reported.45 However, reflective of the pattern of obesity in Soweto, 73% of women and 40% of men in this cohort were obese, linking weight rather than gender per se to the pattern of atrial fibrillation.

These data suggest that, if a country such as South Africa continues to improve life expectancy through positive socioeconomic changes and tackling the HIV epidemic, the number of adults (particularly women) affected by the non-communicable forms of heart disease will soon surpass the number of relatively younger adults affected by historically more preventable forms of disease. The greatest threat to women seems to be due to obesity, which is becoming the norm in many African urban settings. Clearly, culturally appropriate and affordable primary and secondary prevention strategies will need to be developed to facilitate earlier detection and optimal management of such cases in Africa.