Background
Atrial fibrillation is a common finding among elderly in western societies. Its prevalence increases over age and mounts to 10 to 20% after the age of 80 years [
1,
2]. Due to ageing of western populations and improved survival from other cardiovascular disorders, the prevalence of atrial fibrillation has grown over time and is expected to continue growing. As it leads to a heightened risk of thromboembolism, cerebrovascular accidents, and congestive heart failure, its public health burden has grown concurrently [
3,
4].
The majority of the cases of atrial fibrillation can be attributed to the established risk factors obesity, diabetes, hypertension, prior cardiac disease, and smoking. Hypertension is the most important of these, responsible for at least one fifth of the cases [
5,
6]. Still, questions remain about the pathogenesis of atrial fibrillation. It is postulated that, next to these risk factors, inflammation plays an important role in the pathogenesis of atrial fibrillation, but this has not yet been confirmed [
1,
7]. Moreover, it is not clearly understood why atrial fibrillation is less commonly detected in black Americans, while they are more often affected by obesity, diabetes, and hypertension than white Americans [
5,
8,
9]. However, the epidemiology of atrial fibrillation has been studied almost exclusively in western societies [
1,
3], where obesity, diabetes, hypertension, cardiovascular disease, and systemic inflammation are widely present among the elderly [
10]. Little is known about the prevalence of atrial fibrillation in non-western societies, such as in rural Africa [
11,
12]. Knowledge about the risk of atrial fibrillation in the context of different environmental and genetic influences may provide more insight in its pathogenesis [
13].
This study investigates the epidemiology of atrial fibrillation in a traditional rural African community where a sedentary lifestyle is absent. We used electrocardiography to detect atrial fibrillation among inhabitants aged 50 years and older. Established risk factors of atrial fibrillation have been documented, such as obesity, dysglycaemia, hypertension, and myocardial infarction. Circulating levels of interleukin-6 were measured as a marker of proinflammatory immune activation and circulating levels of C-reactive protein as a marker of systemic inflammation.
Discussion
In this study we showed that atrial fibrillation was very scarce after the age of 50 years in a traditional rural community in Africa. The near absence of atrial fibrillation in the Ghanaian study population confirms the low prevalences that have been found by a few studies in other traditional African populations. In rural Tanzanians aged 70 years and older, its prevalence was 0.7% [
11]. In the South African Bantu population, atrial fibrillation was detected in 0.2% of patients attending a cardiac clinic but not diagnosed with cardiac disease [
26]. In patients from the Bantu population hospitalised because of cardiac failure, it was present in 12% [
27].
The prevalence of atrial fibrillation in urban African populations is higher than those in rural African populations. In a South-African study covering both urban and rural communities, atrial fibrillation was detected in 2% of blacks over the age of 30 years [
28]. In two large cardiologic hospitals, 4.6% and 5.5% of the admitted patients had atrial fibrillation at relatively young ages [
29,
30]. Among cardiologic hospitals across several Sub-Saharan African countries, atrial fibrillation was found in 18% of cases with acute heart failure [
31].
The prevalence of atrial fibrillation in western populations is higher than those in rural African populations. Several studies in patient populations and the general populations of the USA and Western Europe have reported its prevalence to rise from less than 2% around the age of 50 years up to 10 to 20% after the age of 80 years [
1]. In the general population of the USA, similar increases over age have been described for both white and black Americans [
2].
The low prevalence of atrial fibrillation in rural African populations compared with urban African and western populations can be explained by a similarly lower prevalence of its established risk factors, including obesity, diabetes, hypertension, and cardiovascular disease. These risk factors are closely related to a sedentary lifestyle [
5,
10]. With the transition, urbanisation, and ageing of African populations, a sedentary lifestyle is adopted and the prevalence of atrial fibrillation rises [
12,
30].
Interestingly, cases of atrial fibrillation described in African populations are accompanied by underlying cardiac disorders in proportions up to 90%, which contrasts with the large proportion of idiopathic cases described in western populations [
3,
4]. Mostly, these cardiac disorders concern hypertensive cardiopathy and rheumatic valvular heart disease [
12,
27,
29,
30]. In the Ghanaian study population, two of the three cases suffered from hypertension. This relationship between cardiac disease and atrial fibrillation supports that atrial fibrillation may be mainly propagated by obesity, diabetes, hypertension, and cardiovascular disease.
Recently, inflammation has been postulated to play an important role in the pathogenesis of atrial fibrillation [
7]. In the Ghanaian study population the level of IL6, an instigator of a proinflammatory response, was similar to that in the general population of the USA. Earlier we have shown that the study population is biochemically and genetically enriched with proinflammatory markers, probably due to the endemic high infectious load [
23,
32,
33]. On the other hand, the level of CRP, a marker of systemic inflammation, was lower compared with the USA. Similarly, we have previously reported that the median level of CRP as well as the prevalence of mildly elevated levels of CRP was lower in the study population compared with the general population in the Netherlands. This difference was attributable to a lower BMI in the Ghanaian study population [
34]. Together, these findings may indicate that, while the capacity to generate an inflammatory response is preserved, systemic inflammation is uncommon in the Ghanaian study population.
Mendelian randomisation has shown that an elevation of CRP is rather an effect than a cause of atrial fibrillation [
35]. This interpretation is supported by observations that deny an association between CRP level and history of atrial fibrillation, but confirm that CRP is elevated during episodes of atrial fibrillation or due to coexistence of hypertension or obesity [
36‐
38]. Inflammatory processes related to atrial fibrillation seem to be caused by ischaemic or oxidative injury of atrial myocytes, which is again caused by obesity, diabetes, hypertension, and cardiac disease [
39,
40]. In the Ghanaian study population, hypertension is present in only about a quarter and obesity, dysglycaemia, and cardiovascular disease are rare. The low levels of CRP match with the close relation between these risk factors and inflammation. We have observed a similar pattern when studying inflammation in relation to peripheral and coronary arterial disease in this study population [
21].
While we found almost no atrial fibrillation in the Ghanaian study population, hypertension was present in a considerable proportion. Similarly, in western populations, black ethnicities are more affected by obesity, diabetes, and hypertension, but less often develop atrial fibrillation compared with white ethnicities [
5,
8,
11]. Meanwhile, the associations between these risk factors and atrial fibrillation are similar in both ethnicities [
5,
9,
41,
42]. A solution of this paradox may be provided by the higher sensitivity that seems required for methods to detect atrial fibrillation in blacks compared with whites [
43]. However, more research in different populations is needed to unravel the interactions between environmental and genetic risk factors [
13].
The low prevalence of atrial fibrillation in the Ghanaian study population may also be a result of a lack of risk factors other than those measured in this study. No data was available on the prevalence of rheumatic heart disease, which is a common cause of atrial fibrillation in African populations [
12,
29,
30]. Furthermore, we had no information on thyroid disease, smoking, and alcohol use, which are risk factors of atrial fibrillation in western populations [
3,
4].
Differences between ethnicities in the risks of atrial fibrillation are possibly caused by genetic factors. Multiple genetic polymorphisms have been associated with an elevated risk of atrial fibrillation, mainly in studies on populations from European decent. Yet, the effects of these associations are modest and differ between ethnicities [
44,
45]. The lower prevalence of atrial fibrillation among black Americans compared with white Americans may be a result of a lower frequency of genetic variants that predispose to atrial fibrillation among blacks. As black Americans show great genetic similarity with populations in West Africa, where the Ghanaian study population is located [
46], a lower frequency of such genetic variants may likewise explain why atrial fibrillation was scarce in the Ghanaian study population. However, this remains speculative: one report states that European genetic admixture does not explain the differences in prevalence of atrial fibrillation between white and black Americans [
47], while another report contradicts this [
48]. Moreover, if the frequency of genetic variants that predispose to atrial fibrillation would be lower among black Americans, the greater prevalence of atrial fibrillation among black Americans compared with the Ghanaian study population reinforces the essential role of lifestyle-related factors rather than such genetic variants.
The scarcity of atrial fibrillation in our study population can also be explained by selective survival of unaffected individuals. When sufficient medical care is absent, patients with atrial fibrillation may decease early from the underlying disorders or complications, such as cardiac disease or stroke. A study on patients with atrial fibrillation in rural Tanzania reports that 8 out of 15 died within a year after detection [
11]. In a larger group in Cameroon one-year mortality was 30%, of which more than half was of cardiovascular origin. Of the survivors, 18% experienced cerebrovascular accidents [
12]. On the other hand, with relatively low risk scores [
12,
30] atrial fibrillation in these populations seems unlikely to be so severely lethal to render infinitesimal prevalence estimates. In line with this, we have determined in another study [
49], by means of verbal autopsy on 1,263 of the 1,406 deaths that were registered in our cohort population, that only 2.7% died from cardiovascular causes. For those who died at the age of 50 years or older, this was 4.5%.
This study on atrial fibrillation in a traditional rural African population has limitations. First, the use of two subsequent electrocardiographic recordings of ten seconds may be insufficient to detect all cases of atrial fibrillation. More elaborate screening techniques used in western populations yield more reliable estimates of its prevalence; this difference in methodology hampers the comparison of our results with data from western populations. Second, the documentation of the cardiovascular risk factors lacks information on history and family history of cardiovascular disease. Third, due to different life expectancies, the number of elderly aged 50 years and older is lower in our population than in western populations. Fourth, due to the cross-sectional nature of this study, presence or absence of causality in the relationships between the established risk factors, systemic inflammation, and atrial fibrillation cannot be demonstrated.
The data on atrial fibrillation and its risk factors in the Ghanaian study population are not necessarily generalisable to other African populations, as they vary genetically and culturally [
46]. In the same manner, the comparison between the Ghanaian study population and the general population of the USA may not reflect a universal difference between African and western populations. Comparisons between divergent populations are informative, but also complicated. As described above, some possible differences between the Ghanaian study population and the general population of the USA remain largely unknown. More research in different non-western populations is needed to overcome the limitations of this study and to extend the scarce knowledge on atrial fibrillation in such populations [
13].
Competing interests
The authors declare that they have no competing interests.
Authors’ contributions
JJEK and DvB have performed the experiments. JWJ has delivered analysis tools. JJEK and JWJ have analysed the data. JJEK and DvB have written the manuscript. All authors have conceived and designed the experiments, have interpreted the data, and have provided intellectual input for the manuscript. All authors have read and approved the final manuscript.