Introduction

Gastroesophageal reflux disease (GERD) is a chronic disorder of the upper gastrointestinal tract characterized by disturbing symptoms that develop from the backflow of stomach contents into the esophagus [1–3]. GERD ranks as the most prevalent gastrointestinal-related diagnosis in medical settings [1–5] and is associated with reduced health-related quality of life [6,7] and disability [8,9]. The disorder raises the chance of Barrett’s esophagus, erosive esophagitis, and esophageal cancer if treatment is not initiated timeously [10–12].

According to available pathophysiology literature, the pathogenesis of GERD is not fully understood. Undoubtedly, intrinsic, structural, or both mechanisms contribute to the onset of this disorder [13]. GERD is believed to be caused by a defect at the gastroesophageal junction, defective esophageal peristalsis, transient relaxations of the lower esophageal sphincter, abnormalities in lower esophageal sphincter pressure, or impaired esophageal bolus transit [11,14]. GERD is also caused by a hiatal hernia, which also lowers lower sphincter pressure and delays stomach emptying [11,15]. The development of GERD is thought to be influenced by esophageal visceral hypersensitivity as well [11,15].

Whatever physiological changes, it allows for regularly evacuating stomach contents such as gastric acid, pepsin, and bile into the esophagus [16]. GERD symptoms include heartburn, regurgitation, and epigastric pain [3,17]. The symptoms can manifest outside the esophagus as dysphagia, odynophagia, belching, nausea, chest pain, asthma, persistent cough, laryngitis, tooth erosions, and occasionally tissue lesions [18–21].

In 2019, there were 783.95 million cases of GERD worldwide [8]. The global pooled prevalence was 13.98% (95% CI: 12.47% to 15.56%) in 2017 [22]. North America had the highest regional pooled prevalence of 19.55 percent, while Latin America and the Caribbean had the lowest of 12.88 percent [22]. The prevalence varies by country, ranging from 4.16 percent in China, 22.4 percent in Turkey [22] to 20.6 to 67.8 percent in Saudi Arabia [2,4]. The prevalence rate in African settings ranges from 32.1 percent in Ethiopia [23], 7.6 percent in Nigeria [24] to a pooled prevalence rate of 15 to 19.9 percent in West African countries [22]. According to two studies, the prevalence of GERD in the South African population ranges from 27 to 40 percent [25,26].

Demographic and lifestyle factors, augmented in some cases by familial predisposition, are associated with a higher GERD risk. Findings from two systematic reviews document increasing age and obesity as risk factors associated with GERD [22,27]. Other demographic risk factors include female gender, low educational level, urban residence, low income, and divorced/separated/widowed [22]. Examples of lifestyle factors are alcohol consumption, smoking, a lack of physical activity, and poor nutrition [28–30]. There is also a 31 percent chance of familial heritability [31]. Family history significantly predicted GERD in Saudi Arabia [2,3]. Genetic factors are also linked to a higher risk of GERD, where reflux symptoms are present. Single-nucleotide polymorphisms at the C allele in FOXF1 rs9936833 (FOXF1), the A allele in MHC rs9257809 (MHC), and Cyclin D1 (CCND1) are examples [31]. DNA repair and anti-inflammatory cytokine genes are also strongly linked to a higher risk of GERD [31].

There has never been research on the prevalence of GERD in the Eastern Cape’s rural communities. Literature on associated factors in the rural Eastern Cape is scarce. Similar research on this topic was conducted among rural residents in the Eastern Cape province of South Africa [32]. However, the study that used 24-hour ambulatory esophageal impedance-pH monitoring only reported the type and extent of reflux in a rural African community [32]. Estimates on reflux prevalence were not reported, but the authors highlighted that mild acid reflux was common in the community [32].

Epidemiological studies are needed to discover etiologies and risk factors in different populations to understand this disease better [33]. Therefore, the present study aims to determine GERD’s prevalence and associated risk factors among residents in Mthatha, a secondary city with predominantly rural communities in the Eastern Cape province of South Africa. Awareness of GERD’s prevalence would help educate people about lifestyle choices that can help them manage GERD symptoms, enhance their quality of life, and avoid GERD complications. Identifying risk factors could help develop public health interventions for populations at high risk of GERD.

Materials and methods

Results

Out of the 353 participants, 113 (32.0% CI: 27.3% to 37.0%) were found to have GERD, while 240 (68.0% CI: 63.0% to 72.7%) had no GERD; that is, one out of every three participants was suffering from GERD. According to the likelihood of having GERD, 68.0 percent (CI: 63.0% to 72.7% n = 240) of the participants had a 50% likelihood, 25.5 percent (CI: 21.2% to 30.2% n = 90) of the participants had a 79% likelihood, and 6.5 percent (CI: 4.3% to 9.5% n = 23) of the participants had 89% likelihood. There was a 46.9 percent prevalence of GERD with a substantial impact on daily life (CI: 37.9% to 56.1% n = 53) and a 53.1 percent prevalence of GERD with a modest effect on daily life (CI: 43.9% to 62.1% n = 60). The most common symptom was heartburn (49.6%; 95% CI: 44.4% − 54.8% n = 175), followed by sleep disturbance (34.8%; 95% CI: 30.0% − 39.9% n = 123), chest pain (32.3%; 95% CI: 27.6% − 37.3% n = 114), and regurgitation (32.0%; 95% CI: 27.3% − 37.0% n = 113). GERD symptoms were mild in most participants.

Females were at a greater risk of having GERD compared to males (crude odds ratio = 1.8, 95% CI: 1.0–3.0; p 0.033). None of the other demographic factors was associated with GERD. However, the probability of having GERD was higher among participants aged 40–59 years, single, still to complete Grade 12, unemployed, and had an average monthly income of R 500.00 to R 1000.00 (Table 1).

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Table 1. Demographic factors associated with GERD among the adult population of Mthatha, South Africa.

https://doi.org/10.1371/journal.pone.0337059.t001

Clinical factors associated with GERD were hypertension and a family history of GERD. A significantly higher proportion (43.9%, p = 0.031) of hypertensive participants had GERD compared to their non-hypertensive counterparts (29.3%). A significantly high proportion (43.7%, p = 0.027) of participants with a family history of GERD had GERD compared to those without familial predisposition (Table 2).

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Table 2. Clinical factors associated with GERD among the adult population of Mthatha, South Africa.

https://doi.org/10.1371/journal.pone.0337059.t002

Lifestyle factors associated with GERD were alcohol consumption, walking less than 30 minutes per week, walking 30 minutes or more per week, swimming less than 30 minutes per week, exercising less than 30 minutes per week, frequency of alcohol consumption, and number of meals a day. A significantly high proportion of participants with GERD consumed alcohol (43.5% p = 0.003), drank alcohol more than three times a week (100.0% p < 0.0001), never walked for less than 30 minutes per week (46.7% p = 0.008), walked only once for 30 minutes or more per week (65.0% p = 0.004), swam only once for less than 30 minutes per week (100.0% p = 0.003), exercise once for less than 30 minutes per week (91.7% p < 0.0001), and consumed more than three meals a day (64.3% p < 0.0001) (Table 3).

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Table 3. Lifestyle factors associated with GERD among the adult population of Mthatha, South Africa.

https://doi.org/10.1371/journal.pone.0337059.t003

GERD was prevalent among non-drinkers of citrus drinks (38.5% p = 0.030), non-users of milk (59.6% p < 0.0001), non-eaters of bread (52.9% p = 0.001), non-consumers of fruits (58.8% p = 0.001), and non-consumers of sugar (41.3% p = 0.0038) (Table 4).

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Table 4. Dietary factors associated with GERD among the adult population of Mthatha, South Africa.

https://doi.org/10.1371/journal.pone.0337059.t004

A binary logistic regression model shows that GERD could be caused independently by hypertension and eating more than three meals a day. It is 3.0 times more likely to develop GERD if hypertensive Firth adjusted odds ratio (FaOR) = 3.0, 95% CI: 1.5–6.4, p = 0.003) and 4.2 times more likely if food consumption exceeds three meals per day (FaOR = 4.2, 95% CI: 1.9–9.2, p = 0 < 0001). Swimming less than 30 minutes per week (FaOR = 3.3, 95% CI: 0.9 to 13.4 p = 0.075), not consuming fruits (FaOR = 2.6, 95% CI: 0.9 to 7.8 p = 0.077), drinking alcohol (FaOR = 1.6, 95% CI: 0.9 to 2.9 p = 0.082), and not eating bread (FaOR = 2.1, 95% CI: 0.9 to 4.8 p = 0.095) was associated with an increased likelihood of having GERD; however, the significance levels were above the threshold (p > 0.05) (Table 5).

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Table 5. Predictors of GERD among the adult population of Mthatha, South Africa.

https://doi.org/10.1371/journal.pone.0337059.t005

Discussion

In the present study, among the 353 sampled participants, 113 were found to have GERD, accounting for 32.0 percent of the population. The rate is lower than 40% in the Western Cape [26]. Population disparities in the prevalence of GERD risk factors, such as rates of smoking, obesity, chronic diseases, dietary habits, or physical inactivity, explain the discrepancies in GERD prevalence between the Western Cape study and the current setting. The prevalence rate is comparable to rates reported using the GerdQ in other settings [1,37–39] but lower when compared with others [2,4,40,41].

The observed prevalence rates from the present setting translate to one in every three people, which is higher than the global rate of 1 in every six people [10,22,27,42]. Given the significant prevalence of Helicobacter pylori infection in the South African community: 54.5 percent [43] to 77.6 percent [44], the high rate of GERD from the present study appears contradictory. Research has shown that the elimination of Helicobacter pylori infection increased esophageal acid production and reflux, reduced esophageal peristalsis, and aggravated GERD symptoms in patients diagnosed with both Helicobacter pylori infection and GERD, suggesting the protective role of Helicobacter pylori against the occurrence of GERD [45]. The high rates of Helicobacter pylori infection in South Africa could suggest low rates of GERD, as in Nigeria, a country with high rates of Helicobacter pylori infection but low GERD rates [24,46]. Despite a high rate of Helicobacter pylori infection, the high rate of GERD in the current population could be attributed to the less virulent phylogenies of the bacteria circulating in South Africa [44]. Although Helicobacter pylori infection status remains unknown in the current population, people suffering from peptic ulcers, who have been demonstrated to have a higher rate of this bacterium in the Mthatha population [43], were excluded.

Therefore, the observed high rates in the current setting could best be explained by demographic, health, and lifestyle differences within and across countries. Populations with more aging populations and population growth have observed a high prevalence of GERD [9]. In the present study, most persons with GERD were above 40. Aging increases the risk of GERD by altering the esophageal and esophagogastric junction mechano-physical properties, decreasing esophageal peristalsis, increasing esophageal acid exposure, or increasing the anatomical disruption of the oesophagogastric junction [47]. Moreover, the gender distribution could contribute to prevalence rates, mainly if there are more females, as with the current study. Female gender has been associated with a higher risk of GERD [25,48]. Also, high obesity rates, as in the present study, could support the high prevalence observed, a finding which corroborates with international [22,27] and national [25] literature.

Larger abdominal circumferences associated with obesity raise intra-abdominal pressure and the transdiaphragmatic gradient, which are linked to the development of GERD [49].

In addition, a high occurrence of hiatus hernia, which has been implicated in the pathogenesis of GERD, has been reported among overweight and obese persons [31,49].

Compared to GERD with minimal impact, the prevalence of GERD with high impact on everyday life was lower at 45 percent. This finding shows that GERD did not have much effect on the daily life of most of the participants in the present setting. Contrarily, more participants had GERD, significantly impacting daily life in Southwestern Saudi Arabia [4].

Heartburn was the most common symptom similar in Western countries [50], Jamaica [51], Brazil [52], Saudi Arabia [53], Taiwan [54], Indonesia [41], and Nigeria [24]. However, regurgitation was the most common symptom in other settings, including Southern Chile [55] and Saudi medical students [3]. Heartburn is the most common symptom among this study’s participants and remains a classical GERD symptom [56]. However, GERD symptoms were mainly mild and related to the low impact on daily life observed in this study. Evidence suggests that not all reflux episodes are accompanied by symptoms, and heartburn frequently manifests as a sour aftertaste in the back of the mouth, either with or without refluxate regurgitation [56]. This could be why most people do not often report severe symptoms. The mild presentation of reflux symptoms in this population aligns with findings from the 24-hour ambulatory pH-metry study in the rural Eastern Cape community [32] and India [37]. Nonetheless, it is important to note that even subclinical reflux has a high propensity for serious long-term complications like Barrett’s esophagus, a significant risk factor for esophageal cancer, which is one of the dominant cancers in this region. Indeed, radiological manifestations confirm the presence of esophageal stricture and esophageal mass in people with GERD and a suggestive diagnosis of esophageal adenocarcinoma and Barrett’s esophagus in non-GERD persons presenting with intra-esophageal and extra-esophageal mild symptoms of GERD in the current setting [57]. These findings, together with the actual observation of the long-term complications of GERD, require proper monitoring and management of patients with mild GERD symptoms with little impact on daily life.

The present study found that having hypertension and having more than three meals per day were significant risk factors for GERD. The relationship between hypertension and GERD and silent GERD has been reported in previous research [58–60]. The observed relationship was more evident with untreated abdominal obesity and uncontrolled hypertension [59]. Although the use of calcium channel blockers showed no association [59], the association between hypertension and GERD has been explained by the effects of common anti-hypertensive drugs on the functioning of the lower esophageal sphincter. These drugs can enhance esophageal motor activity, increase esophageal acid exposure, reduce the tone of LES, or decrease esophageal clearance, thereby increasing GERD [61,62]. A recent systematic review suggested that GERD is a potential risk factor for hypertension [63], probably due to subjective perception of stress, poor lifestyle and dietary practices which has been identified as predictors of GERD [4]. The finding of the association between hypertension and GERD, and the shared predictors should direct public health interventions to reduce incidence as non-communicable diseases and cancer (including esophageal cancer a chronicity of GERD) are two prongs in the quadruple burden of disease in South Africa.

Concerning lifestyle factors, having more than three meals daily is associated with a higher risk of having GERD. The observed 4.2-fold risk with >3 meals/ day can be explained by disruption of the gastroesophageal barrier after eating large meals. Similar results were found where a significant relationship was reported between having 1–2 meals daily, having one big meal in the evening, and GERD [64]. Additionally, eating habits, including irregular meal patterns, eating many meals, and eating right before bed, may be linked to GERD symptoms [65]. Large meals can increase gastric distension and transient lower esophageal sphincter relaxations. This permits the stomach’s contents to return to the esophagus [42,66].

The occurrence of GERD was not associated with other lifestyle factors such as alcohol consumption, indulging in shorter exercise or swimming sessions, although the findings revealed higher likelihood ratios. Contrarily, alcohol consumption has been linked to GERD [67], acting on multiple mechanisms including interfering with the anti-reflux barrier and impairing esophageal motility with resultant poor clearance of refluxate [68]. Again, indulging in physical activity for more than 30 minutes, three times a week, reduces the risk of developing GERD [69], contrary to the findings in the present study, probably due to the similar rate of physical inactivity among those with and without GERD.

Non-consumption of fruits, which has been identified elsewhere [70,71], had no significant association with the occurrence of GERD in the current population. The association between fruit consumption and GERD is an important aspect to discuss since the risk of having GERD is lower for those who consume the most fruits than those with the lowest intake [70]. Physiological mechanisms have been used to explain the underlying correlation between fruit consumption and GERD symptom reduction [70].

Physiologically, dietary nitrites are converted nonenzymatically into significant amounts of nitric oxide in the acidic gastric environment. Nitric oxide may encourage reflux because of its strong LES-relaxant effects [70].

Dietary fibers are known to scavenge stomach nitrites, reducing the substrate available to produce nonenzymatic nitric oxide [72]. Therefore, the absence or limited fruit consumption voids the stomach of dietary fibers to scavenge nitrites, thereby increasing the chances for the synthesis of nitric oxide, an effective LES relaxer [73,74]. Additionally, vitamins A and C, which can be sourced from fruits, prevent the development of GERD [75]. Another crucial dietary finding was the increased but not statistically significant likelihood of GERD with non-consumption of fiber-rich bread. Fiber-rich diet has been associated with a 14% decrease in risk of GERD [71] and reduced possibility of symptoms [71,76] The suggestive mechanism of high fiber intake and decreased risk of GERD include greater bowel movement frequency, which, decreases gastric stasis and the occurrence of reflux events [76], modulation of the gut microbiome, and influence on the gut-brain interactions [77]. These mechanisms increase the minimal lower esophageal sphincter resting pressure, decrease the number of gastroesophageal refluxes, and decrease GERD symptoms.

Conclusions

The prevalence of GERD in Mthatha amounted to 32.0 percent, which is similar to those in other studies that used the same diagnostic tool. This study confirmed a higher prevalence of low-impact GERD compared to a lower prevalence of high-impact GERD among residents of Mthatha. The study found that heartburn was the most common GERD-related symptom. A propensity to have GERD was observed with low fiber and low fruit diets, as well as improper physical activities.

Cardiovascular disease, mainly hypertension, and lifestyle (more than three meals a day) contribute to the prevalence of GERD in this population. There is a need to screen for GERD among hypertensive patients and vice versa, since a significant risk association was observed between the two conditions. Since the literature noted that the risk is increased if hypertension is untreated and uncontrolled, there is a need for early identification and prompt treatment of hypertension in the general population. There is also a need for community education on the association between these two diseases and the probable pathways to protect against their occurrence, for example, by encouraging healthy dietary habits and proper physical activities.

Supporting information

Acknowledgments

We thank the management of Mthatha Regional Hospital for granting permission for this study to be carried out. We thank all the participants whose primary intention in visiting the health facility was not to take part in any research, yet they made a choice to do so. We also thank the Walter Sisulu University Directorate of Research and Innovation for the call to generate and disseminate findings from this work.