On heart and oesophagus: un affaire de coeur

heart disease
heart disease


This paper is a review of the interrelations between gastroesophageal reflux diseases and coronary heart disease. The common link is the thoracic pain called non-cardiac chest pain. The pathogenic factors involved in the occurrence of chest pain are described, starting from common presentation of chest pain mimicking acute coronary syndrome. The clinical practitioners have to be aware of this differential diagnosis. The gastroesophageal reflux disease is overlapping also with other functional gastrointestinal disorders, i.e., the irritable bowel syndrome.


Table of Contents:

1. Introduction

2. Oesophagus, GERD and Heart: Epidemiological Data

3. Non-Cardiac Chest Pain

4. GERD and Arrhythmias

5. Genetic Contribution

6. Conclusion


1. Introduction

Gastro-esophageal reflux disease (GERD) is a harassing condition with large prevalence worldwide.

Its pathogenesis is multifactorial. More data are known on the environmental factors, mainly life style and nutrition, but less data exist on the genetical determination of this disease.

Esophagus, like the heart, are both intrathoracic mediastinal organs. No wonder that one may interfere with another one and that clinical symptoms may lead to confusion. Therefore, a reliable differential diagnosis is essential.

The classical presentation is the non-cardiac chest pain (NCCP) which can be caused either by

GERD or by esophageal dysmotility diagnosed by high resolution manometry.

Less well known are heart dysrhythmias associated with GERD, better known the atrial fibrillation (AF).


2. Oesophagus, GERD and Heart: Epidemiological Data

According to the Montreal definition and classification, unanimously used [1], conclusions confirmed or validated by other groups of experts [2-4], GERD is a condition that is developed when the reflux from the stomach enters in the esophagus causing complaints or complications [2].

GERD features include two main groups of symptoms:

1. Esophageal:

a. Symptomatic syndromes: the typically reflux syndrome, the reflux chest pain syndrome;

b. Syndromes with esophageal injury: reflux esophagitis, reflux stricture, Barrett’s esophagus, esophageal adenocarcinoma.

2. Extraoesophageal:

a.    Established associations: reflux cough syndrome, reflux laryngitis syndrome, reflux asthma syndrome, reflux dental erosion syndrome.

b.    Proposed associations: pharyngitis, sinusitis, idiopathic pulmonary fibrosis, recurrent otitis media [1].

The reports on epidemiology of GERD are very diverse in diverse geographical areas. Average prevalence in Western countries is 10-15% [5], while in Asia it is lower: 5%, with increase with changes in diet and increasing BMI, like in UK [6]. It was also observed that the prevalence of GERD is increasing in children and adolescents, suggesting that the process may begin early in susceptible individuals.

In East Europe there are some studies that show that GERD is also common [6]. The clinical presentation of this spectrum of related conditions is similar to other parts of the world, including the typical heartburn and the extra-digestive symptoms [7, 8]. Epidemiological particularities exist however in this area.

The main feature of GERD in many Eastern European countries i.e. Romania, is the lower severity of the disease and also the lower prevalence of Barrett’s oesophagus. This particularity was attributed to the high prevalence of Helicobacter pylori (H. pylori) infection, but there are no sound studies to confirm these largely empirical impressions. A paper from Jassy, in North-East Romania, reported the prevalence of H. pylori infection at 53% in GERD and 45% in controls (NS). Thus, it has been concluded that there is not sufficient evidence to define the relationship between H. pylori and GERD in North-Eastern Romania [7, 9]. In Romania there are not enough date regarding GERD, because the lack of observational studies.

In Eastern European countries, the diet differs according to geographical situation and traditions. Smoking is frequent and alcohol consumption is common in males. These factors were also connected to reflux and should be addressed by health professionals in any preventive campaign [7]. The relationship between obesity and GERD is also present in these countries, even in areas where the population uses the Mediterranean diet, as shown in an Albanian study [10].

Other concerns of the medical doctors address the quality of life and emotional disorders in GERD. Several studies reported impaired quality of life in GERD patients with severe symptoms [11] and the association with anxiety and depressive disorders [12].


3. Non-Cardiac Chest Pain

GERD is the most common cause for NCCP seen in patients with and without coronary artery disease [13]. Several studies have found an association between GERD and NCCP [14-16].

Studies based on 24-hour oesophageal pH meter showed that almost half of the patients studied with NCCP have abnormal oesophageal acid exposure [13].

Several hypotheses account for the occurrence of NCCP. It has been shown that reflux episodes that were causing chest pain were significantly longer and were preceded by a recent episode of pain [17]. Other hypothesis proposed and investigated in patients with NCCP was hypersensitivity oesophagus. These include peripheral sensitization of oesophageal sensory afferents leading to heightened responses to physiologic and pathologic stimuli and modulation of afferent neural function at the level of the spinal dorsal root or the central nervous system [18].

Another explanation for the mechanism NCCP is oesophageal contractions, as studied high- frequency intraluminal ultrasound, showing a temporal correlation between sustained contractions of the oesophageal longitudinal muscle and spontaneous as well as provoked oesophageal chest pain [19, 20].


4. GERD and Arrhythmias

Moving from chest pain seen in patients with GERD, we want to emphasize the fact that lately was paid attention to arrhythmias that may occur in these patients, as a complication of GERD.

Historically, the association between gastrointestinal symptoms and arrhythmias was described as gastrocardiac syndrome. Tougas et al., first described the association between reflux disease and atrial fibrillation (AF) in 1997 [21].

AF is the most common arrhythmia encountered in clinical practice, having the prevalence of 1% in the general population. There are several observational studies and case reports that have shown that other factors, such as GERD and especially esophagitis, could determine and maintain paroxistic AF. However, until now, the mechanism of AF as a consequence of gastro-oesophageal reflux remains unknown, being possible that inflammation and vagal stimulation to have a key role in these disorders. Several studies have shown that PPIs therapy may improve symptoms related to AFib and facilitate the conversion to sinus rhythm. Further on we recall the most important studies that have been conducted so far.

In a study by Weigl et al., [21] among patients with AFib and GERD, 14 patients had reflux esophagitis and 4 had Barretts oesophagus. Patients received treatment with PPIs taken twice a day. Under this treatment, both gastrointestinal and AFib related symptoms improved in 14 of 18 patients, these having a sinus rhythm on ECG. Another study by Bunch et al., [22] reported conflicting results, in that GERD was not associated with increased risk for AF. Several other studies lead also to controversial conclusions, offering us now the chance to consider that a relation between AF and GERD exist but this is not linear.


5. Genetic Contribution

Thus, there were three studies that analysed the association of IL-1B and IL-1RN polymorphisms with GERD which may modulate the gastric mucosal expression of IL-1, thus altering acid secretion, which influences the severity of gastro-oesophageal reflux disease. One of this study realized by Queiroz et al., [23]. In the absence of Helicobacter pylori (H. pylori) infection, IL-1B-31 CC (or say IL-1B-511 TT) was inversely associated with GERD [23]. Another study showed that the IL-1B-511T allele was associated with the reduced risk of GERD in the presence of H. pylori infection by the induction of corpus atrophy [24]. A third study was conducted by Chourasia et al., [25], whose results showed that the IL-1B-511 CC genotype and C allele were associated with higher risk of GERD than the TT genotype.

Another polymorphism that was tested was that of G protein, which was presumed to be a genetic factor that may contribute to the manifestation of GERD. G-protein-coupled-receptors (GPCRs) mediate the response to acid, neurotransmitters and humoral factors modulating oesophageal sensory function. A functional polymorphism in the G-protein β 3 subunit gene (GNB3) is associated with functional dyspepsia, in which visceral hypersensitivity is implicated in symptom generation [26]. In another paper, de Vries et al., [27] analysed the association of the GNB3 C825T polymorphism with GERD based on the idea presented above. The results showed that GERD is associated with GNB3 C825T and this result support the hypothesis that enhanced perception of reflux events, as a consequence of the increased signal transduction upon GPCR activation associated with the 825T allele [27].


6. Conclusion

GERD is a common oesophageal disorder, as heart disease are also very common. Their association is not coincidence but real. It is true for NCCP and AF. Pathogenic correlation exists.

Future genetic studies will offer us more insight on this topic.


The Authors:

BABIN Alexandru [1]

MURESAN Crina [2]

DUMITRASCU Dan-Lucian [3]

[1] Nicolae Testemitanu State University of Medicine and Pharmacy Kishinew (MOLDOVA).

[2] CHU Mulhouse (FRANCE).

[3] Iuliu Hatieganu University of Medicine and Pharmacy Cluj-Napoca (ROMANIA).


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