|
1
|
Sinha T, Joshi HM, Patel B, Stanikzai H, Hussaini H, Chaudhari SS, Habib I, Hirani S. The Association Between Gastroesophageal Reflux Disease and Atrial Fibrillation: A Systematic Review and Meta-Analysis. Cureus 2025; 17:e78356. [PMID: 40034621 PMCID: PMC11875675 DOI: 10.7759/cureus.78356] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/01/2025] [Indexed: 03/05/2025] Open
Abstract
The relationship between gastroesophageal reflux disease (GERD) and atrial fibrillation (AF) has been increasingly recognized, but its nature and strength remain unclear. We conducted a systematic review and meta-analysis of studies from January 2010 to November 2024 using PubMed, Excerpta Medica Database (EMBASE), and Web of Science databases. Seven studies were included: three cohort studies, two Mendelian randomization studies, one case-control study, and one cross-sectional study. Meta-analysis revealed that GERD was associated with a significantly increased risk of AF (RR: 1.27, 95% CI: 1.15-1.40). This association remained robust in sensitivity analyses. The two Mendelian randomization studies provided genetic evidence supporting a potential causal relationship. The proposed mechanism involves inflammatory pathways extending from the esophagus to the left atrium. The analysis was constrained by the small number of studies, methodological heterogeneity (I-Square: 81%), and limited ability to perform subgroup analyses. The findings suggest that GERD patients may benefit from AF screening, and GERD management could potentially modify AF risk. Future research should focus on prospective studies examining the impact of GERD treatment on AF prevention and progression, as well as identifying high-risk subgroups who might benefit most from targeted interventions.
Collapse
Affiliation(s)
- Tanya Sinha
- Internal Medicine, Tribhuvan University, Kathmandu , NPL
| | - Heer M Joshi
- Internal Medicine, Jackson Park Hospital, Chicago, USA
| | - Bansari Patel
- School of Medicine, American University of Barbados, Bridgetown, BRB
| | | | - Helai Hussaini
- Ear, Nose, and Throat, West Anaheim Medical Centre, Anaheim, USA
| | - Sandipkumar S Chaudhari
- Cardiothoracic Surgery, University of Alabama at Birmingham, Birmingham, USA
- Family Medicine, University of North Dakota School of Medicine and Health Sciences, Fargo, USA
| | - Ihtisham Habib
- Internal Medicine, Medical Teaching Institute, Lady Reading Hospital, Peshawar, PAK
| | | |
Collapse
|
|
2
|
Wang L, Lu YW. Gastroesophageal reflux disease may causally associate with the increased atrial fibrillation risk: evidence from two-sample Mendelian randomization analyses. Front Cardiovasc Med 2024; 11:1393383. [PMID: 38887451 PMCID: PMC11182450 DOI: 10.3389/fcvm.2024.1393383] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2024] [Accepted: 05/21/2024] [Indexed: 06/20/2024] Open
Abstract
Background The risk of atrial fibrillation (AF) is increased in individuals with gastroesophageal reflux disease (GERD), according to observational research. The causal significance of this association is still unclear. This study sought to assess GERD's role as a potential contributing factor in AF. Methods With the use of a two-sample Mendelian randomization (MR) technique, we assessed the causal relationship between GERD and AF. The association of genetic variants with GERD was examined using data from a recent genome-wide association study (GWAS) that included 602,604 people. Data on the association between genetic variations and AF was obtained from a second GWAS with 1,030,836 participants. The effect sizes were examined based on the inverse-variance weighted method. Additional statistical techniques, including MR-Egger, simple mode, weighted mode, MR Pleiotropy Residual Sum, outlier, and weighted median were used in the sensitivity analysis. Results MR analyses in inverse-variance weighted models, using 76 single nucleotide polymorphisms (SNPs) as markers, revealed a relationship between genetically predicted GERD and a greater AF incidence [odds ratio (OR): 1.165, 95% CI 1.102-1.231; P = 7.637 × 10-8]. According to MR-Egger, there was no evidence of gene pleiotropy that could be found (intercept = 0.003, P = 0.581). The findings of the sensitivity study, which used several MR methods, were found to be reliable. Conclusion The MR analysis revealed a correlation between GERD and increased AF incidence, supporting the idea that treating patients with GERD as early as possible might reduce their chance of developing AF.
Collapse
Affiliation(s)
| | - Yi Wei Lu
- Cardiac Department, Aerospace Center Hospital, Beijing, China
| |
Collapse
|
|
3
|
Objectively confirmed gastroesophageal reflux disease and risk of atrial fibrillation: a population-based cohort study in Sweden. Eur J Gastroenterol Hepatol 2022; 34:1116-1120. [PMID: 36052701 DOI: 10.1097/meg.0000000000002419] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVE This study aimed to determine the risk of atrial fibrillation in patients with objectively confirmed GERD. METHODS This was a nationwide population-based cohort study between 2005 and 2018, including the majority ( n = 8 421 115) of all Swedish adult residents (≥18 years). Within this cohort, the exposed group were all individuals with a diagnosis of esophagitis or Barrett's esophagus, and the unexposed group was made up of five times as many individuals without any GERD, matched by age, sex, and calendar year. The outcome was the first diagnosis of atrial fibrillation. Cox regression provided hazard ratios (HRs) with 95% confidence intervals (CIs), adjusted for confounders. RESULTS Among 118 013 individuals with esophagitis or Barrett's esophagus and 590 065 without GERD, 7042 (6.0%) and 40 962 (6.9%) developed atrial fibrillation, respectively. The risk of atrial fibrillation among patients with GERD was 13% increased within the first year of diagnosis (HR, 1.13; 95% CI, 1.06-1.20), but was not increased after that. Among individuals aged less than 60 years, the HR of atrial fibrillation was 55% increased within the first year of diagnosis (HR, 1.55; 95% CI, 1.27-1.88), and this association remained increased after the first year (HR, 1.14; 95% CI, 1.06-1.22). No association was found in older participants (≥60 years). Results were similar in men and women. CONCLUSION This large population-based cohort study indicates that objectively determined GERD increases the risk of atrial fibrillation shortly after diagnosis in men and women younger than 60 years.
Collapse
|
|
4
|
Malik A, Best K, Singh S, Jaggon KS, Michael M. Hiatal Hernia: A Possible Trigger for Atrial Fibrillation. Cureus 2021; 13:e18857. [PMID: 34804710 PMCID: PMC8597673 DOI: 10.7759/cureus.18857] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/17/2021] [Indexed: 11/05/2022] Open
Abstract
Atrial fibrillation is a commonly encountered clinical entity with various cardiovascular consequences. Common risk factors include alcohol abuse, hyperthyroidism, mitral stenosis, hypertension, diabetes mellitus, and coronary artery disease. Another risk factor, yet under scientific scrutiny, is hiatal hernia. This anatomical abnormality, due to its proximity to the heart and high prevalence in atrial fibrillation patients, has merited scientific investigation to determine if an association truly exists between this gastrointestinal pathology and atrial fibrillation. The case herein is of an 81-year-old hospitalized female with a hiatal hernia who was recorded to have recurrent episodes of atrial fibrillation in the absence of traditional risk factors for arrhythmogenesis.
Collapse
Affiliation(s)
- Atika Malik
- Internal Medicine, Punjab Hospital, Sialkot, PAK
| | - Karimah Best
- Internal Medicine, American University of Antigua, Osbourn, ATG
| | | | - Kory S Jaggon
- Internal Medicine, University of Maryland, Baltimore, USA
| | - Miriam Michael
- Internal Medicine, University of Maryland, Baltimore, USA
| |
Collapse
|
|
5
|
Mohamed A, Ochoa Crespo D, Kaur G, Ashraf I, Peck MM, Maram R, Malik BH. Gastroesophageal Reflux and Its Association With Atrial Fibrillation: A Traditional Review. Cureus 2020; 12:e10387. [PMID: 33062508 PMCID: PMC7550002 DOI: 10.7759/cureus.10387] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Atrial fibrillation (AF) is a common arrhythmia, and gastroesophageal reflux disease (GERD) is a common gastroenterology disease; both are highly encountered daily in clinical practice. Since both share common predisposing factors, we can conclude that there is a link between them. To date, the precise mechanism of reflux disease as a possible cause of atrial fibrillation remains uncertain. However, some possibilities can be postulated, such as the inflammation process, and sympathovagal imbalance represents the main factors for how GERD can initiate AF. Vigorous aerobic exercise in healthy people can bring about acidic esophageal reflux, which is a common risk factor for AF. Various inflammatory markers such as C-reaction protein (CRP) and interleukins have been a central role in initiating AF. A large hiatal hernia (HH) can cause direct compression on the left atrium that is possibly predisposing to atrial arrhythmogenesis. It has been sporadically reported that using a proton pump inhibitor to treat GERD in patients with coexisting AF has a noticeable effect on decreasing symptoms of AF and recurrence with less cost and side effects.
Collapse
Affiliation(s)
- Alaa Mohamed
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA.,Internal Medicine, Memorial Hermann Medical Center, Houston, USA
| | - Diego Ochoa Crespo
- Internal Medicine, Clinica San Martin, Azogues, ECU.,Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Gurleen Kaur
- Neurology, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Ibtisam Ashraf
- Internal Medicine, Shalamar Institute of Health Sciences, Lahore, PAK.,Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Mercedes Maria Peck
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Ruchira Maram
- Internal Medicine, Arogyasri Healthcare Trust, Hyderabad, IND.,Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Bilal Haider Malik
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| |
Collapse
|
|
6
|
Kaya H, Barutçu S. Gastroesophageal reflux disease is associated with abnormal ventricular repolarization indices. TURKISH JOURNAL OF GASTROENTEROLOGY 2019; 30:1021-1024. [PMID: 31854306 DOI: 10.5152/tjg.2019.181008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND/AIMS Gastroesophageal Reflux Disease (GERD) is a clinical entity affecting the upper gastrointestinal tract. The pathophysiology of GERD has been associated with autonomic nervous system disorders. Autonomic nervous system disturbances in GERD patients have been shown to lead to fatal ventricular arrhythmias (VAs) that result in electrical and ventricular repolarization anomalies. The maximum to terminal electrocardiographic T wave (Tpe) has been associated with repolarization of transmural dispersion. In addition, a higher Tpe interval (TpeI) and Tpe/QT ratio correspond with VAs. The goal of this report was to assess ventricular repolarization, by TpeI and Tpe/QT ratio, in GERD patients. MATERIALS AND METHODS The study was comprised of 46 GERD subjects and 43 healthy volunteers. TpeI, cTpe, and Tpe/Q ratios were determined from electrocardiograms and associations of the groups were compared. RESULTS The clinical characteristics were similar between the two groups. TpeI, corrected Tpe (cTpe) interval, and Tpe/QT ratio were higher in subjects with GERD in comparison to the control group (P<0.001, P=0.018, and P<0.001, respectively). CONCLUSION TpeI and Tpe/QT ratio were higher in GERD patients. Patients with GERD may have an increased risk for VAs.
Collapse
Affiliation(s)
- Hakan Kaya
- Department of Cardiology, Adıyaman University, Adıyaman, Turkey
| | - Sezgin Barutçu
- Department of Gastroenterology, Adıyaman Training and Research Hospital, Adıyaman, Turkey
| |
Collapse
|
|
7
|
Xu L, Zhang Y, Xie J, Liu Y, Xu L. Association between gastroesophageal reflux disease and atrial fibrillation: a systematic review and meta-analysis. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2019; 111:874-879. [PMID: 31617365 DOI: 10.17235/reed.2019.5389/2017] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
BACKGROUND AND OBJECTIVE associations between gastroesophageal reflux disease (GERD) and atrial fibrillation (AF) are inconclusive. Some studies found that AF was a risk factor for GERD whereas other studies showed opposite results. The primary objective of this study was to systematically evaluate whether GERD and AF have a bidirectional association using a meta-analysis. METHODS a systematic review was conducted of studies on the association between GERD and AF, written in the English language and included in Cochrane CENTRAL, PubMed and EMBASE until February 2017. The search was limited to longitudinal, case-control, and cross-sectional studies. RESULTS among 548 studies found in the above-mentioned databases, seven fulfilled the inclusion criteria. Among these seven studies, two were longitudinal studies, two were case-control studies, and three were cross-sectional studies. The summary adjusted relative risks (RRs) for AF-induced GERD and GERD-induced AF were 1.54 (95% CI, 1.08-2.17) and 1.06 (95% CI, 0.86-1.31), respectively. The subgroup analysis showed that the associations were not significantly modified by sample size, study design, age, or geographic area. CONCLUSIONS this meta-analysis supported the association of AF with increased risk of GERD.
Collapse
Affiliation(s)
- Lu Xu
- Ningbo University Medical School, China
| | - Yu Zhang
- Ningbo University Medical School, China
| | | | - Yi Liu
- Department of Gastroenterology, Ningbo No.1 Hospital, China
| | - Lei Xu
- Department of Gastroenterology, Ningbo No.1 Hospital, China
| |
Collapse
|
|
8
|
Maruyama T, Fukata M, Akashi K. Association of atrial fibrillation and gastroesophageal reflux disease: Natural and therapeutic linkage of the two common diseases. J Arrhythm 2019; 35:43-51. [PMID: 30805043 PMCID: PMC6373829 DOI: 10.1002/joa3.12125] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2018] [Revised: 09/01/2018] [Accepted: 09/13/2018] [Indexed: 12/24/2022] Open
Abstract
Atrial fibrillation (AF) is a common arrhythmia and gastroesophageal reflux disease (GERD) is popular in Japan. The two common diseases share several predisposing factors such as lifestyle and senescence, and inflammation and oxidative stress play an important role in their development and progression. Incidental cases of AF treated successfully by proton pump inhibitor (PPI) applied for coexisting GERD have been sporadically reported. An increasing evidence indicates that GERD induces the initiation and the perpetuation of AF. This is caused by the autonomic nerve influence, mechanical compression, and propagation of local inflammation due to proximity of left atrium (LA) and lower esophagus. Meanwhile, AF also develops GERD by mechanical and inflammatory actions of LA characterized by remodeling and inflammation. The robust association of AF with GERD is not limited to their natural interaction, i.e., pharmacological or nonpharmacological treatment of AF is reported to aggravate GERD. Many cardiac drugs (anticoagulants, calcium antagonists, and nitrates) induce esophageal mucosal damage and lower esophageal sphincter relaxation promoting acid reflux. These drugs are frequently prescribed in patients with AF for stroke prevention, rate control, and for coexisting coronary heart disease. Catheter ablation also yields both GERD and esophageal thermal injury, which is a precursor lesion of atrioesophageal fistula. The notion that AF and GERD are mutually interdependent is widely and empirically recognized. However, mechanistic link of the two common diseases and objective evaluation of PPI as an adjunctive AF treatment warrant future large-scale prospective trials.
Collapse
Affiliation(s)
- Toru Maruyama
- Department of Medicine and Biosystemic ScienceKyushu University Graduate School of Medical SciencesFukuokaJapan
| | - Mitsuhiro Fukata
- Department of Medicine and Biosystemic ScienceKyushu University Graduate School of Medical SciencesFukuokaJapan
| | - Koichi Akashi
- Department of Medicine and Biosystemic ScienceKyushu University Graduate School of Medical SciencesFukuokaJapan
| |
Collapse
|
|
9
|
Pastori D, Farcomeni A, Saliola M, Del Sole F, Pignatelli P, Violi F, Lip GYH. Temporal trends of time in therapeutic range and incidence of cardiovascular events in patients with non-valvular atrial fibrillation. Eur J Intern Med 2018; 54:34-39. [PMID: 29655807 DOI: 10.1016/j.ejim.2018.04.007] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2018] [Revised: 03/03/2018] [Accepted: 04/08/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND Optimal time in therapeutic range (TTR) of vitamin K antagonists (VKAs) is crucial for cardiovascular events (CVEs) prevention in non-valvular atrial fibrillation (NVAF). The relationship between temporal changes of TTR and the incidence of CVEs has been poorly investigated. We investigated 1) temporal trends of TTR in a long-term follow-up of NVAF patients; 2) the incidence of CVEs according to changes of TTR. METHODS Prospective observational study including 1341 NVAF outpatients (mean age 73.5 years, 42.5% male) starting VKAs. Patients were divided into 4 groups: Group 0: Optimal TTR, consistently ≥70% (n = 241); Group 1: Temporally worsening TTR, from above to below 70% (n = 263); Group 2: Temporally improving TTR, from below to above 70% (n = 270); Group 3: Suboptimal TTR, consistently <70% (n = 567). RESULTS In a mean follow-up of 37.7 months (4214.2 patient-years), 108 CVEs occurred (2.6%/year). Survival analysis showed a graded increased risk of CVEs in relation to temporal changes in TTR, with the worst outcomes in Groups 1 and 3 (log-rank test p = 0.013). Multivariable Cox proportional hazards regression analysis showed that Group 1 vs. 0 (HR: 2.096; 95%CI 1.061-4.139, p = 0.033), Group 3 vs. 0 (HR: 2.292; 95%CI 1.205-4.361, p = 0.011), CHA2DS2VASc score (HR:1.316; 95%CI 1.153-1.501, p < 0.001) and PPIs (HR:0.453; 95%CI 0.285-0.721, p = 0.001) were independently associated with CVEs. CONCLUSION A decrease of TTR <70% over time is observed in almost 20% of NVAF patients. Patients with worsening TTR temporally (ie. from initially above 70% to below 70%) have similar risk of CVEs of patients with consistently suboptimal anticoagulation.
Collapse
Affiliation(s)
- Daniele Pastori
- I Clinica Medica, Atherothrombosis Center, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy; Institute for Cardiovascular Sciences, University of Birmingham, Birmingham, United Kingdom
| | - Alessio Farcomeni
- Department of Public Health and Infectious Diseases Sapienza University of Rome, Rome, Italy
| | - Mirella Saliola
- I Clinica Medica, Atherothrombosis Center, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy
| | - Francesco Del Sole
- I Clinica Medica, Atherothrombosis Center, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy
| | - Pasquale Pignatelli
- I Clinica Medica, Atherothrombosis Center, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy
| | - Francesco Violi
- I Clinica Medica, Atherothrombosis Center, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy
| | - Gregory Y H Lip
- Institute for Cardiovascular Sciences, University of Birmingham, Birmingham, United Kingdom; Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
| |
Collapse
|
|
10
|
Pastori D, Pignatelli P, Cribari F, Carnevale R, Saliola M, Violi F, Lip GY. Time to therapeutic range (TtTR), anticoagulation control, and cardiovascular events in vitamin K antagonists-naive patients with atrial fibrillation. Am Heart J 2018; 200:32-36. [PMID: 29898846 DOI: 10.1016/j.ahj.2018.03.004] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2017] [Accepted: 03/03/2018] [Indexed: 12/21/2022]
Abstract
BACKGROUND Vitamin K antagonists (VKAs) reduce cardiovascular events (CVEs) in atrial fibrillation (AF) when a time in therapeutic range (TiTR) >70% is achieved. Factors affecting the time to achieve the TR (TtTR) are unknown. METHODS Prospective observational study including 1,406 nonvalvular AF patients starting VKAs followed for a mean of 31.3months (3,690 patient/year); TiTR, TtTR, and SAMe-TT2R2 score were calculated, and CVEs were recorded. RESULTS Median TtTR was 8.0days (interquartile range 5.0-18.0). Patients with high TtTR (ie, >75th percentile) were more likely to be in AF than in sinus rhythm at entry (odds ratio [OR]: 1.423, P=.011). Median TiTR was 60.0%; low TiTR (below median) was associated with SAMe-TT2R2 score (OR: 1.175, P=.001), high TtTR (>75th percentile, OR: 1.357, P=.017), and number of international normalized ratio checks (OR: 0.998, P=.049). We recorded 113 CVEs (3.1%/y), with a higher rate seen in patients with TtTR >75th percentile compared to those below (log-rank test, P=.006). A multivariable Cox regression analysis showed that SAMe-TT2R2 score (hazard ratio [HR]: 1.331, P<.001), TtTR >75th percentile (HR: 1.505, P=.047), TiTR <70% (HR: 1.931, P=.004), number of international normalized ratio checks (HR: 0.988, P<.001), digoxin (HR: 1.855, P=.008), and proton-pump inhibitors (HR: 0.452, P<.001) were independently associated with CVEs. CONCLUSIONS High TtTR is associated with poorer long-term quality of VKAs therapy. Patients with TtTR >18days or with high SAMe-TT2R2 score should be considered for treatment with non-vitamin K oral anticoagulants.
Collapse
Affiliation(s)
- Daniele Pastori
- I Clinica Medica, Atherothrombosis Center, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy; Institute for Cardiovascular Sciences, University of Birmingham, Birmingham, United Kingdom
| | - Pasquale Pignatelli
- I Clinica Medica, Atherothrombosis Center, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy
| | - Francesco Cribari
- I Clinica Medica, Atherothrombosis Center, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy
| | - Roberto Carnevale
- I Clinica Medica, Atherothrombosis Center, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy; Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy
| | - Mirella Saliola
- I Clinica Medica, Atherothrombosis Center, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy
| | - Francesco Violi
- I Clinica Medica, Atherothrombosis Center, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy
| | - Gregory Yh Lip
- Institute for Cardiovascular Sciences, University of Birmingham, Birmingham, United Kingdom; Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
| |
Collapse
|
|
11
|
Im SI, Heo J, Kim BJ, Cho KI, Kim HS, Heo JH, Hwang JY. Impact of periodontitis as representative of chronic inflammation on long-term clinical outcomes in patients with atrial fibrillation. Open Heart 2018; 5:e000708. [PMID: 29713482 PMCID: PMC5922561 DOI: 10.1136/openhrt-2017-000708] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2017] [Revised: 02/12/2018] [Accepted: 04/03/2018] [Indexed: 12/12/2022] Open
Abstract
Objectives Relationship between atrial fibrillation (AF) and inflammation was shown in previous studies. However, there was limited data about the association between the periodontitis and AF in the long-term follow-up. The aim of this study was to evaluate the impact of periodontitis on long-term clinical outcomes in patients with AF. Methods The Kosin University echocardiography, ECG and periodontitis database were reviewed from 2013 to 2015 to identify patients with AF. Those patients were divided into two groups according to the presence of periodontitis and clinical events including any arrhythmic attack, thromboembolic and bleeding and death were collected during a median of 18 months. Results Among 227 patients with AF, 47 (20.7%) patients had periodontitis. Major adverse cardiac events (MACE) were significantly higher in patients with periodontitis compared with those without periodontitis (p<0.001). Arrhythmias including AF, atrial tachycardia, atrial premature beat, ventricular tachycardia and ventricular premature beat also occurred in 44 (93.6%) patients, which was higher significantly higher incidence in patients with periodontitis than in those without periodontitis (p<0.001). In univariate analysis, age, CHA2DS2-VASc, left atrial volume index (LAVi) and periodontitis were significantly associated with arrhythmic events and MACE including bleeding events, thromboembolic events, arrhythmic events and mortality. In multivariate analysis, LAVi (p=0.005) and periodontitis (p<0.001) were independent risk factors for arrhythmic events and periodontitis (p<0.001) for MACE at the long-term follow-up. Conclusions The periodontitis as representative of chronic inflammation was an independent predictor of arrhythmic events and MACE in patients with AF.
Collapse
Affiliation(s)
- Sung Il Im
- Division of Cardiology, Department of Internal Medicine, Kosin University Gospel Hospital, Kosin University College of Medicine, Busan, Republic of Korea
| | - Jinho Heo
- Department of Dentistry/Oral & Maxillofacial Surgery, Kosin University Gospel Hospital, Kosin University College of Medicine, Busan, Republic of Korea
| | - Bong Joon Kim
- Division of Cardiology, Department of Internal Medicine, Kosin University Gospel Hospital, Kosin University College of Medicine, Busan, Republic of Korea
| | - Kyoung-Im Cho
- Division of Cardiology, Department of Internal Medicine, Kosin University Gospel Hospital, Kosin University College of Medicine, Busan, Republic of Korea
| | - Hyun Su Kim
- Division of Cardiology, Department of Internal Medicine, Kosin University Gospel Hospital, Kosin University College of Medicine, Busan, Republic of Korea
| | - Jung Ho Heo
- Division of Cardiology, Department of Internal Medicine, Kosin University Gospel Hospital, Kosin University College of Medicine, Busan, Republic of Korea
| | - Jin Yong Hwang
- Division of Cardiology, Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University College of Medicine, Jinju, Republic of Korea
| |
Collapse
|
|
12
|
Gesualdo M, Scicchitano P, Carbonara S, Ricci G, Principi M, Ierardi E, Di Leo A, Cortese F, Ciccone MM. The association between cardiac and gastrointestinal disorders: causal or casual link? J Cardiovasc Med (Hagerstown) 2017; 17:330-8. [PMID: 26702598 DOI: 10.2459/jcm.0000000000000351] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Cardiovascular diseases are the leading cause of death worldwide: among them, coronary artery disease and arrhythmias represent the most frequent pathological conditions. Similarly, the gastrointestinal disorders, that is, gastroesophageal reflux and inflammatory bowel diseases, have a high incidence in the general population. Several pieces of evidence have documented a link between cardiac and gastrointestinal disorders as they often share similar risk factors and symptoms. Furthermore, both can simultaneously occur in the same patient, thus creating problems in the correct clinical diagnosis. It is well known that gastrointestinal disorders may present with chest pain and mimic angina pectoris. In contrast, they can also unmask heart disease, such as in the case of the angina-linked ischemia. The aim of this review was to elucidate the mechanisms underlying the relationship between cardiac and gastrointestinal diseases to better understand the causal or casual character of such a linkage.
Collapse
Affiliation(s)
- Michele Gesualdo
- aCardiovascular Diseases Section bDivision of Gastroenterology, Department of Emergency and Organ Transplantation (DETO), University of Bari, Bari, Italy
| | | | | | | | | | | | | | | | | |
Collapse
|
|
13
|
Zhang W, Tao Q, Guo Z, Fu Y, Chen X, Shar PA, Shahen M, Zhu J, Xue J, Bai Y, Wu Z, Wang Z, Xiao W, Wang Y. Systems Pharmacology Dissection of the Integrated Treatment for Cardiovascular and Gastrointestinal Disorders by Traditional Chinese Medicine. Sci Rep 2016; 6:32400. [PMID: 27597117 PMCID: PMC5011655 DOI: 10.1038/srep32400] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2016] [Accepted: 08/04/2016] [Indexed: 02/07/2023] Open
Abstract
Though cardiovascular diseases (CVDs) and gastrointestinal disorders (GIDs) are different diseases associated with different organs, they are highly correlated clinically. Importantly, in Traditional Chinese Medicine (TCM), similar treatment strategies have been applied in both diseases. However, the etiological mechanisms underlying them remain unclear. Here, an integrated systems pharmacology approach is presented for illustrating the molecular correlations between CVDs and GIDs. Firstly, we identified pairs of genes that are associated with CVDs and GIDs and found that these genes are functionally related. Then, the association between 115 heart meridian (HM) herbs and 163 stomach meridian (SM) herbs and their combination application in Chinese patent medicine was investigated, implying that both CVDs and GIDs can be treated by the same strategy. Exemplified by a classical formula Sanhe Decoration (SHD) treating chronic gastritis, we applied systems-based analysis to introduce a drug-target-pathway-organ network that clarifies mechanisms of different diseases being treated by the same strategy. The results indicate that SHD regulated several pathological processes involved in both CVDs and GIDs. We experimentally confirmed the predictions implied by the effect of SHD for myocardial ischemia. The systems pharmacology suggests a novel integrated strategy for rational drug development for complex associated diseases.
Collapse
Affiliation(s)
- Wenjuan Zhang
- College of Life Science, Northwest A & F University, Yangling, Shaanxi 712100, China
- Center of Bioinformatics, Northwest A & F University, Yangling, Shaanxi 712100, China
| | - Qin Tao
- College of Life Science, Northwest A & F University, Yangling, Shaanxi 712100, China
- Center of Bioinformatics, Northwest A & F University, Yangling, Shaanxi 712100, China
| | - Zihu Guo
- College of Life Science, Northwest A & F University, Yangling, Shaanxi 712100, China
- Center of Bioinformatics, Northwest A & F University, Yangling, Shaanxi 712100, China
| | - Yingxue Fu
- College of Life Science, Northwest A & F University, Yangling, Shaanxi 712100, China
- Center of Bioinformatics, Northwest A & F University, Yangling, Shaanxi 712100, China
| | - Xuetong Chen
- College of Life Science, Northwest A & F University, Yangling, Shaanxi 712100, China
- Center of Bioinformatics, Northwest A & F University, Yangling, Shaanxi 712100, China
| | - Piar Ali Shar
- College of Life Science, Northwest A & F University, Yangling, Shaanxi 712100, China
- Center of Bioinformatics, Northwest A & F University, Yangling, Shaanxi 712100, China
| | - Mohamed Shahen
- College of Life Science, Northwest A & F University, Yangling, Shaanxi 712100, China
- Center of Bioinformatics, Northwest A & F University, Yangling, Shaanxi 712100, China
| | - Jinglin Zhu
- College of Life Science, Northwest University, Xi’an, Shaanxi 710069, China
| | - Jun Xue
- College of Life Science, Northwest University, Xi’an, Shaanxi 710069, China
| | - Yaofei Bai
- College of Life Science, Northwest A & F University, Yangling, Shaanxi 712100, China
- Center of Bioinformatics, Northwest A & F University, Yangling, Shaanxi 712100, China
| | - Ziyin Wu
- College of Life Science, Northwest A & F University, Yangling, Shaanxi 712100, China
- Center of Bioinformatics, Northwest A & F University, Yangling, Shaanxi 712100, China
| | - Zhenzhong Wang
- State Key Laboratory of New-tech for Chinese Medicine Pharmaceutical Process, Lianyungang, Jiangsu, 222001, China
| | - Wei Xiao
- State Key Laboratory of New-tech for Chinese Medicine Pharmaceutical Process, Lianyungang, Jiangsu, 222001, China
| | - Yonghua Wang
- College of Life Science, Northwest A & F University, Yangling, Shaanxi 712100, China
- Center of Bioinformatics, Northwest A & F University, Yangling, Shaanxi 712100, China
| |
Collapse
|
|
14
|
Ahmadi B, Alimohammadian M, Yaseri M, Majidi A, Boreiri M, Islami F, Poustchi H, Derakhshan MH, Feizesani A, Pourshams A, Abnet CC, Brennan P, Dawsey SM, Kamangar F, Boffetta P, Sadjadi A, Malekzadeh R. Multimorbidity: Epidemiology and Risk Factors in the Golestan Cohort Study, Iran: A Cross-Sectional Analysis. Medicine (Baltimore) 2016; 95:e2756. [PMID: 26886618 PMCID: PMC4998618 DOI: 10.1097/md.0000000000002756] [Citation(s) in RCA: 68] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2015] [Revised: 01/07/2016] [Accepted: 01/13/2016] [Indexed: 12/21/2022] Open
Abstract
Advances in medicine and health policy have resulted in growing of older population, with a concurrent rise in multimorbidity, particularly in Iran, as a country transitioning to a western lifestyle, and in which the percent of the population over the age of 60 years is increasing. This study aims to assess multimorbidity and the associated risk factors in Iran. We used data from 50,045 participants (age 40-75 y) in the Golestan Cohort Study, including data on demographics, lifestyle habits, socioeconomic status, and anthropometric indices. Multimorbidity was defined as the presence of 2 or more out of 8 self-reported chronic conditions, including cardiovascular diseases, diabetes, chronic obstructive pulmonary disease, chronic kidney disease, liver disease, gastroesophageal reflux disease, tuberculosis, and cancer. Multivariate logistic regression models were used to examine the associations between multiple different factors and the risk factors. Multimorbidity prevalence was 19.4%, with the most common chronic diseases being gastroesophageal reflux disease (76.7%), cardiovascular diseases (72.7%), diabetes (25.3%), and chronic obstructive pulmonary disease (21.9%). The odds of multimorbidity was 2.56-fold higher at the age of >60 years compared with that at <50 years (P < 0.001), and 2.11-fold higher in women than in men (P < 0.001). Other factors associated with higher risk of multimorbidity included non-Turkmen ethnicity, low education, unemployment, low socioeconomic status, physical inactivity, overweight, obesity, former smoking, opium and alcohol use, and poor oral health. Apart from advanced age and female sex, the most important potentially modifiable lifestyle factors, including excess body weight and opium use, and opium user, are associated with multimorbidity. Policies aiming at controlling multimorbidity will require a multidimensional approach to reduce modifiable risk factors in the younger population in developing countries alongside adopting efficient strategies to improve life quality in the older population.
Collapse
Affiliation(s)
- Batoul Ahmadi
- From the Department of Health Management and Economics, School of Public Health, Tehran University of Medical Sciences (BA), Tehran, Iran; Digestive Disease Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences (MA, AM, MB, FI, HP, AFS, AP, FK, AS, RM), Tehran, Iran; Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences (MA, MB, HP, MHD, AFS, AP, AS, RM), Tehran, Iran; Department of Human Ecology, School of Public Health, Tehran University of Medical Sciences (MA), Tehran, Iran; Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences (MY), Tehran, Iran; Surveillance and Health Services Research, American Cancer Society (FI), Atlanta, GA; Institute for Translational Epidemiology and Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai (PB), New York, NY; Division of Cardiovascular and Medical Sciences, Section of Gastroenterology, University of Glasgow (MHD), Glasgow, UK; Liver and Pancreatic-biliary Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences (AP), Tehran, Iran; Division of Cancer Epidemiology and Genetics, National Cancer Institute (CCA, SMD), Bethesda, MD; International Agency for Research on Cancer, Genetic Epidemiology Group (PB), Lyon, France; and Department of Public Health Analysis, School of Community Health and Policy, Morgan State University (FK), Baltimore, MD
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
15
|
Duygu H. Gastroesophageal reflux and atrial fibrillation: A chicken and egg situation. Int J Cardiol 2015; 190:241. [DOI: 10.1016/j.ijcard.2015.04.168] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2015] [Accepted: 04/20/2015] [Indexed: 12/25/2022]
|
|
16
|
Milovanovic B, Filipovic B, Mutavdzin S, Zdravkovic M, Gligorijevic T, Paunovic J, Arsic M. Cardiac autonomic dysfunction in patients with gastroesophageal reflux disease. World J Gastroenterol 2015; 21:6982-6989. [PMID: 26078576 PMCID: PMC4462740 DOI: 10.3748/wjg.v21.i22.6982] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2014] [Revised: 01/26/2015] [Accepted: 03/27/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate autonomic nervous function in patients with a diagnosis of gastroesophageal reflux disease (GERD).
METHODS: The investigation was performed on 29 patients (14 men), aged 18-80 years (51.14 ± 18.34), who were referred to our Neurocardiology Laboratory at the Clinical and Hospital Center “Bezanijska Kosa” with a diagnosis of GERD. One hundred sixteen healthy volunteers matched in age and sex with the examinees served as the control group. The study protocol included the evaluation of autonomic function and hemodynamic status, short-term heart rate variability (HRV) analysis, 24 h ambulatory ECG monitoring with long-term HRV analysis and 24 h ambulatory blood pressure monitoring.
RESULTS: Pathologic results of cardiovascular reflex test were more common among patients with reflux compared to the control group. Severe autonomic dysfunction was detected in 44.4% of patients and in 7.9% of controls (P < 0.001). Parameters of short-term analysis of RR variability, which are the indicators of vagal activity, had lower values in patients with GERD than in the control group. Long-term HRV analysis of time-domain parameters indicated lower values in patients with reflux disease when compared to the control group. Power spectral analysis of long-term HRV revealed lower low- and high-frequency values. Detailed 24 h ambulatory blood pressure analysis showed significantly higher values of systolic blood pressure and pulse pressure in the reflux group than in the control group.
CONCLUSION: Patients with GERD have distortion of sympathetic and parasympathetic components of the autonomic nervous system, but impaired parasympathetic function appears more congruent to GERD.
Collapse
|
|
17
|
Floria M, Drug VL. Atrial fibrillation and gastroesophageal reflux disease: From the cardiologist perspective. World J Gastroenterol 2015; 21:3154-3156. [PMID: 25780320 PMCID: PMC4356942 DOI: 10.3748/wjg.v21.i10.3154] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2014] [Revised: 11/16/2014] [Accepted: 12/22/2014] [Indexed: 02/06/2023] Open
Abstract
We have read with interest the paper by Roman C. and colleagues discussing the relationship between gastroesophageal reflux disease and atrial fibrillation. The review is presenting the available evidence for the common pathogenic mechanisms. However, from a cardiologist perspective, some available data were not highlighted in the review, cardiovascular involvement in gastroesophageal reflux is less assessed. Hypertension, obesity or diabetes mellitus are substrate for left atrial remodeling that initiate and sustained atrial fibrillation development. One of the pathophysiologic mechanisms in atrial fibrillation is the presence of a trigger. Gastroesophageal reflux could be only a trigger for this arrhythmia. We believe that atrial fibrillation should be considered as possible extraesophageal syndrome in the gastroesophageal reflux classification.
Collapse
|
|
18
|
Lioni L, Letsas KP, Efremidis M, Vlachos K, Karlis D, Asvestas D, Mihas CC, Sideris A. Gastroesophageal reflux disease is a predictor of atrial fibrillation recurrence following left atrial ablation. Int J Cardiol 2015; 183:211-3. [DOI: 10.1016/j.ijcard.2015.01.083] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2014] [Revised: 01/13/2015] [Accepted: 01/28/2015] [Indexed: 01/04/2023]
|
|
19
|
Turagam MK, Velagapudi P. Gut To Heart: Acid Reflux Disease In Atrial Fibrillation And The Role Of Proton Pump Inhibitor. J Atr Fibrillation 2014; 7:1031. [PMID: 27957111 DOI: 10.4022/jafib.1031] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2014] [Revised: 09/12/2014] [Accepted: 09/12/2014] [Indexed: 12/13/2022]
Affiliation(s)
- Mohit K Turagam
- Department of Medicine, University of Wisconsin School of Medicine and Public Health-Madison, WI, USA
| | - Poonam Velagapudi
- Division of Cardiovascular Medicine, University of Missouri, Columbia, MO, USA
| |
Collapse
|
|
20
|
Turagam MK, Velagapudi P. Esophagitis and Atrial Fibrillation: Association or Risk Factor. Can J Cardiol 2013; 29:1330.e15. [DOI: 10.1016/j.cjca.2012.10.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2012] [Accepted: 10/24/2012] [Indexed: 10/27/2022] Open
|
|
21
|
Atrial fibrillation ablation in patients with gastroesophageal reflux disease or irritable bowel syndrome—the heart to gut connection! J Interv Card Electrophysiol 2013; 37:259-65. [DOI: 10.1007/s10840-013-9807-5] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2012] [Accepted: 03/21/2013] [Indexed: 12/13/2022]
|
|
22
|
Kubota S, Nakaji G, Shimazu H, Odashiro K, Maruyama T, Akashi K. Further assessment of atrial fibrillation as a risk factor for gastroesophageal reflux disease: a multicenter questionnaire survey. Intern Med 2013; 52:2401-7. [PMID: 24190143 DOI: 10.2169/internalmedicine.52.0923] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
OBJECTIVE Although both atrial fibrillation (AF) and gastroesophageal reflux disease (GERD) are common diseases, the relationship between these two conditions remains controversial, depending on the study design and type of AF. Therefore, we focused on the relationship between nonvalvular AF and GERD. METHODS A total of 479 consecutive subjects (255 men and 224 women, mean age: 60.4 ± 12.8 years), including outpatients at several hospitals (n=201) and participants of an annual health screening program (n=278), were enrolled. Subjects with valvular AF, malignancy or dementia were excluded. The frequency scale for symptoms of GERD (F-scale) was applied after obtaining each patient's informed consent for screening symptomatic GERD with a total cutoff score of 8 points. The score on the questionnaire was correlated with the baseline characteristics extracted from the patients' medical records. RESULTS The total F-scale scores were significantly higher in the older patients (≥ 60 years) than in the younger patients (<60 years) (p=0.017) and increased in the following order: permanent AF > paroxysmal AF > sinus rhythm (p=0.003). The incidence of GERD increased in the same order among the patients with the various heart rhythm classifications (p<0.001). Coronary heart disease, hypertension, diabetes and dyslipidemia were not correlated with the F-scale scores or incidence of GERD. The stepwise discriminant analyses demonstrated that nonvalvular AF alone was significantly associated with symptomatic GERD (Wilks' lambda=0.983, p=0.004). CONCLUSION This multicenter study demonstrated that nonvalvular AF is significantly correlated with symptomatic GERD. This small sample survey warrants a future study of a large-scale cohort.
Collapse
Affiliation(s)
- Satoko Kubota
- Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Japan
| | | | | | | | | | | |
Collapse
|
|
23
|
The relationship between heart and stomach in Iranian traditional medicine: a new concept in cardiovascular disease management. Int J Cardiol 2012; 165:556-7. [PMID: 22974730 DOI: 10.1016/j.ijcard.2012.09.006] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2012] [Revised: 08/28/2012] [Accepted: 09/02/2012] [Indexed: 11/20/2022]
|