Heartburn’s Hidden Impact: A Narrative Review Exploring Gastroesophageal Reflux Disease (GERD) as a Cardiovascular Disease Risk Factor
Abstract
:1. Introduction
2. Materials and Methods
3. Results and Discussion
3.1. Association between GERD and Coronary Atherosclerosis
3.2. Association between GERD and Myocardial Ischemia
3.3. Pathophysiology of GERD as a Risk Factor for CVD
3.3.1. Inflammation and Endothelial Dysfunction
3.3.2. Autonomic Imbalance
3.4. Diagnosing GERD
3.5. Management of GERD and Its Relation to CVD
3.5.1. Lifestyle Modifications
3.5.2. Medical Therapy
3.5.3. Mechanical Interventions
4. Future Direction of Studies
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Year | Authors | Title | Study Type | Conclusions |
---|---|---|---|---|
2023 | Chen J et al. | Risk of incident cardiovascular disease among patients with gastrointestinal disorder: prospective cohort study of 340,862 individuals | Prospective cohort study |
|
2023 | Geng T et al. | Proton pump inhibitor use and risks of cardiovascular disease and mortality in patients with type 2 diabetes | Population-based cohort | PPI use is associated with a higher risk of CVD events and mortality among patients with type 2 diabetes mellitus. |
2023 | Sun L et al. | Helicobacter pylori infection and risk of cardiovascular disease | Meta-analysis | Helicobacter pylori infection is associated with a mildly increased risk of CVD. |
2023 | Teperikidis E et al. | Does the long-term administration of proton pump inhibitors increase the risk of adverse cardiovascular outcomes? A ChatGPT powered umbrella review | Umbrella review | A causal relationship between PPI use and an increased risk of MACE cannot be ruled out. |
2022 | Song J et al. | Association between gastroesophageal reflux disease and coronary atherosclerosis | Retrospective cohort study | GERD was associated with higher degrees of coronary atherosclerosis by CACS (p = 0.008) but did not increase the risk of a higher CACS (OR = 1.018, 95% CI 0.865–1.198). |
2022 | Sun X et al. | A Mendelian randomization study to assess the genetic liability of gastroesophageal reflux disease for cardiovascular diseases and risk factors | Mendelian randomization study | GERD was associated with 7 CVD outcomes and 9 cardiovascular risk factors. |
2022 | Ma Y et al. | Acid suppressants use and risk of atherosclerotic cardiovascular disease in middle-aged and older adults | Prospective cohort study | PPI use is associated with increased risk of ASCVD, particularly amongst participants without indications for medications. |
2022 | Maret-Ouda et al. | Proton pump inhibitor and clopidogrel use after percutaneous coronary intervention and risk of major cardiovascular events [3] | Retrospective cohort study | In patients who receive clopidogrel after PCI, concomitant use of PPI may increase the risk of major cardiovascular events. |
2021 | Bell E et al. | Association of proton pump inhibitors with higher risk of cardiovascular disease and heart failure | Prospective cohort study | Long-term PPI use was associated with twice the risk of total CVD and HF compared with nonusers. |
2021 | Rooney M et al. | Proton pump inhibitor use, hypomagnesemia and risk of cardiovascular diseases: The atherosclerosis risk in communities (ARIC) study | Prospective cohort study | PPI users had a higher prevalence of hypomagnesemia than nonusers. PPI users also had higher CVD risk than nonusers; however, it appears unlikely that hypomagnesemia explains associations of PPIs with CVD risk. |
2020 | Eisa M et al. | The risk of acute myocardial infarction in patients with gastroesophageal reflux disease | Observational | GERD is a risk factor for AMI, higher than male gender and obesity. |
2020 | Wang B et al. | A meta-analysis of the association between helicobacter pylori infection and risk of atherosclerotic cardiovascular disease. | Meta-analysis | H pylori infection increases the risk of adverse cardiovascular events by 51%, with an even greater effect on AMI (OR = 1.80, 95% CI 1.42–2.26) and cerebrovascular disease (OR = 1.54, 95% CI 1.27–1.89). |
2019 | Teragawa H et al. | History of gastroesophageal reflux disease in patients with suspected coronary artery disease | Experimental | The presence of GERD may increase the incidence of vasospastic angina in patients with suspected coronary artery disease (OR 7.8; p < 0.01). |
2019 | Khomenko et al. | Features of endothelial dysfunction in elderly persons with coronary heart disease and concomitant gastroesophageal reflux disease [4] | Experimental | Endothelial dysfunction manifests itself as a decrease in stable nitric oxide metabolite levels and an increase in endothelin-1 levels, disturbance of celiac trunk regional blood flow, causing a decrease in esophageal tissue resistance, leading to lower esophageal sphincter dysfunction |
2018 | Landi et al. | No increase in risk of acute myocardial infarction in privately insured adults prescribed proton pump inhibitors vs. histamine-2 receptor antagonists (2002–2014) [5] | Retrospective cohort study | No difference in increased risk of AMIs with PPIs versus H2RAs. |
2018 | Nguyen et al. | No significant association between proton pump inhibitor use and risk of stroke after adjustment for lifestyle factors and indication [6] | Retrospective Cohort Study | No significant association between PPI use and ischemic stroke, after accounting for indications for PPI use. Prior reports of an increased risk of stroke may be due to residual confounding related to chronic conditions associated with PPI use. |
2017 | Oparin et al. | The role of endothelial dysfunction in the mechanism of gastroesophageal reflux disease development in patients with ischemic heart disease | Experimental | In patients with ischemic heart disease and concomitant GERD, endothelial dysfunction manifested by a significant increase in the levels of endothelin-1 and lipid peroxidation products, with decreased levels of nitric oxide metabolites, regional blood flow and quality of life. |
2017 | Lei W et al. | Risk of acute myocardial infarction in patients with gastroesophageal reflux disease: A nationwide population-based study | Prospective cohort study | GERD was associated with a higher risk of developing an AMI compared to controls (HR = 1.48; 95% CI: 1.31–1.66, p < 0.001). |
2016 | Chen C et al. | Association between gastroesophageal reflux disease and coronary heart disease | Population-based cohort | GERD was associated with a higher risk of developing coronary heart disease compared to controls (aHR = 1.67, 95% CI = 1.34–2.08) and in patients with GERD who were treated with PPI therapy for more than 1 year compared to those treated for less than 1 year (aHR = 1.56, 95% CI = 1.39–1.74). |
2015 | Shah et al. | Proton pump inhibitor usage and the risk of myocardial infarction in the general population [7] | Systematic review | GERD patients exposed to PPIs have a 1.16 fold increased risk of AMI, regardless of clopidogrel use. |
2014 | Shih C et al. | Proton pump inhibitor use represents an independent risk factor for myocardial infarction | Propensity-score matched study case-crossover study | Use of PPIs may be independently associated with an increased risk of MI. However, the benefits of PPIs may greatly outweigh the risks of adverse cardiovascular effects, with number needed to harm of 4357. |
2014 | Unal et al. | The effects of proton pump inhibitors on the development of post-stenting major adverse cardiovascular events in patients with acute coronary syndrome | Prospective cohort study | ADMA and copeptin levels may be significantly increased in patients started on imminent DAPT and PPI therapy after PCI. |
2013 | Ghebremariam Y et al. | Unexpected effect of proton pump inhibitors | Observational | Biochemical, cellular, ex vivo, and in vivo data revealing that PPIs directly interact with and significantly inhibit human DDAH activity, thereby increasing endothelial and serum ADMA levels. The increase in ADMA levels would be anticipated to impair vascular NOS activity, to increase oxidative stress, to reduce vasodilator function, and to impair vasoprotective mechanisms. |
2013 | Luo T et al. | Histamine H2 receptor activation exacerbates myocardial ischemia/reperfusion injury by disturbing mitochondrial and endothelial function | Experimental | H2R activation exaggerates myocardial I/R injury by promoting myocardial mitochondrial dysfunction and by increasing cardiac vascular endothelial permeability. |
2013 | Liu et al. | Acid reflux in patients with coronary artery disease and refractory chest pain [8] | Prospective cohort study | Refractory chest pain in patients with CAD can be partially noncardiac chest pain (NCCP) secondary to acid reflux. The combined use of common cardiac drugs may predispose or aggravate GERD. Short-term proton pump inhibitor (PPI) therapy not only restores a normal esophageal pH, but also significantly improves the general health-related quality of life (HRQL) of patients. |
2012 | Schmidt et al. | Concomitant use of clopidogrel and proton pump inhibitors is not associated with major adverse cardiovascular events following coronary stent implantation [9] | Retrospective cohort study | The use of PPIs as a class did not modify the protective effect of clopidogrel, but its use was associated with major adverse cardiovascular events itself, particularly among patients having used PPIs before percutaneous coronary intervention. |
2010 | Gupta et al. | Risk of adverse clinical outcomes with concomitant use of clopidogrel and proton pump inhibitors following percutaneous coronary intervention [10] | Concomitant use of clopidogrel and PPI in post-PCI patients is associated with a higher risk of MACE. | |
2008 | Jansson C et al. | Severe symptoms of gastro-oesophageal reflux disease are associated with cardiovascular disease and other gastrointestinal symptoms, but not diabetes: a population-based study | Population-based, cross-sectional, case-control study | Myocardial infarction, angina pectoris, stroke and symptoms of nausea, diarrhea and constipation are associated with GERD. |
2001 | Tougas et al. | Cardiac autonomic function and oesophageal acid sensitivity in patients with non-cardiac chest pain | Experimental | Patients with angina-like pain during direct esophageal acidification have decreased resting vagal activity. |
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Gries, J.J.; Chen, B.; Virani, S.S.; Virk, H.U.H.; Jneid, H.; Krittanawong, C. Heartburn’s Hidden Impact: A Narrative Review Exploring Gastroesophageal Reflux Disease (GERD) as a Cardiovascular Disease Risk Factor. J. Clin. Med. 2023, 12, 7400. https://doi.org/10.3390/jcm12237400
Gries JJ, Chen B, Virani SS, Virk HUH, Jneid H, Krittanawong C. Heartburn’s Hidden Impact: A Narrative Review Exploring Gastroesophageal Reflux Disease (GERD) as a Cardiovascular Disease Risk Factor. Journal of Clinical Medicine. 2023; 12(23):7400. https://doi.org/10.3390/jcm12237400
Chicago/Turabian StyleGries, Jacob J., Bing Chen, Salim S. Virani, Hafeez Ul Hassan Virk, Hani Jneid, and Chayakrit Krittanawong. 2023. "Heartburn’s Hidden Impact: A Narrative Review Exploring Gastroesophageal Reflux Disease (GERD) as a Cardiovascular Disease Risk Factor" Journal of Clinical Medicine 12, no. 23: 7400. https://doi.org/10.3390/jcm12237400