Dyspepsia risk factors

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Fahad Hasan, M.D.[2]

Overview

Dyspepsia is a common condition, with a global pooled prevalence of approximately 8.4% (95% CI 7.4–9.5%) according to a 2024 systematic review and meta-analysis of population-based studies applying Rome I–IV criteria; prevalence is higher in women (9.0% versus 7.0% in men) and in developing countries (9.1% versus 8.0% in developed countries).[1] Risk factors for the development of dyspepsia are multifactorial and include Helicobacter pylori infection, chronic use of NSAIDs, family history of peptic ulcer disease, prior acute gastroenteritis (post-infectious dyspepsia), emotional stress and psychological comorbidity (particularly anxiety and depression), female sex, tobacco smoking, and dietary factors including increased intake of high-fiber, high-fat, and greasy foods and overconsumption of caffeine.[2][3] A large meta-analysis of population-based studies found that the prevalence of uninvestigated dyspepsia was significantly higher among women (OR 1.24), smokers (OR 1.25), NSAID users (OR 1.59), and individuals who were H. pylori-positive (OR 1.18).[3] Emerging genetic evidence from a comprehensive Mendelian randomization study additionally supports depression and gastroesophageal reflux disease as causally-linked risk factors for functional dyspepsia.[4] Less common risk factors include alcohol consumption, low body mass index/underweight status, nosocomial stress ulcers related to prolonged mechanical ventilation and coagulopathy, and rare conditions causing gastric acid hypersecretion such as Zollinger-Ellison syndrome. Age ≥60 years and the presence of alarm features (such as unintentional weight loss, gastrointestinal bleeding, dysphagia, or a family history of upper gastrointestinal malignancy) are also recognized as risk markers for underlying organic or malignant disease and warrant prompt upper endoscopy per the 2017 ACG/CAG guideline on the management of dyspepsia.[5]

Risk Factors

Risk factors for the development of dyspepsia can be categorized as common (well-established, higher-strength evidence), less common, and markers of underlying organic/malignant diseases.[6][7][8][9][10][11][12][13]

Risk factor Comments Source
Helicobacter pylori infection Uninvestigated dyspepsia; independent risk factor for functional dyspepsia, particularly in patients ≥64 years [3]
NSAID use Uninvestigated dyspepsia; synergistic with H. pylori for bleeding peptic ulcer (>6-fold increased risk) [3][12]
Female sex Uninvestigated dyspepsia; global pooled prevalence 9.0% (women) vs 7.0% (men) [3][1]
Tobacco smoking Uninvestigated dyspepsia [3]
Prior acute gastroenteritis (post-infectious dyspepsia) Functional dyspepsia >6 months after acute gastroenteritis [14]
Depression / anxiety and psychological comorbidity Genetically-predicted depression causally associated with functional dyspepsia; anxiety independently associated with FD [4][15]
Low body mass index (underweight, BMI <18.5 kg/m²) Independently associated with functional dyspepsia (13.3% of FD subjects vs 3.5% of controls) [15]
Gastroesophageal reflux disease Genetically-predicted GERD causally associated with increased risk of functional dyspepsia [4]
Family history of peptic ulcer disease Increased risk on population-based cohort analysis [11]

Common risk factors

Common risk factors in the development of dyspepsia include:

Less common risk factors

Less common risk factors in the development of dyspepsia include:

Risk factors for underlying organic or malignant disease (alarm features)

According to the 2017 ACG/CAG Clinical Guideline on the Management of Dyspepsia, the presence of alarm features increases the pre-test probability of underlying upper gastrointestinal malignancy by 2- to 3-fold and should prompt upper endoscopy regardless of age; endoscopy is also recommended for new-onset dyspepsia in patients ≥60 years of age to exclude organic pathology, with consideration of earlier endoscopy in patients at increased gastric cancer risk (e.g., those who spent childhood in a high-incidence region or with a positive family history of gastric cancer).[5]

Alarm feature Clinical significance
Unintentional weight loss Suggests underlying malignancy or organic disease
Gastrointestinal bleeding or iron deficiency anemia Suggests peptic ulcer disease or malignancy
Progressive dysphagia or odynophagia Suggests esophageal stricture or malignancy
Persistent vomiting Suggests gastric outlet obstruction or malignancy
Palpable abdominal mass or lymphadenopathy Suggests malignancy
Family history of upper gastrointestinal malignancy Increases pre-test probability of malignancy
Age ≥60 years at symptom onset Increases pre-test probability of malignancy; threshold for prompt endoscopy

References

  1. 1.0 1.1 He J, Guo Q, Zhou J, Liu T, Wang R, Zhou Y (2024). "Global prevalence of functional dyspepsia according to Rome criteria, 1990-2020: a systematic review and meta-analysis". Sci Rep. 14 (1): 3481. doi:10.1038/s41598-024-54716-3. PMID 38378941 Check |pmid= value (help).
  2. Stanghellini V, Chan FK, Hasler WL, Malagelada JR, Suzuki H, Tack J, Talley NJ (2016). "Gastroduodenal Disorders". Gastroenterology. 150 (6): 1380–1392. doi:10.1053/j.gastro.2016.02.011. PMID 27147122.
  3. 3.0 3.1 3.2 3.3 3.4 3.5 Ford AC, Marwaha A, Sood R, Moayyedi P (2015). "Global prevalence of, and risk factors for, uninvestigated dyspepsia: a meta-analysis". Gut. 64 (7): 1049–1057. doi:10.1136/gutjnl-2014-307843. PMID 25147201.
  4. 4.0 4.1 4.2 Xu W, Zhu Y, Ma Z, Fu Z, Chen R, Zhang X (2024). "The associations between functional dyspepsia and potential risk factors: A comprehensive Mendelian randomization study". PLoS One. 19 (5): e0302809. doi:10.1371/journal.pone.0302809. PMID 38718064 Check |pmid= value (help).
  5. 5.0 5.1 Moayyedi PM, Lacy BE, Andrews CN, Enns RA, Howden CW, Vakil N (2017). "ACG and CAG Clinical Guideline: Management of Dyspepsia". Am J Gastroenterol. 112 (7): 988–1013. doi:10.1038/ajg.2017.154. PMID 28631728.
  6. Huang JQ, Sridhar S, Hunt RH (2002). "Role of Helicobacter pylori infection and non-steroidal anti-inflammatory drugs in peptic-ulcer disease: a meta-analysis". Lancet. 359 (9300): 14–22. doi:10.1016/S0140-6736(02)07273-2. PMID 11809181.
  7. Ballinger A, Smith G (2001). "COX-2 inhibitors vs. NSAIDs in gastrointestinal damage and prevention". Expert Opin Pharmacother. 2 (1): 31–40. doi:10.1517/14656566.2.1.31. PMID 11336566.
  8. Holvoet J, Terriere L, Van Hee W, Verbist L, Fierens E, Hautekeete ML (1991). "Relation of upper gastrointestinal bleeding to non-steroidal anti-inflammatory drugs and aspirin: a case-control study". Gut. 32 (7): 730–4. PMC 1378985. PMID 1855677.
  9. Laporte JR, Carné X, Vidal X, Moreno V, Juan J (1991). "Upper gastrointestinal bleeding in relation to previous use of analgesics and non-steroidal anti-inflammatory drugs. Catalan Countries Study on Upper Gastrointestinal Bleeding". Lancet. 337 (8733): 85–9. PMID 1670734.
  10. Wachirawat W, Hanucharurnkul S, Suriyawongpaisal P, Boonyapisit S, Levenstein S, Jearanaisilavong J, Atisook K, Boontong T, Theerabutr C (2003). "Stress, but not Helicobacter pylori, is associated with peptic ulcer disease in a Thai population". J Med Assoc Thai. 86 (7): 672–85. PMID 12948263.
  11. 11.0 11.1 Rosenstock S, Jørgensen T, Bonnevie O, Andersen L (2003). "Risk factors for peptic ulcer disease: a population based prospective cohort study comprising 2416 Danish adults". Gut. 52 (2): 186–93. PMC 1774958. PMID 12524398.
  12. 12.0 12.1 Stack WA, Atherton JC, Hawkey GM, Logan RF, Hawkey CJ (2002). "Interactions between Helicobacter pylori and other risk factors for peptic ulcer bleeding". Aliment. Pharmacol. Ther. 16 (3): 497–506. PMID 11876703.
  13. Everhart JE, Byrd-Holt D, Sonnenberg A (1998). "Incidence and risk factors for self-reported peptic ulcer disease in the United States". Am. J. Epidemiol. 147 (6): 529–36. PMID 9521179.
  14. Futagami S, Itoh T, Sakamoto C (2015). "Systematic review with meta-analysis: post-infectious functional dyspepsia". Aliment Pharmacol Ther. 41 (2): 177–188. doi:10.1111/apt.13006. PMID 25348873.
  15. 15.0 15.1 Beh KH, Chuah KH, Rappek N, Mahadeva S (2021). "The association of body mass index with functional dyspepsia is independent of psychological morbidity: A cross-sectional study". PLoS One. 16 (1): e0245511. doi:10.1371/journal.pone.0245511. PMID 33497382 Check |pmid= value (help). Vancouver style error: initials (help)

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