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 common: uninvestigated dyspepsia affects approximately 20.8% of the general population under broad definitions, while functional dyspepsia has a global pooled prevalence of approximately 8.4% according to a 2024 systematic review and meta-analysis 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, smokers, NSAID users, and individuals who were H. pylori-positive.[3] A single Mendelian randomization study provides emerging, genetically-supported evidence for depression and gastroesophageal reflux disease as risk factors for functional dyspepsia; this inference rests on genetic-instrument assumptions and requires replication.[4] The relationship with body mass index is bidirectional: higher BMI is the more consistent independent predictor of incident functional dyspepsia in longitudinal and large global data, while underweight/leanness is associated with functional dyspepsia in several Asian and primary-care cohorts, and a U-shaped relationship confined to women has been described. Alcohol consumption is a less consistent association. Age ≥60 years is the dominant risk marker for underlying organic or malignant disease and, per the 2017 ACG/CAG guideline, warrants upper endoscopy; alarm features (unintentional weight loss, gastrointestinal bleeding, dysphagia, persistent vomiting, family history of upper GI malignancy) raise concern but do not by themselves mandate endoscopy in patients under 60.[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 (OR 1.18); a subset of infected patients have H. pylori-associated dyspepsia that resolves after eradication | [3] |
| NSAID use | Uninvestigated dyspepsia (OR 1.59); additive with H. pylori for peptic ulcer bleeding (~6-fold with both factors present) | [3][6] |
| 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; pooled OR ~2.2–2.5, highest within 12 months (OR ~4.8) and declining thereafter; mean prevalence ~9.6% | [14][15] |
| Depression / anxiety and psychological comorbidity | Genetically-predicted depression causally associated with functional dyspepsia; anxiety independently associated with FD | [4][16] |
| Body mass index (extremes) | High BMI was an independent longitudinal predictor of incident FD; a large 2026 global analysis found DGBI odds rise with higher BMI, and underweight is inconsistently associated (U-shaped in women in some cohorts) | [17][18] |
| 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:
- Psychological comorbidity is the strongest risk association: baseline anxiety conferred an ~8-fold higher odds of developing FD in a Swedish population survey, and the gut–brain relationship is bidirectional (anxiety/depression precede FD, and FD predicts later anxiety/depression).[17]
- Helicobacter pylori infection
- Chronic use of NSAIDs (including low-dose aspirin)
- Family history of peptic ulcer or upper gastrointestinal disease
- Prior episode of acute gastroenteritis (post-infectious dyspepsia)
- Female sex
- Tobacco smoking
- Eating meals too quickly or consuming too much food at meals
- Overabundance of high-fiber foods
- Overconsumption of caffeine
- Spicy, high-fat, and greasy foods
- Coexisting gastroesophageal reflux disease
- Downgrade note: meal-related dietary factors (high-fat/greasy, spicy, high-fiber foods, caffeine) are better characterized as symptom triggers and primary-prevention targets than as validated risk factors for the development of functional dyspepsia; see primary prevention.
Less common risk factors
Less common risk factors in the development of dyspepsia include:
- Alcohol consumption
- Psychological stress (independent of anxiety/depression)
Risk factors for underlying organic or malignant disease (alarm features)
According to the 2017 ACG/CAG Clinical Guideline, the presence of alarm features confers a 2- to 3-fold relative increase in the pre-test probability of upper gastrointestinal malignancy, but the absolute risk in patients under 60 remains well below 1%, and the guideline conditionally recommends against upper endoscopy on the basis of alarm features alone in this age group. Alarm features have a low positive predictive value for GI cancer (<11%) with a high negative predictive value (>97%). Upper endoscopy is recommended for new-onset dyspepsia in patients ≥60 years, with a lower threshold in those at increased gastric cancer risk (childhood in a high-incidence region, family history of gastric cancer, male sex) and, on a case-by-case basis, in patients <60 with prominent or combined alarm features (e.g., weight loss >20 lb, rapidly progressive dysphagia).[5][19][20]
| 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
- ↑ 1.0 1.1 Lee K, Kwon CI, Yeniova AÖ, et al. (2024). "Global prevalence of functional dyspepsia according to Rome criteria, 1990-2020: a systematic review and meta-analysis". Sci Rep. 14 (1): 4172. doi:10.1038/s41598-024-54716-3. PMID 38378941 Check
|pmid=value (help). - ↑ 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.
- ↑ 3.0 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.
- ↑ 4.0 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). - ↑ 5.0 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.
- ↑ 6.0 6.1 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 11.0 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ Pike BL, Porter CK, Sorrell TJ, Riddle MS (2013). "Acute gastroenteritis and the risk of functional dyspepsia: a systematic review and meta-analysis". Am J Gastroenterol. 108 (10): 1558–1563. doi:10.1038/ajg.2013.147. PMID 23711623.
- ↑ 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) - ↑ 17.0 17.1 Ford AC, Mahadeva S, Carbone MF, Lacy BE, Talley NJ (2020). "Functional dyspepsia". Lancet. 396 (10263): 1689–1702. doi:10.1016/S0140-6736(20)30469-4. PMID 33049222 Check
|pmid=value (help). - ↑ Simadibrata DM, Butt MF, Liu BD, et al. (2026). "Association of body mass index with disorders of gut-brain interaction: a large global population-based analysis". Am J Gastroenterol. doi:10.14309/ajg.0000000000003568. PMID 41955341 Check
|pmid=value (help). - ↑ Shaukat A, Wang A, Acosta RD, et al. (2015). "The role of endoscopy in dyspepsia". Gastrointest Endosc. 82 (2): 227–232. doi:10.1016/j.gie.2015.04.003.
- ↑ Vakil N, Moayyedi P, Fennerty MB, Talley NJ (2006). "Limited value of alarm features in the diagnosis of upper gastrointestinal malignancy: systematic review and meta-analysis". Gastroenterology. 131 (2): 390–401. doi:10.1053/j.gastro.2006.04.029. PMID 16890592.