Peptic Ulcer Disease Risk Factors

Primary Risk Factors

The American Gastroenterological Association notes that prior ulcer complications represent the single most powerful predictor of future peptic ulcer disease, with odds ratios as high as 13.5-15.2 1, 2
The American College of Gastroenterology states that H. pylori infection increases the risk of upper GI complications in NSAID users by 2- to 4-fold 1, 3
The American Heart Association recommends that low-dose aspirin users with H. pylori infection are at increased risk for upper GI bleeding, with an odds ratio of 4.7 4
The American Gastroenterological Association reports that H. pylori has surpassed NSAIDs as the most commonly identified risk factor among patients with bleeding ulcers, found in 53% of cases 2, 5

The American College of Cardiology warns that when aspirin is combined with NSAIDs, the relative risk of GI bleeding increases to more than 10 times that seen with either agent alone 2, 5
The American Gastroenterological Association notes that concomitant use of corticosteroids increases risk in NSAID users 1, 2, 5
The American Heart Association states that anticoagulant use (warfarin) significantly increases risk, particularly when combined with NSAIDs 1, 2, 6

The American Gastroenterological Association states that advanced age is an important independent risk factor 1, 2, 6
The American College of Gastroenterology reports that advancing age increases risk by approximately 4% per year 2, 5

The American Gastroenterological Association supports stratifying patients into progressive risk categories based on the number and nature of risk factors present, with estimated annualized incidence of NSAID-related ulcer complications ranging from 0.8% for low-risk to 18% for very high-risk patients 1, 3, 6
The American College of Gastroenterology recommends the following risk stratification:
Risk Category Estimated Annualized Incidence
Low risk 0.8%
Moderate risk 2%
High risk 7.6-8.6%
Very high risk 18%
1, 3, 6
Etiologies of Peptic Ulcer Disease
Major Etiologic Categories
H. pylori is the main causative agent in gastroduodenal ulcer disease, representing the predominant mechanism worldwide 7
The increasing incidence of H. pylori infection has fundamentally changed the epidemiology of peptic ulcer disease 8, 9
NSAIDs and aspirin are the second most important pharmacologic causes, affecting acid secretion in the gastric mucosa 7
Corticosteroids represent another important pharmacologic cause, affecting acid secretion in the gastric mucosa 7
Smoking contributes as a modifiable risk factor that alters gastric mucosal integrity 7
High-salt-content diet contributes to altered gastric mucosal integrity 7
Alcohol abuse has contributed to changing epidemiology of peptic ulcer disease 8, 9

Risk Category	Estimated Annualized Incidence
Low risk	0.8%
Moderate risk	2%
High risk	7.6-8.6%
Very high risk	18%

Stress ulcers occur particularly in critically ill patients in ICU settings or post-surgery 7
Diagnosis may be obscured in sedated or unconscious patients 7

Endoscopic procedures including endoscopic submucosal dissection (ESD), endoscopic mucosal resection (EMR), and stricture dilation carry perforation risk 7
ERCP-related perforations occur through multiple mechanisms with overall risk <1% but mortality of 7.8-9.9% 7

In low- and middle-income countries, typhoid fever (Salmonella enterica) is the most common cause of gastrointestinal perforation, with mortality ranging from 4.6% to 39%, particularly in children 7
Abdominal tuberculosis affecting the ileocecal region can cause perforation, though less common in gastric locations 7

Blunt or penetrating trauma may cause immediate or delayed perforation through lacerations, transections, mural hematomas, or full-thickness contusions 7

Crohn's disease can cause peptic ulcers, with focal chronic inflammation and architectural abnormalities in biopsies favoring this diagnosis 10