What are the risk factors for Peptic Ulcer Disease (PUD)?

Risk Factors for Peptic Ulcer Disease

The strongest risk factor for peptic ulcer disease and its complications is a history of prior ulcer disease, particularly with previous ulcer complications, which increases the risk by more than 10-fold. 1

Primary Risk Factors

History of Prior Ulcer Disease

• 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
• Previous duodenal ulcer specifically carries an odds ratio of 8.96 for peptic ulcer bleeding 2
• Patients with prior ulcer history who use NSAIDs have a greater than 10-fold increased risk for developing GI bleeding compared to patients without this risk factor 3

Helicobacter pylori Infection

• H. pylori is the main causative agent in gastroduodenal ulcer disease worldwide 4, 5
• H. pylori infection increases the risk of upper GI complications in NSAID users by 2- to 4-fold 1
• Among peptic ulcer bleeding patients, H. pylori infection carries an odds ratio of 8.8 2
• H. pylori has surpassed NSAIDs as the most commonly identified risk factor among patients with bleeding ulcers, found in 53% of cases 1
• H. pylori is the only independent risk factor identified for peptic ulcer recurrence 6
• In low-dose aspirin users, H. pylori infection is an independent risk factor with an odds ratio of 4.7 for upper GI bleeding 1

NSAID and Aspirin Use

• NSAIDs and aspirin are the second most important pharmacologic causes of peptic ulcer disease 4, 5
• NSAID use increases the average relative risk of developing a serious GI complication by 3- to 5-fold 1
• The use of NSAIDs with high-dose or prolonged duration demonstrates a linear dose-response relationship to adverse GI events 1
• NSAIDs with prominent enterohepatic circulation and prolonged half-lives (sulindac, indomethacin, piroxicam, ketorolac) are linked to greater GI toxicity 1
• Low-dose aspirin (even at cardiovascular doses of 81-325 mg/day) increases GI bleeding risk 2-4 times 1
• The use of ASA for pain medication carries an odds ratio of 3.5, while ASA for thrombosis prophylaxis has an odds ratio of 4.07 2
• Non-ASA NSAIDs at ≥1 defined daily dose carry an odds ratio of 6.56 for peptic ulcer bleeding 2

Combination Drug Therapy

• When aspirin is combined with NSAIDs, the relative risk of GI bleeding increases to more than 10 times that seen with either agent alone 1
• Concomitant use of corticosteroids increases risk in NSAID users 1
• Anticoagulant use (warfarin) significantly increases risk, particularly when combined with NSAIDs 1
• Antiplatelet drug combinations increase the risk of peptic ulcer complications 1

Age

• Advanced age is an important independent risk factor 1
• Advancing age increases risk by approximately 4% per year 1
• This relationship stems from the presence of other risk factors more prevalent with advancing age, including comorbidities, concomitant medication use, and age-related physiologic changes such as decreasing GI prostaglandin concentrations 1

Smoking

• Smoking is an independent modifiable risk factor that alters gastric mucosal integrity 4, 5
• Smoking ≥20 cigarettes daily carries an odds ratio of 6.43 for peptic ulcer bleeding 2
• Smoking demonstrates a dose-dependent relationship with peptic ulcer bleeding risk 2
• Male gender combined with smoking increases the risk of peptic ulcer development 6

Cardiovascular Disease

• Presence of cardiovascular diseases is an important risk factor for GI complications in NSAID users 1
• Patients with known cardiovascular disease or risk factors may be at greater risk for adverse events when taking NSAIDs 3

Alcohol Use

• Alcohol abuse has contributed to the changing epidemiology of peptic ulcer disease 1, 5
• Alcohol use carries an odds ratio of 4.2 for upper GI bleeding in aspirin users 1
• The strength and magnitude of alcohol's association with GI risk among NSAID users is less clear than other risk factors 1

Dietary Factors

• High-salt-content diet contributes to altered gastric mucosal integrity 4, 5

Risk Stratification Framework

The evidence supports stratifying patients into progressive risk categories based on the number and nature of risk factors present 1:

• Low risk: Absence of risk factors; estimated annualized incidence of NSAID-related ulcer complications is 0.8% 1
• Moderate risk: 1-2 risk factors present; estimated annualized incidence is 2% 1
• High risk: 3 risk factors or concomitant use of aspirin, steroids, or anticoagulants; estimated annualized incidence is 7.6-8.6% 1
• Very high risk: History of ulcer complications or 4 risk factors; estimated annualized incidence is 18% 1

Important Clinical Considerations

At least two risk factors are present in 65% of peptic ulcer bleeding patients, though their combination does not necessarily potentiate the risk beyond additive effects 2. The five-year recurrence rate of peptic ulcer disease is 30.9%, with no significant difference between duodenal ulcer (33.3%) and gastric ulcer (28.8%) 7. Patients with complicated peptic ulcer disease have a higher recurrence rate (45.9%) compared to uncomplicated disease (19.2%) 7.

Male gender is an independent risk factor for peptic ulcer development 6, and the frequency of women is significantly higher among NSAID-related ulcers compared to H. pylori-related ulcers 8. The mean age of patients with H. pylori-related ulcers is significantly lower than those with NSAID-related or combined etiology ulcers 8.