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ABSTRACT: The risk of peptic ulcer complications, particularly bleeding, is increased in association with the use of low-dose aspirin (LDA). Risk factors for upper gastrointestinal (GI) ulcer or bleeding among LDA users include a history of prior GI events, older age, chronic renal failure, combined antithrombotic therapy and nonsteroidal anti-inflammatory drugs (NSAIDs). Helicobacter pylori and aspirin seem to be independent risk factors for peptic ulcer and bleeding. The studies report conflicting findings about the effect of H. pylori infection on NSAID-related ulcers, and proton-pump inhibitors (PPIs) seem to be superior to eradication only to prevent recurrent ulcer bleeding with LDA. Previous studies indicate that hypoacidity related to corpus atrophy, as well as taking PPIs and co-treatment with angiotensin type 1 receptor blockers (ARBs) and statins seem to reduce peptic ulcer among LDA users. In addition, the interleukin-1β (IL-1β)-511 T allele and angiotensinogen (AGT)-20 CC, which work as the high-producer allele of IL-1β and AGT, are significantly associated with ulcer or ulcer bleeding. The SLCO1B1*1b haplotype, which has the highest transport activity, may diminish the preventive effect of statins or ARBs. The data are still lacking and further prospective studies are needed to identify the specific risk or protective factors for upper GI ulcer and its complications associated with LDA.
Journal of Gastroenterology and Hepatology 04/2012; 27 Suppl 3:8-12. · 2.87 Impact Factor
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ABSTRACT: In the recent case-control study, we showed an inverse association between peptic ulcer and angiotensin type 1 receptor (AT1R) blockers (ARBs) or HMG-Co A reductase inhibitors (statins). The aim was to evaluate whether the genotypes of uptake and efflux transporters of ARBs and statins relate to the presence of peptic ulcer and/or ulcer bleeding associated with aspirin use.
Patients taking 100mg of enteric-coated aspirin for cardiovascular diseases who also participated in endoscopic surveillance were studied. SLCO1B, ABCC2, ABCG2, and MDR1 genotypes were determined by PCR or PCR-RFLP.
492 patients enrolled including 78 with peptic ulcer. The frequencies of the SLCO1B1 521TT genotype were significantly higher in the ulcer group (p=0.006) compared to the controls. After adjustment for significant factors, the SLCO1B1 1b haplotype was significantly associated with peptic ulcer (OR, 3.64; 95% CI, 1.81-7.29).
SLCO1B1 1b haplotype may identify patients at increased risk for aspirin-induced peptic ulcer.
Digestive and Liver Disease 11/2011; 44(3):201-5. · 3.05 Impact Factor
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ABSTRACT: Antithrombotics is increasingly being used for cardiovascular prevention. In more recent studies, small bowel injury and enteropathy associated with low-dose aspirin are increasingly being recognized. Aim of this study was to evaluate small bowel injury using video capsule endoscopy (VCE) in obscure gastrointestinal bleeding (OGIB) patients taking low-dose aspirin including other antithrombotics.
This is a retrospective review of chronic users of antithrombotics who underwent VCE for suspected small bowel bleeding. Small bowel mucosal injury was evaluated using VCE findings.
Fifty-four OGIB patients (36 men and 18 women, mean age 72.4 years) underwent VCE from January 2007 to May 2009. Twenty-two patients were taking 100 mg of enteric-coated aspirin (aspirin group), 8 taking thienopyridine, (ticlopidine or clopidogrel, thienopyridine group), 13 taking aspirin combined with thienopyridine (combined group), and 11 taking warfarin (warfarin group). The mucosal injury, especially ulcers were most frequently detected in the combined group (46.2%, p = 0.01) among the four groups. The median number of redness lesions in the combined group was the highest among the four groups and was significantly higher than that in the warfarin group. The lesions of redness or small erosions in the aspirin and the combined groups tended to exist in the proximal part of small bowel.
Combination of low-dose aspirin therapy and thienopyridine may exacerbate small bowel injury, and the preventive strategies should be established.
Scandinavian journal of gastroenterology 03/2011; 46(3):281-6. · 2.08 Impact Factor
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ABSTRACT: We have previously shown that co-treatment of angiotensin type 1 receptor (AT1R) blocker (ARB) or angiotensin converting enzyme (ACE) inhibitor seem to reduce peptic ulcer among patients taking low dose aspirin. It is reported that a series of renin-angiotensin system (RAS) gene polymorphisms significantly influence the rate of the gene transcription.
The aim of this study was to examine the genotypes of RAS genes related to the risk of peptic ulcer and ulcer bleeding among patients taking low dose aspirin.
Patients taking 100 mg of aspirin who were planning to undergo endoscopy for surveillance or who had history of recent upper GI ulcer bleeding were included. ACE (Ins/Del), angiotensinogen (AGT; G-217A, A-20C, A-6G, T174 M, M235T), and AT1R (T-713G, C-521T, A1166C) genotypes were determined by PCR or PCR-RFLP.
Four hundred twenty-five patients were enrolled including 68 patients with peptic ulcer and 20 patients with ulcer bleeding. Co-treatment of ARB was significantly associated with peptic ulcer and ulcer bleeding. AGT-20 CC (adjusted OR 4.94, 95% CI 1.21-20.2) was significantly associated with ulcer bleeding. The CC genotype of AT1R-521 was significantly associated with peptic ulcer only in the subgroup taking neither ACE inhibitor nor ARB.
Co-treatment of ARB reduces peptic ulcer and bleeding among patients taking low dose aspirin. RAS may play an important role in the development of upper GI mucosal injury induced by low dose aspirin.
Digestive Diseases and Sciences 02/2011; 56(2):465-71. · 2.12 Impact Factor
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ABSTRACT: There are a few studies of the association between genetic polymorphisms and the risks of acetylsalicylic acid (aspirin)-induced ulcer or its complications. Two single nucleotide polymorphisms (SNP) of cyclooxygenase-1 (COX-1), A-842G and C50T, exhibited increased sensitivity to aspirin and had lower prostaglandin synthesis capacity, lacking statistical significance in the association with bleeding peptic ulcer. A recent Japanese study indicated that the number of COX-1-1676T alleles was a significant risk factor for peptic ulcer in users of non-steroidal anti-inflammatory drugs (NSAIDs). There are some genetic polymorphisms for aspirin resistance, such as platelet membrane glycoproteins, thromboxane A2 (TXA2) receptor, platelet activating factor acetylhydrolase and coagulation factor XIII; however, data on the frequency of gastrointestinal (GI) events in these variants are lacking. Carrying the CYP2C9 variants is reported a significantly increased risk of non-aspirin NSAID-related GI bleeding. The polymorphisms of interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) have been associated with development of peptic ulcer or gastric cancer. In a recent investigation, carriage of the IL-1beta-511 T allele was significantly associated with peptic ulcer among low-dose aspirin users. Hypoacidity in corpus gastritis related to polymorphisms of pro-inflammatory cytokines seems to reduce NSAIDs or aspirin-related injury. Data on which polymorphisms are significant risk factors for GI events in aspirin users are still lacking and further large-scale clinical studies are required.
Journal of Gastroenterology and Hepatology 05/2010; 25 Suppl 1:S31-4. · 2.87 Impact Factor
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ABSTRACT: Interleukin-1beta (IL-1beta) polymorphisms are associated with peptic ulcer and atrophic gastritis. This study aimed to examine effects of corpus atrophy and the genotypes of genes related to peptic ulcer, including IL-1beta, on risk of aspirin ulcer.
232 patients taking 100 mg of aspirin for cardiovascular diseases, of whom 40 had peptic ulcer, were enrolled. IL1beta, interleukin-1 receptor antagonist (IL-1RN), tumor necrosis factor (TNF)-alpha, cyclooxygenase (COX)-1, cytochrome p450 2C9 (CYP2C9), UDP-glucuronosyltransferase (UGT1A6) genotypes were determined, and serum pepsinogen levels were measured.
The polymorphisms of IL-1beta-511/-31 were significantly associated with peptic ulcer, but other genotypes were not. Serum pepsinogen I and II levels and I/II ratio were significantly higher in the ulcer group than in the non-ulcer group. Taking PPI [adjusted odds ratio (OR), 0.09; 95% confidence interval (CI), 0.02-0.39], pepsinogen I of less than 50 ng/ml (OR, 0.24; 95% CI, 0.10-0.56) and IL-1beta-511 T carrier (OR, 0.42; 95% CI, 0.18-0.93) were significantly associated with peptic ulcer.
Hypoacidity related to corpus atrophy as well as taking PPI seems to be preventively associated with development of peptic ulcer among low dose aspirin users.
Journal of Gastroenterology 06/2009; 44(7):717-25. · 4.16 Impact Factor
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ABSTRACT: There are few studies on the association of the risks of upper gastrointestinal (GI) ulcer induced by aspirin combined with other medicines. We investigated the association between peptic ulcer and clinical parameters, including Helicobacter pylori infection and combinations of medicines.
Patients taking 100 mg aspirin for cardiovascular diseases who were planning to undergo endoscopy were enrolled. Serum H. pylori IgG antibody was measured.
A total of 305 patients were enrolled, and 38 patients (12.4%) had ulcer lesions. Sex, smoking, drinking, body mass index, endoscopic findings for gastric atrophy (open type), or presence of H. pylori were not significantly associated with ulcer lesions. Cotreatment with anticoagulants [ticlopidine, 34.2% vs. 21.3%; adjusted odds ratio (OR), 3.1; 95% confidence interval (CI), 1.4-7.1; ticlopidine plus warfarin, 13.2% vs. 3.7%; adjusted OR, 4.4; 95% CI, 1.3-15], proton pump inhibitor (PPI 5.3% vs. 34.8%; adjusted OR, 0.10; 95% CI, 0.02-0.43), and antihypertensive medicine were significantly associated with peptic ulcer. Among antihypertensive medicines, AT1 receptor blocker and angiotensin-converting enzyme (ACE) inhibitor tended to be associated with upper GI ulcer.
PPI was superior to H2-receptor antagonist for prevention of peptic ulcer, and cotreatment with AT1 receptor blocker or ACE inhibitor seemed to reduce peptic ulcer among patients taking low-dose aspirin.
Journal of Gastroenterology 02/2009; 44(2):126-31. · 4.16 Impact Factor
