Aspirin, Helicobacter Pylori, and Peptic Ulcer Disease

阿司匹林和其他非甾体抗炎药被广泛用于治疗疼痛和炎症，在低剂量下，阿司匹林也越来越多地被用于心血管预防。然而，这些药物具有相当大的胃肠道毒性，大量患者出现消化性溃疡和胃肠道出血。虽然幽门螺杆菌感染是溃疡的另一个主要危险因素，但阿司匹林和幽门螺杆菌在溃疡发展中的关系仍然存在高度争议。例如，目前尚不清楚这些因素之间是否存在成瘾性或协同性的相互作用，从而导致溃疡风险，如阿司匹林与幽门螺杆菌相互作用以增加溃疡并发症。阿司匹林通过减少前列腺素的产生损害粘膜保护机制，而幽门螺杆菌通过细胞因子和炎症促进粘膜损伤形成溃疡。过去的研究提供了与这两种因素相关的溃疡风险的相互矛盾的数据，但它们受到阿司匹林使用的回忆偏倚、选择偏倚和小样本量和短随访的限制。拟议研究的主要目标是确定与低剂量阿司匹林和幽门螺杆菌感染联合作用相关的消化性溃疡风险，与低剂量阿司匹林和特定毒性幽门螺杆菌菌株（称为cagA+幽门螺杆菌）相关的溃疡风险，以及与未感染的患者相比，与低剂量阿司匹林和幽门螺杆菌（特别是cagA+幽门螺杆菌菌株）相关的胃肠道出血风险。当比较幽门螺杆菌阳性和阴性受试者中阿司匹林使用与溃疡形成的关系时，我们将有80%的能力检测到1.56的优势比差异。随着美国人口的老龄化，阿司匹林用于心血管预防和随后的溃疡发展的长期使用可能会增加，涉及医疗保健费用。拟议的研究将提供重要的信息，以便对阿司匹林相关的胃肠道并发症做出明智的决定，以及幽门螺杆菌感染的患者在服用阿司匹林时是否有溃疡和胃肠道出血的风险。这些结果可能有助于识别高危患者，并导致减少阿司匹林使用者溃疡并发症的策略。

Aspirin and other non-steroidal anti-inflammatory drugs are widely used to treat pain and inflammation, and at low doses, aspirin is also increasingly being used for cardiovascular prophylaxis. However, these drugs have substantial gastrointestinal toxicity and a significant number of patients develop peptic ulcers and GI bleeding. Although infection with Helicobacter pylori is another major risk factor for ulcers, the relationships between aspirin and H. pylori in the development of ulcers remain highly controversial. It is unclear, for example, whether there is an addictive or synergistic interaction between these factors in conferring ulcer risk such that aspirin interacts with H. pylori to increase ulcer complications. Aspirin impairs mucosal protective mechanisms by decreasing prostaglandin production, whereas H. pylori promotes mucosal injury through cytokines and inflammation to form ulcers. Past studies have provided conflicting data on the ulcer risks associated with both factors but they have been limited by recall bias of aspirin use, selection bias, and small sample sizes with short follow-up. The primary goals of the proposed research are to determine the risk of peptic ulcers associated with the joint effects of low dose aspirin and H. pylori infection, the ulcer risk associated with low dose aspirin and a specific virulent strain of H. pylori, known as cagA+ H. pylori, and the risk of GI bleeding associated with low dose aspirin and H. pylori (especially cagA+ H. pylori strains) as compared to those without infection. We will have 80% power to detect a difference of 1.56 in the odds ratio, when comparing the association of aspirin use and ulcer formation in H. pylori positive and negative subjects. As the US population grows older, the chronic use of aspirin for cardiovascular prophylaxis and the subsequent development of ulcers are likely to increase, involving health care costs. The proposed study will provide important information to make an informed decision about aspirin related GI complications and whether H. pylori infected patients are at risk for ulcers and GI bleeding while on aspirin. These results may help identify high-risk patients and lead to strategies that will reduce ulcer complications among aspirin users.