Dataset Information

Influence of Polymorphisms Involved in Platelet Activation and Inflammatory Response on Aspirin-Related Upper Gastrointestinal Bleeding: A Case-Control Study.

ABSTRACT: Background:Despite the wide benefits of aspirin and its cost-effectiveness, aspirin prescriptions have been reduced due to idiosyncratic responses in susceptible individuals. Low-dose aspirin and single-nucleotide polymorphisms (SNPs) are independently associated with increased risk of gastrointestinal hemorrhage; however, to-date, no studies investigated the SNP-aspirin interaction effect on upper gastrointestinal hemorrhage (UGIH). Therefore, we aimed to evaluate the role of 25 SNPs in multiple genes involved in platelet activation, angiogenesis and inflammatory response in aspirin-related UGIH. Methods:A multicenter, full case-control study was conducted in patients exposed and unexposed to aspirin. Three hundred twenty-six cases diagnosed with UGIH were matched with 748 controls (1:3) by age, gender, health center, and recruitment date. Only adults of European origin were included. Participants were stratified by aspirin exposure and genotype [(Aspirin(-), wild-type), (Aspirin(+), wild-type), (Aspirin(+), genetic variation), (Aspirin(-), genetic variation)]. For each SNP, the Odds Ratio of UGIH and their 95% confidence intervals were estimated in each subgroup by using the generalized linear mixed models for dependent binomial variables. SNP-aspirin interaction effect was estimated through Relative Excess Risk due to Interaction (RERI) measures. Results:We observed two categories of SNPs that might modify the risk magnitude of UGIH in aspirin consumers. Seven SNPs (rs1387180 A > G, rs2238631 T > C, rs1799964 T > C, rs5050 T > C/T > G, rs689466 T > C, rs1799983 T > A/T > G, and rs7756935 C > A) were "positive modifiers" associated with an excess of risk from aspirin exposure and carrying that genetic variation (1.75 ? RERI ? 4.95). On the contrary, the following nine SNPs (rs2243086 G > T, rs1131882 G > A, rs4311994 C > T, rs10120688 G > A, rs4251961 T > C, rs3778355 G > C, rs1330344 C > T, rs5275 A > G/A > T, and rs3779647 C > T) were "negative modifiers" and associated with a reduced risk in aspirin users (-2.74 ? RERI ? -0.95). Conclusion:This preliminary study suggests that polymorphisms in genes involved in platelets activity, angiogenesis and inflammatory response might modify the risk of aspirin-related UGIH. Further studies with larger sample size and in different populations are needed to confirm our findings. If confirmed, this might have great impact on public health, thanks to aspirin's prophylactic properties in diseases of high incidence and severity.

SUBMITTER: Mallah N

PROVIDER: S-EPMC7325915 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Influence of Polymorphisms Involved in Platelet Activation and Inflammatory Response on Aspirin-Related Upper Gastrointestinal Bleeding: A Case-Control Study.

Mallah Narmeen N Zapata-Cachafeiro Maruxa M Aguirre Carmelo C Ibarra-García Eguzkiñe E Palacios-Zabalza Itziar I Macías-García Fernando F Domínguez-Muñoz J Enrique JE Piñeiro-Lamas María M Ibáñez Luisa L Vidal Xavier X Vendrell Lourdes L Martin-Arias Luis L Sáinz-Gil María M Velasco-González Verónica V Figueiras Adolfo A

Frontiers in pharmacology 20200609

<h4>Background</h4>Despite the wide benefits of aspirin and its cost-effectiveness, aspirin prescriptions have been reduced due to idiosyncratic responses in susceptible individuals. Low-dose aspirin and single-nucleotide polymorphisms (SNPs) are independently associated with increased risk of gastrointestinal hemorrhage; however, to-date, no studies investigated the SNP-aspirin interaction effect on upper gastrointestinal hemorrhage (UGIH). Therefore, we aimed to evaluate the role of 25 SNPs in ...[more]

PMID: 32655394

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Project description:BackgroundUpper gastrointestinal (GI) bleeding is one of the most common, high risk emergency disorders in the western world. Almost nothing has been reported on longer term prognosis following upper GI bleeding. The aim of this study was to establish mortality up to three years following hospital admission with upper GI bleeding and its relationship with aetiology, co-morbidities and socio-demographic factors.MethodsSystematic record linkage of hospital inpatient and mortality data for 14 212 people in Wales, UK, hospitalised with upper GI bleeding between 1999 and 2004 with three year follow-up to 2007. The main outcome measures were mortality rates, standardised mortality ratios (SMRs) and relative survival.ResultsMortality at three years was 36.7% overall, based on 5215 fatalities. It was highest for upper GI malignancy (95% died within three years) and varices (52%). Compared with the general population, mortality was increased 27-fold during the first month after admission. It fell to 4.3 by month four, but remained significantly elevated during every month throughout the three years following admission. The most important independent prognostic predictors of mortality at three years were older age (mortality increased 53 fold for people aged 85 years and over compared with those under 40 years); oesophageal and gastric/duodenal malignancy (48 and 32 respectively) and gastric varices aetiologies (2.8) when compared with other bleeds; non-upper GI malignancy, liver disease and renal failure co-morbidities (15, 7.9 and 3.9); social deprivation (29% increase for quintile V vs I); incident bleeds as an inpatient (31% vs admitted with bleeding) and male patients (25% vs female).ConclusionOur study shows a high late as well as early mortality for upper GI bleeding, with very poor longer term prognosis following bleeding due to malignancies and varices. Aetiologies with the worst prognosis were often associated with high levels of social deprivation.

Project description:BackgroundNon-alcoholic fatty liver disease (NAFLD) is the leading cause of liver disease globally with an estimated prevalence of 25%, with the clinical and economic burden expected to continue to increase. In the United States, non-variceal upper gastrointestinal bleeding (NVUGIB) has an estimated incidence of 61-78 cases per 100000 people with a mortality rate of 2%-15% based on co-morbidity burden.AimTo identify the outcomes of NVUGIB in NAFLD hospitalizations in the United States.MethodsWe utilized the National Inpatient Sample from 2016-2019 to identify all NVUGIB hospitalizations in the United States. This population was divided based on the presence and absence of NAFLD. Hospitalization characteristics, outcomes and complications were compared.ResultsThe total number of hospitalizations for NVUGIB was 799785, of which 6% were found to have NAFLD. NAFLD and GIB was, on average, more common in younger patients, females, and Hispanics than GIB without NAFLD. Interestingly, GIB was less common amongst blacks with NAFLD. Multivariate logistic regression analysis was conducted, controlling for the multiple covariates. The primary outcome of interest, mortality, was found to be significantly higher in patients with NAFLD and GIB [adjusted odds ratio (aOR) = 1.018 (1.013-1.022)]. Secondary outcomes of interest, shock [aOR = 1.015 (1.008-1.022)], acute respiratory failure [aOR = 1.01 (1.005-1.015)] and acute liver failure [aOR = 1.016 (1.013-1.019)] were all more likely to occur in this cohort. Patients with NAFLD were also more likely to incur higher total hospital charges (THC) [$2148 ($1677-$2618)]; however, were less likely to have a longer length of stay [0.27 d (0.17-0.38)]. Interestingly, in our study, the patients with NAFLD were less likely to suffer from acute myocardial infarction [aOR = 0.992 (0.989-0.995)]. Patients with NAFLD were not more likely to suffer acute kidney injury, sepsis, blood transfusion, intubation, or dialysis.ConclusionNVUGIB in NAFLD hospitalizations had higher inpatient mortality, THC, and complications such as shock, acute respiratory failure, and acute liver failure compared to those without NAFLD.

Dataset Information

Influence of Polymorphisms Involved in Platelet Activation and Inflammatory Response on Aspirin-Related Upper Gastrointestinal Bleeding: A Case-Control Study.

Publications

Influence of Polymorphisms Involved in Platelet Activation and Inflammatory Response on Aspirin-Related Upper Gastrointestinal Bleeding: A Case-Control Study.

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