No Associations Between Regular Use of Proton Pump Inhibitors and Risk of All-Cause and Cause-Specific Mortality: A Population-Based Cohort of 0.44 Million Participants.
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ABSTRACT: Introduction
The association between proton pump inhibitors' (PPIs) use and mortality remains unclear.Methods
This was a prospective analysis of 440,840 UK residents and 13,154 deaths. We evaluated the associations with multivariate Cox regression.Results
After adjusting for confounders, such as over health status and longstanding diseases, the regular use of PPIs was not associated with an increased risk of all-cause mortality and mortality due to neoplasms, circulatory system diseases, respiratory system diseases, digestive system diseases, external causes, and other causes.Discussion
Regular use of PPIs was not associated with an increased risk of all-cause and cause-specific mortality.
SUBMITTER: He Q
PROVIDER: S-EPMC8560155 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveTo estimate all cause mortality and cause specific mortality among patients taking proton pump inhibitors (PPIs).DesignLongitudinal observational cohort study.SettingUS Department of Veterans Affairs.ParticipantsNew users of PPIs (n=157 625) or H2 blockers (n=56 842).Main outcome measuresAll cause mortality and cause specific mortality associated with taking PPIs (values reported as number of attributable deaths per 1000 patients taking PPIs).ResultsThere were 45.20 excess deaths (95% confidence interval 28.20 to 61.40) per 1000 patients taking PPIs. Circulatory system diseases (number of attributable deaths per 1000 patients taking PPIs 17.47, 95% confidence interval 5.47 to 28.80), neoplasms (12.94, 1.24 to 24.28), infectious and parasitic diseases (4.20, 1.57 to 7.02), and genitourinary system diseases (6.25, 3.22 to 9.24) were associated with taking PPIs. There was a graded relation between cumulative duration of PPI exposure and the risk of all cause mortality and death due to circulatory system diseases, neoplasms, and genitourinary system diseases. Analyses of subcauses of death suggested that taking PPIs was associated with an excess mortality due to cardiovascular disease (15.48, 5.02 to 25.19) and chronic kidney disease (4.19, 1.56 to 6.58). Among patients without documented indication for acid suppression drugs (n=116 377), taking PPIs was associated with an excess mortality due to cardiovascular disease (22.91, 11.89 to 33.57), chronic kidney disease (4.74, 1.53 to 8.05), and upper gastrointestinal cancer (3.12, 0.91 to 5.44). Formal interaction analyses suggested that the risk of death due to these subcauses was not modified by a history of cardiovascular disease, chronic kidney disease, or upper gastrointestinal cancer. Taking PPIs was not associated with an excess burden of transportation related mortality and death due to peptic ulcer disease (as negative outcome controls).ConclusionsTaking PPIs is associated with a small excess of cause specific mortality including death due to cardiovascular disease, chronic kidney disease, and upper gastrointestinal cancer. The burden was also observed in patients without an indication for PPI use. Heightened vigilance in the use of PPI may be warranted.
| S-EPMC6538974 | biostudies-literature
Project description:ObjectiveTo investigate the association of grip strength with disease specific incidence and mortality and whether grip strength enhances the prediction ability of an established office based risk score.DesignProspective population based study.SettingUK Biobank.Participants502?293 participants (54% women) aged 40-69 years.Main outcome measuresAll cause mortality as well as incidence of and mortality from cardiovascular disease, respiratory disease, chronic obstructive pulmonary disease, and cancer (all cancer, colorectal, lung, breast, and prostate).ResultsOf the participants included in analyses, 13?322 (2.7%) died over a mean of 7.1 (range 5.3-9.9) years' follow-up. In women and men, respectively, hazard ratios per 5 kg lower grip strength were higher (all at P<0.05) for all cause mortality (1.20, 95% confidence interval 1.17 to 1.23, and 1.16, 1.15 to 1.17) and cause specific mortality from cardiovascular disease (1.19, 1.13 to 1.25, and 1.22, 1.18 to 1.26), all respiratory disease (1.31, 1.22 to 1.40, and 1.24, 1.20 to 1.28), chronic obstructive pulmonary disease (1.24, 1.05 to 1.47, and 1.19, 1.09 to 1.30), all cancer (1.17, 1.13 to 1.21, 1.10, 1.07 to 1.13), colorectal cancer (1.17, 1.04 to 1.32, and 1.18, 1.09 to 1.27), lung cancer (1.17, 1.07 to 1.27, and 1.08, 1.03 to 1.13), and breast cancer (1.24, 1.10 to 1.39) but not prostate cancer (1.05, 0.96 to 1.15). Several of these relations had higher hazard ratios in the younger age group. Muscle weakness (defined as grip strength <26 kg for men and <16 kg for women) was associated with a higher hazard for all health outcomes, except colon cancer in women and prostate cancer and lung cancer in both men and women. The addition of handgrip strength improved the prediction ability, based on C index change, of an office based risk score (age, sex, diabetes diagnosed, body mass index, systolic blood pressure, and smoking) for all cause (0.013) and cardiovascular mortality (0.012) and incidence of cardiovascular disease (0.009).ConclusionHigher grip strength was associated with a range of health outcomes and improved prediction of an office based risk score. Further work on the use of grip strength in risk scores or risk screening is needed to establish its potential clinical utility.
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Project description:RATIONALE:Proton pump inhibitors (PPIs) are popular drugs for gastroesophageal reflux, which are now available for long-term use without medical supervision. Recent reports suggest that PPI use is associated with cardiovascular, renal, and neurological morbidity. OBJECTIVE:To study the long-term effect of PPIs on endothelial dysfunction and senescence and investigate the mechanism involved in PPI-induced vascular dysfunction. METHODS AND RESULTS:Chronic exposure to PPIs impaired endothelial function and accelerated human endothelial senescence by reducing telomere length. CONCLUSIONS:Our data may provide a unifying mechanism for the association of PPI use with increased risk of cardiovascular, renal, and neurological morbidity and mortality.
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Project description:ImportanceAsia is home to the largest diabetic populations in the world. However, limited studies have quantified the association of diabetes with all-cause and cause-specific mortality in Asian populations.ObjectivesTo evaluate the association of diabetes with all-cause and cause-specific mortality in Asia and to investigate potential effect modifications of the diabetes-mortality associations by participants' age, sex, education level, body mass index, and smoking status.Design, setting, and participantsThis pooled analysis incorporated individual participant data from 22 prospective cohort studies of the Asia Cohort Consortium conducted between 1963 and 2006. A total of 1 002 551 Asian individuals (from mainland China, Japan, South Korea, Singapore, Taiwan, India, and Bangladesh) were followed up for more than 3 years. Cohort-specific hazard ratios and 95% confidence intervals for all-cause and cause-specific mortality were estimated using Cox regression models and then pooled using random-effects meta-analysis. Analysis was conducted between January 10, 2018, and August 31, 2018.ExposuresDoctor-diagnosed diabetes, age, sex, education level, body mass index, and smoking status.Main outcomes and measuresAll-cause and cause-specific mortality.ResultsOf 1 002 551 participants (518 537 [51.7%] female; median [range] age, 54.0 [30.0-98.0] years), 148 868 deaths were ascertained during a median (range) follow-up of 12.6 (3.0-38.9) years. The overall prevalence of diabetes reported at baseline was 4.8% for men and 3.6% for women. Patients with diabetes had a 1.89-fold risk of all-cause death compared with patients without diabetes (hazard ratio [HR], 1.89; 95% CI, 1.74-2.04), with the highest relative risk of death due to diabetes itself (HR, 22.8; 95% CI, 18.5-28.1), followed by renal disease (HR, 3.08; 95% CI, 2.50-3.78), coronary heart disease (HR, 2.57; 95% CI, 2.19-3.02), and ischemic stroke (HR, 2.15; 95% CI, 1.85-2.51). The adverse diabetes-mortality associations were more evident among women (HR, 2.09; 95% CI, 1.89-2.32) than among men (HR, 1.74; 95% CI, 1.62-1.88) (P for interaction < .001) and more evident among adults aged 30 to 49 years (HR, 2.43; 95% CI, 2.08-2.84) than among adults aged 70 years and older (HR, 1.51; 95% CI, 1.40-1.62) (P for interaction < .001). A similar pattern of association was found between diabetes and cause-specific mortality, with significant variations noted by sex and age.Conclusions and relevanceThis study found that diabetes was associated with increased risk of death from several diseases among Asian populations. Development and implementation of diabetes management programs are urgently needed to reduce the burden of diabetes in Asia.
| S-EPMC6481439 | biostudies-literature
Project description:BackgroundTo examine the association between regular use of proton pump inhibitors and the risk of incident dementia, including dementia subtypes, and whether the association differs between APOE genotypes.MethodsBased on a prospective analysis of data from the UK Biobank, 501,002 individuals (female, 54.4%) aged between 40 and 70 years, who had no prevalent dementia at baseline, were enrolled between 2006 and 2010 and followed up to 2018. We compared all-cause dementia, Alzheimer's disease (AD), and vascular dementia (VaD) incidence rates between proton pump inhibitor users and non-users by the Cox proportional hazard model.ResultsDuring 4,438,839 person-years of follow-up (median length of follow-up, 9.0 years), there were 2505 incident cases of all-cause dementia, including 932 cases of AD and 524 cases of VaD. The incident rate of all-cause dementia among proton pump inhibitor users was 1.06 events per 1000 person-years, compared with 0.51 events per 1000 person-years among non-users. After adjustment for multiple confounders and indications, the hazard ratios (HRs) of the proton pump inhibitor users were 1.20 (95% CI, 1.07-1.35) for incident all-cause dementia, 1.23 (95% CI, 1.02-1.49) for incident AD, and 1.32 (95% CI, 1.05-1.67) for incident VaD. In addition, the association between proton pump inhibitor use and all-cause dementia differed by APOE genotype (P for interaction = 0.048). Among APOE ε4 heterozygotes, the fully adjusted HR of proton pump inhibitor use was 1.46 (95% CI, 1.22-1.75) and 1.68 (95% CI, 1.36-2.07), especially for individuals aged 65 years and older.ConclusionsThe finding of this large population-based cohort study indicates that the use of proton pump inhibitors is associated with an increased risk of incident dementia, particularly among APOE ε4 heterozygotes.
| S-EPMC9434890 | biostudies-literature
Project description:ObjectivesTo examine the relationship between community-acquired pneumonia (CAP) and proton pump inhibitor (PPI) treatment among patients with laryngeal/voice disorders.Study designRetrospective cohort analysis.SettingLarge national administrative US claims database.Subjects and methodsPatients were included if they were ≥18 years old; had outpatient treatment for a laryngeal/voice disorder from January 1, 2010, to December 31, 2014 (per International Classification of Diseases, Ninth Revision, Clinical Modification codes); had 12 months of continuous enrollment prior to the index date (ie, first diagnosis of laryngeal/voice disorder); had no preindex diagnosis of CAP; and had prescription claims captured from 1 year preindex to end of follow-up. Patient demographics, comorbid conditions, index laryngeal diagnosis, number of unique preindex patient encounters, and CAP diagnoses during the postindex 3 years were collected. Two models-a time-dependent Cox regression model and a propensity score-based approach with a marginal structural model-were separately performed for patients with and without pre-index date PPI prescriptions.ResultsA total of 392,355 unique patients met inclusion criteria; 188,128 (47.9%) had a PPI prescription. The 3-year absolute risk for CAP was 4.0% and 5.3% among patients without and with preindex PPI use, respectively. For patients without and with pre-index date PPI use, the CAP occurrence for a person who had already received a PPI is 30% to 50% higher, respectively, than for a person who had not yet had a PPI but may receive one later.ConclusionsPatients without and with pre-index date PPI use experienced a roughly 30% to 50% increased likelihood of CAP, respectively, as compared with patients who had not had PPI prescriptions.
| S-EPMC6547826 | biostudies-literature
Project description:Proton pump inhibitors (PPIs) are commonly used as a supplement to cancer therapy. Yet, their effect on cancer mortality is largely unknown. Using data from Danish nationwide registries and Cox models regressing of both propensity scores and drug use, we estimated hazard ratios (HRs) with 95% confidence intervals (CIs) for cancer-specific and noncancer death among PPI users (≥2 prescriptions within six months after diagnosis; n = 36,066) compared with nonusers (<2 prescriptions, n = 311,853) or users of histamine H2 -receptor antagonists (H2 RA; n = 5,152). Adjusted HRs for cancer-specific mortality among postdiagnostic PPI users as compared with nonusers or H2 RA users were 1.29 (95% CI, 1.27-1.32) and 1.15 (95% CI, 1.10-1.20), respectively. HRs for cancer mortality associated with PPI use were highest for ovarian (1.35; 95% CI, 1.20-1.52) and lowest for esophageal cancer (0.91; 95% CI, 0.81-1.04). The associations were stronger among new PPI users after cancer diagnosis, indicating potential confounding. To test the effect of PPIs on tumor growth in a model system free for confounding factors, we investigated the effect of pantoprazole on tumor growth in mice. Pantoprazole (5 mg/kg/day) enhanced tumor growth (p = 0.033) and reduced the antitumor activity of gemcitabine (p = 0.008) in fibrosarcoma-bearing Balb/c mice, but not in immunodeficient Balb/c nude mice. In breast carcinoma-bearing FVB/N mice, pantoprazole had no effect on tumor growth alone but it reduced the life-prolonging effect of doxorubicin significantly (p = 0.007). Taken together, these data raise concerns about the increasing use of PPIs and calls for further studies addressing their safety among cancer patients.
| S-EPMC7611279 | biostudies-literature
Project description:Few studies explored the association of different type of physical activity with all-cause mortality in hypertension (HBP) participants. A retrospective cohort analysis was performed using National Health and Nutrition Examination Survey (NHANES) data to explore association of moderate-intensity physical activity (MPA), vigorous-intensity physical activity (VPA), sedentary behavior with mortality in HBP individuals. Among 10,913 HBP participants followed for a median of 6.2 years, VPA was not associated with a reduction in all-cause mortality compared to participants without VPA in multivariate Cox survival analysis. MPA was linked to lower all-cause mortality at durations of 0-150 min/week (HR, 0.72; 95% CI 0.58-0.88), 150-300 min/week (HR, 0.71; 95% CI 0.52-0.96), and > 300 min/week (HR, 0.61; 95% CI 0.49-0.77) compared to no MPA. Sedentary behavior of 6-8 h/day (HR, 1.35; 95% CI 1.15-1.59) and > 8 h/day (HR, 1.55; 95% CI 1.34-1.79) were associated with increased mortality risk versus < 6 h/day. Further research is needed to explore whether VPA can improve outcomes for HBP individuals and to determine the optimal duration of VPA.MPA is linked to lower mortality risk, indicating its potential as the best physical activity intensity for HBP individuals.
| S-EPMC10980699 | biostudies-literature
Project description:Proton pump inhibitors (PPIs) increase osteoporotic fracture risk presumably via hypochlorhydria and consequent reduced fractional calcium absorption (FCA). Existing studies provide conflicting information regarding the direct effects of PPIs on FCA. We evaluated the effect of PPI therapy on FCA. We recruited women at least 5 years past menopause who were not taking acid suppressants. Participants underwent three 24-hour inpatient FCA studies using the dual stable isotope method. Two FCA studies were performed 1 month apart to establish baseline calcium absorption. The third study occurred after taking omeprazole (40?mg/day) for 30 days. Each participant consumed the same foods during all FCA studies; study meals replicated subjects' dietary habits based on 7-day diet diaries. Twenty-one postmenopausal women ages 58?±?7 years (mean?±?SD) completed all study visits. Seventeen women were white, and 2 each were black and Hispanic. FCA (mean?±?SD) was 20%?±?10% at visit 1, 18%?±?10% at visit 2, and 23%?±?10% following 30?±?3 days of daily omeprazole (p?=?.07, ANOVA). Multiple linear regression revealed that age, gastric pH, serum omeprazole levels, adherence to omeprazole, and 25-hydroxyvitamin D levels were unrelated to changes in FCA between study visits 2 and 3. The 1,25-dihydroxyvitamin D(3) level at visit 2 was the only variable (p?=?.049) associated with the change in FCA between visits 2 and 3. PPI-associated hypochlorhydria does not decrease FCA following 30 days of continuous use. Future studies should focus on identifying mechanisms by which PPIs increase the risk of osteoporotic fracture.
| S-EPMC3179281 | biostudies-literature
Project description:Background and aimsProton pump inhibitors (PPIs) are among the top 10 most widely used drugs in the world. PPI use has been associated with an increased risk of enteric infections, most notably Clostridium difficile. The gut microbiome plays an important role in enteric infections, by resisting or promoting colonisation by pathogens. In this study, we investigated the influence of PPI use on the gut microbiome.MethodsThe gut microbiome composition of 1815 individuals, spanning three cohorts, was assessed by tag sequencing of the 16S rRNA gene. The difference in microbiota composition in PPI users versus non-users was analysed separately in each cohort, followed by a meta-analysis.Results211 of the participants were using PPIs at the moment of stool sampling. PPI use is associated with a significant decrease in Shannon's diversity and with changes in 20% of the bacterial taxa (false discovery rate <0.05). Multiple oral bacteria were over-represented in the faecal microbiome of PPI-users, including the genus Rothia (p=9.8×10(-38)). In PPI users we observed a significant increase in bacteria: genera Enterococcus, Streptococcus, Staphylococcus and the potentially pathogenic species Escherichia coli.ConclusionsThe differences between PPI users and non-users observed in this study are consistently associated with changes towards a less healthy gut microbiome. These differences are in line with known changes that predispose to C. difficile infections and can potentially explain the increased risk of enteric infections in PPI users. On a population level, the effects of PPI are more prominent than the effects of antibiotics or other commonly used drugs.
| S-EPMC4853569 | biostudies-literature