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:Background & aimsThe use of proton pump inhibitors (PPIs) has increased rapidly in the past 2 decades. Concerns about the regular use of PPIs contributing to mortality have been raised.MethodsWe conducted a prospective cohort study using data collected from the Nurses' Health Study (2004-2018) and the Health Professionals Follow-up Study (2004-2018). Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% CIs for mortality according to PPI use. We used a modified lag-time approach to minimize reverse causation (ie, protopathic bias).ResultsAmong 50,156 women and 21,731 men followed for 831,407 person-years and a median of 13.8 years, we documented 22,125 deaths, including 4592 deaths from cancer, 5404 from cardiovascular diseases, and 12,129 deaths from other causes. Compared with nonusers of PPIs, PPI users had significantly higher risks of all-cause mortality (HR, 1.19; 95% CI, 1.13-1.24) and mortality due to cancer (HR, 1.30; 95% CI, 1.17-1.44), cardiovascular diseases (HR, 1.13; 95% CI, 1.02-1.26), respiratory diseases (HR, 1.32; 95% CI, 1.12-1.56), and digestive diseases (HR, 1.50; 95% CI, 1.10-2.05). Upon applying lag times of up to 6 years, the associations were attenuated and no longer statistically significant (all-cause: HR, 1.04; 95% CI, 0.97-1.11; cancer: HR, 1.07; 95% CI, 0.89-1.28; cardiovascular diseases: HR, 0.94; 95% CI, 0.81-1.10; respiratory diseases: HR, 1.20; 95% CI, 0.95-1.50; digestive diseases: HR, 1.38; 95% CI, 0.88-2.18). Longer duration of PPI use did not confer higher risks for all-cause and cause-specific mortality.ConclusionsAfter accounting for protopathic bias, PPI use was not associated with higher risks of all-cause mortality and mortality due to major causes.
| S-EPMC9509450 | biostudies-literature
Project description:BackgroundProton pump inhibitor (PPI) use has increased over the last decades and has been associated with multiple adverse events and potentially even overall survival.AimsWe aimed to investigate the association between proton pump inhibitor maintenance use and all-cause and cause-specific mortality, addressing confounding by indication and duration of use.MethodsThis Swedish population-based cohort study included all adult (N = 935,236) PPI and histamine-2 receptor antagonist maintenance users (≥ 180 days use) during 2005-2014. Standardised mortality ratios (SMRs) and 95% confidence intervals were calculated for all-cause and cause-specific mortality comparing the risk among PPI/H2RA users to that of the Swedish background population, stratified by age, sex, calendar period, indication and duration of use. Multivariable Poisson regression models were used to compare PPI use to H2RA use, expressed as incidence rate ratios and 95% confidence intervals.ResultsPPI and histamine-2 receptor antagonist use were associated with an increased risk of all-cause mortality (SMR = 1.35; 1.34-1.36; SMR = 1.31; 1.27-1.36, respectively). The highest SMRs were found in the youngest age groups. In direct comparison, PPI use showed a higher mortality risk than histamine-2 receptor antagonist use (incidence rate ratios = 1.42; 1.38-1.46). PPIs were related to increased cancer (SMR = 1.21; 1.20-1.22), and cardiovascular mortality (SMR = 1.36; 1.35-1.37). Increased SMRs were observed for most indications. Longer duration of use was associated with a higher mortality among PPI users but not among histamine-2 receptor antagonist users.ConclusionMaintenance PPI use was associated with an increased risk of all-cause and cause-specific mortality, and the risk increased with prolonged duration.
| S-EPMC10188584 | 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.
| S-EPMC5939721 | biostudies-literature
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: Not available
| S-EPMC6485982 | biostudies-literature
Project description: Not available
| S-EPMC6464600 | biostudies-literature
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