Dataset Information

Hypouricemia and Mortality Risk in the US General Population.

ABSTRACT:

Objective

The most recent European Alliance of Associations for Rheumatology (EULAR) recommendations for gout advise against maintaining a serum urate (SU) level of <3 mg/dl for prolonged periods of time. While several Asian cohort studies have shown higher rates of mortality in individuals with extremely low SU levels, data from non-Asian cohort studies are scarce, and the relationship between hypouricemia, cardiovascular risk, and mortality remains unclear.

Methods

Using data collected from the 1988-1994 and 1999-2008 National Health and Nutrition Examination Survey (NHANES), we examined the relationship between SU level and overall and cause-specific mortality in 41,807 adults in the US. We calculated multivariable hazard ratios (HRs) that were compared to a referent SU level of 5-6 mg/dl for SU categories <4, 4-5, 6-7, 7-8, and >8 mg/dl in men and SU categories <3, 3-4, 4-5, 6-7, and >7 mg/dl in women.

Results

A higher mortality risk was not observed in women who had an SU level of <3 mg/dl (HR 1.09 [95% confidence interval (95% CI) 0.92-1.28]). A 28% higher mortality risk was observed in men who had an SU level of <4 mg/dl (HR 1.28 [95% CI 1.13-1.45]), with a nearly three-times higher mortality risk from diabetes mellitus also noted (HR 2.89 [95% CI 1.59-5.23]), but no increase in mortality from any other specific cause.

Conclusion

We found no long-term excess mortality risk among American women with SU levels as low as <3 mg/dl, a finding which is incompatible with the notion of a causal relationship between hypouricemia and premature mortality in women. We found excess all-cause mortality and diabetes mellitus-related mortality among hypouricemic American men, which may in part be attributable to the uricosuric effect of hyperglycemia in fatal uncontrolled diabetes mellitus (analogous to reverse causality).

SUBMITTER: D'Silva KM

PROVIDER: S-EPMC8091104 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Hypouricemia and Mortality Risk in the US General Population.

D'Silva Kristin M KM Yokose Chio C Lu Na N McCormick Natalie N Lee Hwajeong H Zhang Yuqing Y Choi Hyon K HK

Arthritis care & research 20210712 8

<h4>Objective</h4>The most recent European Alliance of Associations for Rheumatology (EULAR) recommendations for gout advise against maintaining a serum urate (SU) level of <3 mg/dl for prolonged periods of time. While several Asian cohort studies have shown higher rates of mortality in individuals with extremely low SU levels, data from non-Asian cohort studies are scarce, and the relationship between hypouricemia, cardiovascular risk, and mortality remains unclear.<h4>Methods</h4>Using data co ...[more]

PMID: 33026684

Similar Datasets

Project description:ImportanceImmune dysregulation can increase the risk of infection, malignant neoplasms, and cardiovascular disease, but improved methods are needed to identify and quantify immunologic hazard in the general population.ObjectiveTo determine whether lymphopenia is associated with reduced survival in outpatients.Design, setting, and participantsThis retrospective cohort study of the National Health and Nutrition Examination Survey (NHANES) included participants enrolled from January 1, 1999, to December 31, 2010, a large outpatient sample representative of the US adult population. Associations were evaluated between lymphopenia and other immunohematologic (IH) markers, clinical features, and survival during 12 years of follow-up, completed on December 31, 2011. Spearman correlations, Cox proportional hazards regression models, and Kaplan-Meier curves were used in univariable and multivariable models, allowing for nonlinear associations with bivariate cubic polynomials. Data were analyzed from September 1, 2018, through July 24, 2019.ExposuresAbsolute lymphocyte counts (ALC), red blood cell distribution width (RDW), and C-reactive protein (CRP) level.Main outcomes and measuresAll-cause survival.ResultsAmong the 31 178 participants, the median (interquartile range) age at baseline was 45 (30-63) years, 16 093 (51.6%) were women, 16 260 (52.2%) were nonwhite, and overall 12-year rate of survival was 82.8%. Relative lymphopenia (≤1500/μL) and severe lymphopenia (≤1000/μL) were observed in 20.1% and 3.0%, respectively, of this general population and were associated with increased risk of mortality (age- and sex-adjusted hazard ratios [HRs], 1.3 [95% CI, 1.2-1.4] and 1.8 [95% CI, 1.6-2.1], respectively) due to cardiovascular and noncardiovascular causes. Lymphopenia was also associated with worse survival in multivariable models, including traditional clinical risk factors, and this risk intensified when accompanied by bone marrow dysregulation (elevated RDW) and/or inflammation (elevated CRP level). Ten-year mortality ranged from 3.8% to 62.1% based on lymphopenia status, tertile of CRP level, and tertile of RDW. A high-risk IH profile was nearly twice as common as type 2 diabetes (19.3% and 10.0% of participants, respectively) and associated with a 3-fold risk of mortality (HR, 3.2; 95% CI, 2.6-4.0). Individuals aged 70 to 79 years with low IH risk had a better 10-year survival (74.1%) than those who were a decade younger with a high-risk IH profile (68.9%).Conclusions and relevanceThese findings suggest that lymphopenia is associated with reduced survival independently of and additive to traditional risk factors, especially when accompanied by altered erythropoiesis and/or heightened inflammation. Immune risk may be analyzed as a multidimensional entity derived from routine tests, facilitating precision medicine and population health interventions.

Project description:Peripheral blood cytopenias may precede the development of hematological malignancies and frequently pose clinical challenges in the older population. The natural course of (mild) cytopenias during aging and their association with hematological disorders in community-dwelling individuals are not well studied. Within the population-based Lifelines cohort (n = 167729), we studied changes in peripheral blood counts, occurrence of cytopenias, and associated hematological outcomes in the context of aging. Development of hematological malignancies and (cause-specific) mortality were evaluated by linkage to nationwide registries. Anemia and thrombocytopenia emerged with older age, in line with a general age-related decline in these blood counts. For neutropenia, no increase in prevalence with older age was observed. Using standard reference limits to define cytopenias, anemia (hazard ratio [HR], 1.84; 95% confidence interval [CI], 1.59-2.12), thrombocytopenia (HR, 1.58; 95% CI, 1.32-1.89), and, especially the concomitant presence of anemia and thrombocytopenia (HR, 4.75; 95% CI, 2.98-7.55) were associated with inferior overall survival. Only a minor proportion of deaths was explained by diagnosed hematological malignancies, with the majority attributable to other causes. Neutropenia, either isolated (HR, 0.88; 95% CI, 0.73-1.06) or combined with another cytopenia, did not affect overall survival. For individuals aged ≥60 years, 5-year cumulative incidence of hematological malignancies was 0.60% (95% CI, 0.50-0.70), with higher incidences among those with anemia (P < .001) or thrombocytopenia (P < .001) but not neutropenia (P = .201). Highest cumulative incidences of diagnoses and mortality from hematological malignancies were observed in individuals with >1 cytopenia. We conclude that anemia and thrombocytopenia, but not neutropenia, are associated with inferior overall survival of community-dwelling individuals. Hematological malignancies develop in a small fraction of these cases.

Project description:BackgroundAlthough clinical trials involving psychedelic-assisted psychotherapy have not observed short-term increases in the risk of death, limited data exist on mortality associated with hallucinogen use outside of controlled trial settings. We sought to determine whether people with an emergency department visit or hospital admission involving hallucinogen use were at increased risk of all-cause death compared with the general population and with people with acute care presentations involving other substances.MethodsWe conducted a retrospective cohort study using linked health administrative data on all people aged 15 years and older living in Ontario, Canada, from 2006 to 2022. We compared overall and cause-specific mortality between members of the general population and people with incident acute care (an emergency department visit or hospital admission) involving hallucinogens and other substances.ResultsWe included 11 415 713 people; 7953 (0.07%) had incident acute care involving hallucinogens. In a matched analysis with 77 101 people with a median follow-up of 7 (interquartile range 3-11) years, acute care involving hallucinogens was associated with a 2.6-fold (hazard ratio [HR] 2.57, 95% confidence interval [CI] 2.09-3.15) increased all-cause mortality within 5 years (n = 482, absolute risk 6.1%) relative to the general population (n = 460, absolute risk 0.6%). Analyses excluding people with comorbid mental or substance use disorders showed similar elevations in mortality risk for acute care involving hallucinogens relative to the general population (HR 3.25, 95% CI 2.27-4.63). People with acute care involving hallucinogens were at a significantly elevated risk of death by unintentional drug poisoning (HR 2.03, 95% CI 1.02-4.05), suicide (HR 5.23, 95% CI 1.38-19.74), respiratory disease (HR 2.46, 95% CI 1.18-5.11), and cancer (HR 2.88, 95% CI 1.61-5.14) relative to the general population.InterpretationRequiring hospital-based care for hallucinogen use was associated with increases in risk of death relative to the general population, particularly from suicide. These findings should be considered in clinical and policy decision-making, given the increasing use of hallucinogens and associated problematic use.

Dataset Information

Hypouricemia and Mortality Risk in the US General Population.

Objective

Methods

Results

Conclusion

Publications

Hypouricemia and Mortality Risk in the US General Population.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets