Publications by authors named "Andrew K Gibson"

7 Publications

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Clinical Implications of Estimated Glomerular Filtration Rate Dip Following Sodium-Glucose Cotransporter-2 Inhibitor Initiation on Cardiovascular and Kidney Outcomes.

J Am Heart Assoc 2021 Jun 20;10(11):e020237. Epub 2021 May 20.

Clinical Epidemiology Center Research and Development Service VA Saint Louis Health Care System Saint Louis MO.

Background The frequency of the initial short-term decline in estimated glomerular filtration rate (eGFR), eGFR dip, following initiation of sodium-glucose cotransporter-2 inhibitors (SGLT2i) and its clinical implications in real-world practice are not clear. Methods and Results We built a cohort of 36 638 new users of SGLT2i and 209 025 new users of other antihyperglycemics. Inverse probability weighting was used to estimate the excess rate of eGFR dip, risk of the composite cardiovascular outcome of nonfatal myocardial infarction, nonfatal stroke, hospitalization for heart failure, or all-cause mortality, and risk of the composite kidney outcome of eGFR decline >50%, end-stage kidney disease, or all-cause mortality. In the first 6 months of therapy, compared with other antihyperglycemics, excess rates of eGFR dip >10% and eGFR dip >30% were 9.86 (95% CI: 8.83-11.00) and 1.15 (0.70-1.62) per 100 SGLT2i users, respectively. In mediation analyses that accounted for eGFR dipping, SGLT2i use was associated with reduced risk of cardiovascular and kidney outcomes (hazard ratio, 0.92 [0.84-0.99] and 0.78 [0.71-0.87], respectively); the magnitude of the association reduced by eGFR dipping was small for both outcomes. SGLT2i was associated with reduced risk of both outcomes in those with higher than average probability of eGFR dip >10% or 30%. Compared with discontinuation, continued use of SGLT2i at 6 months was associated with reduced risk of cardiovascular and kidney outcomes in those with no eGFR dip or eGFR dip ≤10%, in those with eGFR dip >10%, and in those with eGFR dip >30%. Conclusions The salutary association of SGLT2i with cardiovascular and kidney outcomes was maintained regardless of eGFR dipping; concerns about eGFR dipping should not preclude use, and occurrence of eGFR dip after SGLT2i initiation may not warrant discontinuation.
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http://dx.doi.org/10.1161/JAHA.120.020237DOI Listing
June 2021

Ambient fine particulate matter air pollution and the risk of hospitalization among COVID-19 positive individuals: Cohort study.

Environ Int 2021 Sep 9;154:106564. Epub 2021 Apr 9.

Clinical Epidemiology Center, Research and Development Service, VA Saint Louis Health Care System, 501 N Grand Blvd, Suite 300, Saint Louis, MO 63103, United States; Veterans Research & Education Foundation of Saint Louis, 501 N Grand Blvd, Suite 300, Saint Louis, MO 63103, United States; Department of Medicine, Washington University in Saint Louis, 4921 Parkview Pl, Saint Louis, MO 63110, United States; Nephrology Section, Medicine Service, VA Saint Louis Health Care System, 915 N Grand Blvd, Saint Louis, MO 63106, United States; Institute for Public Health, Washington University in Saint Louis, 600 S Taylor Ave, Saint Louis, MO 63110, United States. Electronic address:

Background: Ecologic analyses suggest that living in areas with higher levels of ambient fine particulate matter air pollution (PM) is associated with higher risk of adverse COVID-19 outcomes. Studies accounting for individual-level health characteristics are lacking.

Methods: We leveraged the breadth and depth of the US Department of Veterans Affairs national healthcare databases and built a national cohort of 169,102 COVID-19 positive United States Veterans, enrolled between March 2, 2020 and January 31, 2021, and followed them through February 15, 2021. Annual average 2018 PM exposure, at an approximately 1 km resolution, was linked with residential street address at the year prior to COVID-19 positive test. COVID-19 hospitalization was defined as first hospital admission between 7 days prior to, and 15 days after, the first COVID-19 positive date. Adjusted Poisson regression assessed the association of PM with risk of hospitalization.

Results: There were 25,422 (15.0%) hospitalizations; 5,448 (11.9%), 5,056 (13.0%), 7,159 (16.1%), and 7,759 (19.4%) were in the lowest to highest PM quartile, respectively. In models adjusted for State, demographic and behavioral factors, contextual characteristics, and characteristics of the pandemic a one interquartile range increase in PM (1.9 µg/m) was associated with a 10% (95% CI: 8%-12%) increase in risk of hospitalization. The association of PM and risk of hospitalization among COVID-19 individuals was present in each wave of the pandemic. Models of non-linear exposure-response suggested increased risk at PM concentrations below the national standard 12 µg/m. Formal effect modification analyses suggested higher risk of hospitalization associated with PM in Black people compared to White people (p = 0.045), and in those living in socioeconomically disadvantaged neighborhoods (p < 0.001).

Conclusions: Exposure to higher levels of PM was associated with increased risk of hospitalization among COVID-19 infected individuals. The risk was evident at PM levels below the regulatory standards. The analysis identified those of Black race and those living in disadvantaged neighborhoods as population groups that may be more susceptible to the untoward effect of PM on risk of hospitalization in the setting of COVID-19.
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http://dx.doi.org/10.1016/j.envint.2021.106564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040542PMC
September 2021

Ambient Fine Particulate Matter Air Pollution and Risk of Weight Gain and Obesity in United States Veterans: An Observational Cohort Study.

Environ Health Perspect 2021 Apr 1;129(4):47003. Epub 2021 Apr 1.

Clinical Epidemiology Center, Research and Development Service, Veterans Affairs Saint Louis Health Care System, Saint Louis, Missouri, USA.

Background: Experimental evidence and studies of children and adolescents suggest that ambient fine particulate matter [particulate matter in aerodynamic diameter ()] air pollution may be obesogenic, but the relationship between and the risk of body weight gain and obesity in adults is uncertain.

Objectives: Our goal was to characterize the association between and the risks of weight gain and obesity.

Methods: We followed 3,902,440 U.S. Veterans from 2010 to 2018 (median 8.1 y, interquartile range: 7.3-8.4) and assigned time-updated exposures by linking geocoded residential street addresses with satellite-based estimates of surface-level mass (at resolution). Associations with were estimated using Cox proportional hazards models for incident obesity [body mass index (] and a increase in weight relative to baseline and linear mixed models for associations with intra-individual changes in BMI and weight.

Results: A higher average annual concentration was associated with risk of incident obesity [; (95% CI: 1.06, 1.11)] and the risk of a () increase in weight [ (95% CI: 1.06, 1.08)] and with higher intra-individual changes in BMI [ (95% CI: 0.139, 0.142)] and weight [ (95% CI: 0.955, 0.981)]. Nonlinear exposure-response models indicated associations at concentrations below the national standard of . As expected, a negative exposure control (ambient air sodium) was not associated with obesity or weight gain. Associations were consistent in direction and magnitude across sensitivity analyses that included alternative outcomes and exposures assigned at different spatial resolutions.

Discussion: air pollution was associated with the risk of obesity and weight gain in a large predominantly male cohort of U.S. Veterans. Discussions about health effects of should include its association with obesity, and deliberations about the epidemiology of obesity should consider its association with . Investigation in other cohorts will deepen our understanding of the relationship between and weight gain and obesity. https://doi.org/10.1289/EHP7944.
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http://dx.doi.org/10.1289/EHP7944DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016176PMC
April 2021

Temporal Trends in Incidence Rates of Lower Extremity Amputation and Associated Risk Factors Among Patients Using Veterans Health Administration Services From 2008 to 2018.

JAMA Netw Open 2021 01 4;4(1):e2033953. Epub 2021 Jan 4.

Clinical Epidemiology Center, Department of Veterans Affairs, St Louis Health Care Systems, St Louis, Missouri.

Importance: Lower extremity amputation (LEA) is associated with significant morbidity and mortality. However, national temporal trends of LEA incidence rates among US veterans and associated factors have not been well characterized.

Objective: To describe the temporal trends of LEA, characterize associated risk factors, and decompose the associations of these risk factors with changes in temporal trends of LEA among US veterans using Department of Veteran Affairs (VA) services between 2008 and 2018.

Design, Setting, And Participants: This cohort study used VA data from 2008 to 2018 to estimate incidence rates of LEA among veterans using VA services. Cox regression models were used to identify risk factors associated with LEA. Decomposition analyses estimated the associations of changes in prevalence of risk factors with changes in LEA rates. Data were analyzed from October 1, 2007, to September 30, 2018.

Main Outcomes And Measures: Toe, transmetatarsal, below-knee, or above-knee LEA.

Results: A total of 6 493 141 veterans were included (median [interquartile range] age, 64 [54-76] years; 6 060 390 [93.4%] men). Veterans were studied for a median (interquartile range) of 10.9 (5.6-11.0) years. Between 2008 and 2018, rates of LEA increased from 12.89 (95% CI, 12.53-13.25) LEA per 10 000 persons to 18.12 (95% CI, 17.70-18.54) LEA per 10 000 persons, representing a net increase of 5.23 (95% CI, 4.68-5.78) LEA per 10 000 persons. Between 2008 and 2018, toe amputation rates increased by 3.24 (2.89-3.59) amputations per 10 000 persons, accounting for 62.0% of the total increase in LEA rates. Transmetatarsal amputations increased by 1.54 (95% CI, 1.27-1.81) amputations per 10 000 persons; below-knee amputation rates increased by 0.81 (95% CI, 0.56-1.05) amputations per 10 000 persons; and above-knee amputation rates decreased by 0.37 (95% CI, 0.14-0.59) amputations per 10 000 persons. Compared with men, women had decreased risk of any LEA (hazard ratio [HR], 0.34 [95% CI, 0.31-0.37]). Factors associated with increased risk of any LEA included Black race (HR, 1.25 [95% CI, 1.21-1.28]) or another non-White race (ie, Asian, Latino, or other; HR, 2.36 [95% CI, 2.30-2.42]), obesity (HR, 1.59 [95% CI, 1.55-1.63]), diabetes (HR, 6.38 [95% CI, 6.22-6.54]), chronic kidney disease (CKD; eg, CKD stage 5: HR, 3.94 [95% CI, 3.22-4.83]), and smoking status (eg, current smoking: HR, 1.97 [95% CI, 1.92-2.03]). Decomposition analyses suggested that while changes in demographic composition, primarily driven by increased proportion of women veterans, associated with a decrease of 0.18 (95% CI, 0.14-0.22) LEA per 10 000 persons, and decreases in smoking rates, associated with a decrease of 0.88 (95% CI, 0.79-0.97) LEA per 10 000 persons. However, these were overwhelmed by increased rates of diabetes, associated with an increase of 1.86 (95% CI, 1.72-1.99) LEA per 10 000 persons; peripheral arterial disease, associated with an increase of 1.53 (95% CI, 1.41-1.65) LEA per 10 000 persons; CKD, associated with an increase of 1.45 (95% CI, 1.33-1.57) LEA per 10 000 persons; and other clinical factors, including body mass index, cancer, cardiovascular disease, cerebrovascular disease, chronic lung disease, dementia, and hypertension, associated with an increase of 1.45 (95% CI, 1.33-1.57) LEA per 10 000 persons.

Conclusions And Relevance: This cohort study found that incidence rates of LEA among veterans using VA services increased between 2008 and 2018. Efforts aimed at reducing burden of LEA should target the reduction of diabetes, peripheral arterial disease, and CKD at the individual and population levels.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.33953DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823225PMC
January 2021

Acute Kidney Injury in a National Cohort of Hospitalized US Veterans with COVID-19.

Clin J Am Soc Nephrol 2020 12 16;16(1):14-25. Epub 2020 Nov 16.

Clinical Epidemiology Center, Research and Development Service, Veterans Affairs St. Louis Health Care System, St. Louis, Missouri

Background And Objectives: Coronavirus disease 2019 (COVID-19) is associated with higher risk of AKI. We aimed to describe rates and characterize predictors and health outcomes associated with AKI in a national cohort of US veterans hospitalized with COVID-19.

Design, Setting, Participants, & Measurements: In a cohort of 5216 US veterans hospitalized with COVID-19 identified through July 23, 2020, we described changes in serum creatinine and examined predictors of AKI and the associations between AKI, health resource utilization, and death, utilizing logistic regressions. We characterized geographic and temporal variations in AKI rates and estimated variance explained by key variables utilizing Poisson regressions.

Results: In total, 1655 (32%) participants had AKI; 961 (58%), 223 (13%), and 270 (16%) met Kidney Disease Improving Global Outcomes definitions of stage 1, 2, and 3 AKI, respectively, and 201 (12%) received KRT. Eight percent of participants had AKI within 1 day of hospitalization, and 47% did not recover to baseline serum creatinine by discharge. Older age, Black race, male gender, obesity, diabetes, hypertension, and lower eGFR were significant predictors of AKI during hospitalization with COVID-19. AKI was associated with higher mechanical ventilation use (odds ratio, 6.46; 95% confidence interval, 5.52 to 7.57) and longer hospital stay (5.56 additional days; 95% confidence interval, 4.78 to 6.34). AKI was also associated with higher risk of death (odds ratio, 6.71; 95% confidence interval, 5.62 to 8.04); this association was stronger in Blacks ( value of interaction <0.001). Hospital-level rates of AKI exhibited substantial geographic variability, ranging from 10% to 56%. Between March and July 2020, AKI rates declined from 40% to 27%; proportions of AKI stage 3 and AKI requiring KRT decreased from 44% to 17%. Both geographic and temporal variabilities were predominately explained by percentages of Blacks (31% and 49%, respectively).

Conclusions: AKI is common during hospitalization with COVID-19 and associated with higher risk of health care resource utilization and death. Nearly half of patients with AKI did not recover to baseline by discharge. Substantial geographic variation and temporal decline in rates and severity of AKI were observed.

Podcast: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2020_11_16_CJN09610620_final.mp3.
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http://dx.doi.org/10.2215/CJN.09610620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792643PMC
December 2020

Comparative Effectiveness of SGLT2 Inhibitors, GLP-1 Receptor Agonists, DPP-4 Inhibitors, and Sulfonylureas on Risk of Kidney Outcomes: Emulation of a Target Trial Using Health Care Databases.

Diabetes Care 2020 11 16;43(11):2859-2869. Epub 2020 Sep 16.

Clinical Epidemiology Center, Research and Development Service, VA St. Louis Health Care System, St. Louis, MO

Objective: To examine the comparative effectiveness of sodium-glucose cotransporter 2 inhibitors (SGLT2i), glucagon-like peptide 1 receptor agonists (GLP-1), dipeptidyl peptidase 4 inhibitors (DPP-4), and sulfonylureas on risk of kidney outcomes among people with type 2 diabetes.

Research Design And Methods: U.S. veterans initiated on SGLT2i ( = 18,544), GLP-1 ( = 23,711), DPP-4 ( = 39,399), or sulfonylureas ( = 134,904) were followed for up to 3 years to evaluate the risk of the composite outcome of estimated glomerular filtration rate (eGFR) decline >50%, end-stage kidney disease (ESKD), or all-cause mortality. Risks were estimated using survival models adjusted for predefined covariates as well as covariates identified by a high-dimensional variable selection algorithm through application of generalized propensity scores.

Results: Compared with those treated with sulfonylureas, treatment with SGLT2i, GLP-1, and DPP-4 was associated with a lower risk of the composite outcome (hazard ratio 0.68 [95% CI 0.63, 0.74], 0.72 [0.67, 0.77], and 0.90 [0.86, 0.95], respectively). While we did not observe a statistically significant difference in risk between the SGLT2i and GLP-1 arms (0.95 [0.87, 1.04]), both SGLT2i and GLP-1 had a lower risk of the composite outcome than DPP-4 (0.76 [0.70, 0.82] and 0.79 [0.74, 0.85], respectively). Analyses by eGFR category suggested that compared with the sulfonylurea arm, those in the SGLT2i and GLP-1 arms exhibited a lower risk of the composite outcome in all eGFR categories, including eGFR <45 mL/min/1.73 m. Compared with DPP-4, both SGLT2i and GLP-1 exhibited a reduced risk of the composite outcome in eGFR <90 to ≥60, <60 to ≥45, and <45 mL/min/1.73 m.

Conclusions: In type 2 diabetes, treatment with SGLT2i or GLP-1 compared with DPP-4 or sulfonylureas was associated with a lower risk of adverse kidney outcomes.
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http://dx.doi.org/10.2337/dc20-1890DOI Listing
November 2020

Comparative Effectiveness of the Sodium-Glucose Cotransporter 2 Inhibitor Empagliflozin Versus Other Antihyperglycemics on Risk of Major Adverse Kidney Events.

Diabetes Care 2020 11 10;43(11):2785-2795. Epub 2020 Sep 10.

Clinical Epidemiology Center, Research and Development Service, VA St. Louis Health Care System, St. Louis, MO

Objective: To examine the comparative effectiveness of the sodium-glucose cotransporter 2 inhibitor (SGLT2i) empagliflozin and other non-SGLT2i antihyperglycemics on the risk of major adverse kidney events (MAKE) of estimated glomerular filtration rate (eGFR) decline >50%, end-stage kidney disease, or all-cause mortality.

Research Design And Methods: In a cohort study of 379,033 new users of empagliflozin or other non-SGLT2i antihyperglycemics, predefined variables and covariates identified by a high-dimensional variable selection algorithm were used to build propensity scores. Weighted survival analyses were then applied to estimate the risk of MAKE.

Results: Compared with other antihyperglycemics, empagliflozin use was associated with 0.99 (95% CI 0.51, 1.55) mL/min/1.73 m less annual reduction in eGFR, 0.25 (95% CI 0.16, 0.33) kg/m more annual decrease in BMI, and reduced risk of MAKE (hazard ratio [HR] 0.68 [95% CI 0.64, 0.73]). Empagliflozin use was associated with reduced risk of MAKE in eGFR ≥90, ≥60 to <90, ≥45 to <60, and ≥30 to <45 mL/min/1.73 m (HR 0.70 [95% CI 0.60, 0.82], 0.66 [0.60, 0.73], 0.78 [0.69, 0.89]), and 0.71 [0.55, 0.92], respectively), in participants without albuminuria, with microalbuminuria and macroalbuminuria (HR 0.65 [95% CI 0.57, 0.75], 0.72 [0.66. 0.79], and 0.74 [0.62, 0.88], respectively), and in participants with and without cardiovascular disease (HR 0.67 [95% CI 0.61, 0.74] and 0.76 [0.69, 0.83], respectively). The association was evident in per-protocol analyses, which required continuation of the assigned antihyperglycemic medication (empagliflozin or other antihyperglycemics) during follow-up (HR 0.64 [95% CI 0.60, 0.70]), and in analyses requiring concurrent use of metformin in at least the first 90 days of follow-up (HR 0.63 [0.57-0.69]).

Conclusions: Among people with type 2 diabetes, empagliflozin use was associated with eGFR preservation, a greater decline in BMI, and a reduced risk of MAKE compared with other non-SGLT2i antihyperglycemics.
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http://dx.doi.org/10.2337/dc20-1231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576413PMC
November 2020