Risk Of Gout Research Articles

Effect of diuretic medication and coffee consumption on serum uric acid levels: A review of literature

Various factors like diet, medications, beverages, and congenital conditions have shown to have their effect on uric acid levels. Hyperuricemia (serum uric acid level > 6.8mg/dL) is detrimental to health and is an independent risk factor for all cause cardiovascular mortality and ischemic stroke mortality. It is one of the best independent predictors for chronic diseases like obesity, hypertension and diabetes. Hyperuricemia causes inflammatory arthritis also known as gout. In this review, the authors have focused on the iatrogenic cause of hyperuricemia, particularly diuretic medications. The mechanism of action of these medications and the key interactions at cellular and receptor levels, which are responsible for hyperuricemia, were reviewed. In various studies, coffee consumption have shown to facilitate urate excretion and thus lower the risk of gout. This study has reviewed various studies detailing the lowered risk of gout with coffee consumption and have reviewed the possible mechanisms involved in inverse association between coffee consumption and risk of developing gout.

Association of visceral adipose tissue with gout: Observational and Mendelian randomization analyses.

The causal relationship between visceral adipose tissue (VAT) and gout is still unclear. We aimed to examine the potential association between them using observational and Mendelian randomization (MR) analyses. In the observational analyses, a total of 11,967 participants (aged 39.5 ± 11.5 years) were included from the National Health and Nutrition Examination Survey. Logistic regression models were used to investigate the association between VAT mass and the risk of gout. In two-sample MR analyses, 211 VAT mass-related independent genetic variants (derived from genome-wide association studies in 325,153 UK biobank participants) were used as instrumental variables. The random-effects inverse-variance weighted (IVW) method was used as the primary analysis. Additional sensitivity analyses were also performed to validate our results. Observational analyses found that an increase in VAT mass (per standard deviation) was associated with a higher risk of gout after controlling for confounding factors (odds ratio [OR] = 1.27, 95% confidence intervals [CI] = 1.11-1.45). The two-sample MR analyses demonstrated a causal relationship between increased VAT mass and the risk of gout in primary analyses (OR = 1.78, 95% CI = 1.57-2.03). Sensitivity analyses also showed similar findings, including MR-Egger, weighted median, simple mode, weighted mode, and leave-one-out analyses. Observational analyses showed a robust association of VAT mass with the risk of gout. Meanwhile, MR analyses also provided evidence of a causal relationship between them. In summary, our findings suggested that targeted interventions for VAT mass may be beneficial to prevent gout.

The effect of metformin on urate metabolism: Findings from observational and Mendelian randomization analyses.

To evaluate the effect of metformin on urate metabolism. Using the UK Biobank, we first performed association analyses of metformin use with urate levels, risk of hyperuricaemia and incident gout in patients with diabetes. To explore the causal effect of metformin on urate and gout, we identified genetic variants proxying the glycated haemoglobin (HbA1c)-lowering effect of metformin targets and conducted a two-sample Mendelian randomization (MR) utilizing the urate and gout genetic summary-level data from the CKDGen (n = 288 649) and the FinnGen cohort. We conducted two-step MR to explore the mediation effect of body mass index and systolic blood pressure. We also performed non-linear MR in the UK Biobank (n = 414 055) to show the results across HbA1c levels. In 18 776 patients with type 2 diabetes in UK Biobank, metformin use was associated with decreased urate [β = -4.3 μmol/L, 95% confidence interval (CI) -7.0, -1.7, p = .001] and reduced hyperuricaemia risk (odds ratio = 0.87, 95% CI 0.79, 0.96, p = .004), but not gout. Genetically proxied averaged HbA1c-lowering effects of metformin targets, equivalent to a 0.62% reduction in HbA1c, was associated with reduced urate (β = -12.5 μmol/L, 95% CI -21.4, -4.2, p = .004). Body mass index significantly mediated this association (proportion mediated = 33.0%, p = .002). Non-linear MR results suggest a linear trend of the effect of metformin on urate reduction across various HbA1c levels. The effect of metformin may reduce urate levels but not incident gout in the general population.

Causal Association Between Tea Consumption and Gout: A Mendelian Randomization Study.

Evidence from prospective studies on the consumption of tea and risk of gout is conflicting and limited. We aimed to investigate the potential causal effects of tea intake on gout using Mendelian randomization (MR). Genome-wide association studies in UK Biobank included 349 376 individuals and successfully discovered single-nucleotide polymorphisms linked to consumption of one cup of tea per day. Summary statistics from the Chronic Kidney Disease Genetics consortium included 13 179 cases and 750 634 controls for gout. Two-sample MR analyses were used to evaluate the relationship between tea consumption and gout risk. The inverse-variance weighted (IVW) method was used for primary analysis, and sensitivity analyses were also conducted to validate the potential causal effect. In this study, the genetically predicted increase in tea consumption per cup was associated with a lower risk of gout in the IVW method (OR: 0.90; 95% CI: 0.82-0.98). Similar results were found in weighted median methods (OR: 0.88; 95% CI: 0.78-1.00), while no significant associations were found in MR-Egger (OR: 0.89; 95% CI: 0.71-1.11), weighted mode (OR: 0.80; 95% CI: 0.65-0.99), and simple mode (OR: 1.01; 95% CI: 0.75-1.36). In addition, no evidence of pleiotropy was detected by MR-Egger regression (P=0.95) or MR-PRESSO analysis (P=0.07). This study provides evidence for the daily consumption of an extra cup of tea to reduce the risk of gout.

Association between gout and the risk of osteoporosis and fractures: ameta-analysis.

The relationship between gout and osteoporosis is poorly clarified, and the association between gout and fractures incidence remains controversial. Hence, in the present study, we aimed to comprehensively evaluate the available literature to elucidate whether gout is associated with an increased risk of both osteoporosis and fractures. We conducted an exhaustive search of pertinent literature published until 20March2023, in well-recognized databases, namely Medline, Embase and Cochrane Library, focusing on examining the association between gout and the risk of osteoporosis or fracture. Meta-analysis was performed to aggregate the relative risks (RR) using random- or fixed-effects models. Sensitivity analyses were conducted iteratively, whereby each study was removed sequentially to gauge its impact on the overall outcome. Publication bias was assessed using Egger's and Begg's tests. This study was registered with PROSPERO (registry number: CRD42022376822). Herein, we included 10 observational studies comprising atotal of 1,606,095 participants. An independent population sample of four studies validated the significant association between gout and osteoporosis (RR = 1.25, 95% confidence interval [CI] 1.05-1.48), with the results demonstrating robustness. However, our analysis did not detect any association between gout and fracture risk when compared with the control group (RR = 1.09, 95%CI 0.99-1.19), along with high heterogeneity (pfor heterogeneity = 0.000; I2 = 79.7%). Further subgroup analysis revealed that gout is positively associated with fracture risk in the Chinese population (RR = 1.17, 95%CI 1.14-1.21), with no evidence of heterogeneity (pfor heterogeneity = 0.420; I2 = 0.00%). Our meticulous evaluation of the available literature indicates that gout has no discernible impact on fracture incidence, although it is positively associated with an enhanced risk of osteoporosis. Therefore, it is imperative to prioritize preventive measures to prevent osteoporotic complications in individuals diagnosed with gout.

Risk of gout in Taiwan Biobank participants pertaining to their sex and family history of gout among first-degree relatives.

Family history of gout and sex are independently associated with gout. However, there is a paucity of research regarding the joint role of both factors in gout pathogenesis. Therefore, we assessed the independent and combined association of family history of gout and sex with gout. Our analysis included 132,311 Taiwan Biobank (TWB)-enrolled individuals comprising 21,159 gout cases and 111,152 controls. We subcategorized the family history of gout as (1) both siblings and parents had gout), (2) only parents had gout, and (3) only siblings had gout. Generally, sex (men compared to women) and family history of gout were independently associated with a higher risk of gout. The odds ratio (OR); 95% confidence interval (CI) was 9.175; 8.801-9.566 for sex, and 2.306; 2.206-2.410 for family history. For the subcategories 'both siblings and had gout,' 'only parents had gout,' and 'only siblings had gout,' the odds ratios (ORs); 95% confidence intervals (CIs) were 4.944; 4.414-5.538, 2.041; 1.927-2.161, and 2.162; 2.012-2.323, respectively. The interaction between sex and family history was significant (p value = 0.0001). After stratification by sex, family history of gout remained significantly associated with a higher risk of gout in both sexes, even though the odds ratios were higher in men. For the subcategories 'both siblings and parents had gout,' 'only parent had gout,' and 'only siblings had gout,' the corresponding ORs; 95% CIs were 6.279; 5.243-7.520, 2.211; 2.062-2.371, and 2.148; 1.955-2.361 in men and 4.199; 3.566-4.945, 1.827; 1.640-2.035, and 2.093; 1.876-2.336 in women. After integrating sex and family history (reference: women with no family history), the highest risk of gout was observed in men who had at least one parent and sibling with a history of gout (OR; 95% CI 55.774; 46.360-67.101). Sex and family history of gout were independently and interactively associated with gout. Sex-wise, men had a higher risk of gout than women. Family history was associated with a higher risk of gout in both sexes, but men had a higher risk. Notably, men having both siblings and parents with gout had the highest risk of gout.

Increased prevalence of gout in patients with inflammatory bowel disease: A population-based study.

Arthritis is a recognized extra-intestinal manifestation of inflammatory bowel disease (IBD). Studies show altered uric acid metabolism in IBD. This study aims to investigate the association between IBD and gout. We used a multi-center database (Explorys Inc.) consisting of data from several US healthcare systems. We identified adults diagnosed with Crohn's disease (CD) and ulcerative colitis (UC) between 1999 and 2022. In this cohort, we identified patients diagnosed with gout. We collected demographic data and identified patients diagnosed with IBD-associated arthritis and those who had intestinal resection. Risk factors associated with gout were collected. Multivariate analysis was used. Out of the 69 260 780 patients in the database, we identified 209 020 patients with UC (0.30%) of whom 9130 had gout (4.3%). Additionally, 249 480 had CD (0.36%) of whom 14 000 had gout (5.61%). Males were more prevalent in the UC and gout group than in the CD and gout group (58% vs 51%). After adjustment, CD was significantly associated with gout (odds ratio [OR] 1.68, confidence interval [CI]: 1.60-1.75). UC was also significantly associated with gout (OR 1.38, CI: 1.31-1.44). In subgroup analysis with intestinal resection, CD patients who had intestinal resection had higher association with gout versus those without surgery (OR 2.34, CI: 2.25-2.43). Similar increase was observed in the UC group with intestinal resection (OR 1.53, CI: 1.49-1.56). IBD is strongly associated with gout, with higher correlation observed with CD. Intestinal resection is associated with an increase in the risk of gout. Patients with IBD who present with new-onset arthritis should be investigated for gout.

Gout Flares and Mortality After Sodium-Glucose Cotransporter-2 Inhibitor Treatment for Gout and Type 2 Diabetes

Recurrent flares are the hallmark of clinical manifestation of gout. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been associated with a lower risk of incident gout; however, their association with recurrent flares is unknown. To examine the association of SGLT2i vs active comparators (ie, glucagonlike peptide-1 receptor agonists [GLP-1 RA] or dipeptidyl peptidase-4 inhibitors [DPP-4i]) with the risk of recurrent gout flares and all-cause mortality among patients with gout and type 2 diabetes. This population-based retrospective cohort study was performed from January 1, 2013, to March 31, 2022, using a UK primary care database. Participants included patients with gout and type 2 diabetes with visits to their general practitioners. Initiation of treatment with SGLT2i or active comparators. The primary outcome was the number of recurrent gout flares ascertained using recorded codes and prescription records. Secondary outcomes were the first recurrent gout flare and all-cause mortality. The association of SGLT2i compared with active comparators for the risk of recurrent flares, the first recurrent flare, and all-cause mortality was assessed using Poisson regression or the Cox proportional hazards model with propensity score overlap weighting. Of a total of 5931 patients included in the analysis (mean [SD] age, 66.0 [11.6] years; 4604 [77.6%] men), 1548 initiated SGLT2i treatment and 4383 initiated treatment with active comparators during the study period. The relative rate of the recurrent flares with SGLT2i vs active comparators was 0.79 (95% CI, 0.65-0.97). Similar results were observed in the association of SGLT2i with the rate of recurrent flares when compared with DPP-4i or GLP-1 RA. For the first recurrent flare for SGLT2i vs active comparators, rate difference was -8.8 (95% CI, -17.2 to -0.4) per 1000 person-years and the hazard ratio was 0.81 (95% CI, 0.65-0.98). All-cause mortality per 1000 person-years was 18.8 for SGLT2i and 24.9 for active comparators, with rate difference of -6.1 (95% CI, -10.6 to -1.6) per 1000 person-years and hazard ratio of 0.71 (95% CI, 0.52-0.97). The findings of this cohort study suggest that SGLT2i were associated with a lower risk of recurrent gout flares and mortality than their active comparators in patients with gout and type 2 diabetes. These findings further suggest that SGLT2i could help reduce the burden of recurrent gout flares and could also narrow the mortality gap between patients with gout and the general population.

Associations Between Composite Dietary Antioxidant Index and Gout: National Health and Nutrition Examination Survey 2007-2018.

Introduction: To explore the relationship between the composite dietary antioxidant index (CDAI) and gout to provide support for preventing gout through dietary intervention. Methods: Eligible participants from the 2007 to 2018 National Health and Nutrition Examination Survey aged 20years and older were included in this cross-sectional study. The weighted chi-square test was used to compare the categorical variables difference between CDAI quartiles groups. The weighted univariate and binary logistic regression analysis were used to test the association between variables and gout. The weighted multivariable logistic regression was used to test the association of CDAI and gout in 4 different models. Subgroup analysis on the associations of CDAI with gout was conducted with stratified factors. Results: The final participants were 26,117, 13,103 (50.17%) were female, 8718 (33.38%) were 40-59years, 11,200 (42.88%) were white and 1232 (4.72%) had gout. After adjusting for all covariates, the CDAI was associated with gout (odds ratio (OR), .97; 95% CI: .95-1.00). Participants in the highest CDAI quantile group were at low risk of gout (odds ratio (OR), .65; 95% CI: .50-.84) versus those in the lowest quantile group. Subgroup analysis and interaction test showed no significant dependence on diabetes mellitus (DM), marital status, alcohol status, hypertension, poverty income ratio (PIR), education level, body mass index (BMI), smoke status, age, sex, race, and chronic kidney disease (CKD) on this association (all p for interaction >.05). Conclusions: Composite dietary antioxidant index was inversely associated with gout in US adults, and dietary antioxidant intervention might be a promising method in the therapy of gout and greater emphasis should be placed on zinc, selenium, carotenoids, vitamins A, C, and E.

Increased risk of incident gout in patients with hyperthyroidism: a nationwide retrospective cohort study.

Previous studies have reported that thyroid dysfunction is associated with increased serum uric acid levels; however, the relationship between hyperthyroidism and incidence of clinical manifestations of gout has not been fully investigated. Therefore, this study aimed to longitudinally investigate the risk of gout in patients with hyperthyroidism. This nationwide retrospective cohort study used data from the Korean National Health Claims Database. We included 76,494 patients with hyperthyroidism and 76,542 age- and sex-matched controls. A Cox proportional hazard regression model was used to adjust for potential confounders and estimate the risk of incident gout in patients with hyperthyroidism. During a mean follow-up of 9years, incident gout developed in 3,655 (4.8%) patients with hyperthyroidism and 3251 (4.2%) controls. Hyperthyroidism was significantly associated with increased risk of incident gout [adjusted hazard ratio (HR), 1.12; 95% confidence interval (CI) 1.07-1.18], independent of baseline metabolic profiles. The median time from the diagnosis of hyperthyroidism to the development of gout was 6years. When stratified by age and sex, the risk of gout was still significant in the < 50-year age group (HR: 1.2, 95% CI 1.12-1.29) and males (HR: 1.21, 95% CI 1.12-1.30), but not in the older age group (> 50years) and females. Hyperthyroidism is an important risk factor for incident gout, particularly in younger age groups (< 50years) and males. Our results highlight the importance of continuous screening for gout in patients with hyperthyroidism.

A widely distributed gene cluster compensates for uricase loss in hominids

Approximately 15% of US adults have circulating levels of uric acid above its solubility limit, which is causally linked to the disease gout. In most mammals, uric acid elimination is facilitated by the enzyme uricase. However, human uricase is a pseudogene, having been inactivated early in hominid evolution. Though it has long been known that uric acid is eliminated in the gut, the role of the gut microbiota in hyperuricemia has not been studied. Here, we identify a widely distributed bacterial gene cluster that encodes a pathway for uric acid degradation. Stable isotope tracing demonstrates that gut bacteria metabolize uric acid to xanthine or short chain fatty acids. Ablation of the microbiota in uricase-deficient mice causes severe hyperuricemia, and anaerobe-targeted antibiotics increase the risk of gout in humans. These data reveal a role for the gut microbiota in uric acid excretion and highlight the potential for microbiome-targeted therapeutics in hyperuricemia.

Proton pump inhibitor use associated with an increased risk of gout: A population-based case-control study.

In previous reports, proton pump inhibitor (PPI) use increased the risk of gout. However, there is no epidemiological study investigating this association. We aimed to examine the potential impact of PPI treatment on the risk of developing gout. A population-based case-control study was performed using a Longitudinal Health Insurance Database 2000 from Taiwan (population 23 million). We identified gout cases and non-gout controls through propensity score matching at 1:1, which was matched by sex and age. We used a conditional logistic regression model to estimate an odds ratio and 95% confidence intervals (CI) for gout population versus controls. Esomeprazole increased the risk of gout after adjusting confounding variables (adjusted odds ratio [aOR] 1.3; 95% CI 1.0-1.6). The risk of gout was highest within 30 days of PPI treatment (aOR 1.7; 95% CI 1.4-1.9) and attenuated thereafter. The risk of gout was increased among female users of PPI compared with male users (aOR 2.2; 95% CI 1.7-2.8). The aOR of gout in people with PPI use was higher in middle-aged individuals (41-60 years: aOR 2.1; 95% CI 1.7-2.7) than in the older group (≥60 years: aOR 1.8; 95% CI 1.5-2.2). Our findings provide population-level evidence for the hypothesis that PPI treatment is positively associated with the risk of developing gout. Further research on the mechanism underlying this association is warranted.

Causal association between tea intake and risk for gout: a Mendelian randomization study.

Background: Gout, an increasingly prevalent form of inflammatory arthritis, is caused by the accumulation of uric acid crystals in joints, resulting in severe pain, swelling and stiffness that adversely affect physical, mental and emotional wellbeing. The management of gout requires a combination of medication and lifestyle modifications. Recent studies suggest that tea intake may reduce the risk of developing gout; however, further research is needed to establish a causal relationship. Methods: In this study, we employed a bidirectional two-sample Mendelian randomization (MR) approach, utilizing genome-wide association study (GWAS) summary statistics, to investigate the causal association between increased tea intake and gout. We meticulously selected instrumental variables (IVs) based on rigorous criteria and employed five different MR methods. Heterogeneity was assessed using Cochran's Q statistic, and pleiotropy was evaluated using the MR Egger intercept and MR-PRESSO tests. Weak IVs were identified using F values. The Phenoscanner database was consulted to exclude single nucleotide polymorphisms associated with confounding factors or outcomes. Results: The study included one dataset related to tea intake (ukb-b-6066) and three datasets related to gout (ukb-b-12765, finn-b-M13_GOUT, and finn-b-GOUT_STRICT). Our forward MR analysis suggest a causal relationship between increased tea intake and reduced risk of gout in all three gout-related datasets [OR (95% CI): 0.9966 (0.9938-0.9993), p = 0.0167; 0.4842 (0.2683-0.8737), p-value = 0.0160; and 0.4554 (0.2155-0.9623), p = 0.0393, respectively]. The reveres MR showed increased risk of gout (ukb-b-12765) was significantly associated with low tea intake according to the IVW analysis [OR (95% CI): 0.0062 (0.0002-0.154), p = 0.0020]. However, this association was not observed in the Finn-b-M13_GOUT and Finn-b-GOUT_STRICT [OR (95% CI): 0.9992 (0.9909-1.0075), p = 0.8453 and OR (95% CI): 0.9996 (0.9932-1.0059), p = 0.8896, respectively]. No significant heterogeneity or potential pleiotropy was detected, and the possibility of weak IVs was also excluded. Conclusion: Our MR analysis suggest a causal relationship between genetically predicted tea intake and a decreased risk of gout. These findings underscore the potential advantages of increasing tea intake for preventing gout. However, further research is needed to validate these results and elucidate the underlying mechanisms.

Prediagnostic Glycoprotein Acetyl Levels and Incident and Recurrent Flare Risk Accounting for Serum Urate Levels: A Population-Based, Prospective Study and Mendelian Randomization Analysis.

To prospectively investigate population-based metabolomics for incident gout and reproduce the findings for recurrent flares, accounting for serum urate. We conducted a prediagnostic metabolome-wide analysis among 105,615 UK Biobank participants with nuclear magnetic resonance metabolomic profiling data (168 total metabolites) from baseline blood samples collected 2006-2010 in those without history of gout. We calculated hazard ratios (HRs) for incident gout, adjusted for gout risk factors, excluding and including serum urate levels, overall and according to fasting duration before sample collection. Potential causal effects were tested with 2-sample Mendelian randomization. Poisson regression was used to calculate rate ratios (RRs) for the association with recurrent flares among incident gout cases. Correcting for multiple testing, 88 metabolites were associated with risk of incident gout (N=1,303 cases) before serum urate adjustment, including glutamine and glycine (inversely), and lipids, branched-chain amino acids, and most prominently, glycoprotein acetyls (GlycA; P = 9.17 × 10-32 ). Only GlycA remained associated with incident gout following urate adjustment (HR 1.52 [95% confidence interval (95% CI) 1.22-1.88] between extreme quintiles); the HR increased progressively with fasting duration before sample collection, reaching 4.01 (95% CI 1.36-11.82) for ≥8 hours of fasting. Corresponding HRs per SD change in GlycA levels were 1.10 (95% CI 1.04-1.17) overall and 1.54 (95% CI 1.21-1.96) for ≥8 hours of fasting. GlycA levels were also associated with recurrent gout flares among incident gout cases (RR 1.90 [95% CI 1.27-2.85] between extreme quintiles) with larger associations with fasting. Mendelian randomization corroborated a potential causal role for GlycA on gout risk. This prospective, population-based study implicates GlycA, a stable long-term biomarker reflecting neutrophil overactivity, in incident and recurrent gout flares (central manifestation from neutrophilic synovitis) beyond serum urate.

Insulin use and gout risk among patients with type 2 diabetes mellitus: a real-world cohort study in Shanghai, China.

The effect of insulin use on gout risk remains unknown. This study aimed to investigate the association between insulin use and gout risk among patients with type 2 diabetes mellitus (T2DM). Based on the Shanghai Link Healthcare Database, patients with newly diagnosed T2DM, with or without insulin exposure, were identified from January 1, 2014 to December 31, 2020, and followed until December 31, 2021. Apart from the original cohort, we also established a 1:2 propensity score-matched cohort. A time-dependent Cox proportional hazards model was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for gout incidence associated with insulin exposure. A total of 414,258 patients with T2DM, including 142,505 insulin users and 271,753 insulin non-users, were enrolled in this study. After a median follow-up of 4.08years (interquartile range, 2.46-5.90years), the incidence of gout was significantly higher in insulin users than in insulin non-users (319.35 versus 302.20 cases per 100,000 person-years; HR 1.09, 95% CI 1.03-1.16). The results were robust in propensity score-matched cohort, sensitivity analyses, and stratified analysis of aspirin. In other stratified analyses, the association between insulin use and increased gout risk was found only in patients who were female, or aged 40-69years, or without hypertension, dyslipidemia, ischemic heart disease, chronic lung disease, kidney disease, or not using diuretic. Insulin use is associated with a significantly increased risk of gout among patients with T2DM. Key Points • The first real-world study to investigate the effect of insulin use on gout risk. • Insulin use is associated with a significantly increased risk of gout among patients with type 2 diabetes mellitus.

870-P: Empagliflozin and the Risk of Gout—Analysis from the Empagliflozin Comparative Effectiveness and Safety (EMPRISE) Study

Hyperuricemia is frequently observed in patients with type 2 diabetes (T2D) and is associated with increased risk of gout. Empagliflozin lowers serum urate levels by enhancing its urinary excretion. Using claims data from 2 commercial insurance datasets and Medicare (2014-2019), we evaluated the association between treatment with empagliflozin and the risk of incident gout in routine clinical practice. After excluding patients with a history of gout or gout medications, we identified 102,262 pairs of 1:1 propensity score-matched adults with T2D initiating empagliflozin or a DPP4 inhibitor (DPP4i) (Cohort 1), and 131,216 pairs initiating empagliflozin or a GLP-1 receptor agonist (GLP-1RA) (Cohort 2). We estimated pooled HR and RD/1,000 PY with their 95% CI adjusting for 141 baseline covariates and conducted stratified analyses within multiple subgroups (Table). Over a mean follow-up of ~8 months on treatment, the risk of gout was lower in patients initiating empagliflozin compared with patients initiating DPP4i [HR, 0.69 (0.60, 0.79); RD -2.27 (-3.08, -1.46)] or GLP-1RA [HR 0.83 (0.73, 0.94); RD -0.99 (-1.66, -0.32)]. Results were consistent within sex, age, BMI, HF, CKD subgroups and among users of diuretics (Table). In clinical practice, the initiation of empagliflozin was associated with a lower risk of incident gout compared with the initiation of DPP4i or GLP-1RA. Disclosure H.Tesfaye: None. J.M.Paik: None. L.Zabotka: None. P.T.Htoo: Employee; Johnson &amp; Johnson. N.Schmedt: Employee; Boehringer Ingelheim International GmbH. L.Koeneman: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. L.J.Seman: Employee; Boehringer Ingelheim Pharmaceuticals Inc. D.J.Wexler: Other Relationship; Novo Nordisk A/S. E.Patorno: Research Support; Boehringer Ingelheim Inc., National Institutes of Health, Patient-Centered Outcomes Research Institute, US Food and Drug Administration.

Serum uric acid lowering and effects of sodium-glucose cotransporter-2 inhibitors on gout: A meta-analysis and meta-regression of randomized controlled trials.

To pool the effects of sodium-glucose cotransporter-2 (SGLT2) inhibitors on gout and to investigate the association of these effects with baseline serum uric acid (SUA), SUA lowering, and underlying conditions, such as type 2 diabetes mellitus (T2DM)/heart failure (HF). PubMed, Embase, Web of Science, Cochrane Library and clinical trial registry websites were searched for randomized controlled trials (RCTs) or post hoc analyses (≥1-year duration; PROSPERO:CRD42023418525). The primary outcome was a composite of gouty arthritis/gout flares and commencement of anti-gout drugs (SUA-lowering drugs/colchicine). Hazard ratios (HRs) with 95% confidence interval (CI) were pooled using a generic inverse-variance method with a random-effects model. Mixed-effects model univariate meta-regression analysis was performed. Five RCTs involving 29 776 patients (T2DM, n = 23 780) and 1052 gout-related events were identified. Compared to placebo, SGLT2 inhibitor use was significantly associated with reduced risk of composite gout outcomes (HR 0.55, 95% CI 0.45-0.67; I2 = 61%, P < 0.001). Treatment benefits did not differ between trials being conducted exclusively in baseline HF versus those conducted in patients with T2DM (P-interaction = 0.37), but were greater with dapagliflozin 10 mg and canagliflozin 100/300 mg (P < 0.01 for subgroup differences). Sensitivity analysis excluding trials that evaluated the effects of empagliflozin 10/25 mg (HR 0.68, 95% CI 0.57-0.81; I2 = 0%) accentuated the benefits of SGLT2 inhibitors with no between-trial heterogeneity (HR 0.46, 95% CI 0.39-0.55; I2 = 0%). Univariate meta-regression found no impact of baseline SUA, SUA lowering on follow-up, diuretic use, or other variables on their anti-gout effects. We found that SGLT2 inhibitors significantly reduced the risk of gout in individuals with T2DM/HF. Lack of an association with SUA-lowering effects suggests that metabolic and anti-inflammatory effects of SGLT2 inhibitors may predominantly mediate their anti-gout benefits.

Sodium glucose cotransporter 2 inhibitors and gout risk: a sequence symmetry analysis.

To examine the association between sodium-glucose cotransporter 2 inhibitors (SGLT2-I) and gout incidence in patients with diabetes is the objective. National administrative data from the United States Veterans Health Administration were used to identify patients initiated on SGLT2-I from 2012 to 2020. Sequence symmetry analysis was performed to contrast the number of patients with incident gout within the year following SGLT2-I initiation to the number within the year preceding initiation. Exposure counterfactual analyses examined the relationship between potential therapeutic alternatives to SGLT2-I and risk for gout. The primary outcome of incident gout was observed in 441 patients preceding SGLT2-I initiation and 273 patients following SGTL2-I (symmetry ratio (SR) = 0.62; 95% CI: 0.53-0.72). This finding remained consistent across multiple sensitivity analyses. A reduction in gout incidence was also observed in exposure counterfactual cohorts initiating dipeptidyl peptidase-4 inhibitor (SR = 0.67; 95% CI: 0.63-0.72) and thiazolidinediones (SR = 0.72; 95% CI: 0.65-0.79), but not glucagon-like peptide-1 receptor agonist (GLP1-RA) (SR = 0.93; 95% CI: 0.77-1.12). The risk for incident gout was significantly reduced following SGLT2-I initiation. GLP1-RA had minimal to no impact on gout risk. Our findings support pleiotropic benefits of SGLT2-I use in patients with diabetes at elevated risk for gout. Key points • Early studies suggest SGLT2-inhibitors maydecrease risk for gout • Our sequence symmetry analysis confirmed this observation • DPP4s and thiazolidinediones were also associated with lower gout risk • SLGT2 inhibitors may be beneficial in patients with diabetesat risk for gout.

THE ASSOCIATION BETWEEN ANTIHYPERTENSIVE TREATMENT AND SERIOUS ADVERSE EVENTS BY PREVIOUS HISTORY OF ADVERSE EVENTS: AN OBSERVATIONAL COHORT STUDY

Objective: Antihypertensives are effective at reducing the risk of cardiovascular disease, but are also associated with an increased risk of serious adverse events (SAEs), particularly in older people. Since these patients may also be at increased risk of cardiovascular disease, guidelines recommend deprescribing medications only in those with a previous history of adverse events. This study examined whether the association between antihypertensive treatment and adverse events is greater in this population. Design and method: This was an observational cohort study, using data from the Clinical Practice Research Datalink in England (Aurum and Gold databases combined). Patients were eligible if they were aged 40 years or older, with a systolic blood pressure reading between 130-179 mmHg and not previously prescribed antihypertensive treatment. Outcomes were defined as hospitalisation or death within 10 years due to hypotension, syncope, falls, fractures, acute kidney injury (AKI), electrolyte abnormalities and primary care consultations for gout. The association between treatment and SAEs was examined by Cox regression, using propensity score adjustment, sub-grouped by whether or not individuals had a history of adverse events. Results: A total of 3,834,056 patients, aged 57±12 years, were eligible for the study. Of these, 484,187 (12.6%) were prescribed antihypertensive medication in the 12 months prior to the index date. A total of 902,100 patients (23.5%) had a history of previous adverse events. Over 7.1 years, antihypertensives were associated with an increased risk of hypotension, syncope, falls, AKI, electrolyte abnormalities and gout but not fractures. For those with no history of adverse events, the absolute risk of SAEs with treatment small, ranging from 6 (falls) to 16 (AKI) events per 10,000 patients treated per year. However, in those with a previous history of these adverse events, the risk was notably higher, ranging from 19 (falls) to 80 (AKI) events per 10,000 patients treated per year. Conclusions: Antihypertensive treatment is associated with an increased risk of SAEs particularly in those with a history of serious adverse events. Clinical guidelines should continue to recommend that patients with a history of serious adverse events are recommended as candidates for deprescribing interventions.

The Clinical Efficacy and Safety of Bempedoic Acid in Patients at Elevated Risk of Cardiovascular Disease: A Meta-Analysis of Randomized Clinical Trials.

Statins are first-line agents to reduce low-density lipoprotein cholesterol (LDL-C) and cardiovascular risk, however, they are insufficient and/or intolerable in many patients. To that end, we conducted a meta-analysis of Bempedoic Acid (BA), a novel LDL-C lowering agent. We retrieved randomized clinical trials (RCTs) of BA by searching Pubmed, the Cochrane Central Register of Controlled Trials, and Clinicaltrials.gov. We used the Mantel-Haenszel method to pool estimates. The I2 measure was used to quantify heterogeneity. Treatment effects are provided as relative risks (RR), absolute risk differences (ARD), and number needed to treat/harm (NNTB/H). Analyses were conducted using R, version 4.1.2. 11 trials enrolling 18,496 patients were included. Compared to placebo, BA reduced the risk of major adverse cardiovascular events (RR: 0.87; 95% CI: 0.80 to 0.95; ARD: -1.63%; NNT: 62), myocardial infarction (RR: 0.76; 95% CI: 0.66 to 0.89; ARD: -1.03%; NNT: 98), unstable angina hospitalization (RR: 0.70; 95%: CI: 0.55 to 0.89; ARD: -0.57%; NNT: 177), revascularization (RR: 0.81; 95% CI: 0.72 to 0.91; ARD: -1.31%; NNT: 77), and myalgia (RR: 0.85; 95% CI: 0.75 to 0.95; ARD: -0.99%; NNT: 102). BA significantly increased the risk of gout (RR: 1.56; 95% CI: 1.27 to 1.91; ARD: 0.99%; NNH: 101), renal impairment (RR: 1.35; 95% CI: 1.22 to 1.49; ARD: 2.54%; NNH: 40), and cholelithiasis (RR: 1.87; 95% CI: 1.43 to 2.44; ARD: 1.01%; NNH: 100). BA effectively reduces the risk of cardiovascular events and myalgia but increases the risk of gout, cholelithiasis, and renal impairment.