Elevated Serum Uric Acid Research Articles

Attenuation of inflammation, oxidative stress and TGF-β1/Smad3 signaling and upregulation of Nrf2/HO-1 signaling mediate the protective effect of diallyl disulfide against cadmium nephrotoxicity

Heavy metals are toxic environmental pollutants with serious health effects on humans and animals. Cadmium (Cd) is known for its serious nephrotoxic effect and its toxicity involves oxidative stress (OS) and inflammation. Diallyl disulfide (DADS), a main constituent of garlic, exhibited cytoprotective and antioxidant activities. This study investigated the effect of DADS on OS, inflammation, and fibrosis induced by Cd in rat kidney, pointing to the involvement of transforming growth factor-β (TGF-β)/Smad3 and nuclear factor erythroid 2–related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling, and peroxisome proliferator-activated receptor gamma (PPARγ). Rats received DADS for 14 days and Cd on day 7 and blood and kidney samples were collected. Cd elevated serum creatinine, urea and uric acid, provoked kidney histopathological alterations and collagen deposition, increased kidney malondialdehyde (MDA) level, and decreased glutathione (GSH) and antioxidant enzymes. Nuclear factor-kappaB (NF-κB) p65, interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-1β, and CD68 were upregulated in Cd-administered rat kidney. DADS prevented kidney injury, mitigated OS, suppressed NF-κB, CD68 and pro-inflammatory mediators, and boosted antioxidants. DADS downregulated TGF-β1, Smad3 phosphorylation and Kelch-like ECH-associated protein-1 (Keap1), and increased Nrf2, HO-1, cytoglobin, and PPARγ. In conclusion, DADS protects the kidney against Cd toxicity by attenuating OS, inflammation, and TGF-β1/Smad3 signaling, and enhancement of Nrf2/HO-1 signaling, antioxidants, and PPARγ.

Inverse association between uric acid levels and muscle quality index in adults: a cross-sectional analysis of NHANES 2011-2014.

The objective of this study was to delineate the association between serum uric acid (UA) levels and Muscle Quality Index (MQI), assessing muscle strength relative to mass, in adults aged 20 to 59 years. Utilizing data from the National Health and Nutrition Examination Survey (NHANES) 2011-2014, this study examined the association between UA levels and MQI-a ratio of muscle strength to mass. Weighted linear models, adjusted for potential confounders, assessed the relationship, with a generalized additive model (GAM) probing for non-linear patterns. Subgroup analyses and interaction effects were conducted using weighted linear regression across diverse demographic and clinical groups to ensure the robustness and reliability of our findings. Among 5,277 participants, a significant inverse association was observed between UA levels and MQI, with a 0.08 decrease in MQI per 1mg/dL increase in UA (95% CI: -0.11 to -0.06, p < 0.001). The negative trend was dose-dependent across UA quartiles, which was most pronounced in the highest quartile (Q4: -0.28, 95% CI: -0.36 to -0.19, p < 0.001). Curve-fitting analysis revealed a consistent inverse relationship without evidence of non-linearity. Stratified analyses reinforced the core findings across all examined subgroups, highlighting the universal relevance of the observed association. Our findings demonstrate a significant inverse association between elevated serum UA levels and MQI, highlighting the potential importance of uric acid management in enhancing muscle quality among young and middle-aged adults. The consistency of this relationship across different subgroups underscores the need for targeted strategies and interventions to manage UA levels. Future research should explore longitudinal impacts and intervention outcomes to further elucidate the potential benefits of uric acid management on muscle health.

Effects of bariatric surgery on hyperuricemia and gout: a systematic review of the literature.

Gout is the most common form of inflammatory arthritis, and it is due to the deposition of monosodium urate crystals in the articular and extra-articular tissues. Body mass index is strongly correlated with elevated serum uric acid levels and gout is often associated with obesity and metabolic syndrome. Recommended nonpharmacological treatments for hyperuricemia and gout include dietary modifications and weight loss. Many studies have demonstrated that weight loss could reduce serum urate in patients with obesity and it is a commonly recommended treatment for gout. Bariatric surgery-induced weight loss exerts beneficial effects on hyperuricemia and gout, even if a possible raise of gout flares can be observed in patients with hyperuricemia early after surgery. The aim of this review is to systematically analyze all the studies published so far reporting a link between hyperuricemia and/or gout and bariatric surgery to obtain reliable figures on the incidence of this disease and describe the mechanisms underlying this association. Eleven studies accounting for 11,256 patients were included in the review. Mean preoperative prevalence of gout was 4.1%, while the preoperative prevalence of hyperuricemia ranged from 30.6% to 58%. After a mean follow-up of 8.5months, postoperative prevalence of gout significantly decreased to 2.9% (p < .007). The incidence of gout flares after bariatric surgery was higher in the early postoperative phase and progressively decreased over time. Similarly, serum uric acid concentrations showed an increase within the first postoperative month, which was followed by a progressive decrease below the preoperative value.

Hyperuricemia and epiretinal pathologies: a review of pathophysiological links and clinical implications

Hyperuricemia (HUA), defined by elevated serum uric acid levels, is well-established in its association with systemic conditions like gout and cardiovascular diseases. Recently, however, emerging research has revealed a potential connection between HUA and ocular disorders, particularly epiretinal pathologies. This review investigates the pathophysiological mechanisms linking HUA to epiretinal conditions, including epiretinal membrane formation, macular edema, and retinal vascular diseases. By thoroughly analyzing current literature, this review seeks to deepen the understanding of the relationship between HUA and epiretinal disorders, with the aim of informing new therapeutic strategies and enhancing patient outcomes.

Association between change in serum uric acid and rapid decline in kidney function in China

While the elevation of serum uric acid (SUA) is acknowledged as a risk factor for chronic kidney disease, the independent extent to which variations in SUA levels are correlated with temporal changes in estimated glomerular filtration rate (eGFR) remains uncertain. In light of this uncertainty, our research endeavored to elucidate the temporal associations between change in SUA and rapid eGFR decline in China. In this longitudinal study of China’s middle-aged and elderly between 2011 and 2015, we analyzed 5421 individuals with complete SUA and eGFR data. Logistic regression was applied to evaluate the risk factors associated with a rapid eGFR decline (defined by a 5 mL/min/1.73 m2 decrease or falling to less than 15 mL/min/1.73 m2 by 2015), adjusted for age, gender, marital, residence, income, BMI, hypertension, diabetes, dyslipidemia, CRP, Hba1c, baseline eGFR and baseline SUA. Linear regression was used to evaluate the relationship between variations in SUA and changes in eGFR. After multivariable adjustments, the risk factors of a rapid eGFR decline included aging (OR per 1-year increase: 1.1, 95% CI 1.08–1.12, P < 0.001), being female, being single, having hypertension, a higher baseline eGFR, a higher baseline SUA (OR per-1 mg/dL increase: 1.68, 95% CI 1.48–1.90, P < 0.001), and increase in change in SUA (OR per-1 mg/ dL increase: 1.92,95% CI 1.71–2.16, P < 0.001). Pearson’s analysis showed a significant inverse correlation between SUA changes and eGFR decline, particularly pronounced in females, with correlation coefficients of − 0.349 for females and − 0.306 for males (95% CI − 0.347 to − 0.299, P < 0.001). A significant correlation was found between the change in SUA and the rapid decline in eGFR, with this association being particularly pronounced in females.

Associations between elevated uric acid and brain imaging abnormalities in pediatric patients with methylmalonic acidemia under 5 years of age

Methylmalonic acidemia (MMA) is the most common inborn organic acidemia, presenting multisystemic complications. Uric acid may have neurotoxic or neuroprotective effects due to its antioxidant or pro-inflammatory properties; however, its role in MMA brain injury remains unclear. We examined the correlation between the serum uric acid levels and brain imaging features of MMA. Data were collected from a cross-sectional study of 216 patients with MMA and 216 healthy matched controls aged 0–5 years in China. Serum uric acid levels were measured, and magnetic resonance imaging and computed tomography findings were retrieved from hospital records. Overall, 74.1% patients had brain abnormalities. Patients in the MMA group with abnormal brain imaging had higher serum uric acid levels than those in the MMA normal brain imaging and control groups. The area under the curve of serum uric acid was 0.74, 0.91, and 0.93 for MMA diagnosis with abnormal brain images, basal ganglia changes, and globus pallidus changes, respectively. Higher serum uric acid levels were independently associated with abnormal brain images. Children aged < 5 years with abnormal brain images in MMA exhibit elevated serum uric acid levels, serving as an effective auxiliary diagnostic indicator and independent risk factor for brain tissue injury.

A comparative study of postadrenalectomy hyperuricemia and renal impairment in patients with unilateral primary aldosteronism: does histopathology subtype matter?

BackgroundPrimary aldosteronism (PA), which is present in 5–18% of hypertensive patients, is a leading cause of secondary hypertension. Adrenalectomy is often recommended for patients with unilateral primary aldosteronism (uPA), yielding good long-term outcomes. PA patients without hyperuricemia and chronic renal failure before adrenalectomy were enrolled in this cohort study. Serum uric acid (SUA) and renal filtration were measured one year post-adrenalectomy. Their relationships with pathologic features, histopathological subtype (classical or nonclassical (HISTALDO consensus)), and vessel stiffness were explored. The aim of this cohort study is to evaluate the correlation between post-adrenalectomy serum uric acid (SUA) levels and estimated glomerular filtration rate (eGFR) with the pathologic features delineated by the HISTALDO consensus. Additionally, the study seeks to assess the impact of these biochemical markers on peripheral vessel stiffness and brachial-ankle pulse wave velocity (baPWV) at a one-year follow-up visit.MethodsThis prospective cohort study included patients (N = 100) diagnosed with uPA who underwent adrenalectomy from Jan 1, 2007 to Dec 31, 2022.ResultsAt follow-up, elevated SUA, hyperuricemia, and a > 25% eGFR decrease were significantly more common in the classical than the nonclassical group. The incidence of postoperative hyperuricemia, herein referred to as post-adrenalectomy hyperuricemia (PAHU), was 29% (29/100) overall, 34.8% (23/66) in the classical group and 17.6% (6/34) in the nonclassical group. The incidence of eGFR reduction > 25% was 33% (33/100), 43.9% (29/66), and 11.8% (4/34), respectively. baPWV decreased more in the classical group than the nonclassical group.ConclusionFor PA patients with PAHU and/or renal impairment, we suggest monitoring SUA, pH, urine uric acid, and urine crystals and performing a KUB study and peripheral vascular and renal sonography (on which pure uric acid stones in the KUB are radiolucent) to determine whether drug intervention is required for cases of asymptomatic PAHU, especially patients in male gender, classical histopathology, or renal impairment.

Development and validation of an image-based questionnaire ARTROVIS to identify risk factors for the articular syndrome and related conditions

Background: The importance of timely diagnosis of rheumatic diseases is beyond any doubt. However, in the real practice the time from manifestation of the first symptoms to the assessment by a rheumatologist and treatment administration often exceeds the window of opportunity for disease control. At the moment, there has been no Russian-language questionnaire that would allow a primary care physician to suspect a rheumatic disease manifesting with an articular syndrome. Aim: To develop, validate and test a questionnaire to identify risk factors for joint disorders and related conditions. Methods: From November 2022 to April 2024, we performed the study on the image-based questionnaire on identification of the risk factors for joint syndromes and associated conditions (ARTROVIS), which we have developed for early detection of both joint syndromes, as well as comorbid conditions associated with elevated serum uric acid levels (hyperuricemia). The initial test version of the questionnaire was tested in a focus group of respondents (n = 20) who came for regular medical examination. Based on the results of this face validity assessment, we corrected the wording of 10 questionnaire items. At the second study step, we assessed the primary validity and reliability of the questionnaire in a group of 41 rheumatology patients. The third study step involved 828 respondents (408 men and 420 women, median age 19 [18,0; 20,0] years; 21% with joint syndromes), who came for routine medical examination. The reliability of the questionnaire, its face and discriminant validity, as well as sensitivity and specificity (the ROC analysis) were assessed from 827 questionnaires included in the final processing (one was excluded due to questionnaire completion defects). Results: The self-report questionnaire for patients (ARTROVIS) has 24 items aimed at collecting social and demographic data, identifying risk factors for non-communicable diseases, assessing genetic aspects, identifying complaints from various organ systems, providing information on medical treatments taken by the patient (non-steroid anti-inflammatory agents, diuretics, antihypertensives, glucocorticosteroids, chemotherapy and radiation therapy), as well as an additional question for women on current pregnancy pathology. The questionnaire contains visual aids (colored photos) that facilitate the detection of clinical signs of autoimmune (psoriatic arthritis, Reynolds’s syndrome) and inflammatory rheumatic disease (gout), as well as the differential diagnosis of the joint syndrome. The assessment of face validity of the questionnaire showed the total number of missed answers of 3.42%; 62.85% of the respondents gave their full answers to all items. Good discriminant validity was demonstrated. The ROC analysis showed high correlation between the questionnaire score and the presence of a joint syndrome: the area under the curve was 0.884. The Cronbach’s alfa was 0.798, which is sufficient for a medical questionnaire. Conclusion: We have performed the approbation and standardization of the questionnaire to identify risk factors for the joint syndrome and related comorbidities by assessing its validity and reliability. The ARTROVIS as a self-report questionnaire can be used in primary care as a tool enabling general practitioners and internists to decide on further patient routing to corresponding specialists.

High Post-Kidney Transplant Serum Uric Acid Levels Are Associated with Detrimental Outcomes.

The potential effects of post-transplant serum uric acid (SUA) levels and outcomes pose a variety of risks among kidney transplant (KTR) recipients. The association between post-transplant SUA and major detrimental outcomes among KTRs remains uncertain. We evaluated all adult kidney transplant recipients (KTRs) transplanted between 1/1/2000 and 12/31/2019. Recipients were included if they had a functioning allograft without any cardiovascular events (CVE) before their earliest SUA measurement within 5-13 months post-transplant.Survival analyses were performed regarding CVEs, CVE-related mortality, death-censored graft failure (DCGF), and uncensored graft failure, within 10 years after transplantation. A total of 3808 eligible KTRs were followed for a median of 7.5 years after transplantation. Recipients with post-transplant SUA > 6.8 mg/dl had significantly higher risk of congestive heart failure (CHF) than those with SUA <6 mg/dl (adjusted hazard ratio [aHR] = 1.55, 95% CI: 1.10-2.19; p = 0.01); uncensored graft failure (aHR = 1.18, 95% CI: 1.02-1.36; p = 0.03), and DCGF (aHR = 1.28, 95% CI: 1.01-1.61; p = 0.04), after adjustment for multiple variables, including kidney graft function. No statistically significant association was found between SUA levels and other CVEs. There was no statistically significant risk for other outcomes of interest when comparing SUA < 6 mg/dl versus 6-6.8 mg/dl. Elevated early post-transplant SUA levels were associated with detrimental post-transplant outcomes, leading to increased morbidity and mortality through CHF, graft failure, and overall death.

Association of uric acid and fructose levels in polycystic ovary syndrome.

Is there a relationship between serum uric acid and fructose levels in polycystic ovary syndrome (PCOS)? Elevated serum uric acid levels in women with PCOS positively correlate with serum fructose levels, and elevated serum fructose levels are an independent risk factor for hyperuricemia in women with PCOS. Our previous study suggested a link between elevated serum fructose levels and PCOS. Fructose is unique as it generates uric acid during metabolism, and high uric acid levels are associated with metabolic disorders and an increased risk of anovulation. However, the relationship between serum uric acid and fructose levels in women with PCOS remains unclear. In a case-control study of 774 women (482 controls and 292 patients with PCOS) between May and October 2020 at the Shengjing Hospital of China Medical University, the relationship between uric acid and fructose levels in women with PCOS was examined. Participants were divided into subgroups based on various factors, including BMI, insulin resistance, dyslipidemia, metabolic syndrome, and hyperuricemia. Serum uric acid concentrations were measured using enzymatic assays, and serum fructose levels were determined using a fluorescent enzyme immunoassay. Dietary fructose data were collected through a validated food-frequency questionnaire of 81 food items. We applied restricted cubic splines to a flexibly model and visualized the linear/nonlinear relationships between serum uric acid and fructose levels in PCOS. Multivariate logistic analysis was executed to assess the association between serum fructose levels and hyperuricemia in PCOS. Human granulosa cell and oocyte mRNA profile sequencing data were downloaded for mapping uric acid and fructose metabolism genes in PCOS. Further downstream analyses, including Gene Ontology, Kyoto Encyclopedia of Genes and Genomes analysis, and protein-protein interactions were then carried out on the differentially expressed genes (DEGs). The correlation between uric acid and fructose metabolism genes was calculated using the Pearson correlation coefficient. The GeneCards database was used to identify DEGs related to uric acid and fructose metabolism in PCOS, and then several DEGs were confirmed by quantitative real-time PCR. Both serum fructose and uric acid levels were significantly increased in women with PCOS compared with the control women (P < 0.001), and there was no statistically significant difference in dietary fructose intake between PCOS and controls, regardless of metabolic status. There was a positive linear correlation between serum uric acid and fructose levels in women with PCOS (Poverall < 0.001, Pnon-linear = 0.30). In contrast, no correlation was found in control women (Poverall = 0.712, Pnon-linear = 0.43). Additionally, a non-linear association was observed in the obese subgroup of patients with PCOS (Poverall < 0.001, Pnon-linear = 0.02). Serum uric acid levels were linearly and positively associated with serum fructose levels in patients with PCOS with insulin resistance, dyslipidemia, and metabolic syndrome. Furthermore, even after adjusting for confounding factors, elevated serum fructose levels were an independent risk factor for hyperuricemia in patients with PCOS (P = 0.001; OR, 1.380; 95% CI, 1.207-1.577). There were 28 uric acid and 25 fructose metabolism genes which showed a significant correlation in PCOS. Seven upregulated genes (CAT, CRP, CCL2, TNF, MMP9, GCG, and APOB) related to uric acid and fructose metabolism in PCOS ovarian granulosa cells were ultimately successfully validated using quantitative real-time PCR. Due to limited conditions, more possible covariates (such as smoking and ethnicity) were not included, and the underlying molecular mechanism between fructose and uric acid levels in women with PCOS remains to be further investigated. The results of this study and our previous research indicate that the high uric acid status of PCOS may be mediated by fructose metabolism disorders, highlighting the importance of analyzing fructose metabolism, and especially its metabolic byproduct uric acid, during the clinical diagnosis of PCOS. These results suggest the adverse effects of high uric acid in PCOS, and the importance of taking early interventions regarding uric acid levels to reduce the occurrence and development of further clinical signs, such as metabolic disorders in women with PCOS. This work was supported by: the National Natural Science Foundation of China (No. 82371647, No. 82071607, and No. 32100691); LiaoNing Revitalization Talents Program (No. XLYC1907071); Fok Ying Tung Education Foundation (No. 151039); and Outstanding Scientific Fund of Shengjing Hospital (No. 202003). No competing interests were declared. N/A.

7190 Serum uric acid and serum uric acid-to-creatinine ratio and its association with metabolic syndrome in Korean adolescents: the nation-wide population-based study

Abstract Disclosure: S. Jung: None. J. Kim: None. S. Kim: None. Backgrounds: As the prevalence of obesity and metabolic syndrome (MetS) among the pediatric population continues to rise, it is crucial to identify the factors associated with cardiometabolic risk factors (CMRFs) to prevent the future development of diabetes and cardiovascular disease. Elevated serum uric acid (SUA) and SUA-to-creatine ratio (SUA/Cr) levels are associated with MetS, CMRFs, and non-alcoholic fatty liver disease (NAFLD) in adults. However, studies on the usefulness of SUA or SUA/Cr to predict MetS in adolescents were sparse. The aim of this study is to investigate the association between SUA or SUA/Cr level and MetS and CMRFs among Korean adolescents. Material/Methods: Data collected from the Korea National Health and Nutrition Examination Survey between 2016 and 2021, which was nationally representative cross-sectional data, were used. A total of 2,218 subjects (1,185 males, 54.0%) aged 13-18 years were included in this study. They were classified into tertiles of SUA or SUA/Cr levels (T1, lower tertile; T2, mid-tertile; and T3, upper tertile) according to sex. The prevalence of MetS and CMRFs, including alanine aminotransferase (ALT), was compared by tertiles of SUA. Results: The mean SUA and SUA/Cr was higher in males than females (6.37 ± 0.04 mg/dL and 4.66 ± 0.06 mg/dL, P &amp;lt; 0.001 for SUA; 7.90 ± 0.07 mg/dL and 7.30 ± 0.06 mg/dL, P &amp;lt; 0.001 for SUA/Cr). Z-scores of body mass index, waist circumference, waist-height ratio, levels of total cholesterol, triglyceride, and ALT were significantly higher in T3 of SUA and SUA/Cr in both sexes, while high-density lipoprotein cholesterol (HDL-C) was lower. In T3 of SUA and SUA/Cr, the prevalence and odds ratio (95% confidence interval) increased significantly in abdominal obesity [34.5%, 5.5 (4.0, 7.7) vs. 31.3%, 5.3 (3.7, 7.6)], elevated blood pressure [19.5%, 2.1 (1.5, 2.9) vs. 16.3% 1.6 (1.1, 2.2)], elevated triglyceride [29.5%, 2.1 (1.5, 2.8) vs. 27.9%, 2.1 (1.6, 2.8)], low HDL-C [22.5%, 3.4 (2.4, 5.0) vs. 20.2%, 2.6 (1.8, 3.9)], elevated ALT [31.5%, 5.7 (3.8, 8.6) vs. 19.1% 4.9 (3.2, 7.6)], obesity [33.6%, 7.6 (5.2, 11.2) vs. 25.9%, 6.0 (3.9, 9.1)] and MetS [13.7%, 7.4 (4.3, 13.0) vs. 10.8%, 6.8 (3.9, 9.1)], compared with T1 of SUA and SUA/Cr, respectively. In the receiver operating characteristic curve analysis, the area under the curve of predicting MetS was 0.681 for males and 0.823 for females using SUA and 0.653 for males and 0.840 for females using SUA/Cr. The proportion of participants with ≥ 3 CMRFs was 2.1% in T1, 3.5% in T2, and 13.7% in T3 in SUA (P &amp;lt; 0.001) and 2.1% in T1, 5.8% in T2, and 10.8% in T3 in SUA/Cr (P &amp;lt; 0.001). Conclusions: In this nationwide cross-sectional study, SUA and SUA/Cr levels are associated with MetS, its components, and the marker of NAFLD in Korean adolescents. SUA and SUA/Cr seem to be more specific in diagnosing MetS in female adolescents. Both SUA and SUA/Cr could be used as important markers to predict MetS in adolescents. Presentation: 6/1/2024

Association between serum level of uric acid in Japanese young patients with coronary spastic angina receiving coronary angiography.

Endothelial dysfunction may trigger coronary spastic angina (CSA). However, the risk factors for CSA in young patients remain unclear. This study aimed to investigate the age-dependent role of serum uric acid levels in patients with CSA. We enrolled 423 patients who underwent an ergonovine tolerance test during coronary angiography for the CSA evaluation. We categorized the patients as (1) young (age ≤ 65years) CSA-positive (n = 33), (2) young CSA-negative (n = 138), (3) elderly (age > 66years) CSA-positive (n = 42), and (4) elderly CSA-negative (n = 210) groups. In the young groups, the smoker proportion (57.6 vs. 38.4%, p = 0.04) and serum uric acid levels (6.3 ± 1.4 vs. 5.4 ± 1.5mg/dl, p = 0.006) were significantly higher in the CSA-positive compared with the CSA-negative group. Conversely, in the elderly group, the male proportion (66.6 vs. 47.1%, p = 0.02) and alcohol consumption level (40.5 vs. 21.0%, p = 0.01) were significantly higher in the CSA-positive compared with the CSA-negative group. The multivariate analysis in young groups revealed the independent association between the serum uric acid level (p = 0.02) and the presence of CSA. Our results indicate that elevated serum uric acid levels may affect CSA development in young patients.

Serum uric acid trajectories and the risk of cardiovascular disease: a longitudinal association and pathway analysis.

Age-specifically longitudinal associations and potential pathways between serum uric acid (SUA) and cardiovascular disease (CVD) remained unclear. This study aimed to explore SUA trajectories in different age populations and to determine their associations and potential pathways with incident CVD. This prospective cohort included 41,367 participants from the Kailuan study, including 30,938 participants aged <55 years and 10,419 participants aged ≥55. The SUA trajectories during year 2006-2012 were identified by latent class growth models. Three SUA trajectories were identified in the overall, aged <55 and aged ≥55 years participants, as "low-stable" (51.9%, 54.4%, and 43.3%), "moderate-stable" (39.0%, 36.9%, and 45.6%), and "high-stable" (9.1%, 9.7%, and 11.1%), respectively. During a median follow-up of 6.75 years, incident CVD occurred in 2302 participants (5.56%). Overall, a high-stable trajectory was independently associated with a higher risk of CVD (hazard ratio [HR], 1.23; 95% [confidence interval], 1.06-1.42). Notably, the associations differed by age, a significant association was only observed in participants aged ≥55 years (HR, 1.29; 95% CI, 1.05-1.58), rather than those aged <55 years (HR, 1.08; 95% CI, 0.89-1.33). The addition of SUA trajectories to a baseline risk model for CVD improved the integrated discrimination improvement value (P < 0.05) and category-free net reclassification improvement value (P < 0.05). Bayesian network showed the conditional probability of high CVD risk associated with aging, elevated SUA trajectories, blood pressure, glucose, and inflammation was 15.5%. High-stable SUA trajectories were independently associated with an elevated risk of CVD, which is mainly induced by hypertension, diabetes, and inflammation, especially in participants aged ≥55 years.

Uric Acid and SGLT2 Inhibition With Empagliflozin in HeartFailure With Preserved Ejection Fraction: The EMPEROR-Preserved Trial.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors improve outcome in patients with heart failure (HF) and reduce serum uric acid (SUA). The relevance of this metabolic effect in patients with heart failure with preserved ejection fraction (HFpEF) is unclear. The authors investigated the effect of empagliflozin on SUA levels in relation to the therapeutic efficacy in patients with HFpEF. This post hoc analysis of the EMPEROR-Preserved (EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Preserved Ejection Fraction; NCT03057951) trial assessed the clinical effect of SUA reduction in relation to the outcome endpoints of the trial (composite primary outcome of cardiovascular mortality or hospitalization for HF, its individual components, and all-cause mortality in patients with HFpEF). Hyperuricemia (SUA >5.7mg/dL for women, >7.0mg/dL for men) was prevalent in 49% of patients. Elevated SUA (highest tertile SUA 8.8 ± 1.4 g/dL) was associated with advanced HF severity and with higher risk of adverse outcome (primary endpoint HR: 1.23 [95%CI: 0.98-1.53]; P = 0.07; HF hospitalization HR: 1.42 [95%CI: 1.08-1.86]; P= 0.01). SUA was reduced early (after 4weeks vs placebo-0.99 ± 0.03mg/dL; P< 0.0001) and throughout follow-up, with reduction in all prespecified subgroups. Empagliflozin reduced clinical events of hyperuricemia (acute gout, gouty arthritis, or initiation of antigout therapy) by 38% (HR: 0.62 [95%CI: 0.51-0.76]; P< 0.0001). The treatment benefit on the primary endpoint was not influenced by baseline SUA (HR: 0.79 [95%CI: 0.69-0.90]; P = 0.0004). The change in SUA was an independent correlate of the treatment benefit on the primary endpoint (P = 0.07). Hyperuricemia is a common complication in HFpEF and is related to advanced disease severity and adverse outcome. Empagliflozin induced a rapid and sustained reduction of SUA levels and of clinical events related to hyperuricemia.

Serum Uric Acid Level and its Association with Severity in Acute Ischemic Stroke

Background: Cerebrovascular diseases (CVDs) are a major public health issue around the world. Elevated serum uric acid levels may predict an increased risk for cerebrovascular events particularly acute ischemic stroke. Aim of the study: The aim of our study was to assess the association between serum uric acid level and severity of acute ischemic stroke. Methods: This observational case control study was conducted at the department of Neurology and at the department of Medicine in Dhaka Medical College Hospital from July 2018 to June 2020. This study included 50 acute ischemic stroke patients and 50 age and gender matched healthy controls. Along with the routine investigations, estimation of serum uric acid was done in all participants. The severity of stroke was assessed as per national institutes of health stroke scale (NIHSS). After collection of all the required data, analysis was done by SPSS 23.0. Results: The mean age and distribution of the age in different age group were matched between case and control groups (p=0.607 and 0.763 respectively). The mean age of the ischemic stroke cases was 62.14±9.77 years. The mean NIHSS score of the patients was 16.34±10.34. Of all, 18% had minor stroke, 32% had moderate stroke, 20% had moderate to severe stroke and 30% had severe stroke. Among stroke patients 58% had elevated uric acid level and among controls 20% had raised uric acid in serum. The number of patients having elevated serum uric acid is statistically significantly higher in case group than control group (p&lt;0.001). Multivariate regression analysis showed hypertension (OR 4.046; 95% CI 1.432–11.432; p=0.008), DM (OR 3.063; 95% CI 1.030-9.105; p=0.044), dyslipidemia (OR 3.031; 95% CI 1.062-8.654; p=0.038) and elevated serum uric acid level (OR 6.019, 95% CI 2.220–16.317; p&lt;0.001) independently associated with acute ischemic stroke (p&lt;0.05). Conclusion: This study shows elevated serum uric acid level significantly associated with severity of acute...........

A potential marker for increased LDL and hypertriglyceridemia risk

Background and objectives. Serum uric acid (SUA), traditionally associated with gout, is increasingly recognized for its potential role in cardiometabolic disorders, including dyslipidemia. Elevated SUA levels may influence lipid metabolism, thus enhancing cardiovascular disease risk. This study aims to explore the association between SUA levels, dyslipidemia, and related risk factors in a cohort of patients, contributing to a better understanding of their interplay and implications for cardiovascular health. Material and methods. We conducted a retrospective case series involving 30 participants selected from the outpatient Department of General Medicine. The study was approved by the Institutional Review Board, and informed consent was waived due to the retrospective design and use of de-identified data. Participants were aged 18 or older with available data on SUA, LDL cholesterol, and triglycerides, excluding those with a history of gout, renal impairment, or current use of urate-lowering medications. Data were analyzed using descriptive statistics, chi-square tests, and Mann-Whitney U tests, with significance set at p &lt;0.05. Results. The study population had a mean age of 54.7 ± 6.3 years and a mean BMI of 28.4 ± 2.4 kg/m². The mean SUA level was 6.9 ± 0.8 mg/dL, LDL cholesterol was 138 ± 13 mg/dL, and triglycerides were 162 ± 25 mg/dL. Dyslipidemia was present in 60% of the participants. Significant associations were found between hyperuricemia and dietary habits, family history of gout, CVD, and dyslipidemia, as well as the duration of hyperuricemia. Conclusion. Elevated SUA levels are significantly associated with dyslipidemia and other cardiovascular risk factors. The findings suggest the importance of managing SUA levels and lipid profiles concurrently to reduce cardiovascular risks. Further research is needed to explore the long-term cardiovascular outcomes of persistent hyperuricemia and dyslipidemia.

Risk Factors Associated with Angiographic Severity of Coronary Artery Disease Based on Serum Uric Acid: A Study in a Tertiary Care Hospital, Chattogram, Bangladesh

Background: Coronary Artery Disease (CAD) is a leading cause of death worldwide, identifying risk factors and severity is crucial for management and prevention. Serum Uric Acid (SUA) has been proposed as a potential marker for the severity of CAD. Elevated SUA levels are associated with endothelial dysfunction, oxidative stress, and inflammation, all of which contribute to the development and progression of atherosclerosis. This study aims to determine the association of risk factors with the severity of CAD using SUA levels. Materials and methods: This was a cross-sectional observational study conducted in the Department of Cardiology at CMCH in Chattogram over one year from October 2020 to September 2021. After case selection demographic data were collected and transthoracic echocardiography was performed on study patients. Results: The study analyzed the association between SUA level and CAD severity in 130 patients undergoing coronary angiography. The mean SUA level was 5.06 mg/dl and was significantly associated with the presence of CAD, number of vessel involvement and severity of CAD assessed by the Gensini score. The mean SUA level in cases with CAD was significantly higher (5.26 ± 1.32 mg/dl) than in cases without CAD (4.22 ± 1.03 mg/dl). Conclusion: This study concluded that demographic variables and risk factors are associated with the severity of CAD. The severity of CAD was higher in elderly and male patients. The study suggests that when assessing the risk in a CAD patient, hyperuricemia should be considered. IAHS Medical Journal Volume 6(2) December 2023; 48-52

The Relationship Between Ambulatory Blood Pressure Monitoring and Uric Acid Level in Hypertensive Patients

Abstract Introduction: Serum uric acid (SUA) is the end product of purine metabolism. Excessive SUA production or decreased renal excretion causes hyperuricemia. Elevated SUA is known to be a risk factor for cardiovascular diseases. It was reported that blood pressure (BP) was higher in patients with elevated uric acid and a decrease in BP was observed after the administration of uric acid-lowering drugs. Methods: We examined the relationship between SUA levels and hypertension in patients admitted to our hospital with hypertension (HT) and undergoing ambulatory blood pressure monitoring (ABPM). A total of 310 patients were included in the study. SUA levels were determined using an enzymatic colorimetric autoanalyzer. ABPM was performed using noninvasive multitasking CR recorders (TM2425; A&amp;D, Tokyo, Japan). Results: Hyperuricemia was observed in 49.6% of the patients. Daytime, nocturnal, and 24-hour diastolic blood pressure (DBP) were significantly higher in patients with hyperuricemia (p=0.021, p=0.029, and p=0.005, respectively). Mean arterial pressure (MAP) and nocturnal MAP values were higher in patients with hyperuricemia (p=0.022 and p=0.003, respectively). The rate of patients with dipper HT was lower in patients with hyperuricemia than those without hyperuricemia (p=0.041). The rate of reverse-dipper HT was found to be higher in patients with hyperuricemia compared to those without hyperuricemia (p=0.022). Conclusion: Elevated uric acid was correlated with DBP, reverse HT, and MAP. Measurement of SUA could provide a valuable aid for the assessment and reduction of cardiovascular risk. Further studies are required to assess the effect of lowering uric acid on the reduction of nocturnal BP and DBP. Key words: Ambulatory blood pressure monitoring, uric acid, dipper hypertension, non-dipper hypertension, reverse-dipper hypertension

Causal pathways in preeclampsia: a Mendelian randomization study in European populations.

Our study utilizes Mendelian Randomization (MR) to explore the causal relationships between a range of risk factors and preeclampsia, a major contributor to maternal and perinatal morbidity and mortality. Employing the Inverse Variance Weighting (IVW) approach, we conducted a comprehensive multi-exposure MR study analyzing genetic variants linked to 25 risk factors including metabolic disorders, circulating lipid levels, immune and inflammatory responses, lifestyle choices, and bone metabolism. We applied rigorous statistical techniques such as sensitivity analyses, Cochran's Q test, MR Egger regression, funnel plots, and leave-one-out sensitivity analysis to address potential biases like pleiotropy and population stratification. Our analysis included 267,242 individuals, focusing on European ancestries and involving 2,355 patients with preeclampsia. We identified strong genetic associations linking increased preeclampsia risk with factors such as hyperthyroidism, BMI, type 2 diabetes, and elevated serum uric acid levels. Conversely, no significant causal links were found with gestational diabetes, total cholesterol, sleep duration, and bone mineral density, suggesting areas for further investigation. A notable finding was the causal relationship between systemic lupus erythematosus and increased preeclampsia risk, highlighting the significant role of immune and inflammatory responses. This extensive MR study sheds light on the complex etiology of preeclampsia, underscoring the causal impact of specific metabolic, lipid, immune, lifestyle, and bone metabolism factors. Our findings advocate for a multidimensional approach to better understand and manage preeclampsia, paving the way for future research to develop targeted preventive and therapeutic strategies.

P003 ASSOCIATION BETWEEN SERUM URIC ACID AND BLOOD PRESSURE IN BOYS, GIRLS AND ADOLESCENTS WITH OVERWEIGHT and OBESITY ATTENDED IN PEDIATRIC HOSPITALS IN THE AUTONOMOUS CITY OF BUENOS AIRES. “MULTICENTRIC STUDY

Introduction: Childhood overweight and obesity are modifiable risk factors for the development of Hypertension (HTN). Elevated serum uric acid (UA) is a known cardiovascular risk factor in adults. Objective: To evaluate whether there is an association between high serum UA values and elevated BP in overweight and obese children and adolescents. Methods: Multicenter prospective cross-sectional study. Overweight and obese patients aged 5 to 18 years attended in HTN outpatient clinics of three tertiary pediatric hospitals in Buenos Aires were included. Office BP control, 24-hours ambulatory BP monitoring (ABPM) and laboratory tests (metabolic and lipid profile and serum UA measurement) were performed. Results: 173 patients were enrolled, mean age 11.7±2.9 years, 63 women (36.4%), 50 were overweight (28.9%) and 123 obese (71.1%). 143 normotensive (NT) patients were registered, 14 with white-coat HTN, 11 with masked hypertension (MH) and 5 with sustained HTN. The mean value of serum UA was 5.1±1.2, 113 subjects were above the mean value and 24 were above 2SD. Taking serum UA higher than the average (n:113) according to BP we observed 89/143 in NT vs. 13/14 in white-coat HTN (OR 7.8 95% CI 1.1-62.1 p=0.04), 89/143 in NT vs. 8/11 in MH (OR 1.6 95% CI 0.4-6.3 p=0.7) and 89/143 in NT vs. 3/5 in sustained HTN (OR 0.9 95% CI 0.1-5.2 p=0.9). Using serum UA &gt;2SD (n:24) 14/143 above this value in NT vs. 7/14 in white-coat HTN (OR 9.2 95% CI 2.8-30.1 p&lt;0.001), 14/143 in NT vs. 3/11 MH (OR 3.4 95% CI 0.8-14.5 p=0.1) and no subject with sustained HTN had serum UA values &gt;2SD. Conclusions: Elevated serum UA was observed in subjects with white-coat HTN. The number of subjects with sustained HTN was not sufficient to evaluate the association with serum UA values. These findings emphasize the importance of the systematic implementation of 24-hours ABPM for detection of white-coat HTN in overweight and obese children and adolescents.