Background: The prevalence of hyperuricemia, gout, and heart failure (HF) is on the rise, and these conditions often share similar risk factors. The present study aimed to evaluate the relationship among hyperuricemia, gout, HF, and all-cause mortality. Methods: The data on nonpregnant participants aged ≥ 20 years with or without hyperuricemia, gout, and HF from the National Health and Nutrition Examination Survey 2001–2018 and 2007–2018 were included in this study. The binary logistic regression, Kaplan–Meier curve, Cox proportional-hazards model, and restricted cubic spline analysis were employed to evaluate the relationship among hyperuricemia, gout, HF, and all-cause mortality. Results: Of 204,179,060 and 223,702,171 weighted eligible participants, 40,044,228 (19.6%) and 9,158,600 (4.1%) had hyperuricemia and gout, respectively. Older age, diabetes, stroke, and coronary artery disease were the risk factors for HF among patients with hyperuricemia and gout. The median survival time was 7.00 years and 6.25 years and the 5-year survival rate was 59.9% and 55.9% for patients with HF and hyperuricemia and those with HF and gout, respectively. Patients with hyperuricemia or gout were 2.46 and 2.35 times more likely to have HF and 1.37 and 1.45 times more likely to experience all-cause mortality compared with those who did not exhibit these conditions. The restricted cubic spline showed a nonlinear correlation between uric acid levels and HF and a J-shaped correlation between uric acid levels and all-cause mortality. Conclusions: Ambulatory patients with hyperuricemia or gout were more likely to have HF compared with those without hyperuricemia or gout. Patients with HF with hyperuricemia or gout were more likely to experience all-cause mortality in the long-term follow-up.

Background: Cardiac, renal, and metabolic (CRM) conditions are major causes of morbidity and mortality globally. This study aims to explore the relationship between serum uric acid (SUA), hyperuricemia, gout, and CRM conditions in middle‐aged and elderly populations. Methods: Sample 1 included participants from CHARLS (China Health and Retirement Longitudinal Study, n=9341), and Sample 2 from NHANES (National Health and Nutrition Examination Survey, unweighted n=17 913; weighted n=115 646 390). Ordinal logistic regression, Cox regression, and restricted cubic spline analyses were used to assess the relationship between SUA, hyperuricemia, gout, and CRM conditions. A 2‐sample Mendelian randomization analysis was conducted to explore causal associations between SUA and CRM conditions. Results: In both samples, SUA, hyperuricemia, and gout were positively correlated with the risk of CRM conditions. Among participants with 3 or ≥1 CRM condition(s), SUA, asymptomatic hyperuricemia, and gout with poorly controlled hyperuricemia showed significant positive associations with all‐cause mortality, whereas these associations were not observed in patients with gout with normal SUA levels. The restricted cubic spline analysis revealed a positive relationship between SUA levels and the risk of all‐cause mortality in participants with ≥1 CRM condition(s), demonstrating a nonlinear dose–response relationship across both samples ( P for nonlinearity <0.05). Mendelian randomization analysis indicated that SUA was causally associated with cardiovascular disease, chronic kidney disease, and diabetes. Conclusions: Hyperuricemia and gout are strong predictors of increased prevalence and mortality of CRM conditions, emphasizing the importance of managing hyperuricemia and gout in these patients.

Purpose: The results of previous studies on the relationship between serum 25-hydroxyvitamin D [25(OH)D] and hyperuricemia are controversial. We hypothesized that serum 25(OH)D concentrations of U.S. adults would negatively correlate with the risk of hyperuricemia. Method: Data came from the National Health and Nutrition Examination Survey 2007–2014 were used, after excluding those who met at least one of the exclusion criteria, a total of 9096 male individuals and 9500 female individuals aged 18 years or older were included. Binary logistic regression analysis and restricted cubic spline with fully adjusted confounding factors were applied to evaluate the association between serum 25(OH)D and hyperuricemia. We further performed stratified analysis and sensitivity analysis to minimize the influence of gender, metabolic syndrome, obesity and renal dysfunction on the above association. Results: We found a negative correlation between serum 25(OH)D and hyperuricemia. In the binary logistic regression analysis, compared with the highest serum 25(OH)D quartile [Q4: 25(OH)D > 77.10 nmol/L] group, the odds ratios (95% confidence intervals) in the lowest quartile [Q1: 25(OH)D ≤ 43.20 nmol/L] was 1.46 (1.22–1.75) in the fully adjusted model. Restricted cubic spline analysis showed L-shaped and non-linear relationships between 25(OH)D and hyperuricemia. In sensitivity analysis, after restricting to participants without significant renal dysfunction and obesity, the above association remained significant. After restricting to participants who were diagnosed as metabolic syndrome, above association remained significant in the fully adjusted model. In stratified analysis by gender, the association remained significant among males and females. Conclusions: Serum 25(OH)D might be inversely associated with hyperuricemia in general U.S. adults. From our study, for people with unexplained hyperuricemia, screening for serum Vitamin D concentration might be necessary.

Background: Fibromyalgia (FM) is a multifaceted disease. Along with the genetic, environmental and neuro-hormonal factors, inflammation has been assumed to have role in the pathogenesis of FM. The aim of the present study was to explore the differences in clinical features and pathophysiology of FM patients under different inflammatory status. Methods: The peripheral blood gene expression profile of FM patients in the Gene Expression Omnibus database was downloaded. Differentially expressed inflammatory genes were identified, and two molecular subtypes were constructed according to these genes used unsupervised clustering analysis. The clinical characteristics, immune features and pathways activities were compared further between the two subtypes. Then machine learning was used to perform the feature selection and construct a classification model. Results: The patients with FM were divided into micro-inflammation and non-inflammation subtypes according to 54 differentially expressed inflammatory genes. The micro-inflammation group was characterized by more major depression (p = 0.049), higher BMI (p = 0.021), more active dendritic cells (p = 0.010) and neutrophils. Functional enrichment analysis showed that innate immune response and antibacterial response were significantly enriched in micro-inflammation subtype (p < 0.050). Then 5 hub genes (MMP8, ENPP3, MAP2K3, HGF, YES1) were screened thought three feature selection algorithms, an accurate classifier based on the 5 hub DEIGs and 2 clinical parameters were constructed using support vector machine model. Model scoring indicators such as AUC (0.945), accuracy (0.936), F1 score (0.941), Brier score (0.079) and Hosmer–Lemeshow goodness-of-fit test (χ² = 4.274, p = 0.832) proved that this SVM-based classifier was highly reliable. Conclusion: Micro-inflammation status in FM was significantly associated with the occurrence of depression and activated innate immune response. Our study calls attention to the pathogenesis of different subtypes of FM.

Background: Previous observational studies have revealed the association between serum uric acid and 25-hydroxyvitamin D. However, the causality and the direction of the associations remain unknown. Thus, we performed a two-sample bidirectional Mendelian Randomization (MR) analysis to investigate the causal association between uric acid and 25-hydroxyvitamin D and to determine the direction of the association.Method: Based on the summary-level GWAS data from large genome-wide association studies, several steps were taken in our analysis to select eligible single-nucleotide polymorphisms (SNPs), which were strongly related to exposure as the instrumental variables. We used different analytical methods, such as inverse-variance weighting (IVW) method, weighted median, MR-Egger regression, and weighted mode method, to make our result more robust and reliable. The IVW method was used as the primary analysis. The Cochran’s Q test, MR-Egger intercept test, MR-PRESSO method, and “leave-one-out” sensitivity analysis was performed to evaluate the heterogeneities, horizontal pleiotropy, and robustness of the results. MR analyses were also conducted using genetic risk scores (GRS) as instrumental variables in both directions by using the same summary-level GWAS data.Results: Our two-sample MR analysis suggested a causal association of genetically predicted uric acid on 25-hydroxyvitamin D [IVW method: β(SE), −0.0352(0.0149); p = 0.0178], which suggested that a per mg/dl increase in uric acid was associated with a decrease of 0.74 nmol/L of 25-hydroxyvitamin D, and the above results remained stable in the sensitivity analysis. By contrast, four MR methods suggested no causal relationship of 25-hydroxyvitamin D on serum uric acid [IVW β(SE), 0.0139 (0.0635); p = 0.826; MR-Egger β(SE), 0.0671 (0.108); p = 0.537; weighted median β(SE), 0.0933 (0.0495); p = 0.0598; weighted mode β(SE), 0.0562 (0.0463); p = 0.228, respectively]. After excluding the SNPs, which were associated with confounding factors and outlier SNPs, the IVW method suggested that there was still no causal association of 25-hydroxyvitamin D on serum uric acid. The GRS approach showed similar results.Conclusions: Serum uric acid may causally affect the 25-hydroxyvitamin D levels, whereas the causal role of 25-hydroxyvitamin D on uric acid was not supported in our MR analysis. Our findings suggest that increased levels of uric acid should prompt investigation for vitamin D deficiency.

Background: There is a limited number of studies on the dose-response relationship between serum uric acid and impaired glucose metabolism in people without diabetes, and no large-scale research exploring the relationship in women without diabetes is based on menopausal status. Consequently, the present study aimed to investigate the above relationship in United States adults without diabetes.Materials and Methods: Data from 2,498 men and 2,650 women aged ≥20 years were obtained from the National Health and Nutrition Examination Survey 2011–2016 conducted in the United States. Binary logistic regression analysis was applied to evaluate the association between uric acid and impaired glucose metabolism. Restricted cubic spline analysis, sensitivity analysis, and stratified analysis by menopausal status were performed to explore the above relationships.Results: A positive correlation was found between uric acid and the risk of insulin resistance in all participants (P < 0.05). In binary logistic regression analysis, after adjusting for confounding factors, compared with the lowest quartile of uric acid, the odds ratio (95% confidence intervals) of insulin resistance in the highest quartile was 1.9 (1.1–3.1) and 2.2 (1.2–4.3) in men and women, respectively. A significant positive relationship was also observed between uric acid and impaired fasting glucose and hyperinsulinemia in women, while in men, uric acid was positively associated with the risk of hyperinsulinemia but not impaired fasting glucose. Restricted cubic spline showed that the odds ratios of insulin resistance and hyperinsulinemia increased with elevating uric acid levels in both men and women. When stratified by menopause, the association remained significant in pre-menopausal women aged ≥20, but insignificant in post-menopausal women.Conclusion: Uric acid was positively associated with the risk of impaired glucose metabolism in a cohort of United States adults, and uric acid increased the risk of insulin resistance in pre-menopausal, but not in post-menopausal women.