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Higher Serum Uric Acid Levels Are Associated With an Increased Risk of Vision-Threatening Diabetic Retinopathy in Type 2 Diabetes Patients.
Hu, Y, Chan, Z, Li, C, Shi, Y, She, X, Gu, C, Wang, Y, Zhou, C, Zhao, S, Zheng, Z, et al
Investigative ophthalmology & visual science. 2021;(4):23
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Abstract
PURPOSE To investigate the association between serum uric acid (SUA) levels and vision-threatening diabetic retinopathy (VTDR) in patients with type 2 diabetes. METHODS This cross-sectional study evaluated 3481 patients with type 2 diabetes from four communities in China between 2016 and 2019. VTDR was defined as severe nonproliferative, proliferative diabetic retinopathy, or clinically significant macular edema evaluated by fundus photography and optical coherence tomography. Potential association between SUA and VTDR was examined using multivariable logistic regression. Sub-group analyses based on sex were constructed. RESULTS A total of 305 participants had VTDR. Both higher SUA (odds ratio [OR], 1.22 per 100 µmol/L; 95% confidence interval [CI], 1.04-1.44; P = 0.013) and hyperuricemia (OR, 1.47; 95% CI, 1.07-2.04; P = 0.019) were positively associated with VTDR after adjustment for relevant covariates. Compared with those in the lowest SUA quartile, participants in the third (OR, 1.60; 95% CI, 1.07-2.39; P = 0.022) and fourth (OR, 2.05; 95% CI, 1.37-3.08; P = 0.001) sex-specific SUA quartiles showed a significantly increased risk of VTDR after adjustment. No sex-related difference was observed. CONCLUSIONS Higher SUA levels were associated with an increased risk of VTDR in patients with type 2 diabetes in both sexes, although females seemed to be more sensitive to high SUA than males. Prospective cohort studies are needed to verify SUA as a biomarker for predicting the risk of VTDR. Whether decreased SUA levels could decrease the risk of VTDR also requires further investigation.
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Association between baseline serum uric acid and development of LDL-C level in patients with first acute myocardial infarction.
Chen, Y, Ding, C, Hu, L, Ruan, Y, Zou, K, Dai, C, Liao, Y, Liao, H, Xia, Y, Zhao, Y, et al
BMC cardiovascular disorders. 2021;(1):572
Abstract
BACKGROUND Data on the relationship of baseline serum uric acid (SUA) with development of low-density lipoprotein cholesterol (LDL-C) level in patients with first acute myocardial infarction (AMI) are limited. The present study is to evaluate whether elevated SUA predicts the development of LDL-C in the first AMI. METHODS This is a retrospective 6-month cohort study of 475 hospitalized Chinese patients who underwent first AMI between January 2015 and December 2019 and were reevaluated half a year later at the Department of Cardiology, the Second Affiliated Hospital of Nanchang University, Jiangxi Province, China. The associations of baseline SUA with the percentage decrease of LDL-C (%) and LDL-C control were analyzed by using logistic regression analyses, multivariate linear regression analyses and the restricted cubic spline. RESULTS Over the 6-month follow-up, baseline SUA was independently and positively associated with the percentage decrease of LDL-C (%) and LDL-C control in a dose response fashion. After multivariable adjustment, per SD increment of baseline SUA (120.58 μmol/L) was associated with 3.96% higher percentage decrease of LDL-C(%). The adjusted OR (95% CI) for LDL-C control was 5.62 (2.05, 15.36) when comparing the highest tertile (SUA ≥ 437.0 μmol/L) to the lowest tertile (< 341.7 μmol/L) of baseline SUA. CONCLUSIONS Among Chinese patients with first AMI, higher baseline SUA was associated with higher LDL-C deduction percentage (%), and higher rate of LDL-C control in the short-term follow-up, respectively. SUA acquired when AMI occurred was prone to be profitable in predicting the risk stratification of uncontrolled LDL-C and dyslipidemia management.
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Hypouricemia and Mortality Risk in the US General Population.
D'Silva, KM, Yokose, C, Lu, N, McCormick, N, Lee, H, Zhang, Y, Choi, HK
Arthritis care & research. 2021;(8):1171-1179
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OBJECTIVE The most recent European Alliance of Associations for Rheumatology (EULAR) recommendations for gout advise against maintaining a serum urate (SU) level of <3 mg/dl for prolonged periods of time. While several Asian cohort studies have shown higher rates of mortality in individuals with extremely low SU levels, data from non-Asian cohort studies are scarce, and the relationship between hypouricemia, cardiovascular risk, and mortality remains unclear. METHODS Using data collected from the 1988-1994 and 1999-2008 National Health and Nutrition Examination Survey (NHANES), we examined the relationship between SU level and overall and cause-specific mortality in 41,807 adults in the US. We calculated multivariable hazard ratios (HRs) that were compared to a referent SU level of 5-6 mg/dl for SU categories <4, 4-5, 6-7, 7-8, and >8 mg/dl in men and SU categories <3, 3-4, 4-5, 6-7, and >7 mg/dl in women. RESULTS A higher mortality risk was not observed in women who had an SU level of <3 mg/dl (HR 1.09 [95% confidence interval (95% CI) 0.92-1.28]). A 28% higher mortality risk was observed in men who had an SU level of <4 mg/dl (HR 1.28 [95% CI 1.13-1.45]), with a nearly three-times higher mortality risk from diabetes mellitus also noted (HR 2.89 [95% CI 1.59-5.23]), but no increase in mortality from any other specific cause. CONCLUSION We found no long-term excess mortality risk among American women with SU levels as low as <3 mg/dl, a finding which is incompatible with the notion of a causal relationship between hypouricemia and premature mortality in women. We found excess all-cause mortality and diabetes mellitus-related mortality among hypouricemic American men, which may in part be attributable to the uricosuric effect of hyperglycemia in fatal uncontrolled diabetes mellitus (analogous to reverse causality).
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Serum uric acid and fatal myocardial infarction: detection of prognostic cut-off values: The URRAH (Uric Acid Right for Heart Health) study.
Casiglia, E, Tikhonoff, V, Virdis, A, Masi, S, Barbagallo, CM, Bombelli, M, Bruno, B, Cicero, AFG, Cirillo, M, Cirillo, P, et al
Journal of hypertension. 2020;(3):412-419
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OBJECTIVE The Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension conceived and designed an ad-hoc study aimed at searching for prognostic cut-off values of serum uric acid (SUA) in predicting fatal myocardial infaction (MI) in women and men. METHODS The URic acid Right for heArt Health study is a nationwide, multicentre, observational cohort study involving data on individuals aged 18-95 years recruited on a regional community basis from all the territory of Italy under the patronage of the Italian Society of Hypertension with a mean follow-up period of 122.3 ± 66.9 months. RESULTS A total of 23 467 individuals were included in the analysis. Cut-off values of SUA able to discriminate MI status were identified by mean of receiver operating characteristic curves in the whole database (>5.70 mg/dl), in women (>5.26 mg/dl) and in men (>5.49 mg/dl). Multivariate Cox regression analyses adjusted for confounders (age, arterial hypertension, diabetes, chronic kidney disease, smoking habit, ethanol intake, BMI, haematocrit, LDL cholesterol and use of diuretics) identified an independent association between SUA and fatal MI in the whole database (hazard ratio 1.381, 95% confidence intervals, 1.096-1.758, P = 0.006) and in women (hazard ratio 1.514, confidence intervals 1.105-2.075, P < 0.01), but not in men. CONCLUSION The results of the current study confirm that SUA is an independent risk factor for fatal MI after adjusting for potential confounding variables, and demonstrate that a prognostic cut-off value associated to fatal MI can be identified at least in women.
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Association between serum vitamin D and uric acid in the eastern Chinese population: a population-based cross-sectional study.
Chen, Y, Cheng, J, Chen, Y, Wang, N, Xia, F, Chen, C, Han, B, Lu, Y
BMC endocrine disorders. 2020;(1):79
Abstract
BACKGROUND Uric acid (UA) is the end product of purine metabolism, which is thought to be related to many human diseases, such as nephrolithiasis, gout, cardiovascular disease (CVD), type 2 diabetes mellitus, metabolic syndrome. However, the relationship between serum UA (SUA) and 25(OH) D is still unclear in the eastern Chinese population. METHODS We did a population-based observational investigation, which included 12,770 residents living in eastern China. Ultimately, data from 9220 subjects were analyzed. Serum 25(OH) D, SUA, fasting plasma glucose (FPG), fasting insulin, HbA1c and other metabolic parameters were tested. Waist circumference (WC), weight and height were also measured. Questionnaires were collected from these subjects for information on smoking and drinking status. RESULTS We enrolled 9220 Chinese adults, including 3681 males (age 55.57 ± 13.23 years) and 5539 females (age 54.31 ± 12.83 years). The levels of SUA were 352.07 ± 79.25 nmol/L and 269.29 ± 64.68 nmol/L in males and females, respectively. The proportion of adults with hyperuricemia (HUA) was 12.26% in the total population. Levels of SUA were positively associated with 25(OH) D, and the incidence of HUA increased 9.4% for every 10 nmol/L increase in 25(OH) D (P < 0.001). CONCLUSIONS SUA was positively associated with 25(OH) D in the eastern Chinese population. Higher levels of serum 25(OH) D may be a potential predictor of HUA.
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Mendelian randomization study of serum uric acid levels and diabetes risk: evidence from the Dongfeng-Tongji cohort.
Keerman, M, Yang, F, Hu, H, Wang, J, Wang, F, Li, Z, Yuan, J, Yao, P, Zhang, X, Guo, H, et al
BMJ open diabetes research & care. 2020;(1)
Abstract
OBJECTIVE Limited Mendelian randomization (MR) studies have assessed the causal relationship between serum uric acid levels and diabetes risk. Here we investigated causality between the serum uric acid concentration and diabetes risk in Chinese population. RESEARCH DESIGN AND METHODS The observational analysis, based on the Dongfeng-Tongji prospective cohort (n=15 195) we tested the association of serum uric acid levels with incident diabetes risk. In the instrumental variable analysis, we examined the association of the genetic risk score (GRS) of serum uric acid with diabetes risk in case-control design (2539 cases and 4595 controls) via MR analysis. RESULTS During a mean (SD) follow-up of 4.5 (0.5) years, 1156 incident diabetes cases were identified. Compared with those in the lowest quintile of serum uric acid levels, the HRs of incident diabetes were 1.19 (95% CI 0.96 to 1.48), 1.12 (95% CI 0.90 to 1.40), 1.38 (95% CI 1.12 to 1.70), and 1.51 (95% CI 1.23 to 1.87) for Q2, Q3, Q4 and Q5, respectively (P-trend <0.001). The GRS was strongly associated with serum uric acid levels (β=0.17, 95% CI 0.15 to 0.19; P=2.81×10-67). However, no significant association was observed between the GRS and diabetes risk (OR=1.01, 95 CI 0.95 to 1.06; P=0.75). CONCLUSIONS Even though serum uric acid levels were significantly associated with increased incident diabetes risk, the results did not provide evidence for a causal relationship between them.
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Clinical Predictors of the Hypoglycemic Effect of Sodium-Glucose Co-transporter-2 Inhibitors in Hyperuricemic Patients: A Retrospective Descriptive Observational Study.
Hirai, T, Kawagoe, Y, Kei, M, Ogawa, R, Itoh, T
Biological & pharmaceutical bulletin. 2020;(5):782-787
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Sodium-glucose co-transporter-2 (SGLT2) inhibitors decrease glycated hemoglobin (HbA1c) and prevent the progression of cardiovascular and kidney diseases. Because uric acid and electrolytes are physiologically similar to blood glucose in renal excretion, we assessed predictors for the hypoglycemic effect of SGLT2 inhibitor treatment by focusing on serum uric acid and serum electrolytes. We performed a retrospective descriptive observational study at the Tokyo Women's Medical University, Medical Center East, from June 2015 to July 2018. Patients who received treatment with any type of SGLT2 inhibitor were selected, which included a total of 165 patients. The response to SGLT2 inhibitors defined as changes in HbA1c after SGLT2 inhibitor treatment was the main outcome measure. Multiple linear regression analysis was used to assess predictors for the hypoglycemic effect by SGLT2 inhibitors. Among the 165 patients, SGLT2 inhibitor treatment decreased HbA1c from 8.2 to 7.6% after 12 weeks (p < 0.01). Multiple linear regression analysis revealed that predictors of early response to SGLT2 inhibitors were serum uric acid values (p = 0.014) and baseline HbA1c (p < 0.001). Furthermore, late response to SGLT2 inhibitors was associated with serum uric acid value (p = 0.047) and baseline HbA1c (p < 0.001). Serum uric acid did not vary during SGLT2 inhibitor treatment; specifically, the SGLT2 inhibitors did not reduce serum uric acid levels. There was no correlation between changes in serum uric acid and HbA1c (p = 0.13). Thus, this study showed that serum uric acid value is associated with the control of diabetes mellitus during SGLT2 inhibitor treatment. Further studies are required to validate these results.
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Association of serum uric acid change with mortality, renal function and diuretic dose administered in treatment of acute heart failure.
Zhou, HB, Xu, TY, Liu, SR, Bai, YJ, Huang, XF, Zhan, Q, Zeng, QC, Xu, DL
Nutrition, metabolism, and cardiovascular diseases : NMCD. 2019;(4):351-359
Abstract
BACKGROUND AND AIMS Hyperuricemia is reportedly associated with poor outcome in acute heart failure (AHF). The association between changes in Uric acid (UA) levels with renal function change, diuretic doses, and mortality in patients with AHF were studied. METHODS AND RESULTS Consecutive patients hospitalized with AHF were reviewed (n = 535). UA levels were measured at admission and either at discharge or on approximately the seventh day of admission. Patients with an UA change in the top tertile were defined as having an increase (UA-increase) and were compared to those outside the top tertile (non-UA-increase). The endpoint was all-cause mortality, with a mean follow-up duration of 22.2 months. Patients in the UA-increase group presented with greater creatine increase (P < 0.001), and were administered a higher average daily dose of loop diuretic (P = 0.016) compared with the non-UA-increase group. In-hospital UA-increase was associated with higher risk of mortality even after adjusting for confounding variables including creatine change and diuretic dosage [harzard ratio (HR) 1.53, 95% confidence interval (CI) 1.02-2.30, P = 0.042]. In patients with hyperuricemia on admission, UA-increase was associated with increased mortality (adjusted HR 2.21, 95% CI 1.38-3.52, P = 0.001). Whereas, in those without admission hyperuricemia, UA-increase had no significant association with mortality. CONCLUSIONS An increase in UA during in-hospital treatment is associated with an increase in creatine levels and daily diuretic dose. Mortality associated with increased UA is restricted to patients who already have hyperuricemia at admission. A combination of UA levels at admission and UA changes on serial assessment during hospitalization may be additional value in the risk stratification of AHF patients.
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Association of Uric Acid with Incident Metabolic Syndrome in a Japanese General Population.
Sumiyoshi, H, Ohyama, Y, Imai, K, Kurabayashi, M, Saito, Y, Nakamura, T
International heart journal. 2019;(4):830-835
Abstract
Uric acid is associated with cardiovascular disease (CVD) and its risk factors. Here, we examined the association between the serum uric acid level and incident metabolic syndrome in a Japanese general population. This retrospective, observational study was based on data obtained from an annual health checkup program in Gunma Prefecture, Japan. We evaluated 14,793 participants who did not use antihypertensive or antidiabetic medications and did not present with CVD or metabolic syndrome at the study baseline in 2009. Metabolic syndrome was defined as per the Japanese diagnostic criteria. A discrete proportional hazards regression model was used to evaluate the association between the serum uric acid level at baseline and the incident metabolic syndrome through 2012 and was adjusted for age, gender, waist circumference, systolic and diastolic blood pressure, fasting blood glucose, high-density lipoprotein cholesterol, and triglyceride. At baseline, the average age of the participants was 48.9 years, who were comprised of 40% women. The mean serum uric acid level at baseline was 5.3 ± 1.4 mg/dL. During the three-year follow-up, 7% of the cohort (n = 1,031) developed metabolic syndrome. The uric acid level was strongly associated with incident metabolic syndrome in the multivariable model (adjusted hazard ratio: 1.10; 95% confidence interval, 1.04-1.17; P < 0.01 per 1 mg/dL increase for uric acid). Higher uric acid levels were independently associated with a greater risk of incident metabolic syndrome in a Japanese general population.
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Higher levels of serum uric acid influences hepatic damage in patients with non-alcoholic fatty liver disease (NAFLD).
Fernández Rodríguez, CM, Aller, R, Gutiérrez García, ML, Ampuero, J, Gómez-Camarero, J, Martín-Mateos, RMª, Burgos-Santamaría, D, Rosales, JM, Aspichueta, P, Buque, X, et al
Revista espanola de enfermedades digestivas. 2019;(4):264-269
Abstract
BACKGROUND recent evidence suggests a causal link between serum uric acid and the metabolic syndrome, diabetes mellitus, arterial hypertension, and renal and cardiac disease. Uric acid is an endogenous danger signal and activator of the inflammasome, and has been independently associated with an increased risk of cirrhosis. AIM AND METHODS six hundred and thirty-four patients from the nation-wide HEPAMET registry with biopsy-proven NAFLD (53% NASH) were analyzed to determine whether hyperuricemia is related with advanced liver damage in patients with non-alcoholic fatty liver disease (NAFLD). Patients were divided into three groups according to the tertile levels of serum uric acid and gender. RESULTS the cohort was composed of 50% females, with a mean age of 49 years (range 19-80). Patients in the top third of serum uric acid levels were older (p = 0.017); they had a higher body mass index (p < 0.01), arterial blood pressure (p = 0.05), triglyceridemia (p = 0.012), serum creatinine (p < 0.001) and total cholesterol (p = 0.016) and lower HDL-cholesterol (p = 0.004). According to the univariate analysis, the variables associated with patients in the top third were more advanced steatosis (p = 0.02), liver fibrosis (F2-F4 vs F0-1; p = 0.011), NASH (p = 0.002) and NAS score (p = 0.05). According to the multivariate logistic regression analysis, the top third of uric acid level was independently associated with steatosis (adjusted hazard ratio 1.7; CI 95%: 1.05-2.8) and NASH (adjusted hazard ratio 1.8; CI 95%: 1.08-3.0) but not with advanced fibrosis (F2-F4) (adjusted hazard ratio 1.09; CI 95%: 0.63-1.87). CONCLUSION higher levels of serum uric acid were independently associated with hepatocellular steatosis and NASH in a cohort of patients with NAFLD. Serum uric acid levels warrants further evaluation as a component of the current non-invasive NAFLD scores of histopathological damage.