Higher sUA Levels Research Articles

7669 Higher Serum Uric Acid Levels Are Associated With a Deleterious Metabolic and Inflammatory Profile in Brazilian Adolescents: An Exploratory Cross-Sectional Analysis

Abstract Disclosure: F.Q. Iorra: None. M.P. Guahnon: None. P.G. Rodrigues: None. A.T. Barcelos: None. F.V. Cureau: None. M. Drehmer: None. B.D. Schaan: None. Introduction: The association of high serum uric acid (sUA) with metabolic syndrome (MetS) and its components have been widely studied, but there are still gaps in how this breakdown product of purine metabolism might refine cardiovascular risk assessment and correlate with other cardiovascular disease biomarkers, especially in children and adolescents. Objective: To evaluate if sUA is associated with metabolic syndrome components and inflammatory markers in Brazilian adolescents. Methods: For this cross-sectional study, 786 individuals aged 12 to 17 years old, previously enrolled in the Study of Cardiovascular Risk in Adolescents (ERICA) - a Brazilian nationwide school based study, and who were from the city of Porto Alegre, had their sUA measured from blood samples that were stored in a biorepository. Anthropometric, biochemical and blood pressure data were collected. MetS diagnosis was based on the International Diabetes Federation age-specific criteria (2005), and insulin resistance was assessed by the HOMA-IR. In accordance with a non-parametric distribution, sUA was divided into quartiles (3.7 mg/dL, 4.4 mg/dL, 5.3 mg/dL for the 25th, 50th, and 75th percentiles, respectively) for the analysis. A linear regression model and a Poisson regression model with robust error variance were used, both adjusted for age, sex and skin color. Results: Participants were 14.8 ± 1.5 years-old, predominantly women (61.7%), self-identified as white skin color (72%) and eutrophic (66.9%). Through the linear regression model, significant positive associations were found between high sUA levels and body mass index Z-score, waist circumference, systolic and diastolic blood pressure, total cholesterol, triglycerides, HOMA-IR and C-reactive protein, and significant negative associations were observed for HDL cholesterol and adiponectin. No association was found between sUA and glucose or HbA1c. We also computed a metabolic risk score as the mean Z score of waist circumference, systolic blood pressure, HDL cholesterol (negative Z score), triglycerides and glucose, which was positive related to sUA (β ± SE = 0.13 ± 0.02; p < 0.001). Finally, the Poisson regression model was applied to estimate the prevalence ratios (PR) for MetS and its components, between adolescents with sUA in the 4th quartile to those in the 1st quartile. An association was observed for MetS (PR 6.37, 95% CI 1.39 - 29.21, p 0.017), high waist circumference (PR 4.61, 95% CI 2.55 - 8.36, p < 0.001) and increased triglycerides (PR 4.76, 95% CI 1.47 - 15.44, p 0.009). Conclusion: High sUA levels were associated with a worse metabolic and inflammatory profile, as well as a greater prevalence of MetS and some of its components in adolescents. Therefore, uric acid should be considered as a potential additional marker of cardiovascular risk in this population. Support: CNPq, CAPES, FIPE, FAPERGS. Presentation: 6/1/2024

9193 Higher Serum Uric Acid Levels Are Associated With a Deleterious Metabolic and Inflammatory Profile in Brazilian Adolescents: An Exploratory Cross-Sectional Analysis

Abstract Disclosure: F.Q. Iorra: None. M.P. Guahnon: None. P.G. Rodrigues: None. A.T. Barcelos: None. F.V. Cureau: None. M. Drehmer: None. B.D. Schaan: None. Introduction: The association of high serum uric acid (sUA) with metabolic syndrome (MetS) and its components have been widely studied, but there are still gaps in how this breakdown product of purine metabolism might refine cardiovascular risk assessment and correlate with other cardiovascular disease biomarkers, especially in children and adolescents. Objective: To evaluate if sUA is associated with metabolic syndrome components and inflammatory markers in Brazilian adolescents. Methods: For this cross-sectional study, 786 individuals aged 12 to 17 years old, previously enrolled in the Study of Cardiovascular Risk in Adolescents (ERICA) - a Brazilian nationwide school based study, and who were from the city of Porto Alegre, had their sUA measured from blood samples that were stored in a biorepository. Anthropometric, biochemical and blood pressure data were collected. MetS diagnosis was based on the International Diabetes Federation age-specific criteria (2005), and insulin resistance was assessed by the HOMA-IR. In accordance with a non-parametric distribution, sUA was divided into quartiles (3.7 mg/dL, 4.4 mg/dL, 5.3 mg/dL for the 25th, 50th, and 75th percentiles, respectively) for the analysis. A linear regression model and a Poisson regression model with robust error variance were used, both adjusted for age, sex and skin color. Results: Participants were 14.8 ± 1.5 years-old, predominantly women (61.7%), self-identified as white skin color (72%) and eutrophic (66.9%). Through the linear regression model, significant positive associations were found between high sUA levels and body mass index Z-score, waist circumference, systolic and diastolic blood pressure, total cholesterol, triglycerides, HOMA-IR and C-reactive protein, and significant negative associations were observed for HDL cholesterol and adiponectin. No association was found between sUA and glucose or HbA1c. We also computed a metabolic risk score as the mean Z score of waist circumference, systolic blood pressure, HDL cholesterol (negative Z score), triglycerides and glucose, which was positive related to sUA (β ± SE = 0.13 ± 0.02; p < 0.001). Finally, the Poisson regression model was applied to estimate the prevalence ratios (PR) for MetS and its components, between adolescents with sUA in the 4th quartile to those in the 1st quartile. An association was observed for MetS (PR 6.37, 95% CI 1.39 - 29.21, p 0.017), high waist circumference (PR 4.61, 95% CI 2.55 - 8.36, p < 0.001) and increased triglycerides (PR 4.76, 95% CI 1.47 - 15.44, p 0.009). Conclusion: High sUA levels were associated with a worse metabolic and inflammatory profile, as well as a greater prevalence of MetS and some of its components in adolescents. Therefore, uric acid should be considered as a potential additional marker of cardiovascular risk in this population. Support: CNPq, CAPES, FIPE, FAPERGS. Presentation: 6/1/2024

Association between uric acid and cognitive function in maintenance hemodialysis patient

Background: Chronic kidney disease (CKD) is an independent risk factor for cognitive dysfunction. Hyperuricemia is prevalent in CKD patients and has been associated with cognitive dysfunction. Hyperuricemia has been associated with an increased risk for cerebral microvascular disease. Aims and Objectives: The study aimed to evaluate the association between uric acid level and cognitive function in maintenance hemodialysis patients. Materials and Methods: The study was conducted on 90 maintenance hemodialysis patients. Serum uric acid (sUA) level was measured in patients on maintenance hemodialysis and cognitive performance was assessed by the Standardized Mini-Mental State Examination score. Results: There was a significant association between sUA level and cognitive function in hemodialysis patients. Patient with higher sUA levels was found to have poor cognitive function (P<0.05). There was a significant negative correlation between sUA and cognitive function which revealed an increase in sUA will decrease the cognitive function (P<0.05). In our study, there was a significant association between sUA and cognitive function in hemodialysis patients. Patients with hyperuricemia had poor cognitive function. Conclusion: In our study, there was a significant association between sUA and cognitive function in hemodialysis patients. Patients with hyperuricemia had poor cognitive function.

Sex-specific associations between prolonged serum uric acid levels and risk of major adverse cardiovascular events

BackgroundWhile hyperuricemia has been correlated with cardiovascular (CV) diseases, further evidence is required to evaluate the implications of stable serum uric acid (sUA) levels, especially concerning low sUA. This study aimed to investigate prolonged stable sUA levels and CV events/mortality. MethodsWe conducted a retrospective cohort study at a medical center using electronic medical records linked with the national claims database. Patients with at least two sUA measurements, with intervals ranging from 6 months to 4 years, were included. The mean of the first two eligible sUA measurements were analyzed, stratified by sex. Outcomes of interest comprised major adverse cardiovascular events (MACE), heart failure hospitalization, CV and all-cause mortality. ResultsThis study included 33,096 patients (follow-up: men 6.6 years, women 6.4 years). After multivariable adjustment, cubic spline models showed that long-term high sUA levels were consistently associated with a higher risk of MACE, heart failure hospitalization, CV and all-cause mortality. A U-shaped association was observed between sUA levels and all-cause mortality in both sexes and between sUA levels and CV mortality in women. The impact of sUA, especially lower levels, on CV events and mortality was more pronounced in women than in men. ConclusionLong-term high sUA levels are consistently associated with increased risk of CV events and mortality. A U-shaped association between sUA levels and all-cause mortality was observed in both men and women and was pronounced in women. The findings underscore the importance of considering sUA levels, especially in women, when assessing CV risk.

Serum uric acid is associated with midbrain enlarged perivascular spaces: Results from Multi-modality Medical imaging sTudy bAsed on KaiLuan Study (META-KLS)

BackgroundSerum uric acid (SUA) is a major cause of cardiovascular and cerebrovascular diseases. Whether and to what extent the excess risk of enlarged perivascular spaces (EPVS) conferred by SUA is unknown. The study was conducted to investigate the association between SUA and EPVS in different brain regions. MethodsData are from Multi-modality medical imaging study based on Kailuan study (META-KLS) in this cross-sectional study. Participants were divided into five groups based on SUA levels, and EPVS in basal ganglia (BG), centrum semiovale (CSO) and midbrain (MB) was systematically assessed and divided into Low and High group. Odds ratio (OR) and 95% confidence intervals (95% CIs) for high EPVS outcomes were estimated using multivariable logistic regression analysis. Restricted cubic spline (RCS) was used to further investigate dose-response relationship. ResultsA total of 1014 participants aged 25–83 years from 11 centers were enrolled in the study. In the multivariable-adjusted model, SUA, as an independent risk factor, correlated positively with high degree of MB-EPVS (OR, 1.002; 95% CI, 1.000 to 1.004; p = 0.023) in general population. In addition, RCS further demonstrated the linear association between SUA and MB-EPVS (p = 0.072). No association was found between SUA and BG-EPVS or CSO-EPVS. ConclusionSUA was an independent risk factor of MB-EPVS. High SUA levels were more predictive of increased risk occurrence of high degree of MB-EPVS, supporting a linear association between SUA and MB-EPVS and further indicating that SUA may play an important role in cerebral small vessel disease. Trial registrationThe KaiLuan Study and META-KLS were registered online (ChiCTR2000029767 on chictr.org.cn and NCT05453877 on Clinicaltrials.gov, respectively).

Higher serum uric acid is associated with poorer cognitive performance in healthy middle-aged people: a cross-sectional study

Age-related cognitive impairment can occur many years before the onset of the clinical symptoms of dementia. Uric acid (UA), a metabolite of purine-rich foods, has been shown to be positively associated with improved cognitive function, but such association remains controversial. Moreover, most of the previous studies investigating the association included elderly participants with memory-related diseases. Therefore, the present study aimed at investigating whether serum UA (sUA) is associated with cognitive performance in healthy middle-aged individuals. We conducted a cross-sectional study on a cohort of middle-aged individuals (40–60 years old) who participated in the Qatar Biobank. The participants had no memory-related diseases, schizophrenia, stroke, or brain damage. They were divided according to sUA level into a normal group (< 360 μmol/L) and a high group (≥ 360 μmol/L), and underwent an assessment of cognitive function using the Cambridge Neuropsychological Test Automated Battery. Two cognitive function domains were assessed: (a) speed of reaction/reaction time and (b) short-term visual memory. The median age of the 931 participants included in the study was 48.0 years (IQR: 44.0, 53.0), of which 47.6% were male. Adjusted multivariable linear regression analyses showed that higher sUA is associated with poorer performance on the visual memory domain of cognitive function (β = − 6.87, 95% CI − 11.65 to − 2.10, P = 0.005), but not on the speed of reaction domain (β = − 55.16, 95% CI − 190.63 to 80.30, P = 0.424). Our findings support previous studies suggesting an inverse association between high sUA levels and cognitive function in elderly and extend the evidence for such a role to middle-aged participants. Further prospective studies are warranted to investigate the relationship between UA and cognition.

The Interplay between Cardiovascular Risk, Cardiovascular Events, and Disease Activity in Primary Sjögren's Syndrome: Is Uric Acid the Missing Link?

(1) Background: Uric acid is a well-known cardiovascular (CV) risk factor in the general population but its role in the setting of rheumatic diseases other than gout is unclear. (2) Methods: This is a retrospective study investigating a cohort of 105 pSS patients recording clinical, serological, and CV-related variables including adherence to the Mediterranean diet. (3) Results: We observed a strong relationship between disease activity, interstitial lung disease (ILD), and CV events. The association between ILD and CV events was dependent on higher SUA levels but independent of other traditional CV risk factors. All three cases of previous non-fatal stroke were reported by females aged <65 years, with higher SUA levels, and two of them also had pSS-ILD. Forty (38%) patients had a 10-year risk of fatal and non-fatal CV disease events beyond the cut-off recommended for their age, and using the correction factor of 1.5 currently applied only to rheumatoid arthritis, we could better identify patient subsets characterized by different CV risk profiles including different SUA levels. (4) Conclusions: This study is the first to investigate in depth the role of SUA in the CV scenario of pSS. Our findings underpin the importance of assessing SUA levels in pSS in addition to the other traditional CV risk factors and to consider applying the correction factor for CV risk assessment tools to achieve a better stratification of CV risk.

U-shaped association of serum uric acid with cardiovascular disease risk scores and the modifying role of sex among Chinese adults

Background and aimsSerum uric acid (SUA) is involved in the development of cardiovascular disease (CVD). However, information on the dose-response relationship between SUA and CVD is limited in the Chinese population. This study aimed to investigate the potential nonlinear dose-response association of SUA with CVD risk in a Chinese population and to explore the effect of sex on these associations. Methods and resultsCross-sectional data, from 6252 Chinese adults aged 30–74 years who participated in the China Health and Nutrition Survey 2009, were stratified by SUA deciles. The 10-year risk of CVD was determined using the Framingham risk score. A restricted cubic spline (RCS) was incorporated into the logistic models to assess the nonlinear relationship between SUA and CVD. Among the participants, 65%, 20%, and 15% had low, moderate, and high 10-year CVD risks, respectively. Compared with the reference SUA strata of 225 to <249 μmol/L, CVD risk was significantly increased at SUA ≥294 μmol/L, with adjusted ORs ranging from 2.39 (1.33–4.33) to 4.25 (2.37–7.65). An increasingly higher nonsignificant CVD risk was found at SUA <225 μmol/L and showed a nonlinear U-shaped association. In the fitted RCS model, an approximate U-shaped association between SUA and CVD risk scores was found in women, but this significant nonlinear relationship was not found in men. ConclusionThis study showed that both lower and higher SUA levels were associated with a higher 10-year CVD risk among Chinese adults, forming a U-shaped relationship, and this pattern was particularly pronounced for women.

Correlation Between Serum Uric Acid Levels and Coronary Plaque Characteristics on Optical Coherence Tomography.

Elevated serum uric acid (sUA) is associated with increasing risk of coronary heart disease (CHD). However, existing research is limited by potential confounders. Herein, our study aims to probe the association between sUA levels and the morphological characteristics of coronary plaque by a propensity score matching (PSM) analysis.All 420 patients with CHD who had undergone optical coherence tomography of culprit lesions were included. Eligible patients were assigned into 2 groups according to sUA level: high-sUA group (sUA ≥ 6.0 mg/dL) and low-sUA group (sUA < 6.0 mg/dL). PSM was applied to control the balance of baseline characteristics.After PSM, a total of 112 patients were included in our study (56 in each group). The high-sUA group showed a higher prevalence of TCFA (35.7% versus 16.1%, P = 0.03) and macrophage infiltration (33.9% versus 14.3%, P = 0.026) compared with the low-sUA group. Plaques in the high-sUA group had a wider maximum lipid arc (166.51° (115.77°, 224.14°) versus 142.29° (93.95°, 169.06°), P = 0.048), longer calcification length (6.77 (3.90, 20.55) mm versus 4.20 (1.95, 7.45) mm, P = 0.040), and thinner minimum fibrous cap thickness (43.81 (28.17, 62.26) μm versus 92.57 (46.25, 135.37) μm, P = 0.003). Correlation analysis indicated that the sUA value was inversely associated with the minimum fibrous cap thickness (r = -0.332, P = 0.015) and positively associated with the maximum lipid arc (r = 0.399, P = 0.003), average lipid arc (r = 0.347, P = 0.011), and calcification length (r = 0.386, P = 0.006).The relationship between high-sUA levels and typical vulnerable features of plaques persisted after balancing the traditional risk factors.

Correlation of obesity, dietary patterns, and blood pressure with uric acid: data from the NHANES 2017–2018

BackgroundPrevalence rates of hyperuricemia and gout are increasing. Clinical investigations of hyperuricemia-related risk factors aid in the early detection, prevention, and management of hyperuricemia and gout. Ongoing research is examining the association of obesity, dietary patterns, and blood pressure (BP) with serum uric acid (sUA).MethodsA cross-sectional study was conducted based on the National Health and Nutrition Examination Survey. The exposures included body mass index (BMI), dietary patterns, and BP. The outcome variable was sUA level. The weighted multivariate linear regression models and smooth curve fittings were used to assess the association of BMI, dietary patterns, and BP with sUA.ResultsThere was a significantly positive correlation between BMI and sUA (β = 0.059, 95% CI: 0.054 to 0.064, P < 0.00001). Overweight and obese individuals had higher sUA levels than those with the normal BMI (β = 0.451, 95% CI: 0.357 to 0.546, P < 0.00001; β = 0.853, 95% CI: 0.760 to 0.946, P < 0.00001; respectively). Dietary energy intake was positively correlated with sUA (β = 0.000, 95% CI: 0.000 to 0.000, P = 0.01057). Dietary intake of carbohydrate and fiber were negatively correlated with sUA (β = − 0.001, 95% CI: − 0.002 to − 0.000, P < 0.00001; β = − 0.008, 95% CI: − 0.011 to − 0.004, P = 0.00001; respectively). Moreover, systolic BP was positively correlated with sUA (β = 0.006, 95% CI: 0.003 to 0.009, P = 0.00002). However, no statistical differences were found about the associations of dietary intake of total sugars, protein, total fat, cholesterol, and diastolic BP with sUA.ConclusionsThe current cross-sectional investigation of a nationally representative sample of US participants showed that BMI, dietary energy intake, and systolic BP were positively correlated with sUA levels; dietary carbohydrate and fiber intake were negatively correlated with sUA levels. The findings might be helpful for the management and treatment of hyperuricemia and gout.

Impaired Sensitivity to Thyroid Hormones Is Associated with Hyperuricemia, Obesity, and Cardiovascular Disease Risk in Subjects with Subclinical Hypothyroidism.

Background: Subclinical hypothyroidism (SCH) is associated with an increased risk of metabolic disorders and cardiovascular events. There is a delicate interplay between thyroid hormones and thyrotropin (TSH) and metabolic homeostasis. However, the association between thyroid hormone sensitivity and metabolic indices has not been elucidated in SCH. Methods: We enrolled 11,109 participants with SCH. All participants had a TSH level >4.2 mIU/L and normal free thyroxine (fT4; 12.0-22.0 pmol/L). Metabolic indices (body mass index [BMI], blood pressure, serum lipid, serum uric acid [sUA], plasma glucose and glycosylated hemoglobin [HbA1C]) were measured. The thyroid hormone sensitivity indices that include thyroid feedback quantile-based index (TFQI), TSH index (TSHI), and thyrotroph thyroxine resistance index (TT4RI) were calculated based on fT4 and TSH. Higher TFQI quartiles indicated lower thyroid hormone sensitivity. The relationship between thyroid hormone sensitivity indices and metabolic indices and cardiovascular disease (CVD) risk were calculated. Results: Participants with decreased central sensitivity to thyroid hormone had lower BMI and higher sUA levels. The odds ratio of the fourth versus the first quartile of TFQI was 0.85 [confidence interval, CI: 0.73-0.96] for obesity, 1.64 [CI: 1.37-1.92] for hyperuricemia (HUA), and 12.22 [CI: 5.32-28.07] for 10-year risk distribution for CVD >20%. Further adjustment for BMI when analyzing HbA1C, HUA, and CVD risk generated similar results. TSHI and TT4RI also yielded similar results. Conclusions: Impaired sensitivity to thyroid hormone in SCH is associated with higher risk of HUA and CVD and lower risk of obesity. These findings are potentially useful for understanding the interaction between thyroid hormone sensitivity and metabolic diseases in SCH.

A study on association of serum uric acid and blood pressure in hypertensives at a tertiary care centre

Hypertension(HTN) is the most common and significant cardiovascular disease because of its prevalence and severity of the damage to the mankind globally. Hyperuricemia, a condition of increased levels of Serum Uric acid (UA) has been proposed to have an association with hypertension in various studies. In certain studies, serum uric acid levels has been found to be an independent predictor for developing hypertension. On the basis of the above observations, we have proposed to the present study to compare the relationship between serum UA and hypertension in a single cohort with adjustment of all possible confounding factors.A total of 245 subjects were enrolled in this study during a regular routine health checkup. All subjects were informed about the study aims Individuals having a known history of gout and cardiac or severe renal diseases and patients who are already under medication for anti-hyperuricemic were excluded from the study. General information like Name, Age, Sex, Occupation, Address along with history of any drug intake and anthropometric indices - body weight (BW), body height (BH), hip circumference (HC), waist circumference (WC), and lifestyle information have been obtained. The data has been arranged in tables with mean ± SD for further analysis. The data is analyzed using IBM SPSS version 23. The difference between the groups for baseline variables was done by independent sample t-test (two-tailed). Pearson’s correlation coefficient test was performed to assess the interrelationships between baseline variables and SUA concentrations. The differences for the variables among the groups was determined by using One-way ANOVA.Of the 245 subjects, mean age of the participants was 42.4 ± 8.4 years (range 18–70 years). There was no significant difference in the mean levels of Height, Weight and BMI between the two groups. Mean levels of WC, HC were significantly different between two group (p &amp;#60; 0.05) subjects. The mean levels of SBP and DBP were also significantly more in the hypertensive subjects (p &amp;#60; 0.001). In Pearson’s correlation coefficient test, SUA levels were significantly related with SBP and DBP. In this study, we have observed comparatively a stronger relationship for SUA concentration with hypertension and prehypertension in the participants. The extended mechanism for the effect of SUA on hypertension is yet to be elucidated. There are some hypotheses partly explain the association between SUA and high blood pressure. One of the possible mechanism might be uric acid deposition on the blood vessels walls activates the renin-angiotensin system, suppress the liberate of carbon monoxide, enhance inflammation, and leads to vasoconstriction on later stage, which consequently leads to hyperplasia and incidence of hypertension. Another possibility involving oxidative stress and endothelial dysfunction associated with high SUA levels may contribute to high blood pressure.

Coagulation in gout: is there a link with disease activity?

ObjectiveTo investigate the coagulation system in gout patients and associations between disease activity and levels of coagulation markers.MethodsA prospective cohort study was performed with data from 30 Dutch gout patients. Levels of coagulation markers including APTT, PT, D-dimer, prothrombin F1 + 2, von Willebrand factor, and thrombin generation parameters were analyzed at baseline and 1-year visit. These markers were related to clinical markers of gout disease activity including the Gout Activity Score (GAS). Our hypothesis was that patients with gout and active disease have increased levels of coagulation markers and that a decrease in disease activity would lead to normalization of coagulation activity.ResultsA higher GAS was associated with increased levels of thrombin generation parameters including ETP (ß = 0.48, p = 0.01), peak thrombin (ß = 0.60, p = 0.001), and velocity index (ß = 0.57, p = 0.002). Tophaceous gout and higher SUA levels were associated with thrombin generation parameters. After 1 year, thrombin generation parameters showed a small procoagulant trend despite a moderate decrease in disease activity. Prospectively measured changes in disease activity according to the GAS were not associated with any of the coagulation markers.ConclusionPatients with active gout have higher levels of thrombin generation markers, indicating a link between disease activity and coagulation. A change in disease activity after 1 year was not associated with significant changes in coagulation markers, probably due to prolonged low-grade inflammation. Future studies should focus on levels of coagulation markers in comparison with the general population and the effect of adequate gout treatment.Key Points• Patients with gout have an increased risk of cardiovascular events.• High disease activity was associated with higher levels of thrombin generation markers.• Over time, small decreases in inflammation were associated with a decrease in D-dimer and thrombin generation.

English

BACKGROUND The study was conducted in an attempt to correlate serum uric acid levels with Killip class i.e. severity of heart failure in patients with acute myocardial infarction and to assess any influence of serum uric acid levels on predicting prognosis in patients with acute myocardial infarction. Ischaemic heart disease, particularly acute myocardial infarction is one of the leading causes of death across the world accounting for 12.7 % of global mortality. Low and middle-income countries are facing 80 % of the global burden of ischaemic heart disease death. Since the pathophysiology of acute myocardial infarction is complicated, proper risk stratification is essential for appropriate management and better outcome. Serum uric acid levels (SUA) have been correlated with coronary artery calcification and atherosclerosis. High SUA levels also have been identified as a risk marker for cardiovascular disease development, progression and mortality. METHODS The study design was a one-year cross-sectional study. 100 patients admitted with acute myocardial infarction within one day of the start of symptoms in the Department of Cardiology &amp; Medicine were included from September 2018 to September 2019. In this study, patients with known causes of elevated uric acid levels (chronic kidney disease, gout, haematological malignancy, hypothyroidism, metabolic syndrome, myeloproliferative disease, lymphoproliferative disease, drugs– pyrazinamide, diuretics, ethambutol, ethanol, malignancy, G6PD deficiency and psoriasis) were included. Patients on drugs which raise serum uric acid e.g., salicylates (2 gm / d, hydrochlorothiazide, pyrazinamide), and chronic alcoholics were not included. Patients were further subjected to investigations like serum uric acid, ECG, 2D echo and other routine investigations. Urine albumin levels, troponin I, chest x-ray, fundoscopy, and fasting lipid profile were done. Investigation reports were analysed with the clinical profile and the data was compiled and appropriate statistical test was applied. RESULTS There were more cases of myocardial infarction above 40 years as compared to below 40 years of age and males (69 %) were more as compared to females (31 %) with the commonest presentation as chest pain. Majority of the patients had inferior wall myocardial infarction (IWMI) (40 %) and most (91 %) of the patients had left ventricular (LV) dysfunction (mild, moderate and severe). More patients with Killip class III and IV had abnormal uric acid levels as compared to class I, and II. Among 27 patients who expired, 23 were in Killip class III and IV (13 in Killip class III and 10 in class IV) and the mean serum uric acid levels of expired patients were elevated on all the 3 days with maximum elevation on day 1. CONCLUSIONS Patients with higher Killip class had higher levels of serum uric acid in comparison to patients of lower Killip class. Serum uric acid level in association with Killip class is a good predictor of the severity of heart failure and short-term mortality after myocardial infarction.

Serum uric acid is associated with increased risk of posttransplantation diabetes in kidney transplant recipients: a prospective cohort study

BackgroundSerum uric acid (SUA) is associated with fasting glucose in healthy subjects, and prospective epidemological studies have shown that elevated SUA is associated with increased risk of type 2 diabetes. Whether SUA is independently associated with higher risk of posttransplantation diabetes mellitus (PTDM) in kidney transplant recipients (KTR) remains unknown. MethodsWe performed a longitudinal cohort study of 524 adult KTR with a functioning graft ≥1-year, recruited at a university setting (2008–2011). Multivariable-adjusted Cox proportional-hazards regression analyses were performed to assess the association between time-updated SUA and risk of PTDM (defined according the American Diabetes Association's diagnostic criteria). ResultsMean (SD) SUA was 0.43 (0.11) mmol/L at baseline. During 5.3 (IQR, 4.1–6.0) years of follow-up, 52 (10%) KTR developed PTDM. In univariate prospective analyses, SUA was associated with increased risk of PTDM (HR 1.75, 95% CI 1.36–2.26 per 1-SD increment; P < 0.001). This finding remained materially unchanged after adjustment for components of the metabolic syndrome, lifestyle, estimated glomerular filtration rate, immunosuppressive therapy, cytomegalovirus and hepatitis C virus infection (HR 1.89, 95% CI 1.32–2.70; P = 0.001). These findings were consistent in categorical analyses, and robust in sensitivity analyses without outliers. ConclusionsIn KTR, higher SUA levels are strongly and independently associated with increased risk of PTDM. Our findings are in agreement with accumulating evidence supporting SUA as novel independent risk marker for type 2 diabetes, and extend the evidence, for the first time, to the clinical setting of outpatient KTR.

Association between Serum Uric Acid and Nonalcoholic Fatty Liver Disease in Nonobese Postmenopausal Women: A Cross-sectional Study

This study aimed to determine the association between serum uric acid (sUA) and nonalcoholic fatty liver disease (NAFLD) in nonobese postmenopausal women. A total of 4323 female individuals over 18 years of age participated in this cross-sectional study. The subjects were divided into four groups according to menopause status and body mass index. sUA quartiles in this female population were categorized as follows: Q1 ≤ 230 mmol/L, Q2: 231–270 mmol/L, Q3: 271–310 mmol/L and Q4: ≥ 311 mmol/L. The presence or absence of NAFLD was assessed by abdominal ultrasonography. The prevalence of NAFLD was 38.8% in the general population, and the average age was 46.5 ± 11.3 years. Among nonobese and obese subjects, the prevalence of NAFLD was lower in nonmenopausal subjects than in postmenopausal subjects (nonobese: 20.74% vs 45.26%, respectively, P < 0.0001; obese: 70.51% vs 84.35%, respectively, P < 0.0001). After adjusting for age, current smoking status, current alcohol drinking status, diabetes, hypertension disease and triglyceride, the ORs (95% CIs) for NAFLD among individuals in Q2-Q4 were 1.518 (1.062–2.169), 1.431 (1.010–2.027) and 2.054 (1.442–2.927), respectively, P value for trend <0.0001. Higher sUA levels can be used as a predictive biomarker for NAFLD in nonobese postmenopausal women.

Non-alcoholic fatty liver disease: correlation with hyperuricemia in a European Mediterranean population

ABSTRACT Objectives Non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS) are two pathologies that intersect each other. It was found that there is an association between MetS/NAFLD and hyperuricemia. The aim of our study was to demonstrate this association in a European Mediterranean population. Methods We compared 236 patients with NAFLD to 218 patients without NAFLD. We assessed laboratory metabolic parameters (serum uric acid – SUA, fasting glucose, triglycerides, total cholesterol, etc.) and the presence or absence of MetS in a retrospective, cross-sectional, case–control manner. Results Analysis of the two main variables in study showed a moderate direct correlation (p< 0.01; Pearson coefficient 0.443) between SUA and NAFLD. Evaluation for SUA quartiles showed a decreased risk of NAFLD for the first and second quartiles (OR Q1 = 0.20; OR Q2 = 0.59), but increased for the third and fourth quartiles (OR Q3 = 2.22; OR Q4 = 6.97). In females, the risk of NAFLD was less compared to males for the first three quartiles of SUA, but it was more than double for the fourth quartile (OR Q1 0.21 vs 0.16; OR Q2 0.82 vs 0.45; OR Q3 2.50 vs 2.26; OR Q4 4.50 vs 9.83). In the NAFLD group, hyperuricemia was significantly correlated with sex, obesity, hypertension, and with the number of components of the MetS. In the Control group, SUA directly correlated with age, diabetes, and ALT, but not with obesity. Conclusion We have found a significant correlation between NAFLD and hyperuricemia. The higher SUA levels accompanied the risk of NAFLD.

The Effect of Uric Acid Level, Hyperuricemia and Gout on the Risk of Type 2 Diabetes: A Meta-Analysis of Cohort Studies

Background: Epidemiology evidence on the effect of serum uric acid levels (SUAs), hyperuricemia, and gout on the risk of type 2 diabetes (T2DM) is inconsistent. We conducted a meta-analysis of cohort studies to comprehensively summarize the issue. Methods: We searched the PubMed and Embase databases to November 2019 for studies conformed to the inclusion criteria. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated with random-effect meta-analysis. We conducted dose-response meta-analysis to investigate the relation between SUA and T2DM risk. Meta-regression analyses, subgroup analyses and sensitivity analyses were performed to identify potential sources of heterogeneity. Findings: A total of 23 prospective studies involving 737468 participants were identified. A significantly positive association between higher uric acid level, hyperuricemia, gout and T2DM risk was observed, respectively(RR=1.20, 95% CI 1.14, 1.27; RR=1.52, 95% CI 1.21, 1.91; RR=1.35, 95% CI 1.16, 1.57). Piecewise dose-response analysis found a linear trend for SUA higher than 4.5mg/dl, with one mg/dl increase of SUA level associated with 8% increase of T2DM risk (RR=1.08, 95%CI= 1.03, 1.13, P=0.001). Unadjusted for hypertension found a positive association between gout and T2DM risk (RR=1.40, 95% CI 1.22, 1.66), while adjusted for hypertension found the relation to be non-significant (RR=1.31, 95% CI 0.78, 2.21). Interpretation: The present findings suggest that higher SUA levels, hyperuricemia and gout are risk factors for T2DM. It is necessary for hyperuricemia and gout patients to test blood glucose regularly and prevent T2DM. For general population, lowering serum uric acid might protect from incident T2DM. Funding Statement: The authors stated that they received no funding for this work. Declaration of Interests: The authors declare that they have no conflicts of interest. Ethics Approval Statement: The authors planned and conducted this review under the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analyses: the PRISMA statement.

Crystal-proven gout patients have an increased mortality due to cardiovascular diseases, cancer, and infectious diseases especially when having tophi and/or high serum uric acid levels: a prospective cohort study

To investigate the cause-specific mortality and the possible involved clinical characteristics with increased mortality in a cohort of 700 patients with crystal-proven gout. The cause-specific mortality of gout was compared to the mortality of the general population. Patients with arthritis referred for diagnosis were consecutively included in the Gout Arnhem-Liemers Cohort (GOAL). Joint fluid analysis was performed in all patients and only crystal-proven gout patients were included in this study. At inclusion clinical characteristics and laboratory values were collected. At follow-up patients who died were identified. Standardized mortality ratios (SMRs) were calculated for all-causes, cardiovascular diseases, cancer, and infectious diseases using indirect standardization methods for mortality outcomes and compared with the general population. The clinical characteristics of the patients who died were compared with those of the survivors and were analyzed by a logistic regression analysis to identify any associations with mortality. The study population at inclusion contained 573 (81.9%) men and 127 (18.1%) females with an average age of 62.0 (SD 13.4). During 3500 person-years from inclusion visit till 31 May 2016, in 700 gout patients, 66 deaths (27 cardiovascular deaths, 15 cancer-related deaths, 8 infectious deaths, 16 various other causes) occurred in this cohort. The all-cause standardized mortality ratio in gout patients was 2.21 (95% CI 1.68-2.74). In this cohort, gout patients had a higher SMR for death attributed to cardiovascular diseases (6.75; 95% CI 4.64-8.86), infectious diseases (4.66; 95% CI 1.51-7.82) and cancer (3.58; 95% CI 1.77-5.39). Corrected for confounders high serum uric acid levels (SUA; > 0,56mmol/L), tophaceous gout, a history of peripheral vascular disease, myocardial infarction, and heart failure at the inclusion visit were associated with increased mortality during follow-up. Compared to the general population, gout patients have an increased association with all-cause disease mortality, especially attributed to cardiovascular diseases, cancer, and infectious diseases. This association is strongest in hyperuricemic (uric acid levels > 0,56mmol/l) and tophaceous patients and in those with a history of peripheral vascular disease, myocardial infarction, and heart failure. Preventive measures like treatment of high SUA levels and treatment of cardiovascular risk factors need to be considered and evaluated.

Impact of Accumulated Serum Uric Acid on Coronary Culprit Lesion Morphology Determined by Optical Coherence Tomography and Cardiac Outcomes in Patients with Acute Coronary Syndrome

Objectives: We aimed to examine the relations of very high levels of serum uric acid (sUA) with features of culprit lesion plaque morphology determined by optical coherence tomography (OCT) and adverse clinical outcomes in patients with acute coronary syndrome (ACS). Methods: We retrospectively compared ACS patients according to sUA levels of > 8.0 mg/dL (n = 169), 7.1–8.0 mg/dL (n = 163), 6.1–7.0 mg/dL (n = 259), and ≤6.0 mg/dL (n = 717). Angiography and OCT findings were analyzed in patients with preintervention OCT and the 4 sUA groups (> 8.0 mg/dL, n = 61; 7.1–8.0 mg/dL, n = 72; 6.1–7.0 mg/dL, n = 131; and ≤6.0 mg/dL, n = 348) were compared. Results: Cardiogenic shock was more prevalent in ACS patients with sUA > 8.0 mg/dL (22% vs. 19% vs. 10% vs. 6%, p < 0.001). Plaque rupture was observed more prevalently by OCT in patients with sUA > 8.0 mg/dL (67% vs. 47% vs. 56% vs. 45%, p = 0.027). At the 2-year follow-up, Kaplan-Meier estimates showed higher cardiac mortality in patients with sUA > 8.0 mg/dL (25% vs. 12% vs. 5% vs. 5%, p < 0.001). After adjusting for traditional cardiovascular risk factors and creatinine levels, patients with sUA > 8.0 mg/dL showed a 4.5-fold increased risk in 2-year cardiac death by multivariate Cox proportional hazard analysis (hazard ratio 4.54, 95% confidence interval 2.98–6.91; p < 0.001). Conclusions: Very high sUA levels like > 8.0 mg/dL are the primary predictor of 2-year cardiac mortality and could partly be caused by adverse effects of accumulated sUA on plaque morphology in patients with ACS.