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Low Serum Uric Acid Predicts Risk of a Composite Disease Endpoint.

ABSTRACT: Background and objectives: Mortality may increase in hypouricemia as well as inhyperuricemia. We assessed the predictive value of low serum uric acid (SUA) levels on the risk of overall mortality or a composite endpoint of death and nonfatal events. Materials and Methods: In 1013 community-based middle-aged adults, free of uncontrolled diabetes and coronary heart disease at baseline, the association of sex-specific SUA tertiles with defined outcomes was evaluated prospectively by logistic regression, stratified to gender and presence of type-2 diabetes, using recent criteria. Results: Totally, 43 deaths and additional incident nonfatal events in 157 cases were recorded at a median 3.4 years' follow-up. Multivariable linear regression disclosed SUA to be significantly associated among non-diabetic individuals positively with creatinine, triglycerides, and body mass index in women further with fasted glucose. In multivariable-adjusted logistic regression analysis, sex-specifically dichotomized baseline uric acid (<5.1 and <4.1 mg/dL vs. higher values) significantly predicted the non-fatal events in the whole sample (relative risk (RR) 1.51 [95% confidence interval (CI) 1.02; 2.26]), as well as in men, while composite endpoint in the whole sample tended to rise (RR 1.38). Compared with the intermediate one, the top and bottom SUA tertiles combined tended to confer mortality risk (RR 2.40 [95% CI 0.89; 6.51]). Adverse outcomes in diabetic women were predicted by tertiles 2 and 3. Conclusions: Inverse association of SUA with adverse outcomes, especially in men, is consistent with the involvement of uric acid mass in autoimmune activation. The positive association of uric acid with adverse outcomes in diabetic women is likely mediated by concomitant high-density lipoprotein dysfunction.

SUBMITTER: Ozpamuk-Karadeniz F

PROVIDER: S-EPMC8068308 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe severity of coronavirus disease 2019 (COVID-19) is highly variable between individuals, ranging from asymptomatic infection to critical disease with acute respiratory distress syndrome requiring mechanical ventilation. Such variability stresses the need for novel biomarkers associated with disease outcome. As SARS-CoV-2 infection causes a kidney proximal tubule dysfunction with urinary loss of uric acid, we hypothesized that low serum levels of uric acid (hypouricemia) may be associated with severity and outcome of COVID-19.MethodsIn a retrospective study using two independent cohorts, we investigated and validated the prevalence, kinetics and clinical correlates of hypouricemia among patients hospitalized with COVID-19 to a large academic hospital in Brussels, Belgium. Survival analyses using Cox regression and a competing risk approach assessed the time to mechanical ventilation and/or death. Confocal microscopy assessed the expression of urate transporter URAT1 in kidney proximal tubule cells from patients who died from COVID-19.ResultsThe discovery and validation cohorts included 192 and 325 patients hospitalized with COVID-19, respectively. Out of the 517 patients, 274 (53%) had severe and 92 (18%) critical COVID-19. In both cohorts, the prevalence of hypouricemia increased from 6% upon admission to 20% within the first days of hospitalization for COVID-19, contrasting with a very rare occurrence (< 1%) before hospitalization for COVID-19. During a median (interquartile range) follow-up of 148 days (50-168), 61 (12%) patients required mechanical ventilation and 93 (18%) died. In both cohorts considered separately and in pooled analyses, low serum levels of uric acid were strongly associated with disease severity (linear trend, P < 0.001) and with progression to death and respiratory failure requiring mechanical ventilation in Cox (adjusted hazard ratio 5.3, 95% confidence interval 3.6-7.8, P < 0.001) or competing risks (adjusted hazard ratio 20.8, 95% confidence interval 10.4-41.4, P < 0.001) models. At the structural level, kidneys from patients with COVID-19 showed a major reduction in urate transporter URAT1 expression in the brush border of proximal tubules.ConclusionsAmong patients with COVID-19 requiring hospitalization, low serum levels of uric acid are common and associate with disease severity and with progression to respiratory failure requiring invasive mechanical ventilation.

Project description:ObjectiveTo evaluate the associations between serum uric acid (SUA) levels and cardiovascular disease (CVD) risk factors, focusing on potential sex-specific differences.DesignA retrospective cohort study.SettingA large community-based survey was conducted every two years from 2010 to 2018 in Hangzhou, Zhejiang Province, outheastern China.Participants6119 participants aged 40 years and above who underwent at least three times of physical examinations were enrolled.MethodsParticipants were categorised into four groups (Q1-Q4) based on baseline SUA quartiles within the normal range, with hyperuricaemia (HUA) as the fifth group. The Q1 was the reference. By stratifying participants by gender, the relationships between SUA levels and systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG) and total cholesterol (TC) were investigated using linear regression models in the generalised estimating equation. Additionally, the associations of elevated SUA levels and HUA with hypertension, hyperglycaemia and dyslipidaemia were correspondingly examined using multivariate logistic regression models.ResultsAfter adjusting for confounding variables, we found positive associations between SUA levels and SBP, DBP, FBG and TC in women, and with TC in men (p<0.01). Likewise, elevated SUA quartiles and HUA were linked to increased dyslipidaemia risk in both sexes, and increased hyperglycaemia risk only in women, with HRs (95% CI) of 1.64 (1.05 to 2.55) and 2.37 (1.47 to 3.81) in the Q4 and HUA group, respectively. Women with HUA had higher hypertension risk (HR=1.45, 95% CI 1.21 to 1.73), while no such association was observed in men. Stratified analyses revealed significant associations between elevated SUA levels and CVD risk factors in postmenopausal and non-obese women.ConclusionsElevated SUA levels increase the risk of dyslipidaemia in both sexes. SUA levels within normal range and HUA are positively associated with hyperglycaemia and hypertension in postmenopausal women, but not in men.

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Low Serum Uric Acid Predicts Risk of a Composite Disease Endpoint.

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