Hyperuricemia and Risk of Cardiovascular Outcomes: The Experience of the URRAH (Uric Acid Right for Heart Health) Project

Maloberti, Alessandro; Giannattasio, Cristina; Bombelli, Michele; Desideri, Giovambattista; Cicero, Arrigo Francesco Giuseppe; Muiesan, María Lorenza; Rosei, Enrico Agabiti; Salvetti, Massimo; Ungar, Andrea; Rivasi, Giulia; Pontremoli, Roberto; Viazzi, Francesca; Facchetti, Rita; Ferri, Claudio; Bruno, Bernardino; Galletti, Ferruccio; D’Elia, Lanfranco; Palatini, Paolo; Casíglia, Edoardo; Tikhonoff, Valérie; Barbagallo, Carlo M.; Verdecchia, Paolo; Masi, Stefano; Mallamaci, Francesca; Cirillo, Massimo; Rattazzi, Marcello; Pauletto, Paolo; Cirillo, Pietro; Gesualdo, Loreto; Mazza, Alberto; Volpe, Massimo; Tocci, Giuliano; Iaccarino, Guido; Nazzaro, Pietro; Lippa, Luciano; Parati, Gianfranco; Dell’Oro, Raffaella; Quartı-Trevano, Fosca; Grassı, Guıdo; Virdis, Agostino; Borghi, Claudio

doi:10.1007/s40292-020-00368-z

Cited by 101 publications

(62 citation statements)

References 55 publications

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“…Furthermore, a positive association was found between hyperuricemia and albumin levels >3.5 g/dL. More studies are needed to stablish a cut point of UA levels in the renal population, similar to the URRAH project [13] in the hypertensive subject, and to confirm and clarify whether elevated uric acid could be an indicator of increased antioxidant capacity or better nutritional status in this population. Funding: The National Council of Science and Technology (CONACYT) provided a graduate scholarship for the principal investigator (Grant 708801).…”

Section: Resultsmentioning

confidence: 95%

“…Uric acid (UA) is the final product of purine metabolism [11]. Hyperuricemia, defined as UA levels ≥6.0 and ≥7.0 mg/dL in women and men, respectively [12], has been related with cardiovascular (CV) events; for example, in the URRAH Project cohort, the level of uricemia above which the independent risk of CV disease may increase are 4.7 and 5.6 mg/dL for total and CV mortality, respectively [13]. Furthermore, hyperuricemia has been associated with the incidence of CKD in healthy subjects [14]; one of the reasons has been UA role as an oxidizing molecule [15].…”

Section: Introductionmentioning

confidence: 99%

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Association between Serum Uric Acid Levels, Nutritional and Antioxidant Status in Patients on Hemodialysis

et al. 2020

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Purpose: To determine the relationship between uric acid (UA) and nutritional and antioxidant status in hemodialysis (HD) patients, given that hyperuricemia could be an indicator of good nutritional status possibly because of the antioxidant properties of UA. Methods: Cross-sectional study with 93 patients on HD. Hyperuricemia was considered as UA ≥6.0 mg/dL in females and ≥7.0 mg/dL in males. Nutritional variables were registered. Blood samples were taken before the dialysis session to determine oxidative damage as plasma malondialdehyde (MDA) content, and antioxidant capacity measuring 2,2-diphenyl-piclrylhidrazil radical (DPPH●) scavenging activity and oxygen radical absorbance capacity (ORAC) value. Results: Patients with hyperuricemia had higher creatinine (11.9 vs. 10.5 mg/dL; p = 0.004), potassium (5.5 vs. 5.0 mg/dL; p = 0.014) levels; phase angle (5.8 vs. 4.9; p = 0.005), protein consumption (normalized protein nitrogen appearance, nPNA, 1.03 vs. 0.83; p = 0.013) than normouricemic patients. DPPH● scavenging activity was higher in hyperuricemic subjects (1.139 vs. 1.049 mM Trolox equivalents; p = 0.007); likewise, hyperuricemic subjects had less oxidant damage measured by MDA (10.6 vs. 12.7 nmol/mL; p = 0.020). Subjects with normouricemia were at higher risk of having a reactance to height (Xc/H) ratio less than 35 (OR 2.79; 95% CI, 1.1–7.017, p = 0.028); nPNA < 1.0 (OR 3.78; 95% CI, 1.4–10.2, p = 0.007), diagnosis of cachexia (OR 2.95; 95% CI, 1156–7.518, p = 0.021), potassium levels <5 (OR 2.97; 95% CI, 1.136–7.772, p = 0.023) and PA < 5.5° (OR 3.38; 95% CI, 1.309–8.749, p = 0.012.) Conclusions: Patients with hyperuricemia had higher antioxidant capacity and better nutritional status. Purines and protein restrictions in HD patients with hyperuricemia need to be reviewed individually for each patient. More studies are needed to stablish a cut point of UA levels in renal population.

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Section: Resultsmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Association between Serum Uric Acid Levels, Nutritional and Antioxidant Status in Patients on Hemodialysis

et al. 2020

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“…Hyperuricemia increased with increasing serum retinol levels, indicating that the consumption of vitamin A exceeding the recommended values from fortified foods and supplements could be responsible for adverse health outcomes related to hyperuricemia, including not only gout [ 1 ] but also hypertension [ 3 ], metabolic syndrome [ 4 ], chronic kidney disease [ 5 ], and myocardial infarction [ 7 ]. Previous studies have shown that high serum retinol levels had a negative effect on the development of osteoporosis and hip fractures [ 32 , 33 ].…”

Section: Discussionmentioning

confidence: 99%

“…Hyperuricemia is not only a main risk factor for gout [ 1 ] but is also an independent determinant of type 2 diabetes [ 2 ], hypertension [ 3 ], metabolic syndrome [ 4 ], and chronic kidney disease [ 5 ]. Elevated serum uric acid is reported to be associated with an increased risk of non-dipping blood pressure [ 6 ], myocardial infarction [ 7 ], and cardiovascular mortality [ 7 ]. Serum uric acid levels may increase due to heavy alcohol consumption [ 8 ], high purine diet [ 9 ], impaired renal or extra-renal excretion [ 10 ], and increased cell turnover [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Associations of Serum Retinol and α-Tocopherol Levels with Uric Acid Concentrations: Analysis of a Population-Based, Nationally Representative Sample

et al. 2020

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The effects of serum retinol and α-tocopherol on serum uric acid levels have not been established, especially in Asian people. This study evaluated the independent associations of retinol and α-tocopherol with serum uric acid levels in the Korean population. We included 6023 participants aged ≥ 19 years from the Korean National Health and Nutrition Examination Survey (KNHANES). Serum retinol and α-tocopherol levels were divided into quintiles, and a multivariate linear regression model was used to evaluate the association of serum retinol and α-tocopherol levels with uric acid concentration. Additionally, we used multivariate logistic regression to examine the relationships between the levels of these micronutrients and hyperuricemia. Serum retinol levels were positively associated with uric acid concentrations in a dose-dependent fashion in both sexes (ptrend < 0.001); the difference in serum uric acid levels between the highest and lowest quintiles of retinol levels was 0.57 mg/dL in men and 0.54 mg/dL in women. In the multivariable logistic model, the hyperuricemia risk increased linearly with the increase in serum retinol level, regardless of sex (ptrend < 0.001). Although the serum α-tocopherol level appeared to be significantly associated with increased uric acid levels, this association was nullified after adjusting for serum retinol levels. Serum retinol levels were positively associated with serum uric acid levels and hyperuricemia in a dose-response fashion. Maintaining serum retinol concentrations under sub-toxic levels might be necessary to prevent hyperuricemia-related adverse health outcomes.

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“…The ongoing URRAH (Uric Acid Right for Heart Health) project has identified several SUA cutoff values for prediction of total mortality (4.7 mg/dL), CV mortality (5.6 mg/dL), and fatal myocardial infarction (5.7 mg/ dL) [72].…”

Section: Hyperuricemia and Cardiovascular Diseasementioning

confidence: 99%

Hyperuricemia, the heart, and the kidneys – to treat or not to treat?

et al. 2020

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Background: Hyperuricemia is a state in which the serum levels of uric acid are elevated. As such it has a pronounced effect on vascular and renal function with their consequences, while also showing some antioxidant effects that show to be beneficial. Summary: Hyperuricemia has shown to have a J-shaped relationship with mortality, is frequently associated with development and progression of heart and kidney disease, and is correlated with malnutrition-inflammation-atherosclerosis syndrome, although several Mendelian studies have failed to show an association with morbidity and mortality. Hyperuricemia is usually associated with gout flares and tophi development but can also present as asymptomatic hyperuricemia. It is still uncertain whether asymptomatic hyperuricemia is an independent risk factor for cardiovascular or renal disease and as such its treatment is questionable. Key messages: Some possible tools for future decision making are the use of noninvasive techniques such as pulse wave analysis, urinary sediment analysis, and joint ultrasound, which could help identify individuals with asymptomatic hyperuricemia that could benefit from urate lowering therapy most.

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Hyperuricemia and Risk of Cardiovascular Outcomes: The Experience of the URRAH (Uric Acid Right for Heart Health) Project

Cited by 101 publications

References 55 publications

Association between Serum Uric Acid Levels, Nutritional and Antioxidant Status in Patients on Hemodialysis

Association between Serum Uric Acid Levels, Nutritional and Antioxidant Status in Patients on Hemodialysis

Associations of Serum Retinol and α-Tocopherol Levels with Uric Acid Concentrations: Analysis of a Population-Based, Nationally Representative Sample

Hyperuricemia, the heart, and the kidneys – to treat or not to treat?

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