Identification of the Uric Acid Thresholds Predicting an Increased Total and Cardiovascular Mortality Over 20 Years

Virdis, Agostino; Masi, Stefano; Casíglia, Edoardo; Tikhonoff, Valérie; Cicero, A.F.G.; Ungar, Andrea; Rivasi, Giulia; Salvetti, Massimo; Barbagallo, Carlo M.; Bombelli, Michele; Dell’Oro, Raffaella; Bruno, Berardino; Lippa, Luciano; D’Elia, Lanfranco; Verdecchia, Paolo; Mallamaci, Francesca; Cirillo, Massimo; Rattazzi, Marcello; Cirillo, Pietro; Gesualdo, Loreto; Mazza, Alberto; Giannattasio, Cristina; Maloberti, Alessandro; Volpe, Massimo; Tocci, Giuliano; Georgiopoulos, Georgios; Iaccarino, Guido; Nazzaro, Pietro; Parati, Gianfranco; Palatini, Paolo; Galletti, Ferruccio; Ferri, Claudio; Desideri, Giovambattista; Viazzi, Francesca; Pontremoli, Roberto; Muiesan, María Lorenza; Grassı, Guıdo; Borghi, Claudio

doi:10.1161/hypertensionaha.119.13643

Cited by 190 publications

(133 citation statements)

References 21 publications

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“…Also, the use of higher cutoff to define hyperuricemia could have caused a bias in selecting a very high-risk population, where other conditions (i.e., CKD) might play a confounding effect. In our study, we use the recently proposed cutoff of sUA ≥5.6 mg/dl to define hyperuricemia (11). This cutoff allows the association of sUA and LVMi to emerge regardless of age and gender.…”

Section: Discussionmentioning

confidence: 99%

“…Both age and sUA independently correlate with LVMi ( Table 5). Recently, we have proposed lower limits of sUA (5.6 mg/dl) to identify the increased risk of CV death (11). To verify whether this cutoff could also be helpful to identify a population with larger LVMi, we dichotomize our population by sUA > 5.6 mg/dl and observed a larger size of LV in hypertensives with sUA above the fixed threshold ( Figure 1B).…”

Section: Association Between Sua and Lvmimentioning

confidence: 93%

“…Moreover, we reported that the optimal cut point for sUA to discriminate cardiovascular disease (CVD) mortality was 5.6 mg/dl (11) in population with high CV risk; in keeping with these results, the information on levels of sUA above or below 5.6 mg/dl incrementally predicted CVD mortality over Heart Score (11). The ability of sUA to predict CV risk probably associates with its ability to identify target organ damage (TOD), which participates in the definition of CV risk.…”

Section: Introductionmentioning

confidence: 99%

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Serum Uric Acid and Left Ventricular Mass in Essential Hypertension

Visco

Pascale

Virtuoso

et al. 2020

Front. Cardiovasc. Med.

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Serum uric acid (sUA) has been associated with cardiovascular risk. Although the recent mechanistic hypothesis poses the basis for the association between sUA and left ventricular mass index (LVMi), the issue remains poorly investigated in a clinical setup. Through a retrospective analysis of the database of the departmental Hypertension Clinic of University Hospital of Salerno Medical School, we identified 177 essential hypertensives (age 60.3 ± 13.3 years; 85 men), free from uric acid-modulating medications and severe chronic kidney disease, and whose sUA values, anthropometric, clinical, and echocardiographic data were available. In the studied cohort, the average duration of hypertension was 8.4 ± 7.1 years. LVMi associated with classical determinants, such as age, blood pressure, and kidney function, although after multivariate correction, only age remained significant. Also, sUA correlated positively with LVMi, as well as body size, metabolism, and kidney function. In a multivariate analysis, sUA confirmed the independent association with LVMi. Also, levels of sUA >5.6 mg/dl are associated with larger cardiac size. We confirmed our data in a replicate analysis performed in a larger population (1,379 hypertensives) from an independent clinic. Our results demonstrate that sUA increases with LVMi, and a cutoff of 5.6 mg/dl predict larger LV sizes. Our data suggest that hyperuricemia might help to stratify the risk of larger cardiac size in hypertensives.

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Section: Discussionmentioning

confidence: 99%

Section: Association Between Sua and Lvmimentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

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Serum Uric Acid and Left Ventricular Mass in Essential Hypertension

Visco

Pascale

Virtuoso

et al. 2020

Front. Cardiovasc. Med.

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“…Normally, male UA levels greater than 7 mg/dL or female UA levels greater than 6 mg/dL are considered to be hyperuricemia (Hao et al, 2019). However, Virdis et al confirmed that the threshold of UA level increased total mortality (4.7 mg/dL) and cardiovascular mortality (5.6 mg/dL) risk, which was significantly lower than clinical diagnostic criteria (Virdis et al, 2020). With increasingly unhealthy lifestyles, the incidence of hyperuricemia is increasing, and it has become the "fourth highest" after hypertension, hyperglycemia, and hyperlipidemia.…”

Section: Introductionmentioning

confidence: 99%

Uric Acid and Cardiovascular Disease: An Update From Molecular Mechanism to Clinical Perspective

2020

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Uric acid (UA) is the end product of purine nucleotide metabolism in the human body. Hyperuricemia is an abnormally high level of UA in the blood and may result in arthritis and gout. The prevalence of hyperuricemia has been increasing globally. Epidemiological studies have shown that UA levels are positively correlated with cardiovascular diseases, including hypertension, atherosclerosis, atrial fibrillation (AF), and heart failure (HF). Hyperuricemia promotes the occurrence and development of cardiovascular diseases by regulating molecular signals, such as inflammatory response, oxidative stress, insulin resistance/diabetes, endoplasmic reticulum stress, and endothelial dysfunction. Despite extensive research, the underlying molecular mechanisms are still unclear. Allopurinol, a xanthine oxidase (XO) inhibitor, has been shown to improve cardiovascular outcomes in patients with HF, coronary heart disease (CHD), type 2 diabetes (T2D), and left ventricular hypertrophy (LVH). Whether febuxostat, another XO inhibitor, can improve cardiovascular outcomes as well as allopurinol remains controversial. Furthermore, it is also not clear whether UA-lowering treatment (ULT) can benefit patients with asymptomatic hyperuricemia. In this review, we focus on the latest cellular and molecular findings of cardiovascular disease associated with hyperuricemia and clinical data about the efficacy of ULT in patients with cardiovascular disease.

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“…A number of large epidemiologic studies have demonstrated the predictive value of serum uric acid (SUA) on the risk of cardiovascular (CV) disease and mortality, independently from common CV risk factors [ 1 , 2 , 3 ]. Based on these findings, European Guidelines have included SUA among factors to be assessed for the CV risk stratification of patients with arterial hypertension [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

The Complex Relationship Between Serum Uric Acid, Endothelial Function and Small Vessel Remodeling in Humans

Masi

Georgiopoulos

Alexopoulos

et al. 2020

JCM

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Aims: The relationship between serum uric acid (SUA) and microvascular remodeling in humans remains largely unexplored. We assessed whether SUA provides additional information on the severity of microvascular remodeling than that obtained from the European Heart Score (HS), the patterns of microvascular remodeling associated with changes in SUA levels and the mediation by endothelial function and nitric oxide (NO) availability on this relationship. Methods: A total of 162 patients included in the microvascular dataset of the Italian Society of Hypertension with available information on SUA, media-to-lumen (M/L) ratio, media cross-sectional area (MCSA), endothelial function, NO availability and HS were included in the analysis. The top tertile of M/L ratio and MCSA were used to define severe microvascular remodeling. Results: A U-shaped association was observed between SUA and both M/L ratio and MCSA. Adjustment for HS did not affect these associations. SUA was able to reclassify a significant number of subjects without, and with, severe M/L ratio and MCSA remodeling over the HS alone. The microvascular remodeling associated with SUA levels presented a predominant hypertrophic pattern. SUA was inversely associated with endothelial function and NO availability. Structural equation modeling analysis controlling for the HS suggested that the association of SUA with M/L ratio and MCSA was mediated through changes in endothelial function and NO availability. Conclusions: The addition of SUA to the HS improves the identification of subjects with greater microvascular remodeling. The relationship between SUA and microvascular remodeling is mediated by endothelial function and NO availability.

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Identification of the Uric Acid Thresholds Predicting an Increased Total and Cardiovascular Mortality Over 20 Years

Cited by 190 publications

References 21 publications

Serum Uric Acid and Left Ventricular Mass in Essential Hypertension

Serum Uric Acid and Left Ventricular Mass in Essential Hypertension

Uric Acid and Cardiovascular Disease: An Update From Molecular Mechanism to Clinical Perspective

The Complex Relationship Between Serum Uric Acid, Endothelial Function and Small Vessel Remodeling in Humans

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