Association of hyperuricemia and pulmonary hypertension: A systematic review and meta-analysis

Kang, Taeuk; Park, Kyu Yong; Kim, Hyun Jung; Ahn, Hyeong Sik; Yim, Sang‐Youp; Jun, Jae Bum

doi:10.1080/14397595.2018.1537555

Cited by 21 publications

(18 citation statements)

References 45 publications

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“…Therefore, there is a clear need to develop new biomarkers that could be routinely used in clinical practice. Because earlier studies have suggested an association between serum UA levels and the severity of PAH [6][7][8][9][10][11], the prognostic value of circulating UA levels at baseline and during follow-up has been studied in our large cohort of PAH patients. Our data show that patients with high level of UA at baseline had more severe hemodynamic impairment (i.e.…”

Section: Discussionmentioning

confidence: 99%

“…Despite the association of serum uric acid (UA) levels, the end product of the metabolism of purine compounds, with several cardiovascular diseases [5] including PAH [6][7][8][9][10][11], it remains controversial as to whether UA may modulate pathogenic mechanisms underlying the progression of these diseases. Elevated UA levels have indeed long been known to be a poor prognostic sign in idiopathic PAH, before the era of current therapeutic management [9].…”

Section: Introductionmentioning

confidence: 99%

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Serum and pulmonary uric acid in pulmonary arterial hypertension

Savale

Akagi

et al. 2021

Eur Respir J

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RationaleEarlier studies have suggested an association between uric acid (UA) and pulmonary arterial hypertension (PAH) severity, but it remains unknown whether UA contributes to the disease pathogenesis.ObjectivesTo study the prognostic values of circulating UA at era of current management of PAH and investigate the role of UA in the pulmonary vascular remodelling.MethodsSerum UA levels were determined in idiopathic, heritable, or anorexigen PAH at baseline and first re-evaluation in the French PAH registry. We studied protein levels of xanthine oxidase (XO) and the URATv1 transporter in lungs of control and PAH patients and of monocrotaline (MCT) and sugen/hypoxia (SuHx) rats. Functional studies were performed using human pulmonary artery smooth muscle cells (PA-SMCs) and two animal models of pulmonary hypertension (PH).ResultsHigh serum UA levels are associated with a poor prognosis at first follow-up, but not at baseline. Both the generating enzyme XO and URATv1 are upregulated in the wall of remodelled pulmonary arteries in iPAH patients and MCT and SuHx rats. High UA concentrations promote a mild increase in cell growth in iPAH PA-SMCs, but not in control PA-SMCs. Consistent with these observations, we demonstrate that oxonic acid-induced hyperuricemia did not aggravate MCT-induced PH in rats. Finally, we show that chronic treatments of MCT and SuHx rats with benzbromarone mildly attenuate pulmonary vascular remodelling.ConclusionsUA levels in iPAH patients is associated with impaired clinical and hemodynamic profile and might be used as a noninvasive indicator of clinical prognostic during follow-up. Our findings also indicate that metabolism of UA is disturbed in remodelled pulmonary vascular walls in both experimental and human PAH.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Serum and pulmonary uric acid in pulmonary arterial hypertension

Savale

Akagi

et al. 2021

Eur Respir J

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“…There were significantly higher levels of uric acid in patients with PH in our study. Recently, a large meta-analysis showed a 19% increased risk of death among patients with PH who had hyperuricemia, indicating that hyperuricemia may be a prognostic factor for PH [15]. Survival was worse in the PH group.…”

Section: Discussionmentioning

confidence: 99%

Association of Disease Subtype and Duration with Echocardiographic Evidence of Pulmonary Hypertension in Myeloproliferative Neoplasm

et al. 2020

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“…The latter shed new insights into different hazards of various subgroups. The recent meta-analysis has also concluded that hyperuricemia is a risk factor for subsequent or future pulmonary hypertension development and poor prognosis ( 6 ).…”

Section: Discussionmentioning

confidence: 99%

“…Serum uric acid (UA), the end product of purine degradation, has been proposed as a prognostic biomarker in PAH ( 5 , 6 ) and other cardiovascular diseases ( 7 ). Evidence supporting the role of UA in PAH secondary to connective tissue diseases has accumulated over the decades ( 8 , 9 ).…”

Section: Introductionmentioning

confidence: 99%

The Prognostic Impact of Serum Uric Acid on Disease Severity and 5-Year Mortality in Patients With Idiopathic Pulmonary Artery Hypertension

et al. 2022

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BackgroundSerum uric acid (UA) has long been identified as a prognostic factor of adverse outcomes in pulmonary hypertension. However, there remains a paucity of evidence on patients with idiopathic pulmonary artery hypertension (IPAH) in the era of targeted drug therapy. This study aims to explore the impact of serum UA levels on the disease severity and mortality in patients with IPAH.MethodsConsecutive patients diagnosed with IPAH were enrolled, from which UA levels at baseline and the first follow-up were collected. Patients were divided into groups of “hyperuricemia,” which is defined as serum UA level ≥357 μmol/L in women and ≥420 μmol/L in men, and otherwise “normouricemia.” The potential relationship between UA and hemodynamics at right heart catheterization was investigated. Associations between UA and survival were evaluated by Kaplan-Meier analysis and Cox proportional hazard modeling.ResultsOf 207 patients with IPAH, 121 (58.5%) had hyperuricemia. Higher serum UA levels were associated with lower cardiac index (r = 0.47, p < 0.001) and higher pulmonary vascular resistance (r = 0.36, p < 0.001). During a median follow-up of 34 months, there were 32 deaths recorded, accounting for a 15.5% mortality rate. Patients with hyperuricemia had a significantly lower survival rate than those with normouricemia (log-rank test, p = 0.002). Hyperuricemia at baseline was independently associated with a 2.6-fold increased risk of 5-year death, which was consistent across different subgroups, especially in females and those aged ≥30 years (each p < 0.05). Individuals with higher variability in UA had a higher mortality than those with stable UA (log-rank test, p = 0.024).ConclusionsBaseline hyperuricemia and high variability in serum UA at first follow-up were related to a higher rate of 5-year mortality in patients with IPAH. Closely detecting the UA levels may aid in the early recognition of IPAH patients at higher mortality risk.

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Association of hyperuricemia and pulmonary hypertension: A systematic review and meta-analysis

Cited by 21 publications

References 45 publications

Serum and pulmonary uric acid in pulmonary arterial hypertension

Serum and pulmonary uric acid in pulmonary arterial hypertension

Association of Disease Subtype and Duration with Echocardiographic Evidence of Pulmonary Hypertension in Myeloproliferative Neoplasm

The Prognostic Impact of Serum Uric Acid on Disease Severity and 5-Year Mortality in Patients With Idiopathic Pulmonary Artery Hypertension

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