Serum uric acid and outcomes in patients with chronic heart failure through the whole spectrum of ejection fraction phenotypes: Analysis of the ESC-EORP Heart Failure Long-Term (HF LT) Registry

Ambrosio, Giuseppe; Leiro, María G. Crespo; Lund, Lars H.; Coiro, Stefano; Cardona, Andrea; Filippatos, Gerasimos; Ferrari, Roberto; Piepoli, Massimo F; Coats, Andrew J.S.; Anker, Stefan D.; Laroche, Cécile; Almenar‐Bonet, Luis; Põder, Pentti; Valero, D. Bierge; Frisinghelli, Anna; Maggioni, Aldo P.

doi:10.1016/j.ejim.2021.04.001

Cited by 24 publications

(28 citation statements)

References 38 publications

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“…[1][2][3][4][5][6][7][8][9][10][11] However, UA increases cytokine and chemokine production, promotes inflammation, impairs endothelial function and activates the renin-angiotensin system. [1][2][3][4][5][6][7][8][9][10][11] In addition, UA may be a marker of oxidative stress as xanthine oxidase generates superoxide along with UA. [1][2][3][4][5][6][7][8][9][10][11] gout which is common in patients with heart failure, is difficult to manage and may lead to and prolong hospitalization.…”

Section: Introductionmentioning

confidence: 99%

Dapagliflozin reduces uric acid concentration, an independent predictor of adverse outcomes in DAPA‐HF

McDowell

Welsh

Docherty

et al. 2022

European J of Heart Fail

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Blood uric acid (UA) levels are frequently elevated in patients with heart failure and reduced ejection fraction (HFrEF), may lead to gout and are associated with worse outcomes. Reduction in UA is desirable in HFrEF and sodium-glucose cotransporter 2 inhibitors may have this effect. We aimed to examine the association between UA and outcomes, the effect of dapagliflozin according to baseline UA level, and the effect of dapagliflozin on UA in patients with HFrEF in the DAPA-HF trial.

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Section: Introductionmentioning

confidence: 99%

Dapagliflozin reduces uric acid concentration, an independent predictor of adverse outcomes in DAPA‐HF

McDowell

Welsh

Docherty

et al. 2022

European J of Heart Fail

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“…High SUA was found to be an independent prognosticator of adverse outcomes of HF outpatients in cohort studies ( 8 , 9 ). PARAGON-HF showed that sacubitril–valsartan treated HFpEF patients had the lowest incidence rates of the primary composite endpoint, cardiovascular death, heart failure hospitalization, all-cause death, myocardial infarction, and stroke, with baseline SUA levels around 4–6 mg/dl (238–357 μmol/L) ( 29 ).…”

Section: Discussionmentioning

confidence: 99%

“…Elevated serum uric acid (SUA) is a marker of inflammatory cytokine activation, insulin resistance, and oxidative stress ( 7 ). In addition, hyperuricemia may directly contribute to worsening HF outcomes ( 8 , 9 ). Dyslipidemia, hyperglycemia, and hyperuricemia are widely discussed risk factors or markers of cardiovascular diseases (CVD).…”

Section: Introductionmentioning

confidence: 99%

U-Shaped Association Between Serum Uric Acid Level and Hypertensive Heart Failure: A Genetic Matching Case-Control Study

Wang

Liu

et al. 2021

Front. Cardiovasc. Med.

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Background: Heart failure (HF) is a global pandemic and lays an added burden on public healthcare. Previous studies indicated that high and low serum uric acid levels are associated with worse outcomes in many diseases. Reduced serum uric acid may not result in a better outcome.Methods: A comparative, matched cross-sectional study design was implemented. The matching variables were age, sex, BMI, BP, and histories of CKD, CVD, diabetes mellitus, stroke, hyperlipidemia. We reviewed the electronic medical records to identify patients diagnosed with hypertension or hypertensive heart failure (HHF) admitted to Beijing Hospital's cardiology department.Results: The median age of the two groups after matching are 71. There are 55.6% males in the hypertension group and 53.8% in the heart failure group. Univariate logistic regression analysis showed that UA's quadratic term is significant (OR = 1.00, 95% CI 1.00 to 1.00; P = 0.03), which indicated a u-shaped relationship between hypertension and HHF. FBS (OR = 0.22, 95% CI 0.05 to 0.95, p = 0.07) and HDL (OR = 1.23, 95% CI 1.00 to 1.54, P = 0.05) were not significant but close.Conclusion: Our results supported that both low and high uric acid levels were predictive of hypertensive heart failure. Besides, high-density lipoprotein cholesterol and fasting blood sugar were also associated with hypertensive heart failure. Low-density lipoprotein cholesterol was not associated with hypertensive heart failure.

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“…11 In patients with gout, increased urate is linked to RHTN 12 and HF. 13 XO oxidizes hypoxanthine and xanthine to generate hydrogen peroxide (H 2 O 2 ) and superoxide (O 2 •− ) as a byproduct, which damages mitochondria leading to bioenergetic dysfunction and further amplification of oxidant generation. For example, initial damage to mitochondrial proteins by XO-derived oxidants can mediate diminution of ATP as well as enhanced electron leak and further increase the generation of O 2 •− , which can dismute to peroxide or react rapidly with nitric oxide (NO) to form peroxynitrite (ONOO − ) and further propagate the process.…”

mentioning

confidence: 99%

Racial Differences in XO (Xanthine Oxidase) and Mitochondrial DNA Damage-Associated Molecular Patterns in Resistant Hypertension

Butts

Brown²,

Denney

et al. 2022

Hypertension

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Background: We previously reported increased plasma XO (xanthine oxidase) activity in patients with resistant hypertension. Increased XO can cause mitochondrial DNA damage and promote release of fragments called mitochondrial DNA damage-associated molecular patterns (mtDNA DAMPs). Here, we report racial differences in XO activity and mtDNA DAMPs in Black and White adults with resistant hypertension. Methods: This retrospective study includes 91 resistant hypertension patients (44% Black, 47% female) with blood pressure >140/90 mm Hg on ≥4 medications and 37 normotensive controls (30% Black, 54% female) with plasma XO activity, mtDNA DAMPs, and magnetic resonance imaging of left ventricular morphology and function. Results: Black-resistant hypertension patients were younger (mean age 52±10 versus 59±10 years; P =0.001), with higher XO activity and left ventricular wall thickness, and worse diastolic dysfunction than White resistant hypertension patients. Urinary sodium excretion (mg/24 hour per kg) was positively related to left ventricular end-diastolic volume ( r =0.527, P =0.001) and left ventricular mass ( r =0.394, P =0.02) among Black but not White resistant hypertension patients. Patients with resistant hypertension had increased mtDNA DAMPs versus controls ( P <0.001), with Black mtDNA DAMPS greater than Whites ( P <0.001). Transmission electron microscopy of skeletal muscle biopsies in resistant hypertension patients demonstrates mitochondria cristae lysis, myofibrillar loss, large lipid droplets, and glycogen accumulation. Conclusions: These data warrant a large study to examine the role of XO and mitochondrial mtDNA DAMPs in cardiac remodeling and heart failure in Black adults with resistant hypertension.

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Serum uric acid and outcomes in patients with chronic heart failure through the whole spectrum of ejection fraction phenotypes: Analysis of the ESC-EORP Heart Failure Long-Term (HF LT) Registry

Cited by 24 publications

References 38 publications

Dapagliflozin reduces uric acid concentration, an independent predictor of adverse outcomes in DAPA‐HF

Dapagliflozin reduces uric acid concentration, an independent predictor of adverse outcomes in DAPA‐HF

U-Shaped Association Between Serum Uric Acid Level and Hypertensive Heart Failure: A Genetic Matching Case-Control Study

Racial Differences in XO (Xanthine Oxidase) and Mitochondrial DNA Damage-Associated Molecular Patterns in Resistant Hypertension

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