- •Elevated serum uric acid levels are associated with cardiovascular diseases.
- •Serum uric acid is also useful for predicting future cardiovascular outcomes.
- •Whether uric acid is a causal risk factor of cardiovascular disease remains unknown.
- •Some clinical benefits of urate-lowering therapy have been shown in small studies.
- •The efficacy of urate-lowering therapy is not yet established in large-scale trials.
Inflammation, oxidative stress, and endothelial dysfunction
Uric acid and cardiovascular disease
- Wada T.
- Hosoya T.
- Honda D.
- Sakamoto R.
- Narita K.
- Sasaki T.
- et al.
|Population/Study (author)||Sample size||Design||Tested strategies||Comparator||Results|
|Soletsky et al. |
|60||DB, crossover||Allopurinol and probenecid||Placebo||In prehypertensive obese adolescents, urate-lowering therapy reduced clinic SBP (−10.1 vs. −10.2 vs. 1.7 mmHg, p<0.001)|
|Segal et al. |
|110||DB||Allopurinol plus chlorthalidone||Placebo plus chlorthalidone||In hypertensive African-Americans, allopurinol non-significantly reduced clinic SBP (−3.4 vs. 0.8 mmHg, p = 0.06)|
|Higgins et al. |
|80||DB||Allopurinol||Placebo||Allopurinol lowered central and brachial SBP and reduced carotid IMT progression|
|Type 1 DM|
|530||DB||Allopurinol||Placebo||Allopurinol did not delay GFR decline (between-group difference 0.001, 95% CI −1.9 to 1.9 ml/min/1.73 m2)|
Uric acid-lowering and renoprotective effects of topiroxostat, a selective xanthine oxidoreductase inhibitor, in patients with diabetic nephropathy and hyperuricemia: a randomized, double-blind, placebo-controlled, parallel-group study (UPWARD study).
Clin Exp Nephrol. 2018; 22: 860-870
|65||DB||Topiroxostat||Placebo||Changes in eGFR were superior in the topiroxostat group (−0.2 vs. −4.0 ml/min/1.73 m2, p = 0.03)|
|441||DB||Febuxostat||Placebo||In CKD patients with hyperuricemia, febuxostat did not mitigate the decline in eGFR slope (0.23 vs. −0.47 ml/min/1.73 m2 per year, p = 0.1)|
|363||DB||Allopurinol||Placebo||The change in eGFR was not significantly different between the 2 groups (−3.33 vs. −3.23 ml/min/1.73 m2, p = 0.85)|
|Farquharson et al. |
|11||DB, crossover||Allopurinol||Placebo||Allopurinol improved endothelial dysfunction assessed by forearm blood flow response to acetylcholine|
|405||DB||Oxypurinol||Placebo||Clinical improvements including events and HF status did not differ between the 2 groups (45% vs. 43%, p = 0.42)|
|253||DB||Allopurinol||Placebo||In hyperuricemic patients with HFrEF, allopurinol did not improve clinical status, exercise capacity, QOL, or LVEF|
|Noman et al. |
|65||DB, crossover||Allopurinol||Placebo||Allopurinol increased time to ST depression (median difference 43 s, 95% CI 31–58 s) and exercise time (difference 58 s, 95% CI 45–77 s)|
|483||Open-label||Febuxostat||Lifestyle modification||Mean% change of CCA-IMT in the febuxostat group was not significantly different (1.2% vs. 1.4%, p = 0.83)|
|1070||Open-label||Febuxostat||Allopurinol (100 mg) allowed||Febuxostat was superior in the rate of composite cerebral, cardiovascular, and renal events (23.3% vs. 28.7%, p = 0.02)|
|6190||DB||Febuxostat||Allopurinol||Non-inferiority of febuxostat was met (p = 0.002), though all-cause and CV mortality was significantly higher in the febuxostat group|
|6128||Open-label||Febuxostat||Allopurinol||Non-inferiority of febuxostat was met (p<0.001) with no significant increase of risk of death|
Chronic kidney disease
- Doehner W.
- Schoene N.
- Rauchhaus M.
- Leyva-Leon F.
- Pavitt D.V.
- Reaveley D.A.
- et al.
Coronary artery disease
- Saito Y.
- Kobayashi Y.
- Saito Y.
- Mori N.
- Murase T.
- Nakamura T.
- Akari S.
- Saito K.
- et al.
Mendelian randomization and genetic studies
Uric acid lowering treatment on renal and cardiovascular disease
Declaration of Competing Interest
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