Allopurinol as a therapeutic option in cardiovascular disease

Okafor, Osita; Farrington, Ken; Gorog, Diana A.

doi:10.1016/j.pharmthera.2016.12.004

Cited by 79 publications

(59 citation statements)

References 106 publications

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“…24,25 Several studies have previously examined whether UA-lowering therapy with xanthine oxidase inhibitor allopurinol or oxypurinol leads to clinical and functional improvement of HF; however, the results are not consistent. [26][27][28][29][30] Cingolani and colleagues 26 indicated that inhibition of xanthine oxidase by oxypurinol in patients with chronic HF decreased UA level and improved LVEF in patients with LVEF ≤40% after 1 month of treatment. However, other studies showed that oxypurinol did not produce clinical improvements in patients with moderate-to-severe HF.…”

Section: Discussionmentioning

confidence: 99%

Serum uric acid is associated with incidence of heart failure with preserved ejection fraction and cardiovascular events in patients with arterial hypertension

Fan

Zhang

et al. 2018

J of Clinical Hypertension

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The objective of the present study was to evaluate clinical implications of serum uric acid (UA) on the progression of heart failure with preserved ejection fraction (HFpEF) in hypertensive patients. A total of 1009 adult patients with left ventricular hypertrophy and suspected left ventricular diastolic dysfunction were enrolled at our hospital from January 2008 to December 2011. With a median follow‐up of 7.2 years, 136 (13.2%) patients developed new‐onset HFpEF and 151 (15.0%) had major adverse cardiovascular events (MACEs). Compared with the lowest UA tertile of UA (<302 μmol L−1), subjects in the highest tertile (>367 μmol L−1) had a higher risk of developing new‐onset HFpEF (HR: 1.761, 95% CI: 1.119‐2.772, P = .015) as well as MACEs (HR: 1.664, 95% CI: 1.086‐2.547, P = .019). Our findings indicate that hyperuricemia is associated with detrimental effects in terms of the incidence of new‐onset HFpEF as well as MACEs in hypertensive patient.

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Section: Discussionmentioning

confidence: 99%

Serum uric acid is associated with incidence of heart failure with preserved ejection fraction and cardiovascular events in patients with arterial hypertension

Fan

Zhang

et al. 2018

J of Clinical Hypertension

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“…Based on these findings, the authors discuss an adaptive response upon vascular injury in which XOR is upregulated to allow nitrite to be reduced to NO with putative protective effects. The suggested response is intriguing but needs further scientific support in the light of studies showing beneficial effects of XOR inhibition in cardiovascular disease . In addition, vascular arginase 1 levels were increased after injury, which was accompanied by reduced NOS‐generated NO.…”

Section: Organ Systems Involved In the Blood Pressure Reduction By Inmentioning

confidence: 99%

Mechanisms underlying blood pressure reduction by dietary inorganic nitrate

2018

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Nitric oxide (NO) importantly contributes to cardiovascular homeostasis by regulating blood flow and maintaining endothelial integrity. Conversely, reduced NO bioavailability is a central feature during natural ageing and in many cardiovascular disorders, including hypertension. The inorganic anions nitrate and nitrite are endogenously formed after oxidation of NO synthase (NOS)-derived NO and are also present in our daily diet. Knowledge accumulated over the past two decades has demonstrated that these anions can be recycled back to NO and other bioactive nitrogen oxides via serial reductions that involve oral commensal bacteria and various enzymatic systems. Intake of inorganic nitrate, which is predominantly found in green leafy vegetables and beets, has a variety of favourable cardiovascular effects. As hypertension is a major risk factor of morbidity and mortality worldwide, much attention has been paid to the blood pressure reducing effect of inorganic nitrate. Here, we describe how dietary nitrate, via stimulation of the nitrate-nitrite-NO pathway, affects various organ systems and discuss underlying mechanisms that may contribute to the observed blood pressure-lowering effect.

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“…Allopurinol has displayed beneficial effects on blood pressure in adolescents with newly diagnosed essential hypertension [89], and in patients with heart failure, coronary artery disease, and stroke [115]. Allopurinol may thus improve endothelial function and endothelium-dependent vasodilation in chronic heart failure patients [18].…”

Section: Evidence From Clinical Studies Relevance For Humansmentioning

confidence: 99%

Fructose Intake, Serum Uric Acid, and Cardiometabolic Disorders: A Critical Review

et al. 2017

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There is a direct relationship between fructose intake and serum levels of uric acid (UA), which is the final product of purine metabolism. Recent preclinical and clinical evidence suggests that chronic hyperuricemia is an independent risk factor for hypertension, metabolic syndrome, and cardiovascular disease. It is probably also an independent risk factor for chronic kidney disease, Type 2 diabetes, and cognitive decline. These relationships have been observed for high serum UA levels (>5.5 mg/dL in women and >6 mg/dL in men), but also for normal to high serum UA levels (5–6 mg/dL). In this regard, blood UA levels are much higher in industrialized countries than in the rest of the world. Xanthine-oxidase inhibitors can reduce UA and seem to minimize its negative effects on vascular health. Other dietary and pathophysiological factors are also related to UA production. However, the role of fructose-derived UA in the pathogenesis of cardiometabolic disorders has not yet been fully clarified. Here, we critically review recent research on the biochemistry of UA production, the relationship between fructose intake and UA production, and how this relationship is linked to cardiometabolic disorders.

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Allopurinol as a therapeutic option in cardiovascular disease

Cited by 79 publications

References 106 publications

Serum uric acid is associated with incidence of heart failure with preserved ejection fraction and cardiovascular events in patients with arterial hypertension

Serum uric acid is associated with incidence of heart failure with preserved ejection fraction and cardiovascular events in patients with arterial hypertension

Mechanisms underlying blood pressure reduction by dietary inorganic nitrate

Fructose Intake, Serum Uric Acid, and Cardiometabolic Disorders: A Critical Review

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