Cardiovascular Journal of Africa: Vol 28 No 3 (May/June 2017)

67 / 80

CARDIOVASCULAR JOURNAL OF AFRICA • Volume 28, No 3, May/June 2017 AFRICA 201
Xanthine oxidase inhibitors in ischaemic heart disease
Mihnea Zdrenghea, Adela Sitar-Tǎut, Gabriel Cismaru, Dumitru Zdrenghea, Dana Pop
Abstract
Increased uric acid levels are correlated with cardiovascular
disease, particularly with ischaemic heart disease. Xanthine
oxidase inhibitors, especially allopurinol, lower the risk of
ischaemic heart disease due to their effects on reactive oxygen
species and endothelial function. In chronic stable angina
pectoris, allopurinol increases the median time to ST depres-
sion, time to chest pain, and total exercise time. On the other
hand, it has been reported that allopurinol has a beneficial
effect on ischaemic patients referred for angioplasty, but there
are insufficient data regarding its effect on acute myocar-
dial infarction patients. Moreover, other important actions
of allopurinol are regression of left ventricular hypertrophy
and improvement in the results of cardiac rehabilitation. The
efficacy of allopurinol has recently been acknowledged by the
European Society of Cardiology guidelines for stable angina
pectoris, but the particular role of allopurinol in ischaemic
heart disease patients is not fully established.
Keywords: xanthine oxydase inhibitors, ischaemic heart disease,
uric acid
Submitted 30/7/14, accepted 10/7/16
Published online 9/9/16
Cardiovasc J Afr 2017; 28: 201–204
DOI: 10.5830/CVJA-2016-068
There are many cardiovascular conditions and risk factors
associated with elevated uric acid levels.1 Uric acid favours
hypertriglyceridaemia, being involved in the increase of liver
protein synthesis and turnover.2 Hyperuricaemia has been
associated with an increased incidence and prevalence of
hypertension, stroke and carotid, peripheral and coronary
atherosclerotic vascular disease.1
There is also a correlation between elevated levels of uric acid
and inflammatory markers, including C-reactive protein (CRP),
plasminogen activator inhibitor type I, and soluble intercellular
adhesion molecule (ICAM). 3 All these factors represent another
possible link between uric acid and atherosclerosis, especially
ischaemic heart disease.1 In a review on uric acid levels in
cadiovascular disease, Kanbay et al. cite eight prospective studies
based on medical and post mortem records, and coronary events
registries, which demonstrate an increased risk of coronary heart
disease in subjects with hyperuricaemia, with odd ratios (OR)
between 1.12 and 2.30.4
These data suggest that a decrease in serum uric acid level
could be beneficial in patients either at risk for or with established
ischaemic heart disease. The most commonly used drugs to
decrease uric acid levels are inhibitors of xanthine oxidase (XO).
This enzyme is involved in uric acid synthesis, in the production
of superoxide radicals and, consequently, in atherosclerosis.5
Therefore, a decrease in its activity may have anti-atherogenic
and anti-ischaemic effects.6 There are three clinically available
XO inhibitors: allopurinol, oxypurinol and febuxostat, the first
being most widely used in clinical practice.7
The many potential pharmacological cardiovascular benefits
of XO inhibitors include improvement in endothelial function,
decrease in tissue oxidative stress, increase in ATP synthesis
in ischaemic tissue, and improvement in exercise-induced
ischaemia. XO inhibitors may also be beneficial in prevention
of primary cardiovascular disease, left ventricular hypertrophy,
acute coronary syndrome, stroke and heart failure.6 We will
briefly discuss the main areas in which XO inhibitors could be or
have already proven useful.
Anti-atherogenic effects
The anti-atherogenic effects of XO inhibitors have mainly been
studied in relation to endothelial function and oxidative stress
parameters.8 Inflammatory markers and lipid profile have also
been considered.9 XO represents a source of reactive oxygen
species that results in both endothelial dysfunction and vascular
inflammation. Consequently, lowering serum uric acid levels
through XO inhibitors has anti-atherogenic effects.
A review and meta-analysis of 40 studies reports that
circulating markers of oxidative stress, such as malonaldehyde,
were significantly decreased by XO inhibitors in six of the
studies.9 Other studies found that brachial artery flow-mediated
dilatation was increased, with an OR of 2.50. The forearm
blood flow response to acetylcholine infusion was increased by
60.68%.9
In their 2013 review, Kanbay et al. analysed the relationship
between reduction in uric acid level and improvement of
Department of Haematology, Iuliu Hațieganu University of
Medicine and Pharmacy, Cluj-Napoca, Romania
Mihnea Zdrenghea, MD, PhD,
Department of Cardiology, Iuliu Hațieganu University of
Medicine and Pharmacy, Cluj-Napoca, Romania
Adela Sitar-Tǎut, MD, PhD
Gabriel Cismaru, MD,
Dumitru Zdrenghea, MD, PhD
Dana Pop, MD, PhD
Review Article