Effect of statins on functional regulation of eNOS in heart failure.

• Research type

  Research Study

• Full title

  Effect of HMG Co-A reductase inhibition on endothelial dysfunction, bioavailability of tetrahydrobiopterin (BH4) and functional regulation of endothelial nitric oxide synthase (eNOS) in human heart failure.

• Contact name

  Mark Harbinson

• Sponsor organisation

  Belfast Health and Social Care Trust (Belfast City Hospital)

• Eudract number

  2008-002287-33

• Research summary

  Statins are drugs which lower cholesterol and reduce the risk of cardiovascular events such as heart attack and stroke, and are routinely used in patients with coronary heart disease. We have previously shown that statins improve the function of blood vessels in patients with high cholesterol. In this study we plan to look at blood vessel function in patients with heart failure, a disease where the heart's pumping action is impaired. Statin drugs may be less beneficial in this population, though the reasons for this remain unclear. The aim of this work is to investigate whether statins improve blood vessel function in patients with heart failure, and to investigate the mechanisms underlying this, in the hope of identifying mechanisms explaining the variable benefit of statins noted in this patient group. We plan to randomize patients with heart failure to treatment with a statin (simvastatin 40mg) or a matching inert placebo for 6 weeks. Before and after treatment we will measure the levels of chemical substances in the blood which control blood vessel function, and directly assess the effects of statin drugs by imaging blood vessels with ultrasound. We will measure the balance between substances with beneficial (e.g. nitric oxide) and adverse (e.g. peroxynitrite) effects on blood vessel function. The production of these substances depends on the normal function of the enzyme nitric oxide synthase (eNOS). We will also measure tetrahydrobiopterin levels in these patients; this substance in important in promoting normal function of eNOS and hence the production of the beneficial chemicals. The study will allow us to look at the effect of statin treatment on the complex interplay between functioning of the enzyme eNOS, the production of harmful and beneficial chemicals controlling vascular function, the importance of tetrahydrobiopterin, and the functional consequences of these mediators on arteries.

• REC name

  HSC REC A

• REC reference

  08/NIR01/74

• Date of REC Opinion

  28 Oct 2008

• REC opinion

  Further Information Favourable Opinion