Effect of HMG Co-A reductase inhibition on biological and ultrasound measures of endothelial function in human heart failure

• Main Author: Lyons, Kristopher Samuel
• Published: Queen's University Belfast 2013
• Subjects: 616.129
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.602362

Heart failure (HF) is a clinical syndrome in which neurohormonal activation and cardiac remodelling occur in response to an index pathological event. Functional measures and biological markers of blood vessel function have been shown to be altered in HF, and abnormalities of microvascular function have been demonstrated in a variety of vascular beds. Treatment of HF involves medications which target abnormalities in the neurohormonal systems that regulate cardiovascular function, however the role of HMG Co-A reductase inhibitors (statins) in HF is unclear. Some observational and mechanistic studies have suggested benefit, however, results of prospective intervention trails have been disappointing. This thesis reports the vascular and biological abnormalities detectable in HF patients with systolic dysfunction compared to controls, and the vasular and biological effect of treatment with simvastatin in HF patients with systolic dysfunction. Treatment with simvastatin resulted in a significant reduction in Co Q IO levels in HF patients but not in coQ10ILDL ratio. There was a non-significant trend toward reduction in NT-proBNP levels. Other biomarkers studied were unchanged by treatment At baseline, differences between HF patients and controls were apparent in brachial artery flow mediated dilatation and doppler waveforms obtained from the retrobulbar circulation. No such differences were apparent in brachial artery waveforms. Treatment with simvastatin did not result in any change in doppler waveforms obtained from the retrobulbar circulation or brachial artery. Abnormalities in vascular function in HF are widespread and can be detected by novel wavelet analysis of doppler waveforms obtained from the retrobulbar circulation. 4 weeks of treatment with simvastatin did not produce improvements in measures of vascular function suggesting a lack of additional benefit over and above baseline treatment in this population at least over a short treatment period. Further research is required to see if longer periods of treatment may be effective .