Ilyas, Bushra Saeed

2018-03-29T12:17:23Z

2018-03-29T12:17:23Z

2006

BACKGROUND: Arterial stiffness and endothelial dysfunction are implicated in the pathogenesis of atherosclerosis. Both are present in patients with hypercholesterolaemia and diabetes mellitus, and are markers of future cardiovascular events in patients with coronary artery disease (CAD), hypertension and end-stage renal failure. The structural components, elastin and collagen, which influence skin elasticity are also responsible for the elasticity of arteries.

AIMS: To investigate: 1. The association between skin elasticity and arterial elasticity in healthy subjects. 2. The determinants of arterial stiffness in patients with CAD, particularly renal function. 3. The determinants of endothelial dysfunction in patients with CAD. 4. The association between arterial stiffness and endothelial dysfunction in patients with CAD. 5. The survival of subjects from cardiovascular morbidity and mortality as determined by the severity of CAD, renal function, arterial stiffness and endothelial function.

METHODS: Skin elasticity was measured in the arm, leg and back using a suction device which measures the vertical deformation of skin. Arterial stiffness was assessed using pressure pulse wave velocity (PWV), pulse wave analysis (PWA) and digital volume pulse (DVP) analysis. Endothelial function was determined noninvasively using PWA with the administration of glyceryl trinitrate (endotheliumindependent vasodilator) and salbutamol (endothelium-dependent vasodilator). The study in CAD was a cohort study with longitudinal follow up for a median of 18 months. Adverse clinical events were determined through the Information and Statistics Division of the NHS and the General Register Office in Scotland. Renal function was assessed using serum creatinine concentration ([creat]sr) and estimated glomerular filtration rate (eGFR) by using creatinine clearance calculated using the Cockcroft & Gault equation. Subjects with a history of renal disease were excluded. The primary-endpoint was a composite of hospitalisation and mortality due to cardiovascular causes.

RESULTS: 1. Arterial elasticity and skin elasticity were only weakly associated. 2. Arterial stiffness was determined by age, heart rate, central systolic blood pressure and [creat]sr (R2=0.38, P < 0.001). Arterial stiffness was negatively associated with eGFR (R2=0.30, P < 0.001), even within the normal range. 3. Endotheliumindependent changes in the augmentation indices (AIs) were determined by age, body mass index and mean blood pressure (R2=0.09, P < 0.001). Endotheliumdependent changes in AIs were weakly explained by mean blood pressure (R2=0.02, P < 0.001) but not associated with hypercholesterolaemia, as previously reported, or renal function. However, the presence or severity of CAD did not explain the variance in arterial stiffness or endothelial function measures. 4. Endotheliumindependent and dependent changes in AIs were positively correlated. In addition, endothelium-independent changes in AIs were lower in subjects with stiffer arteries (r = 0.20, P < 0.01). 5. Subjects with a high number of diseased coronary vessels (P < 0.001), a low eGFR (P < 0.01), or a PWV above the median (P < 0.05) had a higher risk of developing adverse clinical events. Endothelial function, however, did not appear to predict a poor outcome.

CONCLUSION: In healthy subjects, skin elasticity is an unreliable marker of arterial elasticity. An important finding in the CAD study was that renal function was a determinant of arterial stiffness in patients without a history of renal disease. In this treated group of subjects, traditional cardiovascular risk factors did not determine arterial stiffness or endothelial dysfunction and there was no association between arterial stiffness and endothelial dysfunction. Moreover, endothelial function measured using PWA, with the administration of GTN and salbutamol, is not a useful test in patients with CAD on drug treatment. However, the presence and severity of CAD, renal function, as well as the stiffness of arteries, are predictive of a shorter time to fatal and non-fatal cardiovascular outcomes.

http://hdl.handle.net/1842/29170

The University of Edinburgh

Annexe Thesis Digitisation Project 2018 Block 17

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Arterial stiffness and endothelial dysfunction in patients with coronary artery disease

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PhD Doctor of Philosophy