McLeod, Andrew L.

2018-03-29T12:18:51Z

2018-03-29T12:18:51Z

2005

OBJECTIVES: The aims of the thesis were to assess coronary artery remodelling and plaque load, and to determine whether this influences vascular and endothelial function in vivo in man.

METHODS: Coronary artery remodelled segments were categorised using intravascular ultrasound (IVUS). Plaque type was characterised directly from spectral analysis of the radiofrequency ultrasound signal. Central arterial stiffness was assessed using non-invasive measures of arterial stiffness obtained by applanation tonometry of the radial, carotid and femoral artery. Coronary artery plaque volume was determined following computerised three-dimensional reconstruction of IVUS images obtained during a motorised pullback device. Coronary vessel area, arterial stiffness and vasomotor responses were determined using IVUS and Doppler Flow measurement and endothelial fibrinolytic responses by coronary sinus sampling during selective intracoronary infusions.

RESULTS: Plaque characteristics Positively remodelled segments had a larger vessel area (16.5±1.1 mm2 vs. 8.7±0.9 mm2, p<0.01) and plaque area (7.3+1.1 mm2 vs. 4.4+0.8 mm2, p=0.05) than negatively remodelled segments. Both positive and negatively remodelled segments had a greater percentage of fibrous plaque (p<0.01) than calcified or lipid rich plaque. Comparing positively and negatively remodelled segments, there was no significant difference between the proportion of fibrous, calcified and lipid rich plaque. Comparisons with non-invasive measures Plaque volume positively correlated with carotid-radial pulse wave velocity (r=0.47, p=0.008) and appeared to correlate with carotid-femoral pulse wave velocity (r=0.34, p=0.07). Aortic augmentation (r=0.24, p=0.16), augmentation index (r=0.3, p=0.08), and pulse pressure (r=0.22, p=0.2) did 2 not significantly correlate with proximal coronary artery plaque volume. Structure and function In comparison to non- and positively remodelled segments, negatively remodelled segments had a higher stiffness index (67±16 vs. 33±5 and 38±8 respectively; p<0.02). A significant degree of preservation of vasodilatation to 10"6 M acetylcholine was evident in positively remodelled compared with negatively remodelled segments (p<0.05). Coronary blood flow increased with both substance P and sodium nitroprusside infusions (p<0.001), although coronary sinus plasma t-PA antigen and activity concentrations increased only during substance P infusion (p<0.006 for both). There was a significant inverse correlation between coronary artery plaque burden and the release of active t-PA (r=- 0.61, p=0.003).

CONCLUSIONS: Pulse wave analysis may be a useful non-invasive surrogate marker for the extent of coronary atherosclerosis. Atherosclerotic risk factors and coronary plaque load are associated with impaired vasomotor and endogenous fibrinolytic function. Though plaque type was similar in remodelled types, negative remodelling was associated with more pronounced local vascular and endothelial dysfunction. These findings collectively suggest an important local interrelationship between coronary vascular structure and function that has implications for the pathophysiology of ischaemic heart disease.

http://hdl.handle.net/1842/29269

The University of Edinburgh

Annexe Thesis Digitisation Project 2018 Block 17

Already catalogued

Coronary artery remodelling, atherosclerosis and vascular function

Thesis or Dissertation

Doctoral

MD Doctor of Medicine