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
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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
