Thomas K. Day

By Thomas K. Day

Biomechanical stress applied to the intima of arteries has long been suspected as a factor in the initiation and localisation of atherosclerotic plaque, and it is implicated in the separation of plaque from the underlying arterial wall giving rise to the acute clinical consequences of thrombosis, dissection and embolism. The factors underlying transmural stress were investigated in-vitro using fresh porcine abdominal aortas on an experimental rig in which pulse pressure, pulse waveform, fluid viscosity, pulse rate, vessel wall compliance and systolic and diastolic blood pressure could be varied at will. Vessel wall compliance was progressively reduced by exposure of the artery to formaldehyde vapour for increased periods of time, a saline-treated artery being used as control. Centripetal transmural stress (CTS) and strain were studied by direct observation of the displacement of a compliant false intima (FI) using real-time B and M mode ultrasound, and by measuring the differential pressure between the space beneath the FI and the adjacent vessel lumen. CTS was found to be directly related to pulse pressure (r = 0.907, p < 0.001) and inversely related to vessel wall compliance. It was independently affected by ranked peak pressure waveform (R = 0.93, p < 0.01) being higher with sharp peak pressure and lower when the waveform was rounded, and it peaked in early diastole in untreated vessels, and both in diastole and peak systole in ones stiffened by formaldehyde vapour. Mean arterial pressure exerted a profound effect via its effect on vessel wall stiffness, which was found to rise 7-fold across the mean arterial pressure range 50-130 mmHg and continued to increase in a logarithmic fashion as the upper physiological range of mean arterial pressure was exceeded. There are two potential clinical implications: in mitigating the postulated biomechanical aspects atherogenesis and atherosclerotic plaque detachment, maintaining large vessel wall compliance is important, and the main factor determining this in a healthy artery is mean arterial pressure; if the arterial wall has already become stiffened as a result of disease, and in the absence of critical stenosis, the findings suggest that the appropriate therapeutic targets are modification of pulse pressure and pulse waveform profile. Simply reducing the diastolic pressure in elderly patients may be unwise if the result is a widened pulse pressure and increased transmural strain. The distribution of atheroma at points of focal mechanical strain in the vessel wall may be explicable if the stress induced by an excessive pulse pressure provokes the inflammatory changes seen in repetitive strain injury. Investigation of inflammatory signalling in the vessel wall provoked by repeated mechanical stress may represent a productive area for future research.

Part of the book: Risk Factors for Cardiovascular Disease