Hemodynamic stress and experimental aortoiliac atherosclerosis

Human aortic atherosclerosis is predominantly localized to the infrarenal aorta where flow is bidirectional and wall shear stress oscillates. Similar flow patterns have been related to carotid atherosclerosis. The thoracic aorta is usually spared, where flow and shear stress are unidirectional. We hypothesized that because heart rate and systemic blood pressure modulate flow velocity and shear stress oscillation, both these hemodynamic forces may enhance aortoiliac atherogenesis.

Eighteen male cynomolgus monkeys were fed an atherogenic diet for 6 months (mean serum cholesterol = 535 +/- 35 mg/dl). Heart rate was determined with 24-hour electrocardiographic telemetry at monthly intervals and blood pressure was measured by direct arterial cannulation. The product of mean heart rate and mean blood pressure was used to define hemodynamic stress for each animal. Atherosclerotic lesion formation at three standard thoracic aortic sites was quantitatively compared with lesion formation at five standard infrarenal aortoiliac locations with computer-assisted morphometry.

There was significantly more plaque in the aortoiliac segment than in the thoracic aorta (12.4% +/- 9.0% vs. 6.4% +/- 4.5% area stenosis, p = 0.02). No correlation was found between the degree of serum lipid elevations and lesion formation in either aortic location. Mean heart rate was 113 +/- 18 beats/min (87 to 163 beats/min) and mean blood pressure was 85 +/- 19 mm/Hg (62 to 130 mm Hg). Heart rate and blood pressure alone were not significantly related to lesion formation. A significant correlation was, however, found between hemodynamic stress and maximum lesion thickness (r = 0.47, p < 0.05) in the aortoiliac region but not in the thoracic aorta (r = 0.19, p > 0.10).

This study demonstrates that heart rate and blood pressure exert a mutually potentiating effect on aortoiliac atherosclerosis but not on thoracic aortic atherosclerosis. Regional differences in aortic atherosclerosis may therefore be attributable to the interaction between these hemodynamic forces and the local flow patterns specific to each aortic location. Additional investigation of these hemodynamic factors in relation to human aortic atherosclerosis is warranted.