| Summary: | There is little doubt that disturbed hemodynamic forces play a role in the development of focal atherosclerotic lesions; however, these forces are difficult to measure directly. Instead, it has been proposed that artery geometry, as the primary determinant of local hemodynamics, could be a clinically feasible surrogate “local” risk factor for atherosclerosis. To date this hypothesis has not been satisfactorily tested, owing to superficial geometric surrogates of disturbed flow, small sample sizes (effect of systemic factors) and/or confounding effects of disease on geometry. The primary objective of this thesis was to test this “geometric risk hypothesis” via direct association of definitive geometric factors and an early atherosclerosis marker (e.g. wall thickness), made possible through our access to magnetic resonance imaging and risk factor data from the Atherosclerosis Risk in Communities’ Carotid MRI sub-study. First, it was shown that the 3D geometry of the carotid bifurcation could be characterized rapidly and reliably, even for routine clinical acquisitions. Second, two novel individual geometric variables were proposed, inspired by the influence of flare and tortuosity on flow separation, which were shown to improve the prediction of disturbed flow burden compared to “conventional” shape-based geometric variables. Third, these redefined geometric factors, but not their shape-based counterparts, were shown by multiple regression to be independent predictors of wall thickness, but only after thoroughly accounting for the secondary effects of wall thickening on geometry. These findings provide strong evidence for the geometric risk hypothesis of atherosclerosis in humans group study, and provide important guidance for future investigations of geometric risk; however, the incremental value of optimized geometric risk factors is questionable relative to conventional cardiovascular risk factors, which challenges their future clinical usage as additional non-modifiable local risk factors.
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