Key result
Disturbed wall shear stress uniquely approximates established causation criteria in early atherogenesis.
Why the study?
Despite growing knowledge of early atherogenic processes and evidence-based risk factors, the etiology of atherosclerosis remains unsettled.
This review suggests that disturbed wall shear stress is the primary causal factor in the initiation of early atherogenesis.
Should not yet change clinical risk assessment; leaves open prospective validation of disturbed wall shear stress as a causal target.
Atherosclerosis is a complex chronic inflammatory disease that affects the larger arteries. Early atherogenesis involves a group of pathological processes including endothelial activation and dysfunction, lipoprotein transcytosis and modification, monocyte recruitment and transmigration, and foam cell formation, culminating in fatty streak formation. These processes are mediated by numerous molecules, which could be considered potential diagnostic and therapeutic targets. Atherogenic processes are also driven by several risk factors, including the demographic factors age and sex; family history; dyslipidemia and related chronic lifestyle diseases; unhealthy behaviors related to exercise, diet, alcohol intake, smoking, and sleep; microbial activity; air pollution; and disturbed hemodynamics including low or oscillatory wall shear stress. However, despite our growing knowledge of atherogenesis, the etiology of atherosclerosis remains unsettled. This review first describes early atherogenic processes and their key mediators. The complexity of atherogenesis is then briefly explored to illustrate the uncertainties surrounding the initiation of atherogenesis, including the complex relationships between the evidence-based risk factors identified and atherogenic processes. Finally, the etiology of this important pathology is explored by applying established criteria for causation, including temporality, strength of association, plausibility, and experimental evidence, to the identified risk factors. The review concludes that of all the evidence-based risk factors identified, disturbed wall shear stress is the only one that approximates the criteria for causation, and ends with an overview of the implications.
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Paul A. Brown (2026) conducted a review in Atherosclerosis. Disturbed wall shear stress was evaluated. Disturbed wall shear stress is the only evidence-based risk factor that approximates the established criteria for causation in the etiology of early atherogenesis.
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