Beyond Traditional Risk Factors: Unraveling Residual Vascular Risk After TIA and Minor Stroke

Transient ischemic attack (TIA) and minor ischemic stroke are critical warning events that precede disabling strokes and major cardiovascular complications. While traditional risk factors (TRFs) — hypertension, diabetes, hypercholesterolemia, smoking, and atrial fibrillation — are well-established drivers of cerebrovascular disease, a growing body of evidence indicates that a substantial proportion of patients presenting with TIA or minor stroke carry none of these conventional risks. Strikingly, recent data from large international cohorts such as TIAregistry.org demonstrate that recurrent stroke rates in this population are comparable to those seen in patients with TRFs, particularly within the first year after the index event. This observation points to the existence of poorly understood, non-traditional mechanisms that contribute to residual vascular risk and recurrent cerebrovascular events.Large artery atherosclerosis — identified through the ASCOD phenotyping system — has emerged as a dominant predictor of recurrence in patients without TRFs, yet the pathophysiological drivers of arterial stenosis in the absence of conventional risk factors remain largely unexplored. In parallel, the underuse of evidence-based secondary prevention therapies such as antiplatelet agents and statins in this population raises important questions about clinical recognition, risk stratification, and treatment decision-making when the traditional risk profile appears reassuring.This Research Topic aims to bring together original research, reviews, and clinical perspectives that advance our understanding of vascular risk in TIA and minor stroke patients who lack traditional risk factors. We welcome contributions addressing, but not limited to, the following areas:- Novel and non-traditional risk factors for cerebrovascular disease, including genetic susceptibility, chronic inflammation, autoimmune conditions, environmental exposures, sleep disorders, and psychosocial stress. - Mechanisms of large artery atherosclerosis in the absence of traditional risk factors, such as endothelial dysfunction, clonal hematopoiesis, lipoprotein(a), and vascular aging. - Risk stratification tools and biomarkers that improve prediction of recurrent events beyond conventional scoring systems (e.g., ABCD² score) in low-traditional-risk populations. - Imaging-based characterization of plaque vulnerability, intracranial and extracranial stenosis, and cerebral small vessel disease in patients without TRFs. - Secondary prevention strategies, including pharmacological, interventional, and lifestyle-based approaches, and their efficacy in populations without conventional indications. - Epidemiological and registry-based studies comparing clinical trajectories, treatment patterns, and long-term outcomes between patients with and without TRFs after TIA or minor stroke. - Sex- and ethnicity-specific differences in non-traditional vascular risk profiles and outcomes. - Finally, gaps in clinical guidelines regarding the management of TIA/minor stroke patients who do not meet conventional thresholds for aggressive secondary prevention.By highlighting the residual risk that persists in the absence of traditional risk factors, this Research Topic seeks to catalyze new research directions, inform clinical practice, and ultimately reduce the burden of recurrent cerebrovascular events in an underrecognized patient population. Topic editors: Shinichiro Uchiyama, Takao Hoshino Source: https://www.frontiersin.org/research-topics/80785/beyond-traditional-risk-factors-unraveling-residual-vascular-risk-after-tia-and-minor-stroke