Atherosclerotic stenosis of the major intracranial arteries is an important cause of stroke, accounting for approximately 50,000 strokes per year in the USA at an annual cost of $750,000,000 in the first year after the stroke, and increasing to $4.5 billion over the life time of these patients. Atherosclerosis is attributable to three main pathological processes: endothelial dysfunction, vascular inflammation, and infiltration of the vascular wall by bioactive lipids. It is unknown, however, whether biomarkers that reflect these processes are relevant in patients with intracranial atherosclerosis. To address this question, we propose to study the relationship between promising biomarkers of atherosclerosis and risk of major vascular events in patients with symptomatic intracranial stenosis. This research proposal builds on the existing infrastructure and close collaboration with the recently funded NINDS sponsored trial - """"""""Stenting and Aggressive Medical Management for Preventing Recurrent stroke in Intracranial Stenosis"""""""" (SAMMPRIS - M.Chimowitz, PI) - the first randomized, multi-center Phase III clinical trial designed to evaluate the safety and efficacy of intracranial angioplasty and stenting in patients with symptomatic intracranial atherosclerosis. The Primary Aim of the current proposal is to determine whether serum biomarkers of inflammation in patients with symptomatic intracranial stenosis are independent predictors of recurrent stroke. We hypothesize that elevated levels of inflammatory biomarkers (hsCRP, PAI-1 and E-selectin), measured at the time of enrollment in SAMMPRIS, are associated with an increased risk of the primary endpoint, defined as recurrent stroke in the territory of the symptomatic stenotic artery. Our Exploratory Aim will be to determine whether the number of circulating endothelial progenitor cells (a marker for vascular repair) is an independent predictor of recurrent stroke in the territory of the symptomatic stenotic artery. For the exploratory aim, we will test the hypothesis that decreased levels of circulating endothelial progenitor cells are associated with an increased risk of the primary endpoint. Additional exploratory analyses will include a comparison of the efficacy of intensive medical therapy combined with angioplasty and stenting to intensive medical therapy alone in reducing major vascular events among patient groups with and without elevated levels of biomarkers. For the primary aim in this proposal, the sample size determined for SAMMPRIS (n = 764) provides 80% power to find a statistically significant result if the true hazard ratio for any of the 3 biomarkers is, at a minimum, in the range of 1.8 to 2.0 (after adjusting for multiple comparisons). It is expected that the results of this study will provide unique and novel data on the relationship of atherosclerotic biomarkers with outcome in patients with symptomatic intracranial stenosis. Refining risk assessment in patients with intracranial atherosclerosis could lead to a more tailored approach to treatment as well as a better understanding of the pathological processes involved in this common and understudied disease.
Patients with narrowed brain arteries, known as intracranial stenosis, have a particularly high-risk disease leading to stroke. Approximately 50,000 of these strokes per year occur in the USA at a cost of nearly $750,000,000.
The aim of this project is to determine whether circulating biomarkers (molecules and cells measured in blood samples) that are linked to atherosclerosis (hardening of the arteries) can predict which patients with stroke symptoms due to narrowed brain arteries are at highest risk of developing another stroke.
| Samman Tahhan, Ayman; Hammadah, Muhammad; Raad, Mohamad et al. (2018) Progenitor Cells and Clinical Outcomes in Patients With Acute Coronary Syndromes. Circ Res 122:1565-1575 |
| Hajjar, Ihab; Hayek, Salim S; Goldstein, Felicia C et al. (2018) Oxidative stress predicts cognitive decline with aging in healthy adults: an observational study. J Neuroinflammation 15:17 |
| Samman Tahhan, Ayman; Hammadah, Muhammad; Kelli, Heval Mohamed et al. (2018) Circulating Progenitor Cells and Racial Differences. Circ Res 123:467-476 |
| Schultz, William M; Kelli, Heval M; Lisko, John C et al. (2018) Socioeconomic Status and Cardiovascular Outcomes: Challenges and Interventions. Circulation 137:2166-2178 |
| Ghasemzedah, Nima; Hayek, Salim S; Ko, Yi-An et al. (2017) Pathway-Specific Aggregate Biomarker Risk Score Is Associated With Burden of Coronary Artery Disease and Predicts Near-Term Risk of Myocardial Infarction and Death. Circ Cardiovasc Qual Outcomes 10: |
| Hayek, Salim S; Ko, Yi-An; Awad, Mosaab et al. (2017) Cardiovascular Disease Biomarkers and suPAR in Predicting Decline in Renal Function: A Prospective Cohort Study. Kidney Int Rep 2:425-432 |
| Samman Tahhan, Ayman; Hayek, Salim S; Sandesara, Pratik et al. (2017) Circulating soluble urokinase plasminogen activator receptor levels and peripheral arterial disease outcomes. Atherosclerosis 264:108-114 |
| Hammadah, Muhammad; Al Mheid, Ibhar; Wilmot, Kobina et al. (2017) Telomere Shortening, Regenerative Capacity, and Cardiovascular Outcomes. Circ Res 120:1130-1138 |
| Samman Tahhan, Ayman; Sandesara, Pratik B; Hayek, Salim S et al. (2017) Association between oxidative stress and atrial fibrillation. Heart Rhythm 14:1849-1855 |
| Samman Tahhan, Ayman; Hammadah, Muhammad; Sandesara, Pratik B et al. (2017) Progenitor Cells and Clinical Outcomes in Patients With Heart Failure. Circ Heart Fail 10: |
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