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Mediators of the Age Effect in the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST)
Jenifer H Voeks1, George Howard1, Gary Roubin1
1From the Department of Neurology, Medical University of South Carolina, Charleston (J.H.V.); Department of Biostatistics, University of Alabama at Birmingham (G.H.); Cardiovascular Associates of the Southeast, Birmingham, AL (G.R.); Division of Neuroradiology, Department of Medical Imaging, University of Toronto, Toronto Western Hospital, Toronto, Ontario, Canada (R.F.); Department of Radiology, Novant Health Forsyth Medical Center, Winston-Salem, NC (D.H.); Mercy Clinic Neurology, Mercy Hospital, St. Louis, MO (W.L.); Department of Neurology, Mayo Clinic, Jacksonville, FL (M.L., J.F.M., T.G.B.); and Department of Surgery, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark (A.S., T.G.B.).
Insights
Older age increases stroke or death risk after carotid stenting. Plaque length partially explains this increased risk, but other factors remain significant for elderly patients undergoing stenting.
Area of Science:
- Cardiovascular Medicine
- Interventional Cardiology
- Vascular Surgery
Background:
- Older patients face a higher combined risk of stroke or death (S+D) following carotid artery stenting.
- Patient and arterial characteristics may mediate the increased risk associated with advanced age.
Purpose of the Study:
- To investigate whether patient or arterial factors explain the elevated S+D risk in older individuals undergoing carotid stenting.
- To determine if specific characteristics mediate the relationship between age and adverse outcomes.
Main Methods:
- Mediation analysis was conducted on 1123 patients from the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST).
- Patient data (hypertension, diabetes, dyslipidemia) and arterial characteristics (plaque length, stenosis, etc.) were analyzed.
- The study assessed the association of age with these factors and their link to S+D risk.
Main Results:
- Plaque length, measured at clinical sites, increased with age and was associated with higher S+D risk.
- Plaque length significantly mediated the association between age and S+D risk.
- Adjusting for plaque length only reduced the age-related risk increase by 8%, indicating other factors are involved.
Conclusions:
- Plaque length is a factor in the age-related increase in S+D risk after carotid stenting but does not fully account for it.
- Further research is needed to identify other mechanisms driving the increased risk in elderly patients.
- Plaque length alone is insufficient to identify elderly patients for whom stenting is safer than endarterectomy.
Background And Purpose:
There is higher combined risk of stroke or death (S+D) at older ages with carotid stenting. We assess whether this can be attributed to patient or arterial characteristics that are in the pathway between older age and higher risk.
Methods:
Mediation analysis of selected patient (hypertension, diabetes mellitus, and dyslipidemia) and arterial characteristics assessed at the clinical sites and the core laboratory (plaque length, eccentric plaque, ulcerated plaque, percent stenosis, peak systolic velocity, and location) was performed in 1123 carotid artery stenting-treated patients in the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST). We assessed the association of age with these characteristics, the association of these characteristics with stroke risk, and the amount of mediation of the association of age on the combined risk of periprocedural S+D with adjustment for these factors.
Results:
Only plaque length as measured at the sites increased with age, was associated with increased S+D risk and significantly mediated the association of age on S+D risk. However, adjustment for plaque length attenuated the increased risk per 10 years of age from 1.72 (95% confidence interval, 1.26-2.37) to 1.66 (95% confidence interval, 1.20-2.29), accounting for only 8% of the increased risk.
Conclusions:
Plaque length seems to be in the pathway between older age and higher risk of S+D among carotid artery stenting-treated patients, but it mediated only 8% of the age effect excess risk of carotid artery stenting in CREST. Other factors and mechanisms underlying the age effect need to be identified as plaque length will not identify elderly patients for whom stenting is safe relative to endarterectomy.
Clinical Trial Registration:
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00004732.
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