0

The full content of Annals is available to subscribers

Subscribe/Learn More  >
Original Research |

Small Brain Lesions and Incident Stroke and Mortality: A Cohort StudySmall Brain Lesions and Incident Stroke and Mortality

B. Gwen Windham, MD, MHS; Bradley Deere, MD; Michael E. Griswold, PhD; Wanmei Wang, MS; Daniel C. Bezerra, MD, PhD; Dean Shibata, MD; Kenneth Butler, PhD; David Knopman, MD; Rebecca F. Gottesman, MD, PhD; Gerardo Heiss, MD, PhD; and Thomas H. Mosley Jr., PhD
[+] Article, Author, and Disclosure Information

From University of Mississippi Medical Center, Jackson, Mississippi; Johns Hopkins Bloomberg School of Public Health and Johns Hopkins University School of Medicine, Baltimore, Maryland; University of Washington Medical Center, Seattle, Washington; Mayo Clinic, Rochester, Minnesota; and University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

Acknowledgment: The authors thank the staff and participants of the ARIC Study for their important contributions and Mr. Seth Lirette for analytic assistance during the revision of the manuscript.

Financial Support: The ARIC Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts HHSN268201100005C, HSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C, with the ARIC carotid MRI examination funded by U01HL075572-01.

Disclosures: Dr. Windham reports grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Dr. Griswold reports grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Dr. Butler reports grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Dr. Knopman reports grants from TauRx Therapeutics and personal fees from Lundbeck, the Dominantly Inherited Alzheimer Network, and the American Academy of Neurology outside the submitted work. Dr. Mosley reports grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M14-2057.

Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer.

Reproducible Research Statement:Study protocol and data set: Protocols and data for the ARIC and ARIC Brain MRI Study may be obtained by approved persons through written agreements with the ARIC Steering Committee and the research sponsor (National Heart, Lung, and Blood Institute) (e-mail, tmosley@umc.edu). Statistical code: Available from Dr. Griswold (e-mail, MINDSET@umc.edu).

Requests for Single Reprints: B. Gwen Windham, MD, MHS, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216; e-mail, gwindham@umc.edu.

Current Author Addresses: Drs. Windham, Deere, Griswold, Butler, and Mosley and Ms. Wang: University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216.

Dr. Bezerra: Visconde Silva 52 / 804, Rio de Janeiro, Brazil 22271-092.

Dr. Shibata: University of Washington, 1959 NE Pacific Street, Seattle, WA 98195.

Dr. Knopman: Mayo Clinic, 200 First Street SW, Rochester, MN 55905.

Dr. Gottesman: Johns Hopkins Medicine, Phipps 446D, 600 North Wolfe Street, Baltimore, MD 21287.

Dr. Heiss: University of North Carolina at Chapel Hill, 137 East Franklin Street, Suite 306, Chapel Hill, NC 27514-4145.

Author Contributions: Conception and design: B.G. Windham, M.E. Griswold, T.H. Mosley.

Analysis and interpretation of the data: B.G. Windham, B. Deere, M.E. Griswold, W. Wang, D. Shibata, D. Knopman, R.F. Gottesman, T.H. Mosley.

Drafting of the article: B.G. Windham, B. Deere, M.E. Griswold, D.C. Bezerra.

Critical revision of the article for important intellectual content: B.G. Windham, M.E. Griswold, D.C. Bezerra, K. Butler, D. Knopman, R.F. Gottesman, T.H. Mosley.

Final approval of the article: B.G. Windham, M.E. Griswold, D.C. Bezerra, K. Butler, D. Knopman, R.F. Gottesman, G. Heiss, T.H. Mosley.

Provision of study materials or patients: G. Heiss, T.H. Mosley.

Statistical expertise: M.E. Griswold, W. Wang.

Obtaining of funding: G. Heiss, T.H. Mosley.

Administrative, technical, or logistic support: M.E. Griswold, G. Heiss.

Collection and assembly of data: D. Shibata, K. Butler, G. Heiss, T.H. Mosley.


Ann Intern Med. 2015;163(1):22-31. doi:10.7326/M14-2057
Text Size: A A A

Background: Although cerebral lesions 3 mm or larger on imaging are associated with incident stroke, lesions smaller than 3 mm are typically ignored.

Objective: To examine stroke risks associated with subclinical brain lesions (<3 mm only, ≥3 mm only, and both sizes) and white matter hyperintensities (WMHs).

Design: Community cohort from the ARIC (Atherosclerosis Risk in Communities) Study.

Setting: Two ARIC sites with magnetic resonance imaging (MRI) data from 1993 to 1995.

Participants: 1884 adults aged 50 to 73 years with MRI, no prior stroke, and average follow-up of 14.5 years.

Measurements: Lesions on MRI (by size), WMH score (scale of 0 to 9), incident stroke, all-cause mortality, and stroke-related mortality. Hazard ratios (HRs) were estimated with proportional hazards models.

Results: Compared with no lesions, stroke risk tripled with lesions smaller than 3 mm only (HR, 3.47 [95% CI, 1.86 to 6.49]), doubled with lesions 3 mm or larger only (HR, 1.94 [CI, 1.22 to 3.07]), was 8-fold higher with lesions of both sizes (HR, 8.59 [CI, 4.69 to 15.73]), and doubled with a WMH score of at least 3 (HR, 2.14 [CI, 1.45 to 3.16]). Risk for stroke-related death tripled with lesions smaller than 3 mm only (HR, 3.05 [CI, 1.04 to 8.94]) and was 7 times higher with lesions of both sizes (HR, 6.97 [CI, 2.03 to 23.93]).

Limitation: Few strokes (especially hemorrhagic) and few participants with lesions smaller than 3 mm only or lesions of both sizes.

Conclusion: Very small cerebrovascular lesions may be associated with increased risks for stroke and death; presence of lesions smaller than 3 mm and 3 mm or larger may result in a particularly striking risk increase. Larger studies are needed to confirm findings and provide more precise estimates.

Primary Funding Source: National Heart, Lung, and Blood Institute.

Figures

Grahic Jump Location
Appendix Figure 2.

Standardized cumulative hazards of stroke and stroke-related mortality, by lesion size and WMH grade.

Figures shown with conditional standardization based on covariates in primary models reported in Table 2 set at mean and mode values for continuous and categorical variables, respectively. Results are similar to those shown in the unadjusted Kaplan–Meier plots in the Figure. WMH = white matter hyperintensity.

Grahic Jump Location
Grahic Jump Location
Appendix Figure 1.

Study flow diagram.

ARIC = Atherosclerosis Risk in Communities; MRI = magnetic resonance imaging.

Grahic Jump Location
Grahic Jump Location
Figure.

Cumulative incidence of stroke and stroke-related mortality, by lesion size and WMH grade.

WMH = white matter hyperintensity.

Grahic Jump Location

Tables

References

Letters

NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Comments

Submit a Comment/Letter
Routine screening for WMH in elderly hypertensive patients is vital
Posted on July 11, 2015
Gauranga Dhar
Bangladesh Institute of Family Medicine and Research
Conflict of Interest: None Declared
White matter hyperintensities (WMH) are common in the elderly. Up to 30% of elderly population with hypertension found to have silent infarcts is found in routine MRI [1]. Take home message of this study is extremely vital to prevent further development of stroke and death.

Reference:
1. Vermeer SE, Longstreth WTJ, Koudstaal PJ. Silent brain infarcts: a systematic re-
view. Lancet Neurol 2007; 6: 611ñ619.
Submit a Comment/Letter

Summary for Patients

Clinical Slide Sets

Terms of Use

The In the Clinic® slide sets are owned and copyrighted by the American College of Physicians (ACP). All text, graphics, trademarks, and other intellectual property incorporated into the slide sets remain the sole and exclusive property of the ACP. The slide sets may be used only by the person who downloads or purchases them and only for the purpose of presenting them during not-for-profit educational activities. Users may incorporate the entire slide set or selected individual slides into their own teaching presentations but may not alter the content of the slides in any way or remove the ACP copyright notice. Users may make print copies for use as hand-outs for the audience the user is personally addressing but may not otherwise reproduce or distribute the slides by any means or media, including but not limited to sending them as e-mail attachments, posting them on Internet or Intranet sites, publishing them in meeting proceedings, or making them available for sale or distribution in any unauthorized form, without the express written permission of the ACP. Unauthorized use of the In the Clinic slide sets will constitute copyright infringement.

Toolkit

Buy Now for $32.00

to gain full access to the content and tools.

Want to Subscribe?

Learn more about subscription options

Advertisement
Related Articles
Related Point of Care
Topic Collections
PubMed Articles
Forgot your password?
Enter your username and email address. We'll send you a reminder to the email address on record.
(Required)
(Required)