Brain Perivascular Spaces as Biomarkers of Vascular Risk: Results from the Northern Manhattan Study.
OBJECTIVE
Dilated perivascular spaces in the brain are associated with greater arterial pulsatility. We hypothesized that perivascular spaces identify individuals at higher risk for systemic and cerebral vascular events.


METHODS
Stroke-free participants in the population-based Northern Manhattan Study had brain MR imaging performed and were followed for myocardial infarction, any stroke, and death. Imaging analyses distinguished perivascular spaces from lesions presumably ischemic. Perivascular spaces were further subdivided into lesions with diameters of ≤3 mm (small perivascular spaces) and >3 mm (large perivascular spaces). We calculated relative rates of events with Poisson models and hazard ratios with Cox proportional models.


RESULTS
The Northern Manhattan Study participants who had MR imaging data available for review (n= 1228; 59% women, 65% Hispanic; mean age, 71 ± 9 years) were followed for an average of 9 ± 2 years. Participants in the highest tertile of the small perivascular space score had a higher relative rate of all deaths (relative rate, 1.38; 95% CI, 1.01-1.91), vascular death (relative rate, 1.87; 95% CI, 1.12-3.14), myocardial infarction (relative rate, 2.08; 95% CI, 1.01-4.31), any stroke (relative rate, 1.79; 95% CI, 1.03-3.11), and any vascular event (relative rate, 1.74; 95% CI, 1.18-2.56). After we adjusted for confounders, there was a higher risk of vascular death (hazard ratio, 1.06; 95% CI, 1.01-1.11), myocardial infarction (hazard ratio, 2.22; 95% CI, 1.12-4.42), and any vascular event (hazard ratio, 1.04; 95% CI, 1.01-1.08) with higher small perivascular space scores.


CONCLUSIONS
In this multiethnic, population-based study, participants with a high burden of small perivascular spaces had increased risk of vascular events. By gaining pathophysiologic insight into the mechanism of perivascular space dilation, we may be able to propose novel therapies to better prevent vascular disorders in the population.
From the Departments of Neurology (J.G., M.S.V.E.) jg3233@cumc.columbia.edu.
J
http://orcid.org/0000-0002-2175-8078
J
Gutierrez
From the Departments of Neurology (J.G., M.S.V.E.).|Department of Epidemiology (M.S.V.E.), Mailman School of Public Health, Columbia University, New York, New York.
M S V
http://orcid.org/0000-0003-2562-1156
MSV
Elkind
Department of Neurology (C.D., T.R., R.L.S., C.B.W.), Miller School of Medicine, University of Miami, Miami, Florida.
C
http://orcid.org/0000-0002-8606-0682
C
Dong
Medicine (M.D.), Columbia University Medical Center, New York, New York.
M
http://orcid.org/0000-0002-3031-4196
M
Di Tullio
Department of Neurology (C.D., T.R., R.L.S., C.B.W.), Miller School of Medicine, University of Miami, Miami, Florida.
T
http://orcid.org/0000-0002-7115-9815
T
Rundek
Department of Neurology (C.D., T.R., R.L.S., C.B.W.), Miller School of Medicine, University of Miami, Miami, Florida.
R L
http://orcid.org/0000-0003-4629-684X
RL
Sacco
Department of Neurology (C.D., T.R., R.L.S., C.B.W.), Miller School of Medicine, University of Miami, Miami, Florida.
C B
http://orcid.org/0000-0002-9797-6215
CB
Wright
D000368:Aged; D001921:Brain / Q000473:pathology*; D004108:Dilatation, Pathologic; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology*; D016016:Proportional Hazards Models; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology*; D013346:Subarachnoid Space / Q000473:pathology*