Vitamin D and Vulnerable Carotid Plaque.
OBJECTIVE
MR imaging-detected carotid intraplaque hemorrhage indicates vulnerable plaque with high stroke risk. Angiotensin II stimulates intraplaque hemorrhage in animal models, and the angiotensin system is highly regulated by vitamin D. Our purpose was to determine whether low vitamin D levels predict carotid intraplaque hemorrhage in humans.


METHODS
In this cross-sectional study, 65 patients with carotid disease underwent carotid MR imaging and blood draw. Systemic clinical confounders and local lumen imaging markers were recorded. To determine the association of low vitamin D levels with MR imaging detected intraplaque hemorrhage, we performed multivariable Poisson regression by using generalized estimating equations to account for up to 2 carotid arteries per patient and backward elimination of confounders. MR imaging detected intraplaque hemorrhage volume was also correlated with vitamin D levels and maximum plaque thickness. Thirty-five patients underwent carotid endarterectomy, and histology-detected intraplaque hemorrhage was correlated with vitamin D levels and total plaque area.


RESULTS
Low vitamin D levels (<30 ng/mL, prevalence ratio = 2.05,P= .03) were a significant predictor of MR imaging detected intraplaque hemorrhage, along with plaque thickness (prevalence ratio = 1.40,P< .001). MR imaging detected intraplaque hemorrhage volume linearly correlated with plaque thickness (partialr= 0.45,P< .001) and low vitamin D levels (partialr= 0.26,P= .003). Additionally, histology-detected intraplaque hemorrhage area linearly correlated with plaque area (partialr= 0.46,P< .001) and low vitamin D levels (partialr= 0.22,P= .03). The association of intraplaque hemorrhage volume with low vitamin D levels was also higher with ischemic stroke.


CONCLUSIONS
Low vitamin D levels and plaque thickness predict carotid intraplaque hemorrhage and outperform lumen markers of vulnerable plaque. This research demonstrates a significant link between low vitamin D levels and carotid intraplaque hemorrhage.
From the Department of Radiology and Imaging Sciences, Utah Center for Advanced Imaging Research (J.S.M., B.W.A., S.-E.K., M.S.M., L.B.E., D.L.P.) scott.mcnally@hsc.utah.edu.
J S
http://orcid.org/0000-0003-3770-1153
JS
McNally
Department of Neurology (T.M.B., J.J.M.).
T M
http://orcid.org/0000-0001-9077-9238
TM
Burton
From the Department of Radiology and Imaging Sciences, Utah Center for Advanced Imaging Research (J.S.M., B.W.A., S.-E.K., M.S.M., L.B.E., D.L.P.).
B W
http://orcid.org/0000-0003-1805-0359
BW
Aldred
From the Department of Radiology and Imaging Sciences, Utah Center for Advanced Imaging Research (J.S.M., B.W.A., S.-E.K., M.S.M., L.B.E., D.L.P.).
S-E
http://orcid.org/0000-0002-7232-3621
SE
Kim
From the Department of Radiology and Imaging Sciences, Utah Center for Advanced Imaging Research (J.S.M., B.W.A., S.-E.K., M.S.M., L.B.E., D.L.P.).
M S
http://orcid.org/0000-0002-3733-9847
MS
McLaughlin
From the Department of Radiology and Imaging Sciences, Utah Center for Advanced Imaging Research (J.S.M., B.W.A., S.-E.K., M.S.M., L.B.E., D.L.P.).
L B
http://orcid.org/0000-0001-9294-7645
LB
Eisenmenger
Department of Orthopedics, Study Design and Biostatistics Center (G.J.S).
G J
http://orcid.org/0000-0002-6292-276X
GJ
Stoddard
Department of Neurology (T.M.B., J.J.M.).
J J
http://orcid.org/0000-0003-3191-262X
JJ
Majersik
Department of Pathology (D.V.M.).
D V
DV
Miller
Department of Surgery at the University of Utah and VA Salt Lake City Health Care System, Salt Lake City, Utah (G.S.T.).
G S
http://orcid.org/0000-0002-1376-2536
GS
Treiman
From the Department of Radiology and Imaging Sciences, Utah Center for Advanced Imaging Research (J.S.M., B.W.A., S.-E.K., M.S.M., L.B.E., D.L.P.).
D L
http://orcid.org/0000-0003-2557-8952
DL
Parker