Inflammatory biomarkers of vascular risk as correlates of leukoariosis.
OBJECTIVE
Inflammatory biomarkers, including lipoprotein-associated phospholipase A2 (Lp-PLA2), myeloperoxidase (MPO), and high-sensitivity C-reactive protein (hsCRP) are associated with ischemic stroke risk. White matter hyperintensities (WMH) seen on brain MRI scans are associated with vascular risk factors and an increased risk of incident stroke, but their relation to inflammatory biomarkers is unclear.


METHODS
The Northern Manhattan Study includes a stroke-free community-based sample of Hispanic, black, and white participants with quantitative measurement of WMH volume (WMHV) and inflammatory biomarkers. We measured the association between Lp-PLA2, MPO, and hsCRP levels, and log-transformed WMHV after adjusting for sociodemographic and vascular risk factors.


RESULTS
The hsCRP (median, 2.42 mg/L; IQR, 1.04, 5.19), Lp-PLA2 (median, 220.97 ng/mL; IQR, 185.77, 268.05), and MPO (median, 15.14 ng/mL; IQR, 12.32, 19.69) levels were available in 527 The Northern Manhattan Study participants with WMHV data but no subclinical infarcts. Those with hsCRP in the upper quartile (Q4 >4.92 mg/L or >3 mg/L), Lp-PLA2 in Q4 (>or=264.9 ng/mL), or MPO levels in Q3 (15.04-19.39 ng/mL) or Q4 (>19.39 ng/mL) each had greater WMHV, adjusting for sociodemographic and vascular risk factors. Adjusting for all biomarkers simultaneously, WMHV was 1.3-fold greater for Lp-PLA2 levels in Q4 compared to Q1 (beta=0.28; P=0.008) and 1.25-fold greater for MPO levels above the median compared to below (beta=0.22; P=0.02), but hsCRP was not associated with WMHV.


CONCLUSIONS
Relative elevations of the inflammatory markers Lp-PLA2 and MPO were associated with a greater burden of WMH independent of hsCRP.
Wright
Clinton B
CB
Department of Neurology, Miller School of Medicine, University of Miami, Evelyn F McKnight Center for Age-related Memory Loss, Miami, FL 33136, USA. cwright@med.miami.edu
Moon
Yeseon
Y
Paik
Myunghee C
MC
Brown
Truman R
TR
Rabbani
LeRoy
L
Yoshita
Mitsuhiro
M
DeCarli
Charles
C
Sacco
Ralph
R
Elkind
Mitchell S V
MS
D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002561:Cerebrovascular Disorders / Q000097:blood* / Q000150:complications / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D049292:Leukoaraiosis / Q000097:blood* / Q000175:diagnosis / Q000473:pathology*; D008297:Male; D012307:Risk Factors; D014652:Vascular Diseases / Q000097:blood* / Q000175:diagnosis / Q000473:pathology*
D015415:Biomarkers; D018836:Inflammation Mediators
Circulation. 2005 Aug 9;112(6):900-5
16061741
Biochem J. 1999 Mar 1;338 ( Pt 2):479-87
10024526
Circulation. 2006 Oct 10;114(15):1591-8
17015791
Stroke. 2003 May;34(5):1126-9
12690219
Ann Neurol. 2007 May;61(5):491-5
17431876
JAMA. 2001 Jun 6;285(21):2729-35
11386928
Arch Intern Med. 2005 Nov 28;165(21):2479-84
16314544
Stroke. 2009 Oct;40(10):3233-7
19644070
Circulation. 2003 Jan 28;107(3):499-511
12551878
N Engl J Med. 2007 Nov 1;357(18):1821-8
17978290
Arterioscler Thromb Vasc Biol. 2007 Oct;27(10):2094-9
17626905
Stroke. 1999 Mar;30(3):529-36
10066847
Neurology. 2006 Dec 12;67(11):2045-7
17159117
J Am Coll Cardiol. 2007 May 22;49(20):1993-2000
17512353
N Engl J Med. 1997 Apr 3;336(14):973-9
9077376
Stroke. 2004 Aug;35(8):1821-5
15178824
Neurology. 2007 Mar 27;68(13):1032-8
17389308
Acta Neuropathol. 1968 Dec 18;12(1):1-15
5708546
Arterioscler Thromb Vasc Biol. 2006 Nov;26(11):2523-9
16960105
Am J Epidemiol. 1998 Feb 1;147(3):259-68
9482500
Neurology. 1995 Nov;45(11):2077-84
7501162
Arch Intern Med. 2006 Oct 23;166(19):2073-80
17060536
Eur Heart J. 2008 Jan;29(2):224-30
18156137
Ann Neurol. 2006 Jan;59(1):139-44
16278861
Circulation. 2005 Feb 8;111(5):570-5
15699277
N Engl J Med. 2003 Mar 27;348(13):1215-22
12660385
Stroke. 1997 Aug;28(8):1614-23
9259759
Atherosclerosis. 2003 Apr;167(2):223-30
12818404
N Engl J Med. 2003 Oct 23;349(17):1595-604
14573731
Ann Neurol. 2008 Jan;63(1):72-80
18157909
Arch Neurol. 2004 May;61(5):668-72
15148142
Circulation. 2004 Feb 24;109(7):837-42
14757686
Stroke. 2009 Mar;40(3 Suppl):S20-3
19064797
Neurology. 1993 Sep;43(9):1683-9
8414012
Stroke. 2008 Jul;39(7):1952-9
18436879
Circulation. 2003 Jul 15;108(2):166-70
12821545