title: Inflammatory biomarkers of vascular risk as correlates of leukoariosis.
abstract: 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.
authors.affiliation: 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
authors.forename: Clinton B
authors.initials: CB
authors.lastname: Wright
authors.forename: Yeseon
authors.initials: Y
authors.lastname: Moon
authors.forename: Myunghee C
authors.initials: MC
authors.lastname: Paik
authors.forename: Truman R
authors.initials: TR
authors.lastname: Brown
authors.forename: LeRoy
authors.initials: L
authors.lastname: Rabbani
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Yoshita
authors.forename: Charles
authors.initials: C
authors.lastname: DeCarli
authors.forename: Ralph
authors.initials: R
authors.lastname: Sacco
authors.forename: Mitchell S V
authors.initials: MS
authors.lastname: Elkind
mesh_terms: 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*
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators
references.citation: Circulation. 2005 Aug 9;112(6):900-5
references.pmid: 16061741
references.citation: Biochem J. 1999 Mar 1;338 ( Pt 2):479-87
references.pmid: 10024526
references.citation: Circulation. 2006 Oct 10;114(15):1591-8
references.pmid: 17015791
references.citation: Stroke. 2003 May;34(5):1126-9
references.pmid: 12690219
references.citation: Ann Neurol. 2007 May;61(5):491-5
references.pmid: 17431876
references.citation: JAMA. 2001 Jun 6;285(21):2729-35
references.pmid: 11386928
references.citation: Arch Intern Med. 2005 Nov 28;165(21):2479-84
references.pmid: 16314544
references.citation: Stroke. 2009 Oct;40(10):3233-7
references.pmid: 19644070
references.citation: Circulation. 2003 Jan 28;107(3):499-511
references.pmid: 12551878
references.citation: N Engl J Med. 2007 Nov 1;357(18):1821-8
references.pmid: 17978290
references.citation: Arterioscler Thromb Vasc Biol. 2007 Oct;27(10):2094-9
references.pmid: 17626905
references.citation: Stroke. 1999 Mar;30(3):529-36
references.pmid: 10066847
references.citation: Neurology. 2006 Dec 12;67(11):2045-7
references.pmid: 17159117
references.citation: J Am Coll Cardiol. 2007 May 22;49(20):1993-2000
references.pmid: 17512353
references.citation: N Engl J Med. 1997 Apr 3;336(14):973-9
references.pmid: 9077376
references.citation: Stroke. 2004 Aug;35(8):1821-5
references.pmid: 15178824
references.citation: Neurology. 2007 Mar 27;68(13):1032-8
references.pmid: 17389308
references.citation: Acta Neuropathol. 1968 Dec 18;12(1):1-15
references.pmid: 5708546
references.citation: Arterioscler Thromb Vasc Biol. 2006 Nov;26(11):2523-9
references.pmid: 16960105
references.citation: Am J Epidemiol. 1998 Feb 1;147(3):259-68
references.pmid: 9482500
references.citation: Neurology. 1995 Nov;45(11):2077-84
references.pmid: 7501162
references.citation: Arch Intern Med. 2006 Oct 23;166(19):2073-80
references.pmid: 17060536
references.citation: Eur Heart J. 2008 Jan;29(2):224-30
references.pmid: 18156137
references.citation: Ann Neurol. 2006 Jan;59(1):139-44
references.pmid: 16278861
references.citation: Circulation. 2005 Feb 8;111(5):570-5
references.pmid: 15699277
references.citation: N Engl J Med. 2003 Mar 27;348(13):1215-22
references.pmid: 12660385
references.citation: Stroke. 1997 Aug;28(8):1614-23
references.pmid: 9259759
references.citation: Atherosclerosis. 2003 Apr;167(2):223-30
references.pmid: 12818404
references.citation: N Engl J Med. 2003 Oct 23;349(17):1595-604
references.pmid: 14573731
references.citation: Ann Neurol. 2008 Jan;63(1):72-80
references.pmid: 18157909
references.citation: Arch Neurol. 2004 May;61(5):668-72
references.pmid: 15148142
references.citation: Circulation. 2004 Feb 24;109(7):837-42
references.pmid: 14757686
references.citation: Stroke. 2009 Mar;40(3 Suppl):S20-3
references.pmid: 19064797
references.citation: Neurology. 1993 Sep;43(9):1683-9
references.pmid: 8414012
references.citation: Stroke. 2008 Jul;39(7):1952-9
references.pmid: 18436879
references.citation: Circulation. 2003 Jul 15;108(2):166-70
references.pmid: 12821545