Inflammation is increasingly recognized to play a central role in atherosclerosis and coronary artery disease, and peripheral blood markers of inflammation have been associated with cardiac events. The relationship of these potentially modifiable risk markers to ischemic stroke risk is less clear. Additional epidemiological studies have suggested that the burden of past exposure to common infectious diseases may be one of the factors contributing to increased levels of inflammation. The proposed research study will capitalize on the on-going Northern Manhattan Study (N INDS R01 29993, PI RL S acco), a prospective cohort study of stroke risk factors in a multi-ethnic urban population, to test the following hypotheses: (1) high-sensitivity C -reactive protein and other inflammatory markers (serum amyloid A, interleukin 6, tumor necrosis factor receptor levels) are independent risk factors for (a) ischemic stroke and (b) ot her vascular outcomes in whites, blacks and Hispanics; (2) the burden of common infectious serologies (C. pneumoniae, H.pylori, CMV, EBV, HSV 1 and 2) is an independent risk factor for stroke and other vascular outcomes in these populations; (3) these inflammatory and infectious marker s are associated with sub-clinical vascular brain diseases seen on MRI scanning, such as white matter hyperintensities and silent infarcts. Levels of these markers will be measured using nephelometric and immunoassay techniques on stored baseline serum samples from 2000 of 3298 initially stroke-free subjects, of whom 1400 will undergo MRI scanning as part of the parent project. Follow-up serum samples will also be collected on these 1400 participants. Outcomes of ischemic stroke, total stroke, myocardial infarction, vascular mortality and total mortality will be ascertained. Cox proportional hazard model analysis will be used to assess the significance of the main exposure variables after adjustment for other risk factors, and inflammatory and infectious markers will be analyzed as time dependen t covariates when follow up values are available. The cross-sectional associations between inflammatory and infectious markers and quantitative MRI abnormalities will also be assessed.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS048134-03
Application #
7027014
Study Section
Special Emphasis Panel (ZRG1-BMRD (03))
Program Officer
Jacobs, Tom P
Project Start
2004-03-01
Project End
2009-02-28
Budget Start
2006-03-01
Budget End
2007-02-28
Support Year
3
Fiscal Year
2006
Total Cost
$295,367
Indirect Cost
Name
Columbia University (N.Y.)
Department
Neurology
Type
Schools of Medicine
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
Dhamoon, Mandip S; Cheung, Ying-Kuen; Gutierrez, Jose et al. (2018) Functional Trajectories, Cognition, and Subclinical Cerebrovascular Disease. Stroke 49:549-555
Dhamoon, Mandip S; Cheung, Ying-Kuen; Bagci, Ahmet et al. (2018) Periventricular White Matter Hyperintensities and Functional Decline. J Am Geriatr Soc 66:113-119
Liang, John W; Cheung, Ying Kuen; Willey, Joshua Z et al. (2017) Quality of life independently predicts long-term mortality but not vascular events: the Northern Manhattan Study. Qual Life Res 26:2219-2228
Dhamoon, Mandip S; Cheung, Ying-Kuen; Moon, Yeseon P et al. (2017) Association Between Serum Tumor Necrosis Factor Receptor 1 and Trajectories of Functional Status: The Northern Manhattan Study. Am J Epidemiol 186:11-20
Wright, Clinton B; Gardener, Hannah; Dong, Chuanhui et al. (2015) Infectious Burden and Cognitive Decline in the Northern Manhattan Study. J Am Geriatr Soc 63:1540-5
Dhamoon, Mandip S; Dong, Chuanhui; Elkind, Mitchell S V et al. (2015) Ideal cardiovascular health predicts functional status independently of vascular events: the Northern Manhattan Study. J Am Heart Assoc 4:
Katan, Mira; Moon, Yeseon P; Paik, Myunghee C et al. (2014) Lipoprotein-associated phospholipase A2 is associated with atherosclerotic stroke risk: the Northern Manhattan Study. PLoS One 9:e83393
Dhamoon, Mandip S; Moon, Yeseon Park; Paik, Myunghee C et al. (2014) Diabetes predicts long-term disability in an elderly urban cohort: the Northern Manhattan Study. Ann Epidemiol 24:362-368.e1
Luna, Jorge M; Moon, Yeseon P; Liu, Khin M et al. (2014) High-sensitivity C-reactive protein and interleukin-6-dominant inflammation and ischemic stroke risk: the northern Manhattan study. Stroke 45:979-87
Dhamoon, Mandip S; McClure, Leslie A; White, Carole L et al. (2014) Quality of life after lacunar stroke: the Secondary Prevention of Small Subcortical Strokes study. J Stroke Cerebrovasc Dis 23:1131-7

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