Serum markers of infection and inflammation have been associated with both incident myocardial infarction (Ml) and prognosis after Ml, but very little data about the relationship of these markers to stroke incidence or prognosis is available. Preliminary studies by the applicant have shown that chronic infection with Chlamydia pneumoniae (C. pneumoniae) is associated with stroke risk, and that elevated white blood cell count and soluble tumor necrosis factor receptor levels are associated with carotid atherosclerosis. The applicant has training in epidemiology, but no advanced training in laboratory techniques or in the basic biology of inflammation or infection. This career development award will train the applicant in the pathobiology of inflammation and infection, in basic techniques of molecular biology, and in advanced epiderniologic and biostatistical analysis. The proposed study will test the following hypotheses: 1) Elevated levels of markers of inflammation (CRP, interleukin 6, tumor necrosis factor receptor levels) and specific infections (C. pneumoniae, CMV) are independent predictors of first ischemic stroke, and 2) elevated levels of these markers of inflammation and infection are associated with worse prognosis after stroke. Two concurrent prospective study designs are proposed to test these hypotheses. For hypothesis 1, levels of these markers will be compared in 125 stroke cases and 250 controls, all of whom are drawn from the 3300 initially strokefree subjects in the Northern Manhattan Stroke Study (NOMASS, NINDS 2RO1-29993). ELISA will be used to measure marker levels. The blood samples analyzed will be those drawn at baseline, prior to stroke occurrence, using a strong design, the nested casecontrol study. Multiple conditional logistic regression analysis will be used to assess the significance of the main exposure variables after matching for age, gender, and race/ethnicity, and after adjustment for other risk factors. For hypothesis 2, 300 prospectively enrolled stroke patients in the Aortic Plaque and Risk of Ischemic Stroke Study (APRIS, NINDS R01-36286) will be followed up annually for 3 years for the occurrence of stroke, death, or Ml, and the levels of these markers in blood samples will be analyzed by ELISA. Cox proportional hazards modeling will be used to assess survival based on baseline inflammatory marker status after adjustment for other risk factors and stroke severity. The applicant will pursue coursework in infectious diseases and pathobiology of inflammation, as well as in advanced epidemiologic and biostatistical analysis. He will participate in laboratory practicums at Columbia and the CDC to gain handson knowledge of laboratory techniques, including ELISA and PCR, necessary for the present and future studies. It is anticipated that these experiences and the successful completion of the proposed project will allow him to compete for independent investigator awards. Nationally recognized experts in stroke epidemiology and basic vascular biology will serve as mentors for these studies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
1K23NS042912-01
Application #
6417577
Study Section
NST-2 Subcommittee (NST)
Program Officer
Marler, John R
Project Start
2002-01-15
Project End
2006-12-31
Budget Start
2002-01-15
Budget End
2002-12-31
Support Year
1
Fiscal Year
2002
Total Cost
$169,576
Indirect Cost
Name
Columbia University (N.Y.)
Department
Neurology
Type
Schools of Medicine
DUNS #
167204994
City
New York
State
NY
Country
United States
Zip Code
10032
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
Economos, Alexis; Wright, Clinton B; Moon, Yeseon Park et al. (2013) Interleukin 6 plasma concentration associates with cognitive decline: the northern Manhattan study. Neuroepidemiology 40:253-9
Elkind, Mitchell S V; Luna, Jorge M; Moon, Yeseon Park et al. (2010) Infectious burden and carotid plaque thickness: the northern Manhattan study. Stroke 41:e117-22
Rundek, Tatjana; Gardener, Hannah; Xu, Qiang et al. (2010) Insulin resistance and risk of ischemic stroke among nondiabetic individuals from the northern Manhattan study. Arch Neurol 67:1195-200
Elkind, Mitchell S V (2010) Infectious burden: a new risk factor and treatment target for atherosclerosis. Infect Disord Drug Targets 10:84-90
Elkind, Mitchell S V (2010) Inflammatory mechanisms of stroke. Stroke 41:S3-8
Della-Morte, David; Gardener, Hannah; Denaro, Federica et al. (2010) Metabolic syndrome increases carotid artery stiffness: the Northern Manhattan Study. Int J Stroke 5:138-44
Grinspan, Zachary M; Willey, Joshua Z; Tullman, Mark J et al. (2009) Clinical Reasoning: a 28-year-old pregnant woman with encephalopathy. Neurology 73:e74-9
Takei, Yasuyoshi; Di Tullio, Marco R; Homma, Shunichi et al. (2009) Soluble tumor necrosis factor receptor 1 level is associated with left ventricular hypertrophy: the northern Manhattan study. Am J Hypertens 22:763-9
Elkind, Mitchell S V; Leon, Vladimir; Moon, Yeseon P et al. (2009) High-sensitivity C-reactive protein and lipoprotein-associated phospholipase A2 stability before and after stroke and myocardial infarction. Stroke 40:3233-7

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