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FRAMINGHAM: INFLAMMATION, GENES & CARDIOVASCULAR DISEASE

Award Number: R01HL076784
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/01/2004
PERIOD OF PERFORMANCE END DATE: 05/31/2009

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FRAMINGHAM: INFLAMMATION, GENES & CARDIOVASCULAR DISEASE - DESCRIPTION (provided by applicant): Recent experimental and clinical studies support the concept that vascular inflammation is central to the development of atherosclerosis, and that systemic inflammatory markers predict a wide array of CVD events. There is increasing interest in the role of genetic variation in inflammation contributing to the susceptibility for CVD. To date mostly small case-control studies have suggested that polymorphisms in inflammatory genes are associated with subclinical and clinical CVD, but the studies have differed with regard to which genes are central. We have previously measured systemic markers of vascular inflammation (e.g. CRP, sICAM-1, MCP-1, IL-6) and oxidative stress (isoprostanes), in a population-based sample of 3800 middle-aged and elderly men and women of the Framingham Heart Study offspring cohort. We propose to genotype inflammatory candidate genes in the Framingham offspring cohort which have been phenotyped for CVD risk factors, subclinical CVD. We also propose to measure systemic inflammatory markers in the Framingham Study Generation III cohort, who are the children of the offspring cohort. The central hypothesis of this application is that systemic vascular inflammation represents a complex phenotype that evolves over a lifetime and is influenced by both environmental and genetic factors. We further postulate that variations in the inflammatory phenotype (marker levels) and genotype predispose to the development of CVD. The purpose of this application is to determine the contribution of genetic and environmental factors to vascular inflammation, and to define the extent to which inflammatory phenotypes and genotypes predict subclinical and clinical CVD, and enhance risk prediction models. The specific aims are: Aim 1. To examine the environmental determinants of systemic inflammation in the community. Aim 2. To investigate the genetic determinants of systemic inflammation. Aim 3. To identify the inflammatory phenotypic and genetic determinants of subclinical CVD. Aim 4. To determine the contribution of inflammatory phenotype versus genotype to prevalent and incident CVD and to incident hypertension. The investigation will increase understanding as to whether inflammation is a core risk factor for CVD or is merely a marker of presence and burden of other CVD risk factors. These insights will fundamentally contribute to knowledge about the pathophysiology of CVD and may lead to improved prevention, risk stratification and management of CVD.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2008 ( Subtotal = $771,807 )
2008	2008	BOSTON UNIVERSITY	25 BUICK STREET	BOSTON	MA	02215	SUFFOLK	USA	Cardiovascular Diseases Research	000	5	5/9/2008	NON-COMPETING CONTINUATION	$771,807
														Subtotal = $771,807

Issue Date FY: 2007 ( Subtotal = $787,498 )
2007	2007	BOSTON UNIVERSITY	25 BUICK STREET	BOSTON	MA	02215	SUFFOLK	USA	Cardiovascular Diseases Research	000	4	5/9/2007	NON-COMPETING CONTINUATION	$787,498
														Subtotal = $787,498

Issue Date FY: 2006 ( Subtotal = $777,030 )
2006	2006	BOSTON UNIVERSITY	25 BUICK STREET	BOSTON	MA	02215	SUFFOLK	USA	Cardiovascular Diseases Research	000	3	5/23/2006	NON-COMPETING CONTINUATION	$777,030
														Subtotal = $777,030

Issue Date FY: 2005 ( Subtotal = $802,666 )
2005	2005	BOSTON UNIVERSITY	25 BUICK STREET	BOSTON	MA	02215	SUFFOLK	USA	Cardiovascular Diseases Research	000	2	5/16/2005	NON-COMPETING CONTINUATION	$802,666
														Subtotal = $802,666

Issue Date FY: 2004 ( Subtotal = $802,013 )
2004	2004	BOSTON UNIVERSITY	25 BUICK STREET	BOSTON	MA	02215	SUFFOLK	USA	Cardiovascular Diseases Research	000	1	5/20/2004	NEW	$802,013
														Subtotal = $802,013

Grand Total All Awards = $3,941,014

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FRAMINGHAM: INFLAMMATION, GENES & CARDIOVASCULAR DISEASE

Award Number: R01HL076784

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 06/01/2004

PERIOD OF PERFORMANCE END DATE: 05/31/2009

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