Increasingly, researchers understand that endothelial dysfunction and increased vascular stiffness contribute to the pathogenesis of cardiovascular disease (CVD). The Framingham Heart Study (FHS) has been examining vascular function in about 3600 middle-aged and elderly participants of the FHS Offspring and minority OMNI cohorts. The current proposal is to characterize vascular function by performing noninvasive studies of endothelial function with brachial ultrasound flow-mediated dilation, and of vascular stiffness with arterial tonometry, in 3850 adult offspring of the FHS Offspring and OMNI cohorts. The total of over 7000 vascular examinations in an extensively studied multi-generational community-based cohort will provide the opportunity to characterize the environmental and genetic determinants, and the prognosis of altered vascular function. The study hypotheses are: vascular function is determined by both environmental and genetic factors; endothelial function and vascular stiffness phenotypes are associated with each other: and vascular dysfunction predisposes to the development of hypertension (HTN) and CVD.
Specific aims :
Aim 1. To determine the cross-sectional relations of risk factors to vascular function in the community in young and middle-aged adults.
Aim 2. To study the heritability of vascular phenotypes.
Aim 3. To relate endothelial function and vascular stiffness to each other, and to other markers of subclinical CVD in early and middle adulthood.
Aim 4. To assess the relations of vascular function measures to longitudinal changes in blood pressure. The third generation cohort provides a large, community-based sample of young and middle-aged adults with a wealth of risk factor data and the availability of longitudinal follow-up beyond the length of the proposed grant. The resultant data will complement data already collected on their parents, will increase the power for heritability analyses, and will permit the characterization of vascular phenotypes in a younger cohort, prior to the development of HTN, CVD medication usage and clinical CVD. The combination of investigator expertise and a well-characterized multi-generational sample will provide a unique vascular function data set, and will increase the understanding of the pathophysiology of HTN and CVD.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL070100-01
Application #
6465426
Study Section
Special Emphasis Panel (ZRG1-CCVS (01))
Program Officer
Sorlie, Paul
Project Start
2002-05-01
Project End
2006-03-31
Budget Start
2002-05-01
Budget End
2003-03-31
Support Year
1
Fiscal Year
2002
Total Cost
$701,043
Indirect Cost
Name
Boston University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118
Seiler, Stephan; Fletcher, Evan; Hassan-Ali, Kinsy et al. (2018) Cerebral tract integrity relates to white matter hyperintensities, cortex volume, and cognition. Neurobiol Aging 72:14-22
Nayor, Matthew; Enserro, Danielle M; Xanthakis, Vanessa et al. (2018) Comorbidities and Cardiometabolic Disease: Relationship With Longitudinal Changes in Diastolic Function. JACC Heart Fail 6:317-325
Fetterman, Jessica L; Liu, Chunyu; Mitchell, Gary F et al. (2018) Relations of mitochondrial genetic variants to measures of vascular function. Mitochondrion 40:51-57
Fricker, Zachary P; Pedley, Alison; Massaro, Joseph M et al. (2018) Liver Fat is Associated With Markers of Inflammation and Oxidative Stress in Analysis of Data From the Framingham Heart Study. Clin Gastroenterol Hepatol :
Lu, Ake T; Xue, Luting; Salfati, Elias L et al. (2018) GWAS of epigenetic aging rates in blood reveals a critical role for TERT. Nat Commun 9:387
Zachariah, Justin P; Rong, Jian; Larson, Martin G et al. (2018) Metabolic Predictors of Change in Vascular Function: Prospective Associations From a Community-Based Cohort. Hypertension 71:237-242
Lee, Jane J; Pedley, Alison; Hoffmann, Udo et al. (2018) Longitudinal Associations of Pericardial and Intrathoracic Fat With Progression of Coronary Artery Calcium (from the Framingham Heart Study). Am J Cardiol 121:162-167
Long, Michelle T; Benjamin, Emelia J (2018) Prevalent Cardiovascular Disease Events and T1 Mapping Defined Hepatic Fibrosis. Circ Cardiovasc Imaging 11:e007553
Pursnani, Amit; Massaro, Joseph M; D'Agostino Sr, Ralph B et al. (2017) Guideline-Based Statin Eligibility, Cancer Events, and Noncardiovascular Mortality in the Framingham Heart Study. J Clin Oncol 35:2927-2933
Ferencik, Maros; Pencina, Karol M; Liu, Ting et al. (2017) Coronary Artery Calcium Distribution Is an Independent Predictor of Incident Major Coronary Heart Disease Events: Results From the Framingham Heart Study. Circ Cardiovasc Imaging 10:

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