Progressive left ventricular (LV) remodeling is a fundamental substrate of heart failure (CHF). Alterations in LV and vascular remodeling (VVR) with age, i.e., a stiffer heart ejecting into a noncompliant vascular tree, predispose to CHF, especially diastolic CHF. Prior studies indicate sex differences in LV remodeling, vascular stiffness and diastolic dysfunction. We propose to assess VVR and diastolic function via concurrent echocardiography (echo) and arterial tonometry in 3500 participants of the Framingham Heart Study (FHS) Offspring and Omni cohorts. We will test 4 major hypotheses: 1. Sex differences in arterial stiffness contribute to dissimilarities in LV mass, geometry, and systolic function in women vs. men, and to the greater female susceptibility to diastolic CHF. 2. Environmental and genetic factors influence LV diastolic function, 3. Environmental and genetic factors determine longitudinal changes in vascular stiffness and LV measurements. 4. Individuals with accelerated LV and vascular aging have greater propensity for developing HTN, CHF and vascular events (CVD).
Our specific aims are to examine: 1) the cross-sectional relations between vascular stiffness measures and LV remodeling;2) the environmental and genetic correlates of LV diastolic function indexes;3) the environmental and genetic factors determine longitudinal changes in vascular stiffness, and LV remodeling;and 4) the relations of measures of VVR, diastolic function, and longitudinal changes in LV and vascular stiffness measures to the incidence of HTN, CHF, and CVD. The FHS is uniquely suited for this proposal because it provides a large, single site, community-based sample of middle-age to older men and women with extensive antecedent risk factor data. The forthcoming examination cycle is ideal to perform vascular testing and echo because the aging participants are experiencing marked increases in vascular stiffness, LV diastolic dysfunction, and CHF risk. LV and vascular stiffness measures at prior examinations facilitate the evaluation of longitudinal changes and associated risk.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL080124-05
Application #
7620353
Study Section
Special Emphasis Panel (ZRG1-CICS (01))
Program Officer
Paltoo, Dina
Project Start
2005-05-01
Project End
2011-04-30
Budget Start
2009-05-01
Budget End
2011-04-30
Support Year
5
Fiscal Year
2009
Total Cost
$705,437
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
Vasan, Ramachandran S; Xanthakis, Vanessa; Lyass, Asya et al. (2018) Epidemiology of Left Ventricular Systolic Dysfunction and Heart Failure in the Framingham Study: An Echocardiographic Study Over 3 Decades. JACC Cardiovasc Imaging 11:1-11
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:
Torjesen, Alyssa; Cooper, Leroy L; Rong, Jian et al. (2017) Relations of Arterial Stiffness With Postural Change in Mean Arterial Pressure in Middle-Aged Adults: The Framingham Heart Study. Hypertension 69:685-690
Maillard, Pauline; Mitchell, Gary F; Himali, Jayandra J et al. (2017) Aortic Stiffness, Increased White Matter Free Water, and Altered Microstructural Integrity: A Continuum of Injury. Stroke 48:1567-1573
Niiranen, Teemu J; Kalesan, Bindu; Larson, Martin G et al. (2017) Aortic-Brachial Arterial Stiffness Gradient and Cardiovascular Risk in the Community: The Framingham Heart Study. Hypertension 69:1022-1028
Cooper, Leroy L; Palmisano, Joseph N; Benjamin, Emelia J et al. (2016) Microvascular Function Contributes to the Relation Between Aortic Stiffness and Cardiovascular Events: The Framingham Heart Study. Circ Cardiovasc Imaging 9:
Hoffmann, Udo; Massaro, Joseph M; D'Agostino Sr, Ralph B et al. (2016) Cardiovascular Event Prediction and Risk Reclassification by Coronary, Aortic, and Valvular Calcification in the Framingham Heart Study. J Am Heart Assoc 5:

Showing the most recent 10 out of 83 publications