Aortic stiffness increases markedly with advancing age and is associated with incident CVD, stroke, cognitive impairment, white matter brain lesions, and kidney dysfunction. Unfortunately, our current understanding of arterial stiffening and the pathophysiology of elevated pulse pressure (PP) is limited. Recent data from our group suggests that increased forward wave amplitude due to mismatch between ambient flow and an inappropriately smaller aortic diameter accounts for a major component of increased PP in hypertensive individuals and in the community. We have also found markedly nonlinear cross-sectional relations between age and key central hemodynamic measures such as forward wave amplitude and PP. Whether longitudinal changes in hemodynamics will mirror these cross-sectional relations is unknown. Our hypotheses for this proposal are 3 fold: 1) that proximal aortic wall stiffening and mismatch between aortic diameter and flow are major sources of excessive pressure pulsatility in older people, 2) that the consequent increase in pulsatile hemodynamic stress contributes to development of systolic hypertension and target organ damage in the heart, brain and kidneys, and 3) that change in arterial properties will predict incident clinical events. We will test these hypotheses with the following specific aims:
Aim 1. To examine risk factors for change in key central hemodynamic measures across an interval of 6 years in the Framingham Offspring and OMNI-I participants. We will perform arterial tonometry in ~3000 Framingham Offspring and minority Omni cohort participants at their next routine Heart Study exam (2011- 2014) to comprehensively characterize arterial stiffness and its change from their previous examination (2005- 2008).
Aim 2. To examine relations between observed and predicted longitudinal change in key central hemodynamic measures in order to identify factors associated with discrepancies in longitudinal and cross-sectional age relations.
Aim 3. To relate baseline and change in measures of aortic function to baseline and change in measures of target organ damage and incident clinical disease involving the heart, brain and kidneys. The proposed research will characterize longitudinal changes in arterial stiffness with aging and its contribution to the development of cardiovascular disease, stroke and cognitive impairment and renal dysfunction in the community.

Public Health Relevance

Aortic stiffness increases markedly with advancing age and is associated with increased pulse pressure, incident CVD, stroke, cognitive impairment, white matter brain lesions, and kidney dysfunction. Unfortunately, our current understanding of arterial stiffening and the pathophysiology of elevated pulse pressure is limited. The proposed research will characterize longitudinal changes in arterial stiffness with aging and its contribution to the development of cardiovascular disease, stroke and cognitive impairment, and renal dysfunction in the community.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL107385-02
Application #
8251152
Study Section
Clinical and Integrative Cardiovascular Sciences Study Section (CICS)
Program Officer
OH, Youngsuk
Project Start
2011-04-15
Project End
2015-03-31
Budget Start
2012-04-01
Budget End
2013-03-31
Support Year
2
Fiscal Year
2012
Total Cost
$662,018
Indirect Cost
$70,852
Name
Boston University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118
Tsao, Connie W; Himali, Jayandra J; Beiser, Alexa S et al. (2016) Association of arterial stiffness with progression of subclinical brain and cognitive disease. Neurology 86:619-26
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Pase, Matthew P; Himali, Jayandra J; Mitchell, Gary F et al. (2016) Association of Aortic Stiffness With Cognition and Brain Aging in Young and Middle-Aged Adults: The Framingham Third Generation Cohort Study. Hypertension 67:513-9
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Andersson, Charlotte; Enserro, Danielle; Sullivan, Lisa et al. (2016) Relations of circulating GDF-15, soluble ST2, and troponin-I concentrations with vascular function in the community: The Framingham Heart Study. Atherosclerosis 248:245-51
Cooper, Leroy L; Woodard, Todd; Sigurdsson, Sigurdur et al. (2016) Cerebrovascular Damage Mediates Relations Between Aortic Stiffness and Memory. Hypertension 67:176-82
Delling, Francesca N; Rong, Jian; Larson, Martin G et al. (2016) Evolution of Mitral Valve Prolapse: Insights From the Framingham Heart Study. Circulation 133:1688-95
Maillard, Pauline; Mitchell, Gary F; Himali, Jayandra J et al. (2016) Effects of Arterial Stiffness on Brain Integrity in Young Adults From the Framingham Heart Study. Stroke 47:1030-6
Andersson, Charlotte; Quiroz, Rene; Enserro, Danielle et al. (2016) Association of Parental Hypertension With Arterial Stiffness in Nonhypertensive Offspring: The Framingham Heart Study. Hypertension 68:584-9

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