Increased global aortic stiffness (AoS) is associated with significant morbidity and mortality and impacts the large aging population. The pathogenesis of AoS-related cardiovascular disease (CVD) may be due to and potentiated by abnormal hemodynamics created by the interactions between the proximal aorta, left ventricle (LV), and distal vasculature. Both resting proximal AoS and exercise-induced increases in AoS likely play fundamental roles in LV remodeling, systolic and diastolic function, and the evolution of heart failure with a preserved LV ejection fraction (HFPEF), to which women may be particularly susceptible due to greater age- associated increases in AoS. The uniqueness and compliance of proximal aorta are reflected in its elastic composition, distinct from that of the distal aorta. Yet, this region has not been well evaluated due to limitations of traditional imagin techniques. This application will utilize cardiovascular magnetic resonance (CMR), which fully images the proximal aorta and aortic arch, to study the properties of the local ascending and proximal descending aorta and regional aortic arch (collectively labeled CMR AoS). Dr. Tsao will investigate the relationships of CMR AoS with: 1) LV and central aortic hemodynamics (with rest/exercise in both hospital- based patients and community-dwelling individuals), 2) subclinical CVD reflected in echocardiographic LV systolic and diastolic dysfunction and increased carotid intima-medial thickness, and 3) prognosis of adverse clinical CVD outcomes, with comparison to risk prediction by global AoS. She will also conduct analyses of effect modification by gender in the relations of CMR AoS with her phenotypes of interest. Her preliminary data demonstrate the feasibility of using CMR to target this crucial segment of the aorta and suggest associations with age, female sex, exercise blood pressure, and measures of adverse LV remodeling and function. Together, data from these studies will enhance the scientific community's understanding of the pathophysiologic relationships of AoS, and ultimately aim to identify targets for prevention and therapy. Dr. Connie Tsao is a non-invasive cardiologist with clinical and research experience in CMR techniques and cardiovascular epidemiology, with a goal to continue patient-oriented and epidemiologic research applying non-invasive imaging to investigate vascular disease pathophysiology in an academic setting. The current proposal will expand Dr. Tsao's experience and training in the study of vascular physiology and imaging, as well as the longitudinal epidemiologic methods that she will employ in future expansion of her work. Her career development plan leverages the resources of her institutions, Beth Israel Deaconess Medical Center/ Harvard Medical School and the Framingham Heart Study, to provide opportunities for continued learning and to synthesize a superb team of mentors, advisors, and co-investigators with complementary expertise in all aspects of this application. Dr. Tsao's mentors and advisors are all well-established and well-funded clinical and translational researchers who will supervise her training and support her transition to independence.

Public Health Relevance

Global stiffening of the aorta occurs with aging and is associated with cardiovascular risk factors and poor outcomes, including coronary heart disease and stroke. However, the proximal aorta, the direct segment which couples the left ventricle to the neurovasculature and distal aorta, is distinct in structure and function from the distal aorta and has not been well described. This project's investigations of the hemodynamic and clinical associations of proximal aortic stiffness will increase our understanding of the development and consequences of increased central arterial stiffness, a growing problem in our aging population and a precursor of strokes, heart attacks, and heart failure.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
1K23HL118529-01A1
Application #
8635709
Study Section
Special Emphasis Panel (ZHL1-CSR-X (O1))
Program Officer
Scott, Jane
Project Start
2014-01-01
Project End
2018-12-31
Budget Start
2014-01-01
Budget End
2014-12-31
Support Year
1
Fiscal Year
2014
Total Cost
$143,506
Indirect Cost
$9,186
Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02215
Yeon, Susan B; Salton, Carol J; Gona, Philimon et al. (2015) Impact of age, sex, and indexation method on MR left ventricular reference values in the Framingham Heart Study offspring cohort. J Magn Reson Imaging 41:1038-45
Tsao, Connie W; Pencina, Karol M; Massaro, Joseph M et al. (2014) Cross-sectional relations of arterial stiffness, pressure pulsatility, wave reflection, and arterial calcification. Arterioscler Thromb Vasc Biol 34:2495-500