Advanced age is the single most powerful risk factor for cardiovascular disease (CVD) for reasons that remain unclear. The contemporary paradigm of cardiovascular aging is that ventricular and vascular disease evolves over the life course in the setting of chronic exposure to traditional risk factors. However, the relative burden of CVD varies widely even among individuals of similar chronologic age and risk exposure. In effect, little is known about what causes the development and progression of subclinical CVD over an individual's lifetime. We postulate that discrete abnormalities in both myocardial and arterial function are among the earliest features of cardiovascular aging, developing in parallel and in response to cumulative risk factor exposure and, in turn, contributing to age-associated risk for CVD including heart failure (HF).
In Aim 1, we will use advanced strain-based analyses of existing imaging data to assess variations in myocardial function in a large community-based sample of aging men and women in the Framingham Heart Study. We will also analyze the relation of these advanced myocardial measures with traditional risk factors, conventional echocardiographic traits, and pathway biomarkers associated with the development of HF.
In Aim 2, we will examine the relations of these myocardial functional measures to incident HF, CVD, and mortality in the same aging sample.
In Aim 3, we will use a novel methodology to prospectively assess arterial strain, a sensitive measure of arterial function, in a sample of adults free of baseline HF or CVD. We will examine the association of age-related variation in arterial strain to clinical correlates, concurrent myocardial function, and outcomes. The overarching goal of this proposal is to improve phenotyping of myocardial and arterial function - and determine the extent to which novel measures of pre-clinical dysfunction can clarify the pathway from risk factors to disease and also predict adverse outcomes. This research will be accomplished in the setting of a comprehensive career development program designed to provide the candidate with the skills needed to become an independent physician-scientist in cardiovascular medicine. An advisory committee of established scientists/mentors in the fields of epidemiology, cardiac and vascular imaging, aging biology, biostatistics, and translational science will guide the candidate in her transition to scientific independence over the course of the award period.

Public Health Relevance

Over the next decade, the number of adults age 65 and older will exceed 50 million in the United States alone. Cardiovascular disease is the leading cause of death and disability in this rapidly growing aging population. We will investigate how biologic aging contributes to discrete alterations in cardiac and vascular function, which could lead to novel therapies for alleviating age-associated cardiovascular risk.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Career Transition Award (K99)
Project #
5K99HL107642-02
Application #
8399062
Study Section
Special Emphasis Panel (ZHL1-CSR-P (O2))
Program Officer
Carlson, Drew E
Project Start
2012-01-01
Project End
2014-01-19
Budget Start
2012-12-01
Budget End
2014-01-19
Support Year
2
Fiscal Year
2013
Total Cost
$137,970
Indirect Cost
$10,220
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
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Walford, Geoffrey A; Porneala, Bianca C; Dauriz, Marco et al. (2014) Metabolite traits and genetic risk provide complementary information for the prediction of future type 2 diabetes. Diabetes Care 37:2508-14
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Cheng, Susan; Lam, Carolyn; Shah, Amil et al. (2014) Age and the effectiveness of anti-hypertensive therapy on improvement in diastolic function. J Hypertens 32:174-80
Cheng, Susan; Claggett, Brian; Correia, Andrew W et al. (2014) Temporal trends in the population attributable risk for cardiovascular disease: the Atherosclerosis Risk in Communities Study. Circulation 130:820-8
Cheng, Susan; Enserro, Danielle; Xanthakis, Vanessa et al. (2014) Association of exhaled carbon monoxide with subclinical cardiovascular disease and their conjoint impact on the incidence of cardiovascular outcomes. Eur Heart J 35:2980-7
Cheng, Hui-Wen; Fisch, Sudeshna; Cheng, Susan et al. (2014) Assessment of right ventricular structure and function in mouse model of pulmonary artery constriction by transthoracic echocardiography. J Vis Exp :e51041
Lieb, Wolfgang; Gona, Philimon; Larson, Martin G et al. (2014) The natural history of left ventricular geometry in the community: clinical correlates and prognostic significance of change in LV geometric pattern. JACC Cardiovasc Imaging 7:870-8
Lam, Carolyn S P; Gona, Philimon; Larson, Martin G et al. (2013) Aortic Root Remodeling and Risk of Heart Failure in the Framingham Heart Study. JACC Heart Fail 1:79-83
Uraizee, Imran; Cheng, Susan; Hung, Chung-Lieh et al. (2013) Relation of N-terminal pro-B-type natriuretic peptide with diastolic function in hypertensive heart disease. Am J Hypertens 26:1234-41

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