This is an application for a K23 award for Dr. Jennifer Ho, a cardiology research fellow at Massachusetts General Hospital, Boston. Dr. Ho is establishing a career in patient-oriented clinical research in cardiac remodeling and heart failure The K23 award will enable Dr. Ho to accomplish the following training goals critical to her future career: (1) to continue her training in advanced biostatistical methods;(2) to gain expertise in advanced noninvasive cardiac and vascular imaging;(3) to become facile with patient-oriented intervention studies in cardiovascular physiology;and (4) to establish an independent clinical research career. In order to achieve these goals, Dr. Ho will work closely with her mentoring team, consisting of her primary mentor, Dr. Thomas Wang, Director of the Program in Human Cardiovascular Physiology and Metabolism at Massachusetts General Hospital, and her two co-mentors, Dr. Daniel Levy, Director of the Framingham Heart Study, and Dr. Carolyn Ho, an expert in noninvasive cardiovascular imaging and genetic cardiomyopathies. Dr. Ho's long-term goals are to define subclinical disease phenotypes that lead to overt heart failure using informative biomarkers and non-invasive imaging, allowing the identification and potential treatment of at-risk individuals with therapies targeted at the underlying pathophysiology. Her proposed research will focus on one such potential pathway, Galectin-3. Experimental evidence suggests that Galectin-3 is an important mediator of cardiac fibrosis, an important contributor to the pathophysiology of heart failure. As a biomarker, Galectin-3 also predicts prognosis in patients with heart failure. Preliminary data shows Galectin-3 to predict incident heart failure events in the community. Dr. Ho's research will focus on elucidating the relation of Galectin-3 to subclinical cardiovascular phenotypes that precede overt heart failure. Specifically, she will study the relation to ventricular and vascular function in the community (Aim 1), and the relation of Galectin-3 to cardiac phenotypes in hypertrophic cardiomyopathy, a condition marked by cardiac fibrosis (Aim 2). Lastly, Dr. Ho will conduct a pilot randomized placebo-controlled trial t study the effect of Galectin-3 inhibition on collagen metabolism and subclinical cardiovascular phenotypes in hypertensive individuals with elevated Galectin-3 levels (Aim 3). This research and training plan will form the basis of a biomarker-guided targeted therapy trial in an at-risk population, to be proposed in an R01 grant application before the end of the K23 award.

Public Health Relevance

Heart failure is often diagnosed late in the course of the disease, when prognosis is poor. Strategies that identify and target high-risk individuals earlier in the disease course may prevent complications associated with heart failure. This proposal seeks to study one such potential pathway, which may allow the identification of at-risk individuals and guide potential targeted treatment to delay the onset of 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 #
5K23HL116780-02
Application #
8643566
Study Section
Special Emphasis Panel (ZHL1-CSR-X (O1))
Program Officer
Scott, Jane
Project Start
2013-04-01
Project End
2018-02-28
Budget Start
2014-04-01
Budget End
2015-02-28
Support Year
2
Fiscal Year
2014
Total Cost
$157,680
Indirect Cost
$11,680
Name
Boston Medical Center
Department
Type
DUNS #
005492160
City
Boston
State
MA
Country
United States
Zip Code
02118
Tsao, Connie W; Lyass, Asya; Enserro, Danielle et al. (2018) Temporal Trends in the Incidence of and Mortality Associated With Heart Failure With Preserved and Reduced Ejection Fraction. JACC Heart Fail 6:678-685
de Boer, Rudolf A; Nayor, Matthew; deFilippi, Christopher R et al. (2018) Association of Cardiovascular Biomarkers With Incident Heart Failure With Preserved and Reduced Ejection Fraction. JAMA Cardiol 3:215-224
Yao, Chen; Chen, George; Song, Ci et al. (2018) Genome-wide mapping of plasma protein QTLs identifies putatively causal genes and pathways for cardiovascular disease. Nat Commun 9:3268
Bhambhani, Vijeta; Kizer, Jorge R; Lima, Joao A C et al. (2018) Predictors and outcomes of heart failure with mid-range ejection fraction. Eur J Heart Fail 20:651-659
Eisman, Aaron S; Shah, Ravi V; Dhakal, Bishnu P et al. (2018) Pulmonary Capillary Wedge Pressure Patterns During Exercise Predict Exercise Capacity and Incident Heart Failure. Circ Heart Fail 11:e004750
Jiang, Jiyang; Thalamuthu, Anbupalam; Ho, Jennifer E et al. (2018) A Meta-Analysis of Genome-Wide Association Studies of Growth Differentiation Factor-15 Concentration in Blood. Front Genet 9:97
Suthahar, Navin; Meijers, Wouter C; Ho, Jennifer E et al. (2018) Sex-specific associations of obesity and N-terminal pro-B-type natriuretic peptide levels in the general population. Eur J Heart Fail 20:1205-1214
Savji, Nazir; Meijers, Wouter C; Bartz, Traci M et al. (2018) The Association of Obesity and Cardiometabolic Traits With Incident HFpEF and HFrEF. JACC Heart Fail 6:701-709
Ho, Jennifer E; McCabe, Elizabeth L; Wang, Thomas J et al. (2017) Cardiometabolic Traits and Systolic Mechanics in the Community. Circ Heart Fail 10:
Ho, Jennifer E (2017) High-Sensitivity Troponin in the General Population: Time for a New Normal? J Am Coll Cardiol 70:569-571

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