Despite knowledge that hypertension is a major risk factor for heart failure, it is unclear why some individuals with hypertension develop the heart failure syndrome while others do not. Since abnormalities in cardiac mechanics occur during the progression from hypertension to heart failure, understanding the determinants of abnormal cardiac mechanics in hypertension is a critical unmet need. Sensitive echocardiographic indices (myocardial tissue velocities, strain, and non-invasive pressure-volume analysis) can provide insight into cardiac mechanics in large epidemiologic studies. We propose to use state-of-the-art speckle tracking analysis to quantify cardiac mechanics in the Hypertension Genetic Epidemiology Network (HyperGEN) Study of the Family Blood Pressure Program (FBPP). By studying cardiac mechanics in a population-based epidemiologic study, we aim to: (1) determine the acquired risk factors for abnormal cardiac mechanics in hypertension;(2) determine heritability of systolic and diastolic cardiac mechanics in African Americans and whites;and (3) identify novel genetic loci associated with abnormal cardiac mechanics in a genome-wide association study with replication in the Coronary Artery Risk Development in Young Adults (CARDIA) Study and the Hutterite Family Health Study. We anticipate that results from this study will: (1) provide greater understanding of risk factors for the development of abnormal cardiac mechanics in hypertension;and (2) lead to a breakthrough in the understanding of the molecular pathways which dictate the transition between hypertension, hypertrophy, and heart failure.

Public Health Relevance

Hypertension is the most common risk factor for heart failure, and both hypertension and heart failure are major public health problems which cause substantial morbidity and mortality. It is therefore important to improve understanding of why some individuals with hypertension develop heart failure while others do not. Since abnormal cardiac mechanics in hypertension lead to the heart failure syndrome, determining the acquired and genetic factors associated with abnormal cardiac mechanics in this epidemiologic study will provide novel insights into the pathogenesis of heart failure in hypertension and may ultimately identify novel therapeutic targets for the prevention and treatment of hypertensive heart disease.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
Project #
Application #
Study Section
Cardiovascular and Sleep Epidemiology (CASE)
Program Officer
Maric-Bilkan, Christine
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Northwestern University Chicago
Internal Medicine/Medicine
Schools of Medicine
United States
Zip Code
Aguilar, Frank G; Selvaraj, Senthil; Martinez, Eva E et al. (2016) Archeological Echocardiography: Digitization and Speckle Tracking Analysis of Archival Echocardiograms in the HyperGEN Study. Echocardiography 33:386-97
Dubin, Ruth F; Guajardo, Isabella; Ayer, Amrita et al. (2016) Associations of Macro- and Microvascular Endothelial Dysfunction With Subclinical Ventricular Dysfunction in End-Stage Renal Disease. Hypertension 68:913-20
Shah, Sanjiv J; Kitzman, Dalane W; Borlaug, Barry A et al. (2016) Phenotype-Specific Treatment of Heart Failure With Preserved Ejection Fraction: A Multiorgan Roadmap. Circulation 134:73-90
Selvaraj, Senthil; Martinez, Eva E; Aguilar, Frank G et al. (2016) Association of Central Adiposity With Adverse Cardiac Mechanics: Findings From the Hypertension Genetic Epidemiology Network Study. Circ Cardiovasc Imaging 9:
Kunamalla, Aaron; Ng, Jason; Parini, Vamsi et al. (2016) Constitutive Expression of a Dominant-Negative TGF-β Type II Receptor in the Posterior Left Atrium Leads to Beneficial Remodeling of Atrial Fibrillation Substrate. Circ Res 119:69-82
Freed, Benjamin H; Collins, Jeremy D; François, Christopher J et al. (2016) MR and CT Imaging for the Evaluation of Pulmonary Hypertension. JACC Cardiovasc Imaging 9:715-32
Unger, Erin D; Dubin, Ruth F; Deo, Rajat et al. (2016) Association of chronic kidney disease with abnormal cardiac mechanics and adverse outcomes in patients with heart failure and preserved ejection fraction. Eur J Heart Fail 18:103-12
Freed, Benjamin H; Daruwalla, Vistasp; Cheng, Jeanette Y et al. (2016) Prognostic Utility and Clinical Significance of Cardiac Mechanics in Heart Failure With Preserved Ejection Fraction: Importance of Left Atrial Strain. Circ Cardiovasc Imaging 9:
Goldberger, Jeffrey J; Arora, Rishi; Green, David et al. (2015) Evaluating the Atrial Myopathy Underlying Atrial Fibrillation: Identifying the Arrhythmogenic and Thrombogenic Substrate. Circulation 132:278-91
Shah, Sanjiv J; Katz, Daniel H; Selvaraj, Senthil et al. (2015) Phenomapping for novel classification of heart failure with preserved ejection fraction. Circulation 131:269-79

Showing the most recent 10 out of 37 publications