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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL107577-04
Application #
8645708
Study Section
Cardiovascular and Sleep Epidemiology (CASE)
Program Officer
Maric-Bilkan, Christine
Project Start
2011-05-21
Project End
2015-03-31
Budget Start
2014-04-01
Budget End
2015-03-31
Support Year
4
Fiscal Year
2014
Total Cost
$334,907
Indirect Cost
$103,906
Name
Northwestern University Chicago
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
Polsinelli, Vincenzo B; Shah, Sanjiv J (2017) Advances in the pharmacotherapy of chronic heart failure with preserved ejection fraction: an ideal opportunity for precision medicine. Expert Opin Pharmacother 18:399-409
Polsinelli, Vincenzo B; Sinha, Arjun; Shah, Sanjiv J (2017) Visceral Congestion in Heart Failure: Right Ventricular Dysfunction, Splanchnic Hemodynamics, and the Intestinal Microenvironment. Curr Heart Fail Rep 14:519-528
Luo, Yuan; Ahmad, Faraz S; Shah, Sanjiv J (2017) Tensor Factorization for Precision Medicine in Heart Failure with Preserved Ejection Fraction. J Cardiovasc Transl Res 10:305-312
Patel, Jay N; Shah, Sanjiv J (2017) Inorganic vs. organic nitrates for heart failure with preserved ejection fraction: it's not all in your head! Eur J Heart Fail 19:1516-1519
Khan, Sadiya S; Shah, Sanjiv J; Klyachko, Ekaterina et al. (2017) A null mutation in SERPINE1 protects against biological aging in humans. Sci Adv 3:eaao1617
Shah, Sanjiv J (2017) Innovative Clinical Trial Designs for Precision Medicine in Heart Failure with Preserved Ejection Fraction. J Cardiovasc Transl Res 10:322-336
Freed, Benjamin H; Shah, Sanjiv J (2017) Stepping Out of the Left Ventricle's Shadow: Time to Focus on the Left Atrium in Heart Failure With Preserved Ejection Fraction. Circ Cardiovasc Imaging 10:
Shah, Sanjiv J (2017) Precision Medicine for Heart Failure with Preserved Ejection Fraction: An Overview. J Cardiovasc Transl Res 10:233-244
Selvaraj, Senthil; Djoussé, Luc; Aguilar, Frank G et al. (2017) Association of Estimated Sodium Intake With Adverse Cardiac Structure and Function: From the HyperGEN Study. J Am Coll Cardiol 70:715-724
Raphael, Roseanne; Purushotham, Diana; Gastonguay, Courtney et al. (2016) Combining patient proteomics and in vitro cardiomyocyte phenotype testing to identify potential mediators of heart failure with preserved ejection fraction. J Transl Med 14:18

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