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 #
5R01HL107577-03
Application #
8452206
Study Section
Cardiovascular and Sleep Epidemiology (CASE)
Program Officer
Maric-Bilkan, Christine
Project Start
2011-05-21
Project End
2015-03-31
Budget Start
2013-04-01
Budget End
2014-03-31
Support Year
3
Fiscal Year
2013
Total Cost
$325,372
Indirect Cost
$101,229
Name
Northwestern University at Chicago
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
Katz, Daniel H; Selvaraj, Senthil; Aguilar, Frank G et al. (2014) Association of low-grade albuminuria with adverse cardiac mechanics: findings from the hypertension genetic epidemiology network (HyperGEN) study. Circulation 129:42-50
Selvaraj, Senthil; Aguilar, Frank G; Martinez, Eva E et al. (2014) Association of comorbidity burden with abnormal cardiac mechanics: findings from the HyperGEN study. J Am Heart Assoc 3:e000631
Ball, Molly K; Waypa, Gregory B; Mungai, Paul T et al. (2014) Regulation of hypoxia-induced pulmonary hypertension by vascular smooth muscle hypoxia-inducible factor-1?. Am J Respir Crit Care Med 189:314-24
Selvaraj, Senthil; Aguilar, Frank G; Martinez, Eva E et al. (2014) Diastolic wall strain: a simple marker of abnormal cardiac mechanics. Cardiovasc Ultrasound 12:40
Katz, Daniel H; Burns, Jacob A; Aguilar, Frank G et al. (2014) Albuminuria is independently associated with cardiac remodeling, abnormal right and left ventricular function, and worse outcomes in heart failure with preserved ejection fraction. JACC Heart Fail 2:586-96
Selvaraj, Senthil; Ilkhanoff, Leonard; Burke, Michael A et al. (2014) Association of the frontal QRS-T angle with adverse cardiac remodeling, impaired left and right ventricular function, and worse outcomes in heart failure with preserved ejection fraction. J Am Soc Echocardiogr 27:74-82.e2
Sauer, Andrew J; Selvaraj, Senthil; Aguilar, Frank G et al. (2014) Relationship between repolarization heterogeneity and abnormal myocardial mechanics. Int J Cardiol 172:289-91
Shah, Sanjiv J; Katz, Daniel H; Deo, Rahul C (2014) Phenotypic spectrum of heart failure with preserved ejection fraction. Heart Fail Clin 10:407-18
Shah, Sanjiv J; Aistrup, Gary L; Gupta, Deepak K et al. (2014) Ultrastructural and cellular basis for the development of abnormal myocardial mechanics during the transition from hypertension to heart failure. Am J Physiol Heart Circ Physiol 306:H88-100
Shah, Sanjiv J (2013) Matchmaking for the optimization of clinical trials of heart failure with preserved ejection fraction: no laughing matter. J Am Coll Cardiol 62:1339-42

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