Heart failure (HF) is an enormous public health problem with over 500,000 cases annually, and African American individuals share a disproportionate amount of this burden including a higher prevalence and mortality when compared with white individuals. Beta adrenergic antagonists (beta-blockers, BB) are the foundation of modern HF care, but their effectiveness in African Americans is not clear. Pivotal clinical trials of BB in HF were woefully underpowered to assess African American patients, and many experts have suggested a differential BB benefit in African American patients when compared with white patients. This issue requires additional data and clarity because improved understanding and elimination of such disparities is a national research priority (Healthy People 2010). Multiple factors may contribute to a racial disparity in BB effect such as genetic factors, medication adherence, and comorbid illnesses. All of these factors must be characterized in detail in order to evaluate which factor(s) contribute to this. Existing pharmacogenetic studies have suggested that specific variants may explain racial differences in BB effectiveness, but these studies have not quantified drug exposure or adherence and have not included a sufficient number of African Americans. In order to answer these questions, we propose a racially diverse, prospective, pharmacogenomic registry of 1000 HF patients. Our center has important advantages to achieve this including the fact that roughly half of our HF patients are African American, and we have experience and infrastructure in quantifying adherence and drug exposure using pharmacy claims data. Using this cohort we will assess the influence of race and genetic factors on BB effectiveness, measured by clinical events (time to hospitalization or death) and health status. Ultimately these data will clarify the benefit of BB in African Americans, and contribute to improved targeting of BB therapy to those with highest likelihood of favorable response while avoiding those likely to respond unfavorably.

Public Health Relevance

Heart failure is an enormous public health problem and African American individuals share a disproportionate amount of this burden including a higher prevalence and mortality when compared with white individuals. Beta blockers are the foundation of modern heart failure care, but their effectiveness in African American individuals is not clear. This project seeks to clarify whether beta blockers are equally effective in African American patients when compared with white patients and identify the underlying factors that impact this difference, particularly genetic factors.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL103871-01A1
Application #
8107362
Study Section
Clinical and Integrative Cardiovascular Sciences Study Section (CICS)
Program Officer
Sopko, George
Project Start
2011-07-01
Project End
2016-03-31
Budget Start
2011-07-01
Budget End
2012-03-31
Support Year
1
Fiscal Year
2011
Total Cost
$694,522
Indirect Cost
Name
Henry Ford Health System
Department
Type
DUNS #
073134603
City
Detroit
State
MI
Country
United States
Zip Code
48202
Lanfear, David E; Levy, Wayne C; Stehlik, Josef et al. (2017) Accuracy of Seattle Heart Failure Model and HeartMate II Risk Score in Non-Inotrope-Dependent Advanced Heart Failure Patients: Insights From the ROADMAP Study (Risk Assessment and Comparative Effectiveness of Left Ventricular Assist Device and Medical Man Circ Heart Fail 10:
Abuzaanona, Ahmed; Lanfear, David (2017) Pharmacogenomics of the Natriuretic Peptide System in Heart Failure. Curr Heart Fail Rep 14:536-542
Lanfear, David E; Gibbs, Joseph J; Li, Jia et al. (2017) Targeted Metabolomic Profiling of Plasma and Survival in Heart Failure Patients. JACC Heart Fail 5:823-832
Wells, Karen E; Cajigal, Sonia; Peterson, Edward L et al. (2016) Assessing differences in inhaled corticosteroid response by self-reported race-ethnicity and genetic ancestry among asthmatic subjects. J Allergy Clin Immunol 137:1364-1369.e2
Morgan, Jeffrey A; Go, Pauline H; Xuereb, Linnea et al. (2016) Outcomes on Continuous Flow Left Ventricular Assist Devices: A Single Institutional 9-Year Experience. Ann Thorac Surg 102:1266-73
Sleder, Anna T; Kalus, James; Lanfear, David E (2016) Cardiovascular Pharmacokinetics, Pharmacodynamics, and Pharmacogenomics for the Clinical Practitioner. J Cardiovasc Pharmacol Ther 21:20-6
Shafiq, Ali; Brawner, Clinton A; Aldred, Heather A et al. (2016) Prognostic value of cardiopulmonary exercise testing in heart failure with preserved ejection fraction. The Henry Ford HospITal CardioPulmonary EXercise Testing (FIT-CPX) project. Am Heart J 174:167-72
Luzum, Jasmine A; Lanfear, David E (2016) Pharmacogenetic Risk Scores for Perindopril Clinical and Cost Effectiveness in Stable Coronary Artery Disease: When Are We Ready to Implement? J Am Heart Assoc 5:e003440
Depta, J P; Lenzini, P A; Lanfear, D E et al. (2015) Clinical outcomes associated with proton pump inhibitor use among clopidogrel-treated patients within CYP2C19 genotype groups following acute myocardial infarction. Pharmacogenomics J 15:20-5
Brawner, Clinton A; Shafiq, Ali; Aldred, Heather A et al. (2015) Comprehensive analysis of cardiopulmonary exercise testing and mortality in patients with systolic heart failure: the Henry Ford Hospital cardiopulmonary exercise testing (FIT-CPX) project. J Card Fail 21:710-8

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