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.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Clinical and Integrative Cardiovascular Sciences Study Section (CICS)
Program Officer
Sopko, George
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Henry Ford Health System
United States
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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
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
Velez, Mauricio; Peterson, Edward L; Wells, Karen et al. (2015) Association of antidiabetic medications targeting the glucagon-like peptide 1 pathway and heart failure events in patients with diabetes. J Card Fail 21:2-8
Yessayan, L; Shafiq, A; Peterson, E et al. (2015) Race, Calcineurin Inhibitor Exposure, and Renal Function After Solid Organ Transplantation. Transplant Proc 47:2968-72
Padhukasahasram, Badri; Reddy, Chandan K; Li, Yan et al. (2015) Joint impact of clinical and behavioral variables on the risk of unplanned readmission and death after a heart failure hospitalization. PLoS One 10:e0129553
El-Refai, Mostafa; Hrobowski, Tara; Peterson, Edward L et al. (2015) Race and association of angiotensin converting enzyme/angiotensin receptor blocker exposure with outcome in heart failure. J Cardiovasc Med (Hagerstown) 16:591-6
Lanfear, David E; Li, Jia; Abbas, Raza et al. (2015) Genetic Factors Influencing B-type Natriuretic Peptide-Mediated Production of Cyclic Guanosine Monophosphate and Blood Pressure Effects in Heart Failure Patients. J Cardiovasc Transl Res 8:545-53
Brewer, Robert J; Cabrera, Rafael; El-Atrache, Mazen et al. (2014) Relationship of tricuspid repair at the time of left ventricular assist device implantation and survival. Int J Artif Organs 37:834-8
Amiri, Loabat; Cassidy-Bushrow, Andrea E; Dakki, Heather et al. (2014) Patient characteristics and participation in a genetic study: a type 2 diabetes cohort. J Investig Med 62:26-32
Oni-Orisan, Akinyemi; Lanfear, David E (2014) Pharmacogenomics in heart failure: where are we now and how can we reach clinical application? Cardiol Rev 22:193-8

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