Dr. David Aguilar is a non-invasive cardiologist strongly committed to a career in clinical research. He completed his internal medicine residency and cardiology fellowship at the Brigham and Women's Hospital, Harvard Medical School and is currently an Assistant Professor of Medicine at Baylor College of Medicine (BCM). This Mentored Career Development Award (K01) will develop Dr. Aguilar's career through several mechanisms, including weekly mentoring meetings, the Clinical Scientist Training Program, and didactic coursework at the University of Texas School of Public Health and BCM. As part of the award, Dr. Aguilar will address the importance of aortic and left ventricular (LV) diastolic stiffness in diabetic patients with heart failure (HF) and normal ejection fraction (EF) and will test the effects of a treatment strategy with a glucagon-like peptide-1 (GLP-1) receptor activator (exenatide) on aortic and LV diastolic stiffness. Diabetes is commonly seen in patients with HF and normal EF and is associated with increased morbidity and mortality. The mechanisms contributing to these adverse outcomes in diabetic patients are poorly understood and represent a barrier to improving outcomes. We hypothesize that, in patients with HF and normal EF, LV diastolic stiffness will be greater in diabetic patients than in non-diabetic patients and that this increased LV diastolic stiffness will correlate with increased aortic stiffness. We also hypothesize that this increased LV diastolic stiffness will correlate with serum biomarkers of increased myocardial collagen accumulation. The importance of advanced glycation end products (AGEs) in this process will be examined by also testing the hypothesis that increased aortic stiffness and LV diastolic stiffness are directly correlated with increased serum levels of AGEs. Finally, we hypothesize that treatment of type 2 diabetes with exenatide for 12 weeks in individuals with HF and normal EF will be associated with improvement in aortic and LV diastolic stiffness and in serum biomarkers of abnormal myocardial collagen accumulation. Given the increasing prevalence of diabetes and the burden of disease attributed to both diabetes and HF with normal EF, this work has significant public health implications. Dr. Aguilar will study mechanisms contributing to the adverse outcomes in diabetic individuals with HF and normal EF and will test a diabetes-specific treatment strategy in hopes of improving outcomes in this high-risk group of patients.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01HL092585-04
Application #
8116024
Study Section
Special Emphasis Panel (ZHL1-CSR-G (F1))
Program Officer
Meadows, Tawanna
Project Start
2008-08-15
Project End
2013-07-31
Budget Start
2011-08-01
Budget End
2013-07-31
Support Year
4
Fiscal Year
2011
Total Cost
$136,560
Indirect Cost
Name
Baylor College of Medicine
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
051113330
City
Houston
State
TX
Country
United States
Zip Code
77030
Shivas, Jessica M; Skop, Ahna R (2012) Arp2/3 mediates early endosome dynamics necessary for the maintenance of PAR asymmetry in Caenorhabditis elegans. Mol Biol Cell 23:1917-27
Nasir, Saifullah; Aguilar, David (2012) Congestive heart failure and diabetes mellitus: balancing glycemic control with heart failure improvement. Am J Cardiol 110:50B-57B
Aguilar, David (2011) Heart failure and diabetes: time to pay attention. Am Heart J 162:795-7
Aguilar, David; Chan, Wenyaw; Bozkurt, Biykem et al. (2011) Metformin use and mortality in ambulatory patients with diabetes and heart failure. Circ Heart Fail 4:53-8
Ather, Sameer; Chan, Wenyaw; Chillar, Annirudha et al. (2011) Association of systolic blood pressure with mortality in patients with heart failure with reduced ejection fraction: a complex relationship. Am Heart J 161:567-73
Aguilar, David (2011) Glycated hemoglobin as a prognostic risk marker in nondiabetic patients after acute myocardial infarction: what now? Circulation 124:666-8
Addison, Daniel; Aguilar, David (2011) Diabetes and cardiovascular disease: the potential benefit of incretin-based therapies. Curr Atheroscler Rep 13:115-22
Aguilar, David; Deswal, Anita; Ramasubbu, Kumudha et al. (2010) Comparison of patients with heart failure and preserved left ventricular ejection fraction among those with versus without diabetes mellitus. Am J Cardiol 105:373-7
Aguilar, David; Bozkurt, Biykem; Ramasubbu, Kumudha et al. (2009) Relationship of hemoglobin A1C and mortality in heart failure patients with diabetes. J Am Coll Cardiol 54:422-8