Heart failure (HF) is a major health problem with a high annual mortality rate in the US. The incidence of HF continues to rise despite medical progress in heart failure interventions. Depression is an important psychosocial predictor of HF, with a 2 to 3-fold risk of increased mortality. To understand the role of depression in HF morbidity and mortality, there is a need to determine pathophysiological mechanisms linking depression to HF outcomes. Inflammatory processes play a primary pathophysiologic role in HF, and there is substantial overlap between inflammatory markers related to adverse HF outcomes and those known to be increased in depression. Using a prospective design, the proposed research will determine the role of pro-inflammatory markers (IL6, TNFa, CRP) as measures linking depression to heart failure progression. Two hundred heart failure patients will be monitored repeatedly for depression and inflammatory markers for 2 years. This study will: (1) determine the association between depression and inflammation and the role of neurohormones (catecholamines and cortisol) in this relationship; and (2) determine whether inflammatory processes play a role in the pathophysiological pathways linking depression to adverse heart failure outcome (mortality and HF-related hospitalization). Unique to this study is the use of repeated measures to document the temporal associations between depression and inflammatory markers. Such assessments are important to disentangle whether depression precedes, coincides with, or follows inflammation in heart failure patients. Information from this research will provide important knowledge for patient risk stratification, will elucidate pathophysiological mechanisms by which depression increases risk of adverse heart failure outcomes, and may lead to novel treatment targets in patients at high-risk of life- threatening heart failure complications. Lay language: Heart failure is a serious health problem, with a high mortality rate. Many patients with heart failure also suffer from depression, and these patients are at a substantially greater risk of being hospitalized or dying. This study examines the role of inflammation and immune pathways by which depression results in poor heart failure outcomes. This knowledge will help identify high risk patients and may lead to potential new treatments for depressed heart failure patients. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL079376-03
Application #
7277141
Study Section
Psychosocial Risk and Disease Prevention Study Section (PRDP)
Program Officer
Czajkowski, Susan
Project Start
2006-08-15
Project End
2011-04-30
Budget Start
2008-05-01
Budget End
2009-04-30
Support Year
3
Fiscal Year
2008
Total Cost
$483,393
Indirect Cost
Name
University of Maryland Baltimore
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
188435911
City
Baltimore
State
MD
Country
United States
Zip Code
21201
Kop, Willem J; Galvao, Tatiana F; Synowski, Stephen J et al. (2015) Effects of environmental stress following myocardial infarction on behavioral measures and heart failure progression: The influence of isolated and group housing conditions. Physiol Behav 152:168-74
Kop, Willem J; Gottdiener, John S; deFilippi, Christopher R et al. (2012) Cardiac microinjury measured by troponin T predicts collagen metabolism in adults aged >=65 years with heart failure. Circ Heart Fail 5:406-13
Pandhi, Jay; Gottdiener, John S; Bartz, Traci M et al. (2011) Comparison of characteristics and outcomes of asymptomatic versus symptomatic left ventricular dysfunction in subjects 65 years old or older (from the Cardiovascular Health Study). Am J Cardiol 107:1667-74
Kop, Willem J; Seliger, Stephen L; Fink, Jeffrey C et al. (2011) Longitudinal association of depressive symptoms with rapid kidney function decline and adverse clinical renal disease outcomes. Clin J Am Soc Nephrol 6:834-44
van den Broek, Krista C; Defilippi, Christopher R; Christenson, Robert H et al. (2011) Predictive value of depressive symptoms and B-type natriuretic peptide for new-onset heart failure and mortality. Am J Cardiol 107:723-9
Kop, Willem J; Synowski, Stephen J; Gottlieb, Stephen S (2011) Depression in heart failure: biobehavioral mechanisms. Heart Fail Clin 7:23-38
Kop, Willem J; Synowski, Stephen J; Newell, Miranda E et al. (2011) Autonomic nervous system reactivity to positive and negative mood induction: the role of acute psychological responses and frontal electrocortical activity. Biol Psychol 86:230-8
Kop, Willem J; Kuhl, Emily A; Barasch, Eddy et al. (2010) Association between depressive symptoms and fibrosis markers: the Cardiovascular Health Study. Brain Behav Immun 24:229-35
Weinstein, Ali A; Deuster, Patricia A; Francis, Jennifer L et al. (2010) Neurohormonal and inflammatory hyper-responsiveness to acute mental stress in depression. Biol Psychol 84:228-34
Francis, Jennifer L; Weinstein, Ali A; Krantz, David S et al. (2009) Association between symptoms of depression and anxiety with heart rate variability in patients with implantable cardioverter defibrillators. Psychosom Med 71:821-7