Related Experiment Video
Updated: May 16, 2025
Dynamic Proteomic and miRNA Analysis of Polysomes from Isolated Mouse Heart After Langendorff Perfusion
Published on: August 29, 2018
Proteomic Profile of Ischemic Heart Disease in Heart Failure: A Community Study
Kayode O Kuku1, Maryam Hashemian1, Jungnam Joo2
1Heart Disease Phenomics Laboratory, Epidemiology and Community Health Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.
Insights
Ischemic heart disease (IHD) in heart failure (HF) has distinct proteomic profiles. IHD significantly increases cardiovascular mortality in HF patients with reduced ejection fraction (EF).
Area of Science:
- Cardiovascular Medicine
- Proteomics
- Heart Failure Research
Background:
- Ischemic heart disease (IHD) is a prevalent comorbidity in patients with heart failure (HF).
- Understanding the molecular underpinnings and prognostic implications of IHD in HF is crucial for patient management.
- Previous studies have not fully elucidated the proteomic signatures associated with IHD within a heart failure cohort.
Purpose of the Study:
- To investigate the clinical characteristics of prevalent IHD in a heart failure cohort.
- To analyze the outcomes, specifically cardiovascular mortality, associated with IHD in heart failure.
- To identify and characterize the plasma proteomic profiles linked to IHD in heart failure patients.
Main Methods:
- A community-based heart failure cohort (N=1351) was studied with linked medical records.
- Plasma protein targets (7289) were measured using an aptamer-based assay.
- Cause-specific hazards models and linear regression were employed to assess associations between IHD, cardiovascular mortality, ejection fraction, and proteomic profiles.
Main Results:
- Ischemic heart disease was identified in 678 patients (median age 78 years, 40% female).
- The association between IHD and cardiovascular mortality was significantly modified by ejection fraction (Pinteraction=.002).
- IHD was linked to increased 5-year cardiovascular mortality in the reduced ejection fraction group (HR 2.14) but not in the preserved ejection fraction group (HR 1.04); 52 proteins were associated with IHD.
Conclusions:
- Unique proteomic profiles characterize ischemic heart disease in heart failure, highlighting the value of molecular data for HF phenotyping.
- Ischemic heart disease carries significant prognostic implications for cardiovascular mortality, particularly in heart failure patients with reduced ejection fraction.
- These findings emphasize the need to consider both IHD status and ejection fraction when assessing cardiovascular risk in heart failure.
Objective:
To investigate the clinical characteristics, outcomes, and proteomic profiles of prevalent ischemic heart disease (IHD) in heart failure (HF) in a clinically phenotyped cohort.
Methods:
We studied an HF community cohort (N=1351) enrolled between September 10, 2003, and September 18, 2012, with linked medical records and measured 7289 plasma protein targets using an aptamer-based assay. Ischemic heart disease was defined by prior myocardial infarction, angiographic coronary disease, or revascularization. Cause-specific hazards model was used to test the association between IHD status and cardiovascular (CV) mortality while considering the interaction by ejection fraction (EF) group. Linear regression adjusting for age, sex, and estimated glomerular filtration rate with multiple testing correction was used to evaluate the cross-sectional association of proteins with IHD status and with CV risk factors.
Results:
There were 678 patients with IHD (median age, 78 years [interquartile range, 69 to 84 years]; 271 [40%] female). The association between IHD status and CV mortality was markedly influenced by EF (Pinteraction=.002). Ischemic heart disease was associated with excess 5-year CV mortality in the reduced EF group (hazard ratio, 2.14; 95% CI, 1.42 to 3.21) but not in the preserved EF group (hazard ratio, 1.04; 95% CI, 0.80 to 1.36). Fifty-two proteins (31 up-regulated, 21 down-regulated) were associated with IHD compared with non-IHD, including 42 proteins associated with risk factors and 10 with no association with risk factors.
Conclusion:
These data suggest that unique proteomic profiles reveal biologic signatures of IHD in HF, emphasizing the importance of molecular data in classifying HF phenotypes. In addition, our findings underscore the prognostic significance of IHD in HF with reduced EF.
Related Concept Videos
01:19Blood Studies for Cardiovascular System II: CRP, Hcy, and Cardiac Natriuretic Peptide Markers
These markers indicate stress or strain on the heart muscle:
Natriuretic Peptides (BNP)
Cardiac myocytes produce these hormones in response to ventricular stretching...
01:17Pathophysiology of Heart Failure
01:20Blood Studies for Cardiovascular System I: Cardiac Biomarkers
The essential diagnostic tools for detecting myocardial necrosis and monitoring individuals suspected of having acute coronary syndrome (ACS) include:
Troponins
Troponins, particularly cardiac troponins I and T, are the most precise and sensitive markers of myocardial injury. They are detectable within 4-6 hours of myocardial injury and remain...
01:33Proteomics
Proteomics is the study of proteomes' function. It involves the large-scale systematic study of the proteome to denote the protein complement expressed by a genome. Scientist Mark Wilkins coined the term...