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N8-Acetylspermidine: A Polyamine Biomarker in Ischemic Cardiomyopathy With Reduced Ejection Fraction
Aditi Nayak1, Chang Liu1,2, Anurag Mehta1
1Emory Clinical Cardiovascular Research Institute Division of Cardiology Department of Medicine Emory University School of Medicine Atlanta GA.
Insights
N8-acetylspermidine (N8AS) is a novel biomarker for adverse outcomes in patients with ischemic cardiomyopathy (ICM). Higher N8AS levels correlate with increased mortality and incident heart failure (HF) in ICM patients, independent of traditional markers.
Area of Science:
- Cardiovascular Medicine
- Biomarker Discovery
- Metabolomics
Background:
- Ischemic cardiomyopathy (ICM) is associated with poorer patient outcomes compared to coronary artery disease alone or non-ICM conditions.
- N8-acetylspermidine (N8AS), a polyamine, plays a role in regulating ischemic cardiac apoptosis and dysfunction.
- The study hypothesizes N8AS as a mechanistic biomarker for adverse outcomes in ICM patients.
Purpose of the Study:
- To investigate the association between N8-acetylspermidine (N8AS) levels and adverse outcomes in patients with ischemic cardiomyopathy (ICM).
- To determine if N8AS can serve as a mechanistic biomarker for mortality and incident heart failure (HF) in ICM.
- To validate findings in an external cohort and assess N8AS association with incident HF in patients without baseline HF.
Main Methods:
- High-resolution plasma metabolomics and mass spectrometry were employed to quantify N8AS levels.
- A discovery cohort of 474 coronary artery disease patients (154 with ICM) and an external validation cohort of 85 ICM patients were analyzed.
- Cox regression models were used to examine the association between N8AS and outcomes (all-cause mortality, incident HF), adjusting for traditional HF markers.
Main Results:
- N8AS levels were significantly higher in patients with ICM compared to those without ICM (10.39 vs. 8.29 nmol/L, P<0.001).
- Higher N8AS levels were independently associated with increased all-cause mortality in ICM patients (HR, 1.48 per SD increase, P=0.001).
- Elevated N8AS also predicted incident heart failure in patients without baseline HF (HR, 4.16 per SD increase, P=0.01).
Conclusions:
- N8-acetylspermidine (N8AS) is a novel mechanistic biomarker associated with adverse outcomes in ischemic cardiomyopathy (ICM).
- Higher N8AS levels predict higher mortality and incident heart failure in ICM patients, independent of established biomarkers.
- N8AS offers potential for improved risk stratification and understanding of disease mechanisms in ICM.
Abstract:
Background Patients with ischemic cardiomyopathy (ICM) have worse outcomes than those with coronary artery disease alone and those with non-ICM. N8-acetylspermidine (N8AS) is a polyamine that regulates ischemic cardiac apoptosis and resultant cardiac dysfunction. We hypothesized that N8AS is a mechanistic biomarker of adverse outcomes in patients with ICM. Methods and Results High-resolution plasma metabolomics profiling and mass spectrometry were used to quantitate N8AS levels in a discovery cohort of 474 patients with coronary artery disease (age: 68±11 years, 12% black, 26% women): 154 with ICM, and 320 without ICM; and in an external validation cohort of 85 patients with ICM (age: 60±12 years, 37% black, 19% women). Patients without heart failure (HF) at baseline were followed for incident HF. The association between N8AS (log2-transformed, standardized) and outcomes of all-cause mortality and incident HF were examined using Cox regression. N8AS was higher (10.39 [interquartile range, 7.21-17.75] versus 8.29 nmol/L [interquartile range, 5.91-11.42]; P<0.001) in patients with ICM compared with patients who had coronary artery disease without ICM. Higher N8AS levels were associated with higher mortality in patients with ICM (hazard ratio [HR], 1.48; 95% CI, 1.19-1.85 per SD increase [P=0.001]), independent of B-type natriuretic peptide, high-sensitivity troponin I, and high-sensitivity C-reactive protein. Findings were validated in the independent cohort. Moreover, higher N8AS level was associated with incident HF in patients without HF at baseline (HR, 4.16; 95% CI, 1.41-12.25 per SD increase [P=0.01]). Conclusions Independent of traditional HF measures, higher N8AS levels are associated with higher mortality in patients with ICM and incident HF in those who have coronary artery disease without HF. N8AS is a novel mechanistic biomarker in ICM.
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