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Published on: July 26, 2018
Acylation-stimulating protein and heart failure progression in arrhythmogenic right ventricular cardiomyopathy
Jie Ren1, Liang Chen1, Xiao Chen1
1State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Insights
Plasma acylation-stimulating protein (ASP) levels are elevated in arrhythmogenic right ventricular cardiomyopathy (ARVC) patients and predict adverse heart failure-associated events (HFAEs). This finding highlights ASP as a potential biomarker for ARVC prognosis.
Area of Science:
- Cardiology
- Immunology
- Biochemistry
Background:
- The complement system plays a critical role in the prognosis of arrhythmogenic right ventricular cardiomyopathy (ARVC).
- Acylation-stimulating protein (ASP), derived from the alternate complement pathway, influences lipogenesis and triglyceride metabolism.
- Previous research suggests a link between the complement system and ARVC, but the specific role of ASP in ARVC progression remains unclear.
Purpose of the Study:
- To investigate the potential of plasma ASP levels as a predictive biomarker for adverse cardiac events in patients with ARVC.
- To assess the association between ASP levels and cardiac structural and functional parameters in ARVC.
- To determine if ASP levels can predict heart failure-associated events (HFAEs) in an ARVC cohort.
Main Methods:
- Plasma ASP levels were measured using enzyme-linked immunosorbent assays in 111 ARVC patients and 106 healthy controls.
- Correlations between plasma ASP levels and cardiac remodeling parameters (e.g., RV dimensions, LVEF) were analyzed.
- Patients were followed for adverse HFAEs (heart transplantation, transplant list, or death from heart failure); survival analysis utilized LASSO and Cox regression.
Main Results:
- ARVC patients exhibited significantly higher plasma ASP levels compared to healthy controls (P < 0.001).
- Plasma ASP levels correlated with cardiac structural and functional abnormalities in ARVC patients.
- Elevated plasma ASP levels were significantly associated with an increased risk of HFAEs in ARVC patients (HR = 1.004, P = 0.002), independent of other factors.
Conclusions:
- Plasma ASP levels are elevated in ARVC patients and are associated with cardiac remodeling.
- ASP serves as an independent predictor of adverse heart failure-associated events in ARVC.
- Plasma ASP may represent a valuable biomarker for predicting adverse outcomes in ARVC patients.
Aims:
Our previous studies suggested that the complement system was critical in the prognosis of arrhythmogenic right ventricular cardiomyopathy (ARVC). The acylation-stimulating protein (ASP), generated through the alternate complement pathway, was reported to regulate lipogenesis and triglyceride storage. This study aimed to investigate the role of ASP in predicting adverse cardiac events in an ARVC cohort.
Methods And Results:
We enrolled 111 ARVC patients and 106 healthy volunteers, and measured their plasma ASP levels using enzyme-linked immunosorbent assays. Plasma ASP levels were significantly higher in the ARVC patients than in the healthy controls (2325.22 ± 20.08 vs. 2189.75 ± 15.55, P < 0.001), with a similar trend observed in the myocardial explant assay. Spearman correlation analysis indicated plasma ASP level associated with cardiac structural (right ventricular internal dimension, P = 0.006) and functional remodelling (left ventricular ejection fraction, P = 0.002) in ARVC patients. The ARVC patients were followed up for an average of 17.79 ± 1.09 months. Heart failure-associated events (HFAEs) were defined as heart transplantation, on a cardiac transplant list, or death due to end-stage heart failure. Plasma ASP levels in patients with HFAEs were significantly higher than in those without clinical events (2486.03 ± 26.70 vs. 2268.83 ± 23.51, P < 0.001) or those with malignant arrhythmic events (2486.03 ± 26.70 vs. 2297.80 ± 60.46, P = 0.008). LASSO (least absolute shrinkage and selection operator) and multivariable Cox regression analyses showed the ASP level (HR = 1.004, 95% CI [1.002,1.006], P = 0.002) was an independent predictor for adverse HFAEs in ARVC patients. The spline-fitting procedure was applied to illustrate the HFAE-free probabilities at different time points.
Conclusions:
Our results suggest that plasma ASP may be a useful biomarker in prediction of adverse HF-associated events in ARVC patients.
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