Abstract
Identification of novel circulating biomarkers predicting death and major cardio-metabolic events in obese patients with heart failure (HF) remains a research priority. In this study, we compared multi-marker profile of non-obese (NOB) and obese (OB) HF patients in relation to mortality outcome. The new multiplex proximity extension assay technology was used to analyze the levels of 92 proteins in plasma samples from HF patients according to body mass index (BMI) categories. At 2-year follow-up, all-cause mortality rates were significantly greater in NOB patients (BMI < 30 kg/m2) compared to the OB patients (BMI > 30 kg/m2) with HF (odds ratio 26; 95% CI: 1.14–624, p < 0,04). Quantitative proteomic analysis revealed thirteen distinct proteins expression profiles of OB and NOB HF patients. Among these proteins, RAGE, CXCL6, CXCL1, CD40, NEMO, VEGF-A, KLK6, PECAM1, PAR1, MMP1, BNP and NTproBNP were down-regulated, whereas leptin was up-regulated in OB HF patients. In addition, an inverse correlation between plasma BNP levels and leptin in OB HF patients was observed (r = −0.58 p = 0.02). This study identifies specific plasma protein signature in OB and NOB patients with HF in relation to mortality outcome.
Highlights
The co-occurring of obesity and heart failure (HF) is one of the key issues and critical challenges in clinical practice
In order to assess the plasma protein fingerprint associated with cardio-inflammatory and metabolic status of HF patients in relation to body mass index (BMI), we compared the plasma protein levels obtained by Proximity extension immunoassay (PEA) immunoassay in NOB and OB patients
Plasma levels of 92 proteins were assessed simultaneously in 1 μl of human plasma and revealed distinct circulating multi-marker profile in OB and NOB HF patients
Summary
The co-occurring of obesity and heart failure (HF) is one of the key issues and critical challenges in clinical practice. Longitudinal studies have shown the existence of an “obesity paradox”, a clinical phenomenon in which obese (OB) persons have a lower risk of mortality or better survival within clinical subpopulations[4] This paradoxical benefit of obesity has been shown to exist for a wide range of cardiovascular diseases (CVD)—myocardial infarction, hypertension, aortic stenosis, patients who have had a coronary bypass, atrial fibrillation, and patients with cardiac implants[5]. The utility of this panel of indicators to serve as clinically useful biomarkers in OB patients with HF is limited by a lack of data regarding unique cardiovascular signature in conditions combining obesity and HF9. We retrospectively selected 16 male patients (mean age 63 ± 9 years) in order to compare plasma level of 92 proteins related to cardiovascular, inflammatory and metabolic status in NOB and OB HF phenotypes. A list of CVD measured proteins is presented in Supplementary Table S1
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