Association of ventricular-arterial coupling with biomarkers involved in heart failure pathophysiology - the STANISLAS cohort

Abstract

Aims: Impaired left ventricular-arterial coupling (VAC) has been shown to correlate with worse prognosis in cardiac diseases and heart failure (HF). The extent of the relationship between VAC and circulating biomarkers associated with HF has been scarcely documented. We aimed to explore associations of VAC with proteins involved in HF pathophysiology within a large population-based cohort of middle-aged individuals.

Methods and results: In the forth visit of the STANISLAS family cohort, involving 1309 participants (mean age 48 ± 14 years; 48% male) from parent and children generations, we analysed the association of 32 HF-related proteins with non-invasively assessed VAC using pulse wave velocity (PWV)/global longitudinal strain (GLS) and arterial elastance (E_a)/ventricular end-systolic elastance (E_es). Among the 32 tested proteins, fatty acid-binding protein adipocyte 4, interleukin-6, growth differentiation factor 15, matrix metalloproteinase (MMP)-1, and MMP-9 and adrenomedullin were positively associated with PWV/GLS whereas transforming growth factor beta receptor type 3, MMP-2 and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were negatively associated. In multivariable models, only MMP-2 and NT-proBNP were significantly and inversely associated with PWV/GLS in the whole population and in the parent generation. Higher levels of NT-proBNP were also negatively associated with E_a/E_es in the whole cohort but this association did not persist in the parent subgroup.

Conclusion: Elevated MMP-2 and NT-proBNP levels correlate with better VAC (lower PWV/GLS), possibly indicating a compensatory cardiovascular response to regulate left ventricular pressure amidst cardiac remodelling and overload.

Keywords: Cardiovascular; Echocardiography; Hypertension; Ventricular–arterial coupling.

Figure 1

Protein–protein interactions of the nine circulating biomarkers significantly associated to pulse wave velocity/global longitudinal strain in univariable analysis. Biomarkers are represented in red and other proteins in grey. Solid line depicts physical interaction and dashed lines indicate proteins sharing pathways. ADM, adrenomedullin; FABP4, fatty acid‐binding protein‐4; GDF‐15, growth differentiation factor 15; IL, interleukin; MMP, matrix metalloproteinase; NFKB1/NFKB2, nuclear factor of kappa light polypeptide gene enhancer in B‐cells 1/2; NT‐proBNP, N‐terminal pro‐B‐type natriuretic peptide; RELA/RELB, v‐rel avian reticuloendotheliosis viral oncogene homolog A/B; STAT3, signal transducer and activator of transcription 3; TGFB‐1, transforming growth factor beta 1; TGFBR‐3, transforming growth factor beta receptor type 3.

Figure 2

Protein‐signalling pathway explanations of the nine circulating biomarkers significantly associated with pulse wave velocity/global longitudinal strain in univariable analysis. Proteins are represented in red and pathway function in green. ADM, adrenomedullin; EPH, ephrin; ESR, estrogen receptor; FABP4, fatty acid‐binding protein‐4; GPCR, G protein coupled receptor; IGF, insulin‐like growth factor; IGF BP, insulin‐like growth factor binding protein; IL‐6, interleukin‐6; MAPK, mitogen‐activated protein kinase; MMP, matrix metalloproteinase.

Figure 3

Network analysis focus on N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP). ADM, adrenomedullin; ESR, estrogen receptor; IL‐6, interleukin‐6; MMP, matrix metalloproteinase.