Assessment of causality of natriuretic peptides and atrial fibrillation and heart failure: a Mendelian randomization study in the FINRISK cohort

Aims Natriuretic peptides are extensively studied biomarkers for atrial fibrillation (AF) and heart failure (HF). Their role in the pathogenesis of both diseases is not entirely understood and previous studies several single-nucleotide poly-morphisms (SNPs) at the NPPA-NPPB locus associated with natriuretic peptides have been identified. We investigated the causal relationship between natriuretic peptides and AF as well as HF using a Mendelian randomization approach.Methods and results N-terminal pro B-type natriuretic peptide (NT-proBNP) (N= 6669), B-type natriuretic peptide (BNP) (N= 6674), and mid-regional pro atrial natriuretic peptide (MR-proANP) (N= 6813) were measured in the FINRISK 1997 cohort. N=30 common SNPs related to NT-proBNP, BNP, and MR-proANP were selected from studies. We performed six Mendelian randomizations for all three natriuretic peptide biomarkers and for both outcomes, AF and HF, separately. Polygenic risk scores (PRSs) based on multiple SNPs were used as genetic instrumental variable in Mendelian randomizations. Polygenic risk scores were significantly associated with the three natriuretic peptides. Polygenic risk scores were not significantly associated with incident AF nor HF. Most cardiovascular risk factors showed significant confounding percentages, but no association with PRS. A causal relation except for small causal betas is unlikely.Conclusion In our Mendelian randomization approach, we confirmed an association between common genetic variation at the NPPA-NPPB locus and natriuretic peptides. A strong causal relationship between natriuretic peptides and incidence of AF as well as HF at the community-level was ruled out. Therapeutic approaches targeting natriuretic peptides will therefore very likely work through indirect mechanisms

Elastin in vascular grafts

The clinical demand for a superior vascular graft is rising due to the increase in cardiovascular disease with an aging population. Despite decades of research, clinically translatable solutions remain limited. Recent progress in vascular graft engineering has highlighted the significance of biological integration for the success of implanted grafts. Thus there has been an increase in the usage of biological materials in vascular graft manufacture. Elastin, a natural protein that makes up a significant portion of the natural vascular extracellular matrix, has been demonstrated to be particularly important with both mechanical and biological modulatory roles. Progress in understanding elastogenesis, the process by which elastin is naturally synthesized, and increased access to synthetic elastin-based materials, has increased the usage of elastin in vascular graft engineering. In this chapter, we explore recent advances in the utilization of elastin as a material for vascular graft engineering. In particular, we focus on the myriad of methods which incorporate elastin into vascular grafts which demonstrate superior biological functionality and closer resemblance to native blood vessels