Contrasting signals of cardiovascular health among natriuretic peptides in subjects without heart disease

Timothy C. R. Prickett,Vicky A. Cameron,Yusmiati Liau,Martin A. Kennedy,Janet K. Spittlehouse,Joseph M. Boden,Allison L. Miller,Richard W. Troughton,Eric A. Espiner,John F. Pearson

doi:10.1038/s41598-019-48553-y

Abstract

Natriuretic Peptides (NP) are important in maintaining normal cardiac and metabolic status and have been used to predict cardiovascular events. Whether plasma concentrations of NP products within the normal range reflect cardio-metabolic health is unknown. Plasma NTproANP, NTproBNP and NTproCNP and their bioactive counterparts were measured in a random sample of 348 community dwellers aged 49–51 yr without heart disease and associations sought with established vascular risk factors, echocardiographic indices and a genetic variant previously linked with BNP. Stratified by sex, each of ten vascular risk factors were positively associated with NTproCNP whereas associations with NTproBNP and NTproANP were all negative. In both sexes, higher plasma NTproCNP was associated with higher arterial elastance, lower LV stroke volume and lower LV end diastolic volume. Exactly opposite associations were found with plasma NTproBNP or NTproANP. Sex specific differences were identified: positive association of NTproBNP with LV end systolic volume and the negative association with LV elastance were found only in males. The genetic variant rs198358 was independently associated with NTproBNP but not with NTproANP. In conclusion, higher NTproCNP is likely to be an adaptive response to impaired LV relaxation whereas genetic factors likely contribute to higher NTproBNP and improved cardio-metabolic health at midlife.

Highlights

Since their discovery, increasing evidence shows that Atrial Natriuretic Peptide (ANP) and B-type Natriuretic Peptide (BNP), acting via the specific receptor NPR1, play a critical role in maintaining cardiovascular health, in addition to regulating lipogenesis and energy balance[1]
With respect to sex differences, significantly higher waist, stroke volume, LV mass, LVEDV, LVESV, hs-Troponin, plasma albumin, urate, creatinine, eGFR, GGT, lipids, hematocrit (HCT) and NTproCNP values were found in males whereas LV and arterial elastance and plasma NTproBNP and NTproANP were all significantly lower than those of females
In this first study of all three natriuretic peptides (NP) in subjects without history of heart disease, we provide new evidence of links of paracrine C-type Natriuretic Peptide (CNP) with arterial stiffening and myocardial structural integrity

Summary

Introduction

Since their discovery, increasing evidence shows that Atrial Natriuretic Peptide (ANP) and B-type Natriuretic Peptide (BNP), acting via the specific receptor NPR1, play a critical role in maintaining cardiovascular health, in addition to regulating lipogenesis and energy balance[1]. The degree to which plasma concentrations relate to indices of cardio-metabolic health in community subjects without heart disease requires further study – preferably in settings where comprehensive analysis of established vascular risks and cardiac function are made at the time of sampling. Clarifying the relationships of natriuretic peptides (NP) with cardiovascular health – for example at mid-life when risk of events is increasing – is a key issue in the light of the reported positive association of BNP peptides with increased cardio-vascular risk in older subjects[15] This issue is addressed in a study of 348 community dwellers aged 49–51 yr – after excluding those with known heart disease – recruited as part of the Canterbury Health Ageing and Life Course (CHALICE) health survey conducted in Christchurch New Zealand during 2010–201316.

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Results

Conclusion