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

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.

Effect of statin therapy on plasma C-type Natriuretic Peptides and Endothelin-1 in males with and without symptomatic coronary artery disease

“…Although the bio inactive product NTproCNP is not likely to be degraded at source, whether efflux from extracellular fluids is sufficient to affect plasma concentrations is unclear. While difficult to rigorously assess in humans, our findings from veno-arterial sampling across organs 26,27 , and recent findings linking higher values of plasma NTproCNP (and to a lesser extent, CNP) with vascular stress in adults without history of heart disease 5,6 , support the view that vascular endothelial proCNP does contribute to circulating levels in some settings. Furthermore, in endothelial cell-specific CNP knock out mice, plasma CNP is significantly reduced 9,28,29 .…”

Broadening the Spectrum of Loss-of-Function Variants in NPR-C-Related Extreme Tall Stature

“… Abbreviations: wt, wild-type; cr, creatinine. a Adult reference interval (IQR) aged 50 years [ 34 ]. b Elecsys proBNP II Data Sheet reference interval (IQR) for individuals aged 40–49 years with no known cardiovascular disease.…”

“… a Conversion factor of 3.6 (unpublished comparative data) applied to the Elecsys proBNP II result to allow comparison with the Boudin cases 1 and 2 (measured by RIA). b Adult male reference interval (IQR) aged 50 years [ 34 ]. c Childhood male reference interval (IQR) for children aged 10-15 years [ 30 ].…”

“…The finding of a lean habitus and low value of lipids in the proband (Supplementary Table 2 [ 20 ]) aligns with findings of reduced weight/height ratios in the previous report [ 18 ] and NP actions on lipid and energy homeostasis [ 49 , 50 ]. There is an inverse association between high NP levels and insulin insensitivity [ 34 ], yet homeostasis model assessment of insulin resistance (HOMA-IR) of the proband is comparable with siblings (Supplementary Table 2 [ 20 ]).…”

Maternal plasma pro-atrial and C-type natriuretic peptide levels and their associations with cardiovascular and renal function in the second half of normal pregnancy: a longitudinal study

“…CNP promotes endothelial cell proliferation and nitric oxide synthetase activity in endothelial cells. Prior studies in men and non-pregnant women have shown an association between CNP levels and arterial stiffness/elastance and NO-dependent FMD [ 38 , 39 ]. However, our study, first to investigate the association between plasma CNP and maternal endothelial function as well as systemic hemodynamics, did not reveal any significant correlation between CNP and brachial artery FMD% (a gold standard measure of endothelial function) or systemic hemodynamics including SVRI, which is considered as an indirect measure of vascular tone and endothelial function [ 40 ].…”