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

Timothy C R Prickett,Richard W Troughton,Eric A Espiner

doi:10.1038/s41598-020-64795-7

Timothy C R Prickett, Richard W Troughton + Show 1 more

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https://doi.org/10.1038/s41598-020-64795-7

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Journal: Scientific Reports	Publication Date: May 13, 2020
Citations: 5	License type: open-access

Affiliation: University of Otago

Abstract

C-type Natriuretic Peptide (CNP) and Endothelin-1 (ET-1) have reciprocal roles in maintaining vascular homeostasis and are acutely modulated by statins in human cultured endothelial cells. Whether these actions of statins in vitro are reflected in studies in vivo is unknown. In a prospective study of 66 subjects with or without post- acute coronary syndrome (ACS), plasma concentrations of bioactive CNP and bio-inactive aminoterminal proCNP (NTproCNP), ET-1, B-type Natriuretic Peptide (BNP) and high sensitivity C Reactive Protein (hsCRP) were measured together with lipids before and at intervals of 1, 2 and 7 days after commencing atorvastatin 40 mg/day - and for a further period of 6months in those with ACS. Plasma lipids fell significantly in all subjects but plasma CNP, NTproCNP and ET-1 were unchanged by atorvastatin. In ACS, baseline hsCRP, BNP and CNP but not NTproCNP or ET-1 were significantly raised compared to values in age-matched controls. The ratio of NTproCNP to CNP was significantly lower in ACS throughout the study and was unaffected by statin therapy. We conclude that conventional doses of atorvastatin do not affect plasma CNP products or ET-1. Elevated CNP after cardiac injury likely results from regulated changes in clearance, not enhanced production.

Highlights

Statin therapy is widely employed to prevent coronary artery disease and stroke
Baseline plasma ET-1 was higher in the older group (F = 9.9, p = 0.003), but in both groups was unchanged by statin treatment (Fig. 3)
Inverse associations were identified between B-type Natriuretic Peptide (BNP) and NTproCNP, and the ratio NTproCNP/C-type Natriuretic Peptide (CNP), but not when analysed within each group (Table 2). This is the first in-vivo study examining the impact of statin therapy on CNP products in any species

Summary

Introduction

Statin therapy is widely employed to prevent coronary artery disease and stroke. Statins reduce serum cholesterol and have contributed to reduced morbidity and mortality of cardiovascular disease in the last three decades. While evidence supports a largely paracrine mode of action of CNP, clinical studies show that products of proCNP in plasma (aminoterminal proCNP, NTproCNP, and bio active CNP) are increased in settings of vascular stress in both young adults[5] and at mid-life6 – possibly as an adaptive response to inflammation and/or shear stress[7,8]. These results together with other findings suggest that tissue changes in CNP or ET-1 production[9] may be captured by concurrent changes in plasma if studied under well standardised conditions. We further posited that the responses of CNP (increase) and ET (decline) to statins would be reciprocal

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