Rapid responses of catecholamines, natriuretic peptides and inflammatory markers to acute type B aortic dissection (NeuroendOcrine horMone release in acute type b Aortic Dissection [NOMAD] Study)

Abstract

Background

We have recently demonstrated that muscle sympathetic nerve activity and normetanephrine levels are transiently increased for several days immediately after acute type B aortic dissection. We now report other markers of sympathetic activation, natriuresis and inflammation over the same time frame.

Methods

In 13 patients with known acute type B aortic dissection (median age, 71 years; 95% confidence interval, 29-89 years), we undertook serial measurements of catecholamine metabolites including normetanephrine, metanephrine, and their second messenger cyclic adenosine monophosphate; renin and aldosterone; N terminal-pro-brain natriuretic peptide (NT-proBNP), and its second messenger cyclic, guanosine monophosphate; C-type natriuretic peptide; the inflammatory growth differentiation factor 15; the stress hormone copeptin; mid-regional-proadrenomedullin; and the marker of cardiac muscle damage Troponin T. Venous sampling times were on admission, then 12 hours, 24 hours, 1 week, and 6 weeks later. Serial measurements were also undertaken in 12 controls (median age, 61 years; 95% confidence interval, 25-86 years) who presented with chest pain.

Results

During the first week after dissection, normetanephrine levels were increased: 617 to 792 vs 425 to 489 pmol/L in controls (analysis of variance [ANOVA] P = .01). There was also a simultaneous increase in NT-proBNP levels: 49 to 93 vs 14-21 pmol/L (ANOVA P = .07), and growth differentiation factor 15 levels: 1507 to 2873 vs 1146 to 1448 pg/mL (ANOVA P = .01) over the same period.

Conclusions

The increase in normetanephrine levels during the week after type B dissection confirms sympathetic nerve activity as a likely mechanism for hypertension in these patients. This surge of sympathetic activity may be partially antagonized by a simultaneous increase in NT-proBNP, which is possibly triggered by acute inflammation and oxidative stress caused by the dissection.

Clinical Relevance

This pilot study focused on assessing the timeline of neuroendocrine hormone release in acute type B aortic dissection. Our results demonstrated an increase in normetanephrine levels suggesting the involvement of the sympathetic nerve activity in driving hypertension in the acute setting of type B aortic dissection. There was also a concurrent increase in N-terminal pro-brain natriuretic peptide and growth differentiation factor 15 levels seen, suggesting an underlying inflammatory process and vascular stress. These can be the focus of future research in the development of pharmaceutical targets or the use of natriuretic drugs and anti-inflammatory agents in the mainstay treatment of type B aortic dissection.