Natriuretic Peptides, Cognitive Impairment and Dementia: An Intriguing Pathogenic Link with Implications in Hypertension.

Giovanna Gallo,Massimo Volpe,Speranza Rubattu,Maria Cotugno,Franca Bianchi

doi:10.3390/jcm9072265

Abstract

The natriuretic peptides (NPs) belong to a family of cardiac hormones that exert relevant protective functions within the cardiovascular system. An increase of both brain and atrial natriuretic peptide levels, particularly of the amino-terminal peptides (NT-proBNP and NT-proANP), represents a marker of cardiovascular damage. A link between increased NP levels and cognitive decline and dementia has been reported in several human studies performed both in general populations and in cohorts of patients affected by cardiovascular diseases (CVDs). In particular, it was reported that the elevation of NP levels in dementia can be both dependent and independent from CVD risk factors. In the first case, it may be expected that, by counteracting early on the cardiovascular risk factor load and the pathological processes leading to increased aminoterminal natriuretic peptide (NT-proNP) level, the risk of dementia could be significantly reduced. In case of a link independent from CVD risk factors, an increased NP level should be considered as a direct marker of neuronal damage. In the context of hypertension, elevated NT-proBNP and mid-regional (MR)-proANP levels behave as markers of brain microcirculatory damage and dysfunction. The available evidence suggests that they could help in identifying those subjects who would benefit most from a timely antihypertensive therapy.

Highlights

Natriuretic peptides (NPs) are a family of cardiovascular hormones mainly secreted by the heart (atrial (ANP) and brain (BNP) natriuretic peptides) and by the endothelium (C-type natriuretic peptide (CNP)) that play important protective functions within the cardiovascular system [1,2]
Whereas the prognostic impact of NPs in patients with cardiovascular diseases (CVDs) can be explained as a reflection of the underlying cardiovascular dysfunction and damage, the predictive role of increased NP levels toward future cardiovascular events in apparently healthy individuals is a very intriguing and still unexplained issue
Despite these important observations, no clinical guidelines include the use of NT-proBNP level for CVD risk prediction

Summary

Introduction

Natriuretic peptides (NPs) are a family of cardiovascular hormones mainly secreted by the heart (atrial (ANP) and brain (BNP) natriuretic peptides) and by the endothelium (C-type natriuretic peptide (CNP)) that play important protective functions within the cardiovascular system [1,2]. The evidence regarding the link between NP level and cardiovascular risk prediction in both healthy subjects and patients with a known history of CVD appears tightly connected to another relevant issue in the context of disease prevention, which is the emerging relationship of NP circulating levels with cognitive decline, vascular dementia and any type of dementia. This important aspect of the pathophysiological implications of NPs has been highlighted over the last recent years, and it certainly deserves to be further characterized. This article discusses the available evidence on the intriguing relationship between NPs and cognitive decline/dementia, the most plausible explanations and the clinical implications, focusing on hypertension-mediated organ damage

Populations-Based Evidence

CVD-Dependent Pathogenic Mechanisms

Findings

CVD-Independent Pathogenic Mechanisms