Pathophysiological and clinical relevance of circulating levels of cardiac natriuretic hormones: are they merely markers of cardiac disease?

Several specific and sensitive markers for myocardial injury as well as diagnostic tests for the assessment and stratification of cardiovascular risk have been recently introduced in clinical laboratories. However, until a few years ago, there were no laboratory tests for diagnosis, stratification and follow-up of patients with heart failure. The assay for cardiac natriuretic hormones (CNH) fills this gap. Heart failure is not only the most frequent "final common pathway" in cardiovascular disease, but is also the most common primary hospital discharge diagnosis, as well as the most common cause of death in patients over 50 years of age in Western countries; therefore, CNH assay may be destined to assume a growing relevance in clinical cardiology. However, to consider CNH assay only as a general and functional indicator of cardiac structural disease, without recalling that atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are powerful hormones, may lead to underestimation of the physiological role they play in healthy subjects as well as in patients with heart failure. Indeed, the circulating levels of CNH should be always interpreted taking into account not only hemodynamic factors and myocardial performance, but also their relationship with the counter-regulatory neuroendocrine system (including renin-angiotensin-aldosterone system, sympathetic system, endothelins, cytokines and vasopressin), as well as other hormones (such as sex steroid hormones, thyroid hormones and glucocorticoids).