The paradox of low B‐type natriuretic peptide levels in obesity revisited: does sex matter?

Abstract

This article refers to 'Sex-specific associations of obesity and N-terminal pro-B-type natriuretic peptide levels in the general population' by N. Suthahar et al., published in this issue on pages 1205-1214.Obesity has reached epidemic proportions worldwide and represents a common co-morbidity in patients with heart failure (HF), especially in those with preserved ejection fraction (HFpEF). 1,2 Obesity has many deleterious effects on the cardiovascular system, mediated by changes in volume status, cardiac load, energy substrate utilization, tissue metabolism, and systemic inflammation, which are believed to promote cardiac disease progression. 3 -5 Furthermore, obesity is strongly associated with other common non-cardiac clinical conditions, such as systemic arterial hypertension, diabetes mellitus, metabolic syndrome, and obstructive sleep apnoea; these co-morbidities are also common in patients with HFpEF. 2,6 Several studies reported that circulating levels of B-type natriuretic peptide (BNP) and its related peptide N-terminal fragment of proBNP (NT-proBNP) are inversely related to body mass index (BMI) in the general population, as well as in HF patients, as recently reviewed. 1,2 It is also well known that both atrial natriuretic peptide and BNP circulating levels are strongly gender-dependent in healthy subjects. Plasma BNP concentration is minimal during the first years of life with similar values in children and pre-adolescent girls and boys, while the normal cycling women have about two-fold higher BNP levels than men at the same age. 1,2,7 These data suggest that sex steroid hormones play a relevant role in the regulation of production/secretion of cardiac natriuretic peptides. Clinical studies demonstrate that oestrogens, administered as hormonal contraceptives in pre-menopausal women or as hormone replacement therapy in postmenopausal women, increase the circulating levels of BNP and Moreover, androgen receptor blockade and, to a lesser extent, androgen suppression cause an increase in NT-proBNP in men with prostate cancer. 7 These data suggest antagonist effects of androgens (inhibitory) and oestrogens (excitatory) on cardiac endocrine function.The opinions expressed in this article are not necessarily those of the Editors of the European Journal of Heart Failure or of the European Society of Cardiology.

Regional adiposity and heart failure with preserved ejection fraction

“…10 The proposed mechanisms are summarized in Table 1. 19,37,[67][68][69][70]74,79,82,[88][89][90][98][99][100][101][102][103][104][106][107][108][109] While most people do not undergo CT, MRI, or DXA imaging for purposes of screening for HF, interpreting regional fat distribution when imaging is obtained for other purposes could shed light on subpopulations who are at . increased risk of developing HFpEF.…”

“…Xue et al 88 Huby et al 89 Briones et al 90 Clerico et al 109 Vascular compliance and splanchnic coupling Intra-abdominal hypertension Worsened renal impairment Increased splanchnic vascular tone Increased abdominal compartment volume overload Varela et al 98 Lambert et al 99 Malbrain et al 100 Mullens et al 101 Mullens et al 102 Fudim et al 103 Fudim et al 104 AVO 2 , arteriovenous oxygen difference; PCWP, pulmonary capillary wedge pressure.…”

Evidence on clinical relevance of cardiovascular risk evaluation in the general population using cardio-specific biomarkers

“…Furthermore, individuals of both sexes with higher BMI values (without cardiac disease and type 2 DM) show lower values than apparently healthy subjects with normal BMI values [80,81]. However, overweight and obese patients with congestive heart failure show on average lower all-cause and cardiovascular mortality rates than patients with normal or lower BMI values [80,81].…”

“…female positive, male negative) on the production/release of cNP by cardiomyocytes, women show significantly higher level (up to 50%) of circulating BNP and NT-proBNP values during their fertile age up to age of menopause (about 55 years) than men of the same age [71,79]. Furthermore, individuals of both sexes with higher BMI values (without cardiac disease and type 2 DM) show lower values than apparently healthy subjects with normal BMI values [80,81]. However, overweight and obese patients with congestive heart failure show on average lower all-cause and cardiovascular mortality rates than patients with normal or lower BMI values [80,81].…”

Novel aspects of heart failure biomarkers: Focus on inflammation, obesity and sex differences

“…was written by Clerico and colleagues. 28 In Chapter 6, we proceeded along the lines of the editorial, and conducted a literature review focussing on the overlapping effects of sex and obesity on HF biomarkers. We formulated several clinical pointers and potential research questions -which may particularly be of interest to cardiology residents and students interested in HF research.…”