{'fraction_non_alphanumeric': 0.03210349784379492, 'fraction_numerical': 0.006229036895064686, 'mean_word_length': 5.6923076923076925, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 2, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
The paradox of low B‐type natriuretic peptide levels in obesity revisited: does sex matter?

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 NT-proBNP.7 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.