Pediatric Brain Natriuretic Peptide Concentrations Vary with Age and Sex and Appear to Be Modulated by Testosterone

Saenger, Amy K.; Dalenberg, Daniel A.; Bryant, Sandra C.; Grebe, Stefan K.; Jaffe, Allan S.

doi:10.1373/clinchem.2009.123778

Cited by 22 publications

(28 citation statements)

References 20 publications

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“…The Dallas Heart Study, observed by Chang et al (9), reported no association between estrogen status and NT-proBNP levels, whereas a strong inverse association was found between measures of free testosterone and NT-proBNP in young women (age range, 35-49 yr). Saenger et al (76) reported an inverse association of NT-proBNP with serum testosterone, a direct association with sex hormone-binding globulin, and no significant association with circulating levels of estradiol in a large population of girls and boys (age range, from 2 mo up to 18 yr).…”

Section: The Cross Talk Between Cardiac Natriuretic and Sex Steroid Hmentioning

confidence: 99%

Thirty years of the heart as an endocrine organ: physiological role and clinical utility of cardiac natriuretic hormones

Clerico

Giannoni

Vittorini

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

173

217

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Clerico A, Giannoni A, Vittorini S, Passino C. Thirty years of the heart as an endocrine organ: physiological role and clinical utility of cardiac natriuretic hormones. Am J Physiol Heart Circ Physiol 301: H12-H20, 2011. First published May 6, 2011; doi:10.1152/ajpheart.00226.2011 reported that atrial extracts contain some biologically active peptides, which promote a rapid and massive diuresis and natriuresis when injected in rats. It is now clear that the heart also exerts an endocrine function and in this way plays a key role in the regulation of cardiovascular and renal systems. The aim of this review is to discuss some recent insights and still-debated findings regarding the cardiac natriuretic hormones (CNHs) produced and secreted by cardiomyocytes (i.e., atrial natriuretic peptide and B-type natriuretic peptide). The functional status of the CNH system depends not only on the production/secretion of CNHs by cardiomyocytes but also on both the peripheral activation of circulating inactive precursor of natriuretic hormones and the transduction of the hormone signal by specific receptors. In this review, we will discuss the data supporting the hypothesis that the production and secretion of CNHs is the result of a complex integration among mechanical, chemical, hemodynamic, humoral, ischemic, and inflammatory inputs. The cross talk among endocrine function, adipose tissue, and sex steroid hormones will be discussed more in detail, considering the clinically relevant relationships linking together cardiovascular risk, sex, and body fat development and distribution. Finally, we will review the pathophysiological role and the clinical relevance of both peripheral maturation of the precursor of B-type natriuretic peptides and hormone signal transduction.B-type natriuretic peptide; sex steroids; adipokines; heart failure; cardiovascular risk THIRTY YEARS AGO, De Bold et al. (20) reported that atrial extracts contain some biological active peptides, which promote a rapid and massive diuresis and natriuresis when injected in rats. Several endogenous peptide hormones with natriuretic and vasodilator activity have been identified in the human blood and peripheral tissues (3,30,69,85,86). Atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and their related peptides are predominantly produced by atrial and ventricular cardiomyocytes. The term "cardiac natriuretic hormones" (CNHs) will be used in this review to indicate these two families of natriuretic peptides. Another natriuretic peptide, named C-type natriuretic peptide (CNP), is predominantly produced by the endothelial cells, including those of cardiac vessels. Finally, urodilatin is an NH 2 -terminal (NT) 4-amino acid (aa) extented form of ANP, which is produced by the same ANP gene and secreted into the urine by renal tubular cells (16,34,69).From the original observations made 30 years ago, the advances in this particular research field have determined a complete revision about the role of the heart. It is now clear that the heart also exerts a...

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Section: The Cross Talk Between Cardiac Natriuretic and Sex Steroid Hmentioning

confidence: 99%

Thirty years of the heart as an endocrine organ: physiological role and clinical utility of cardiac natriuretic hormones

Clerico

Giannoni

Vittorini

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

173

217

View full text Add to dashboard Cite

show abstract

“…On the other hand, a significant and positive association between SHBG and cardiac natriuretic peptide levels (3)(4)(5) may require an alternative interpretation to the one suggested by Lam et al (5), indicating a relevant influence (instead of no effect) of estrogenic status on BNP/NTproBNP levels. Indeed, sex steroid hormones regulate the liver production of SHBG in an opposite way: estrogens show a powerful stimulatory action, whereas androgens have an inhibitory one (8).…”

Section: See Page 618mentioning

confidence: 88%

“…More recently, 3 large population-based studies have indicated that male sex steroid hormones might modulate cardiac endocrine function too (3)(4)(5). These studies demonstrated a significant inverse association between the circulating levels of B-type natriuretic peptide (BNP) or N-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP) and male sex steroid hormones (i.e., total and free testosterone) in both sexes (3)(4)(5), whereas the association with estradiol was found to be weak or not significant at all (3,4).…”

Section: See Page 618mentioning

confidence: 99%

“…These studies demonstrated a significant inverse association between the circulating levels of B-type natriuretic peptide (BNP) or N-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP) and male sex steroid hormones (i.e., total and free testosterone) in both sexes (3)(4)(5), whereas the association with estradiol was found to be weak or not significant at all (3,4). Furthermore, these studies reported that levels of sex hormone-binding globulin (SHBG) are positively associated with NT-proBNP levels in both male and female adolescents (4), as well as in adult women (3,5) and men (5).…”

Section: See Page 618mentioning

confidence: 99%

“…Furthermore, environmental, social, economical, and ethnic differences all play an important role in determining the age of onset of both puberty and menopause, greatly increasing the between-subject variability in female sex steroid levels. Because of great biological variability in estradiol concentrations, it is not surprising to find weak or even absent association between estradiol and BNP/NT-proBNP levels in large population-based studies (3,4).…”

Section: See Page 618mentioning

confidence: 99%

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When Gonads Talk to the Heart

Clerico¹,

Passino²,

Emdin³

2011

Journal of the American College of Cardiology

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Pisa, ItalyCardiovascular risk is significantly lower in normally cycling women compared with men. This difference is abolished after menopause, suggesting a link with sex steroid hormones. Early studies on cardiac endocrine function disclosed higher natriuretic peptide concentrations in women than in men, suggesting the hypothesis that female sex steroid hormones could directly stimulate cardiomyocyte hormone production and secretion (1). Kuroski de Bold (2) hypothesized that an improved cardiovascular risk profile in cycling women could be associated with some estrogen stimulatory effect on cardiac endocrine function. Indeed, cardiac natriuretic peptides exert several protective actions on the heart and vessels, including: 1) vasodilatation; 2) promotion of diuresis/natriuresis; and 3) inhibition of hypertrophy, fibrosis, and apoptosis either directly or via inhibition of the sympathetic and renin-angiotensin-aldosterone systems, as well as the release or action of endothelin and vasopressin (1). See page 618More recently, 3 large population-based studies have indicated that male sex steroid hormones might modulate cardiac endocrine function too (3)(4)(5). These studies demonstrated a significant inverse association between the circulating levels of B-type natriuretic peptide (BNP) or N-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP) and male sex steroid hormones (i.e., total and free testosterone) in both sexes (3-5), whereas the association with estradiol was found to be weak or not significant at all (3,4). Furthermore, these studies reported that levels of sex hormone-binding globulin (SHBG) are positively associated with NT-proBNP levels in both male and female adolescents (4), as well as in adult women (3,5) and men (5). Testosterone and estradiol circulate in the bloodstream mostly bound to SHBG, with levels that directly influence bioavailability of sex hormones; only a small fraction of total steroid concentration is unbound or "free" (1% to 5%) and biologically active (i.e., able to enter a cell and activate its receptors).Lam et al. (5), in this issue of the Journal, evaluate plasma NT-proBNP, total testosterone, and SHBG concentrations in 4,056 adult men and women from the Framingham Heart Study Third-Generation Cohort; estradiol was not measured. They found lower NT-proBNP plasma levels in men than in age-matched women and higher NT-proBNP levels in women receiving hormonal contraceptives than in women who were not (5). Moreover, serum free (non-protein-bound) testosterone was positively and serum SHBG was negatively related to circulating NT-proBNP levels (5). The investigators suggested the hypothesis that androgens suppress NT-proBNP and that differences in free testosterone levels may largely explain the sex-and hormone-related differences in circulating levels of natriuretic peptides. They concluded that lower levels of circulating androgens and the potentiating effect of exogenous female hormone therapy contribute to the higher circulating NT-proBNP levels in women.These findi...

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Distribution of High-Sensitivity Cardiac Troponin and N-Terminal Pro–Brain Natriuretic Peptide in Healthy Transgender People

et al. 2022

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ImportanceSex-specific differences in the commonly used cardiac biomarkers high-sensitivity cardiac troponin (hs-cTn) and N-terminal pro–brain natriuretic peptide (NT-proBNP) are apparent. There is an absence of medical literature delineating the concentration differences for these biomarkers in transgender individuals without cardiac disease.ObjectiveTo determine the distribution of hs-cTn and NT-proBNP in healthy transgender people.Design, Setting, and ParticipantsIn this cross-sectional prospective study, healthy transgender individuals prescribed testosterone or estradiol for 12 months or more were recruited from internal medicine and primary care clinics that specialize in transgender medical care between November 1, 2017, and July 1, 2018.ExposuresTestosterone or estradiol for 12 months.Main Outcomes and MeasuresConcentrations for hs-cTnI (troponin I), hs-cTnT (troponin T), and NT-proBNP were measured.ResultsTransgender people prescribed testosterone (n = 79; mean [SD] age, 28.8 [7.8] years) or estrogen (n = 93; mean [SD] age, 35.1 [11.7] years) were recruited. The concentration of hs-cTn was significantly higher in transgender men relative to transgender women. For Abbott hs-cTnI levels, the median (IQR) concentration observed in transgender men and women was 0.9 (0.6-1.7) ng/L and 0.6 (0.3-1.0) ng/L, respectively. Results were similar across 2 additional hs-cTn assays. In contrast, NT-proBNP level was higher in transgender women. The median (IQR) NT-proBNP concentration was significantly higher in transgender women ( 49 [32-86] ng/L) than in transgender men (17 [13-27] ng/L).Conclusions and RelevanceFindings of this cross-sectional study suggest that the differences in concentration for hs-cTn and NT-proBNP between transgender men and women were similar to what is observed between cisgender men and women. Sex hormones, rather than sex assigned at birth, may be a stronger driver of the observed concentration differences between healthy men and women for biomarkers of cardiac disease.

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Pediatric Brain Natriuretic Peptide Concentrations Vary with Age and Sex and Appear to Be Modulated by Testosterone

Cited by 22 publications

References 20 publications

Thirty years of the heart as an endocrine organ: physiological role and clinical utility of cardiac natriuretic hormones

Thirty years of the heart as an endocrine organ: physiological role and clinical utility of cardiac natriuretic hormones

When Gonads Talk to the Heart

Distribution of High-Sensitivity Cardiac Troponin and N-Terminal Pro–Brain Natriuretic Peptide in Healthy Transgender People

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