Background: Animal models and human genetic investigations suggest that lower levels of natriuretic peptides (NP), which are cardiac-derived hormones, are associated with the development of obesity, insulin resistance, type 2 diabetes, and hypertension. However, whether lower resting NP levels in humans reflect a true hormone deficiency (analogous to other hormone deficiencies like adrenal insufficiency) is unknown, in part, because a diagnostic test for NP deficiency is currently lacking. One strategy for developing a diagnostic test for NP deficiency is to identify a stimulus that provokes an increase in NP concentrations. Dexamethasone is a potent stimulus for NP production in animals, but its effect on NP levels in humans is not well defined. Objective: We sought to define the effects of dexamethasone on circulating NPs over time in healthy humans. We hypothesized that dexamethasone would stimulate increases in NP levels, and that we could characterize the magnitude and timing of the changes as a primary step toward developing a diagnostic test for NP deficiency. Methods: 10 healthy, lean women (mean age 28 + 5 years, mean BMI 22.5 + 1.6 kg/m 2 ) received a single 4 mg IV dose of dexamethasone after an overnight fast. Plasma levels of N-terminal pro-atrial natriuretic peptide (NT-proANP) and N-terminal pro- b-type natriuretic peptide (NT-proBNP) were serially measured during 2 time periods following dexamethasone: 1) “Acute Phase”: 0-8 hours, and 2) “Extended Phase”: at 24, 48, and 72 hours. Changes in NPs were analyzed using a piecewise random effects model for the 2 time periods. Results : During the Acute Phase after dexamethasone, a biphasic change in NT-proANP was observed (nonlinear, p<0.001). Median NT-proANP initially increased, with a peak increase of 24% occurring at 2.5 hours, and thereafter decreased until 8 hours (to 21% below baseline). During the “Extended Phase,” NT-proANP levels rebounded (p<0.001) and returned to near baseline by 72 hours. Next, median NT-proBNP increased during the Acute Phase (p= 0.016), with a peak increase of 27% occurring at 8 hours, and subsequently declined during the Extended Phase (p= 0.04) to a median value 24% lower than baseline at 72 hours. Discussion : Dexamethasone appears to acutely stimulate NP production in humans, as evidenced by an initial increase, followed by a subsequent decline, in circulating NP levels. The time course differs between NT-proANP and NT-proBNP, with NT-proANP peaking earlier than NT-proBNP. These pilot data may inform larger studies for establishing population norms for the NP response to glucocorticoids and evaluating whether a NP stimulation test with glucocorticoids may be a useful test for diagnosing NP deficiency.
Background: Relative natriuretic peptide (NP) deficiencies are associated with hypertension, diabetes, and obesity. The prevalence of these conditions varies by race, affecting more black than white individuals. We assessed whether circulating NP levels and factors associated with NP levels differ by race in clinically referred patients. Methods: Using Vanderbilt University Medical Center electronic health records from 2002 to 2013, we examined plasma B-type natriuretic peptide (BNP) levels and correlates in 30,487 black (17%) or white adult patients. Multivariable-adjusted models including interaction terms by race and stratification by heart failure (HF) status were used. Results: In 18,850 patients without HF, BNP levels were lower in black [median 58 pg/ml (25 th , 75 th percentile: 23, 179)] compared with white individuals [97 pg/ml (38, 247)], p< 0.001. Factors most strongly correlated with BNP differed between black (creatinine, age, chronic kidney disease, body mass index (BMI), left ventricular [LV] ejection fraction) and white (age, BMI, LV mass, chronic kidney disease, sex) patients ( Figure ). Lower BNP levels in black patients were observed across the spectrum of heart rate, blood pressure, body mass index, glucose, LV ejection fraction and mass, and renal function. The directional association of cardiometabolic risk factors with BNP levels was largely similar by race, with exceptions of significant interactions by BMI and creatinine. Higher BMI was associated with lower BNP levels in whites, while among black patients beyond a BMI of approximately 35 kg/m 2 , BNP levels did not decline any further. With higher creatinine, the rise in BNP levels was steeper in black compared with white patients. In contrast to patients without HF, among patients with HF (n = 11,637), BNP levels and its correlates were similar between black and white patients ( Figure ). Conclusion: The associations between cardiometabolic factors and BNP levels vary by race and HF status.
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