Adiposity has unique influence on the renin-aldosterone axis and blood pressure in black children

OBJECTIVE: To comparatively examine the effects of adiposity on the levels of plasma renin activity (PRA), plasma aldosterone concentration (PAC), and aldosterone-renin ratio (ARR) in young black and white children. STUDY DESIGN: We prospectively assessed 248 black and 345 white children and adolescents. A novel analytical technique was used to assess the concurrent influences of age and body mass index (BMI) on PRA, PAC, and ARR. The estimated effects were depicted by colored contour plots. RESULTS: In contrast to whites, blacks had lower PRA (2.76 vs 3.36 ng/mL/h; P < .001) and lower PAC (9.01 vs 14.59 ng/dL; P < .001). In blacks, BMI was negatively associated with PRA (P = .001), consistent with an association with a more expanded plasma volume; there was no association with PAC. In whites, BMI was positively associated with PAC (P = .005); we did not detect a BMI-PRA association. The effects of BMI on ARR were directionally similar in the two race groups but more pronounced in blacks. Mean systolic blood pressure was greater in blacks with lower PRA (P < .01), higher PAC (P = .015), and higher ARR (P = .49). CONCLUSIONS: An increase in adiposity was associated with a suppressed PRA in blacks and an increase in PAC in whites. The unique relationship between adiposity and renin-aldosterone axis in blacks suggests the possible existence of a population-specific mechanism characterized by volume expansion, which could in turn enhance the influences of adiposity on blood pressure in black children and adolescents

Varying Influences of Aldosterone on the Plasma Potassium Concentration in Blacks and Whites

BACKGROUND: Aldosterone acts to restrain the extracellular potassium (K+) concentration. Blacks have on average lower plasma aldosterone concentrations (PACs) than Whites. Whether this ethnic difference is associated with similar changes in the concentration of K+ is unclear. METHODS: Subjects were Blacks and Whites from an observational study of blood pressure regulation. PAC was known to be significantly lower in Blacks than Whites. We sought to test the hypothesis that the concentration of K+ remains constant despite variability in PAC. Initial enrollment took place in childhood in 1986. Some of the original enrollees were studied again in adulthood: 160 healthy Blacks and 271 healthy Whites (ages 5 to 39 years; all were studied as children and as adults). RESULTS: Plasma renin activity [a biomarker of angiotensin II and, more proximally, extracellular fluid volume (ECFV)] and PAC were lower in Blacks (P < 0.0354 and P < 0.001, respectively, for all ages). At the same time no ethnic difference in levels of K+ was observed regardless of age. Plasma K+ concentration and PAC associated differently based on ethnicity: PAC increased in Blacks by 1.5-2.0 and in Whites by 2.3-3.0 ng/dl per mmol/l increase in K+ (P < 0.001). CONCLUSIONS: Lower aldosterone levels in Blacks did not translate into higher K+ concentrations. We speculate that reaching the right concentration of K+ was an endpoint of aldosterone production in the presence of varying levels of ECFV and angiotensin II

GENETIC VARIATION IN CYP4A11 AND BLOOD PRESSURE RESPONSE TO MINERALOCORTICOID RECEPTOR ANTAGONISM OR ENAC INHIBITION: AN EXPLORATORY PILOT STUDY IN AFRICAN AMERICANS

Background An rs3890011 variant of CYP4A11, which is in linkage disequilibrium with the loss-of-function variant rs1126742, is associated with hypertension in humans. In mice, Cyp4a deficiency results in salt-sensitive hypertension through activation of ENaC. We tested the hypothesis that the rs3890011 variant is associated with blood pressure response to drugs acting via the ENaC pathway. Methods and Results African Americans with volume-dependent, resistant hypertension were randomized to treatment with placebo, spironolactone, amiloride, or combination. Blood pressure responses were analyzed by CYP4A11 genotypes. Rs3890011 (GG:GC:CC=20:35:28) and rs1126742 (TT:TC:CC=45:31:7) were in linkage disequilibrium (D′=1, r=0.561). Expected small number of rs1126742 CC homozygotes precluded analysis of the effect of this genotype on treatment responses. Spironolactone reduced blood pressure in rs3890011 GG and GC individuals, but not in CC homozygotes (p=0.002), whereas amiloride reduced blood pressure similarly in all rs3890011 genotypes. The antihypertensive effects of spironolactone and amiloride were comparable in GG and GC participants, but only amiloride reduced pressure in CC homozygotes (−6.3±7.3/−3.2±4.0 versus +6.8±7.9/+4.8±8.6 mmHg, p<0.01/<0.05). The aldosterone response to spironolactone was also blunted in the CC genotype. Conclusions In individuals homozygous for the CYP4A11 rs3890011 C allele, blood pressure is resistant to mineralocorticoid receptor antagonism, but sensitive to ENaC inhibition, consistent with ENaC activation. Studies in a larger population are needed to replicate these findings

Racial differences in sensitivity of blood pressure to aldosterone

Blacks in comparison with whites are at risk for a more serious form of hypertension with high rates of complications. Greater sodium retention is thought to underlie the blood pressure (BP)-determining physiology of blacks, but specific mechanisms have not been identified. In a prospective observational study of BP, 226 black children and 314 white children (mean age, 10.6 years) were enrolled initially. Assessments were repeated in 85 blacks and 136 whites after reaching adulthood (mean age, 31 years). The relationship of BP to plasma aldosterone concentration in the context of the prevailing level of plasma renin activity was studied in blacks and whites. In a secondary interventional study, 9-α fludrocortisone was administered for 2 weeks to healthy adult blacks and whites to simulate hyperaldosteronism. BP responses in the 2 race groups were then compared. Although black children had lower levels of plasma renin activity and plasma aldosterone, their BP was positively associated with the plasma aldosterone concentration, an effect that increased as plasma renin activity decreased (P=0.004). Data from black adults yielded similar results. No similar relationship was observed in whites. In the interventional study, 9-α fludrocortisone increased BP in blacks but not in whites. In conclusion, aldosterone sensitivity is a significant determinant of BP in young blacks. Although its role in establishing the risk of hypertension is not known, it could be as relevant as the actual level of aldosterone

Emphasizing responder speed or accuracy modulates but does not abolish the distractor-induced quitting effect in visual search

Acknowledgements This research project was initially presented at the 2023 Australasian Experimental Psychology Conference (Lawrence et al., 2023c April 12–14). The authors would like to acknowledge the feedback and insights provided by Professor Allison Waters throughout the conceptualization and execution of this project. Funding This research was supported by a Griffith University New Researcher Grant awarded to RKL.Peer reviewedPublisher PD

Associations between menarche-related genetic variants and pubertal growth in male and female adolescents

PURPOSE: Previous studies have identified novel genetic variants associated with age at menarche in females of European descent. The pubertal growth effects of these variants have not been carefully evaluated in non-European descent groups. We aimed to examine the effects of 31 newly identified menarche-related single-nucleotide polymorphisms (SNPs) on growth outcomes in African-American (AA) and European-American (EA) children in a prospective cohort. METHODS: We analyzed longitudinal data collected from 263 AAs and 338 EAs enrolled between ages 5 and 17 years; the subjects were followed semiannually for an average of 6 years. The associations between the SNPs and growth-related outcomes, including weight, height, and body mass index (BMI), were examined using mixed-effect models. RESULTS: Longitudinal analyses revealed that 4 (near or in genes VGLL3, PEX2, CA10, and SKOR2) of the 14 menarche-only-related SNPs were associated with changes in weight and BMI in EA and AA (p ≤ .0032), but none of them was associated with changes in height. Of the eight menarche-timing and BMI-related SNPs, none was associated with changes in height, but three (in or near genes NEGR1, ETV5, and FTO) were associated with more rapid increases in weight and/or BMI in EA (p ≤ .0059). Among the nine menarche-timing and height-related SNPs, four (in or near genes ZBTB38, LOC728666, TBX2, and CABLES) were associated with changes in weight or height in EA and AA (p ≤ .0042). CONCLUSIONS: Genetic variants related to age at menarche were found to be associated with various growth parameters in healthy adolescents. The identified associations were often race and sex specific

The Effect of Body Mass Index on Blood Pressure Varies by Race among Children

poster abstractThe effect of adiposity on blood pressure (BP) intensifies as children become obese, and black children tend to have greater body mass index (BMI) and higher BP than age-matched white children. But few studies have compared the magnitude of the effect of BMI on BP in obese black and white children. We used a novel analytic technique to examine the influence of age and BMI on BP in children seen at a hospital-based obesity clinic. The study sample included 821 overweight and obese children (age and sex adjusted BMI% ranged from 87% to 100%; 306 males, 515 females, 362 blacks, and 459 whites). The mean age of the study subjects was 11.72 ± 3.48 years, the mean BMI was 36.22 ± 8.51 kg/m2, and the mean systolic and diastolic BP were 109.36 ± 16.10 and 69.99 ± 10.48 mmHg, respectively. In comparison, blacks and whites were similar in age (11.89 vs 11.58; p=0.197); while black patients had higher BMI (37.32 vs 35.34 kg/m2; p=0.0010), and higher systolic BP% than whites (58.71 vs 50.72 mmHg; p=0.00062). Semiparametric regression models showed that while age and BMI were significantly associated with systolic BP% in both race groups, black children had significantly higher BP% values as compared with white children of the same age and BMI (Fig 1 (a) and (b)). Although BP% values have taken into account the effect of age, there continued to be a significant effect of age on BP% in black children. In conclusion, among children referred for treatment of obesity, black children are at a significantly greater risk for having elevated BP as compared with their white peers of similar age and severity of obesity. Further research is needed to better understand this population-specific intensification of the adiposity effect on BP in obese black children

The effect of body mass index on blood pressure varies by race among obese children

Objective: Previous studies have shown that the effect of adiposity on blood pressure (BP) intensifies as children become increasingly obese. Black children tend to have greater body mass index (BMI) and higher BP than age-matched white children. It is unclear whether the BP effects of BMI are race-specific among black and white children, and data on obese Hispanic children are sparse. We compared the BP effect of BMI in obese white, black, and Hispanic children. Methods: We examined the medical records of children enrolled in a pediatric obesity clinic. Height, weight, BP, and fasting insulin were assessed as part of routine clinical care. The concurrent effects of age and BMI on BP percentile values were examined using semiparametric regression, which allows the accommodation of nonlinear effects. Results: The study included 873 children (338 male; 354 black, 447 white, 72 Hispanic; 11.7±3.5 years, BMI 36.2±8.5 kg/m2). While BMI Z-scores were similar among the groups, systolic BP (SBP) was higher in black children and Hispanic children (white: 107 mm Hg; black: 112 mm Hg; Hispanic: 112 mm Hg; p=0.0001). Age, sex, and height-adjusted SBP percentiles were significantly different among the three groups (white: 50; black: 59; Hispanic: 59; p=0.0006). In children of the same age, BP was higher at any given BMI in black children and Hispanic children. Conclusions: Among children referred for treatment of obesity, black children and Hispanic children are at a greater risk for having elevated BP when compared to white children of similar age and BMI

Triamterene Enhances the Blood Pressure Lowering Effect of Hydrochlorothiazide in Patients with Hypertension

BACKGROUND: Triamterene, because of its potassium-sparing properties, is frequently used in combination with hydrochlorothiazide (HCTZ) to treat patients with hypertension. By inhibiting the epithelial sodium channel (ENaC) in the cortical collecting duct, triamterene reduces potassium secretion, thus reducing the risk of hypokalemia. Whether triamterene has an independent effect on blood pressure (BP) has not been well studied. OBJECTIVE: To determine if triamterene provides an effect to further lower BP in patients treated with HCTZ. DESIGN: We conducted an observational study using electronic medical record data from the Indiana Network for Patient Care. Participants were 17,291 patients with the diagnosis of hypertension between 2004 and 2012. MAIN MEASURES: BP was the primary outcome. We compared the BP between patients who were taking HCTZ, with and without triamterene, either alone or in combination with other antihypertensive medications, by using a propensity score analysis. For each medication combination, we estimated the propensity score (i.e., probability) of a patient receiving triamterene using a logistic regression model. Patients with similar propensity scores were stratified into subclasses and BP was compared between those taking triamterene or not within each subclass; the effect of triamterene was then assessed by combining BP differences estimated from all subclasses. KEY RESULTS: The mean systolic BP in the triamterene + HCTZ group was 3.8 mmHg lower than in the HCTZ only group (p < 0.0001); systolic BP was similarly lower for patients taking triamterene with other medication combinations. Systolic BP reduction was consistently observed for different medication combinations. The range of systolic BP reduction was between 1 and 4 mm Hg, depending on the concurrently used medications. CONCLUSIONS: In the present study, triamterene was found to enhance the effect of HCTZ to lower BP. In addition to its potassium-sparing action, triamterene's ability to lower BP should also be considered