IU Indianapolis ScholarWorks :: Browsing by Author "Pratt, J. Howard"

Browsing by Author "Pratt, J. Howard"

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Adiposity has unique influence on the renin-aldosterone axis and blood pressure in black children
(Elsevier, 2013-11) Yu, Zhangsheng; Eckert, George; Liu, Hai; Pratt, J. Howard; Tu, Wanzhu; Medicine, School of Medicine
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.
Association of Circulating Renin and Aldosterone With Osteocalcin and Bone Mineral Density in African Ancestry Families
(American Heart Association, 2016-05) Kuipers, Allison L.; Kammerer, Candace M.; Pratt, J. Howard; Bunker, Clareann H.; Wheeler, Victor W.; Patrick, Alan L.; Zmuda, Joseph M.; Medicine, School of Medicine
Hypertension is associated with accelerated bone loss, and the renin-angiotensin-aldosterone system is a key regulator of blood pressure. Although components of this system are expressed in human bone cells, studies in humans are sparse. Thus, we studied the association of circulating renin and aldosterone with osteocalcin and bone mineral density. We recruited 373 African ancestry family members without regard to health status from 6 probands (mean family size: 62 and relative pairs: 1687). Participants underwent a clinical examination, dual-energy x-ray absorptiometry, and quantitative computed tomographic scans. Renin activity, aldosterone concentration, and osteocalcin were measured in fasting blood samples. Aldosterone/renin ratio was calculated as aldosterone concentration/renin activity. All models were analyzed using pedigree-based variance components methods. Full models included adjustment for age, sex, body composition, comorbidities, lifestyle factors, blood pressure, and antihypertensive medication. Higher renin activity was significantly associated with lower total osteocalcin and with higher trabecular bone mineral density (both P<0.01). There were also significant genetic correlations between renin activity and whole-body bone mineral density. There were no associations with aldosterone concentration in any model and results for aldosterone/renin ratio were similar to those for renin activity. This is the first study to report a significant association between renin activity and a marker of bone turnover and bone mineral density in generally healthy individuals. Also, there is evidence for significant genetic pleiotropy and, thus, there may be a shared biological mechanism underlying both the renin-angiotensin-aldosterone system and bone metabolism that is independent of hypertension.
Associations between menarche-related genetic variants and pubertal growth in male and female adolescents
(Elsevier, 2015-01) Tu, Wanzhu; Wagner, Erin K.; Eckert, George J.; Yu, Zhangsheng; Hannon, Tamara; Pratt, J. Howard; He, Chunyan; Department of Epidemiology, School of Public Health
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.
Big Data and Causal Inference: What Does a New Analysis of the UK BioBank Data Tell Us?
(AHA, 2020) Tu, Wanzhu; Pratt, J. Howard; Biostatistics, School of Public Health
The Effect of Body Mass Index on Blood Pressure Varies by Race among Children
(Office of the Vice Chancellor for Research, 2013-04-05) Li, Zhuokai; Eckert, George; Tu, Wanzhu; Gupta, Sandeep; Carroll, Aaron; Pratt, J. Howard; Hannon, Tamara S.
The 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
(De Gruyter, 2015-05) Hannon, Tamara S.; Gupta, Sandeep; Li, Zhuokai; Eckert, George; Carroll, Aaron E.; Pratt, J. Howard; Tu, Wanzhu; Department of Pediatrics, Indiana University School of Medicine
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.
GENETIC VARIATION IN CYP4A11 AND BLOOD PRESSURE RESPONSE TO MINERALOCORTICOID RECEPTOR ANTAGONISM OR ENAC INHIBITION: AN EXPLORATORY PILOT STUDY IN AFRICAN AMERICANS
(Elsevier, 2014-07) Laffer, Cheryl L.; Elijovich, Fernando; Eckert, George J.; Tu, Wanzhu; Pratt, J. Howard; Brown, Nancy J.; Department of Biostatistics, School of Public Health
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
(Ovid Technologies Wolters Kluwer -American Heart Association, 2014-06) Tu, Wanzhu; Eckert, George J.; Hannon, Tamara S.; Liu, Hai; Pratt, Linda M.; Wagner, Mary Anne; Dimeglio, Linda A.; Jung, Jeesun; Pratt, J. Howard; Department of Medicine, IU School of Medicine
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.
Response to "is high prorenin level related to relative aldosterone excess?"
(Oxford University Press, 2013-02) Tu, Wanzhu; Eckert, George J.; Pratt, J. Howard; Danser, A.H. Jan; Department of Medicine, IU School of Medicine
Comment in: Is high prorenin levels related to relative aldosterone excess? [Am J Hypertens. 2013] Comment on: Plasma levels of prorenin and renin in blacks and whites: their relative abundance and associations with plasma aldosterone concentration. [Am J Hypertens. 2012]
Small potassium (SK) channels: speculation on a role to regulate aldosterone production and blood pressure
(American Heart Association, 2016-09) Tu, Wanzhu; Pratt, J. Howard; Medicine, School of Medicine

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