Casey M Rebholz1, Jing Chen, Qi Zhao, Ji-Chun Chen, Jianxin Li, Jie Cao, Luis Gabriel Navar, Lotuce Lee Hamm, Dongfeng Gu, Jiang He. 1. aDepartment of Epidemiology, Tulane University School of Public Health and Tropical Medicine bDepartment of Medicine, Tulane University School of Medicine cTulane Hypertension and Renal Center of Excellence, Tulane University School of Medicine, New Orleans, Louisiana, USA dDepartment of Population Genetics and Prevention, Fu Wai Hospital and Cardiovascular Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Abstract
OBJECTIVE: Urinary excretion of angiotensinogen [urine angiotensinogen (UAGT)] has been proposed as a biomarker of intrarenal renin-angiotensin system activity. We investigated the association between UAGT and salt-sensitivity and potassium-sensitivity of blood pressure (BP) among Genetic Epidemiology Network of Salt Sensitivity study participants. METHODS: The intervention consisted of a 7-day low-sodium diet (51.3 mmol sodium/day), 7-day high-sodium diet (307.8 mmol sodium/day), and 7-day high-sodium diet with potassium supplementation (307.8 mmol sodium/day and 60 mmol potassium/day). Twenty-four-hour UAGT was estimated at baseline and at the end of each intervention for 100 randomly selected participants. RESULTS: Median UAGT (μg/24 h) and UAGT-to-creatinine ratio (UAGT/Cr, μg/g) were significantly reduced during the low-sodium and potassium-supplementation interventions and increased during the high-sodium intervention (both P = 0.01). Baseline log-transformed UAGT and UAGT/Cr ratio were significantly positively associated with BP at baseline and at the end of each intervention. For example, one standard deviation higher log-UAGT/Cr ratio (1.2 μg/g) was associated with a 5.0-mmHg (95% confidence interval 2.3-7.8) higher SBP at the end of the high-sodium intervention, after adjusting for multiple covariates (P = 0.003). In addition, one standard deviation higher log-UAGT/Cr ratio was associated with a 1.6-mmHg increase in age-adjusted and sex-adjusted SBP from the low-sodium intervention to the high-sodium intervention (95% confidence interval 0.1-3.1, P = 0.04). This association was no longer statistically significant after multivariable adjustment. CONCLUSION: These data indicate that elevated UAGT are associated with BP sodium sensitivity. Augmentation of intrarenal renin-angiotensin system activity may play an important role in developing salt-sensitive hypertension.
OBJECTIVE: Urinary excretion of angiotensinogen [urine angiotensinogen (UAGT)] has been proposed as a biomarker of intrarenal renin-angiotensin system activity. We investigated the association between UAGT and salt-sensitivity and potassium-sensitivity of blood pressure (BP) among Genetic Epidemiology Network of Salt Sensitivity study participants. METHODS: The intervention consisted of a 7-day low-sodium diet (51.3 mmol sodium/day), 7-day high-sodium diet (307.8 mmol sodium/day), and 7-day high-sodium diet with potassium supplementation (307.8 mmol sodium/day and 60 mmol potassium/day). Twenty-four-hour UAGT was estimated at baseline and at the end of each intervention for 100 randomly selected participants. RESULTS: Median UAGT (μg/24 h) and UAGT-to-creatinine ratio (UAGT/Cr, μg/g) were significantly reduced during the low-sodium and potassium-supplementation interventions and increased during the high-sodium intervention (both P = 0.01). Baseline log-transformed UAGT and UAGT/Cr ratio were significantly positively associated with BP at baseline and at the end of each intervention. For example, one standard deviation higher log-UAGT/Cr ratio (1.2 μg/g) was associated with a 5.0-mmHg (95% confidence interval 2.3-7.8) higher SBP at the end of the high-sodium intervention, after adjusting for multiple covariates (P = 0.003). In addition, one standard deviation higher log-UAGT/Cr ratio was associated with a 1.6-mmHg increase in age-adjusted and sex-adjusted SBP from the low-sodium intervention to the high-sodium intervention (95% confidence interval 0.1-3.1, P = 0.04). This association was no longer statistically significant after multivariable adjustment. CONCLUSION: These data indicate that elevated UAGT are associated with BP sodium sensitivity. Augmentation of intrarenal renin-angiotensin system activity may play an important role in developing salt-sensitive hypertension.
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