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Urine angiotensinogen and salt-sensitivity and potassium-sensitivity of blood pressure

Rebholz, Casey M.a; Chen, Jinga,b,c; Zhao, Qia; Chen, Ji-Chund; Li, Jianxind; Cao, Jied; Gabriel Navar, Luisc; Lee Hamm, Lotucea,b,c; Gu, Dongfengd; He, Jianga,b,cfor the GenSalt Collaborative Research Group

doi: 10.1097/HJH.0000000000000564
ORIGINAL PAPERS: Renin-angiotensin system

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.

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

Correspondence to Jing Chen, MD, Department of Medicine, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA 70112, USA. Tel: +1 504 988 6110; fax: +1 504 988 7448; e-mail: jchen@tulane.edu

Abbreviations: BP, blood pressure; GenSalt study, Genetic Epidemiology Network of Salt Sensitivity study; UAGT, urine angiotensinogen; UAGT/Cr, urine angiotensinogen-to-creatinine ratio

Received 1 October, 2014

Revised 9 February, 2015

Accepted 9 February, 2015

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