We propose to conduct a prospective longitudinal study to: 1. examine the relationship between blood pressure (BP) responses to sodium and potassium interventions (salt-sensitivity and potassium-sensitivity) and subsequent change in BP levels and risk of hypertension during long-term follow-up;2. examine the relationship between BP responses to cold pressor test and subsequent change in BP levels and risk of hypertension during long-term follow-up;3. test the reproducibility of BP responses to sodium and potassium interventions and the cold pressor test;and 4. examine the association between variants in candidate genes and risk of hypertension. The proposed study is very cost-effective because we will use study participants and data from the Genetic Epidemiology Network of Salt Sensitivity (GenSalt), an NHLBI-sponsored family feeding-study conducted in rural China. In GenSalt, each family was ascertained through a proband with untreated pre-hypertension or stage-1 hypertension. The dietary intervention included a 7-day low sodium-feeding (51.3 mmol/day), a 7-day high sodium-feeding (307.8 mmol/day), and a 7-day high sodium-feeding with an oral potassium supplementation (60 mmol/day) conducted among 1,906 probands and their sibs, spouses, and offspring. Three BP measurements were obtained on each of 3-days during the baseline and each of the 3 intervention periods. In addition, a cold pressor test was conducted among 2,001 participants. Single nucleotide polymorphisms from 30 biological candidate genes have been genotyped. In the proposed study, we will follow-up the GenSalt study participants to obtain data on incidence of hypertension and change in BP. In addition, we will repeat the dietary sodium and potassium interventions as well as the cold pressor test in a random sub-sample of GenSalt study participants to estimate the reproducibility of the BP response to these interventions. The proposed study has important public health and clinical implications. Establishing a relationship between sodium and potassium sensitivity and risk of hypertension will help identify individuals at high risk for hypertension and who should be a priority to receive a low sodium and high potassium dietary intervention.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL087263-04
Application #
7908929
Study Section
Cardiovascular and Sleep Epidemiology (CASE)
Program Officer
Jaquish, Cashell E
Project Start
2007-08-15
Project End
2012-07-31
Budget Start
2010-08-01
Budget End
2011-07-31
Support Year
4
Fiscal Year
2010
Total Cost
$529,299
Indirect Cost
Name
Tulane University
Department
Biostatistics & Other Math Sci
Type
Schools of Public Health
DUNS #
053785812
City
New Orleans
State
LA
Country
United States
Zip Code
70118
Li, Hongfan; Han, Xikun; Hu, Zunsong et al. (2018) Associations of NADPH oxidase-related genes with blood pressure changes and incident hypertension: The GenSalt Study. J Hum Hypertens 32:287-293
Gu, Xiaoying; Gu, Dongfeng; He, Jiang et al. (2018) Resequencing Epithelial Sodium Channel Genes Identifies Rare Variants Associated With Blood Pressure Salt-Sensitivity: The GenSalt Study. Am J Hypertens 31:205-211
Li, Changwei; Kim, Yun Kyoung; Dorajoo, Rajkumar et al. (2017) Genome-Wide Association Study Meta-Analysis of Long-Term Average Blood Pressure in East Asians. Circ Cardiovasc Genet 10:e001527
Zhang, Dingding; Gu, Dongfeng; He, Jiang et al. (2017) Associations of the Serum/Glucocorticoid Regulated Kinase Genes With BP Changes and Hypertension Incidence: The Gensalt Study. Am J Hypertens 30:95-101
Han, Xikun; Hu, Zunsong; Chen, Jing et al. (2017) Associations Between Genetic Variants of NADPH Oxidase-Related Genes and Blood Pressure Responses to Dietary Sodium Intervention: The GenSalt Study. Am J Hypertens 30:427-434
Nierenberg, Jovia L; Li, Changwei; He, Jiang et al. (2017) Blood Pressure Genetic Risk Score Predicts Blood Pressure Responses to Dietary Sodium and Potassium: The GenSalt Study (Genetic Epidemiology Network of Salt Sensitivity). Hypertension 70:1106-1112
Li, Changwei; He, Jiang; Chen, Jing et al. (2017) Genome-Wide Gene-Potassium Interaction Analyses on Blood Pressure: The GenSalt Study (Genetic Epidemiology Network of Salt Sensitivity). Circ Cardiovasc Genet 10:
Spracklen, Cassandra N; Chen, Peng; Kim, Young Jin et al. (2017) Association analyses of East Asian individuals and trans-ancestry analyses with European individuals reveal new loci associated with cholesterol and triglyceride levels. Hum Mol Genet 26:1770-1784
Kelly, Tanika N; Li, Changwei; Hixson, James E et al. (2017) Resequencing Study Identifies Rare Renin-Angiotensin-Aldosterone System Variants Associated With Blood Pressure Salt-Sensitivity: The GenSalt Study. Am J Hypertens 30:495-501
Wen, Wanqing; Kato, Norihiro; Hwang, Joo-Yeon et al. (2016) Genome-wide association studies in East Asians identify new loci for waist-hip ratio and waist circumference. Sci Rep 6:17958

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