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.
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