Blood Pressure Response to Sodium in the Diet

University of Virginia

Status: Unknown

Conditions: Hypertension

Treatments: Other: High sodium diet and low sodium diet

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT01899495

P01HL074940 (U.S. NIH Grant/Contract)

11494

Details and patient eligibility

About

Previous studies have demonstrated that single nucleotide polymorphisms (SNPs) of the sodium-bicarbonate co-transporter gene (SLC4A5) are associated with hypertension. We tested the hypothesis that SNPs in SLC4A5 are associated with salt sensitivity of blood pressure in 185 whites consuming an isocaloric constant diet with a randomized order of 7 days of low sodium (Na+) and 7 days of high Na+ intake. Salt sensitivity was defined as a ≥7-mm Hg increase in mean arterial pressure during a randomized transition between low and high Na+ diet.

A total of 35 polymorphisms in 17 candidate genes were assayed, 25 of which were tested for association. Association analyses with salt sensitivity revealed 3 variants that associated with salt sensitivity. Of these, 2 SNPs in SLC4A5 (rs7571842 and rs10177833) demonstrated highly significant results and large effects sizes, using logistic regression. These 2 SNPs had P values of 1.0×10-4 and 3.1×10-4 with odds ratios of 0.221 and 0.221 in unadjusted regression models, respectively, with the G allele at both sites conferring protection. These SNPs remained significant after adjusting for body mass index and age (P=8.9×10-5 and 2.6×10-4 and odds ratios 0.210 and 0.286, respectively). Furthermore, the association of these SNPs with salt sensitivity was replicated in a second hypertensive population. Meta-analysis demonstrated significant associations of both SNPs with salt sensitivity (rs7571842 [P=1.2×10-5]; rs1017783 [P=1.1×10-4]).

In conclusion, SLC4A5 variants are strongly associated with salt sensitivity of blood pressure in 2 separate white populations.

Full description

Subjects are placed on an isocaloric diet, one week with high sodium(300mEq) and one week with low sodium(10mEq), in randomized order. Twenty-four hour urine sodium and urine creatinine levels verify diet compliance. Blood pressure measurements are recorded during each diet week by automated blood pressure monitoring system. Each blood pressure is taken in the right arm 3 times while the subject is sitting quietly for 45 minutes .

Enrollment: 400 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Ages 18-70 (inclusive)
• Sex Male and female
• Race Caucasian and African-American/black
• BMI 18.-0-29.9
• BP Normal

Exclusion criteria

• hypertension
• blood pressure > 140/90 mmHg

Trial design

Primary purpose: Diagnostic

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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400 participants in 1 patient group

High sodium diet and low sodium diet

Experimental group

Description:

Each subject experiences both a high sodium and a low sodium diet.

Treatment:

Other: High sodium diet and low sodium diet