Blood Pressure Response to Sodium in the Diet

D1 and AT1 Receptor Interaction in Human Hypertension: Sodium Sensitivity of Blood Pressure

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.

Study Overview

• Status: Unknown
• Conditions: Hypertension
• Intervention / Treatment: Other: High sodium diet and low sodium diet

Detailed 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 .

• Study Type: Interventional
• Enrollment (Anticipated): 400
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • Recruiting
      • University of Virginia
      • Contact: Mahabuba Akhter, M.B.B.S, MS; Phone Number: 434-924-8757; Email: SaltSensitivityStudy@email.virginia.edu
      • Principal Investigator: Robert M Carey, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High sodium diet and low sodium diet; Each subject experiences both a high sodium and a low sodium diet.	Other: High sodium diet and low sodium diet; Isocaloric diet with 60 mEq of potassium and 1gm protein/kg body weight with high sodium 300mEq; low sodium 10 mEq.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood pressure; Change in Mean Arterial Pressure from low salt diet to high salt diet	The mean arterial pressure that will determine salt sensitivity will be assessed during the last day of the diet week. The study will be stopped for any individual during any visit if there is an average blood pressure of >180/114 mmHg.	Study subjects will be observed 5 times during the 2 week intervention

Secondary Outcome Measures

Outcome Measure	Time Frame
Urine sodium	Urine chemistry analysis will be assessed from a 24-hour urine collection on the last day of each diet week.
Genetic analysis for specified genes associated with hypertension	During the screening visit

Collaborators and Investigators

• Sponsor: University of Virginia
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Robert M Carey, MD, University of Virginia

Publications and helpful links

General Publications

• http://hyper.ahajournals.org/content/early/2012/09/17/HYPERTENSIONAHA.112.196071.full.pdf

Study record dates

Study Major Dates

• Study Start: January 1, 2005
• Primary Completion (Anticipated): August 1, 2021
• Study Completion (Anticipated): August 1, 2021

Study Registration Dates

• First Submitted: January 22, 2013
• First Submitted That Met QC Criteria: July 10, 2013
• First Posted (Estimate): July 15, 2013

Study Record Updates

• Last Update Posted (Estimate): October 18, 2016
• Last Update Submitted That Met QC Criteria: October 14, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: hypertension; blood pressure; salt sensitivity
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension
• Other Study ID Numbers: 11494; P01HL074940 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED