The Natriuretic Peptide System in African-Americans.

This study aims to assess the natriuretic peptide response to dietary salt loading in African-American individuals compared with white individuals.

Study Overview

• Status: Completed
• Conditions: Healthy; Prehypertension
• Intervention / Treatment: Dietary supplement: Low-Salt Diet; Dietary supplement: High-Salt Diet

Detailed Description

High blood pressure, or hypertension, is a major cause of heart disease, heart failure, and stroke. Natriuretic peptides are cardiac derived hormones that may protect against hypertension. The classical actions of the natriuretic peptides include natriuresis, vasodilation, and inhibition of the renin-angiotensin-aldosterone system (RAAS), which support a key role for these hormones in blood pressure regulation.

Race based differences exist in the risk and severity of hypertension and cardiovascular disease, with African-American individuals typically being at greater risk compared with white individuals. Nearly half of African-American adults have hypertension, compared with one-third of whites. Additionally, salt-sensitivity denotes the impaired ability to handle a salt load with resulting increases in blood pressure. It is estimated that 75% of hypertensive African-Americans exhibit salt-sensitivity, compared with 35% of hypertensive whites. Why this predilection towards salt-sensitivity exists, particularly among African-American individuals, is not well understood. Thus, establishing the origins of salt retention in African Americans has biologic, preventative, and therapeutic importance, and may provide insight regarding racial differences in cardiovascular risk.

The natriuretic peptide system is the principal counter-regulatory mechanism to salt retention. However, little is known regarding racial differences in the natriuretic peptide system. Recently, it was discovered that African-Americans have lower natriuretic peptide levels compared with whites, raising the possibility that African-Americans individuals can have a relative "natriuretic peptide deficiency" with reduced natriuretic peptide responses to salt loading. However, the prior studies were based on epidemiologic data with individuals on random salt backgrounds. This highlights the need for more detailed physiologic studies, under controlled salt conditions and with standardized assessment of the natriuretic peptide and RAAS and tissue sodium stores.

The aim of this study is to assess the natriuretic peptide response to dietary salt loading in African-American individuals compared with white individuals. This study will test the primary hypothesis that compared with whites, African-American individuals have blunted natriuretic peptide responses to dietary salt loading.

Secondary hypotheses include:

1. Compared with white individuals, African-American individuals have higher baseline tissue sodium content, and
2. Compared with white individuals, African-American individuals have impaired "target organ" responses to salt loading, as manifested by higher blood pressure and increased frequency of salt-sensitive hypertension, decreased urinary sodium excretion, less suppression of plasma renin and serum aldosterone, and lack of increase in left ventricular early diastolic relaxation velocities.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Vanderbilt Univeristy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• age between 18 and 55 years
• BMI between 18 and <25 kg/m2
• normotensive or pre-hypertensive
• willing to adhere to study diets

Exclusion Criteria:

• prevalent cardiovascular disease or use of medications for cardiovascular disease
• Current or prior history of hypertension or use of blood pressure lowering medications
• Current or prior history of diabetes mellitus or use of anti-diabetic medications
• Prevalent renal disease (eGFR < 60 ml/min/1.73m2), abnormal serum sodium or potassium
• Current or prior smoker
• Current pregnancy
• Current steroid use
• Contraindications to MRI

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: African-American; 40 healthy African-American subjects will be enrolled and each will undergo study procedures at 4 separate visits, with each visit occurring 7-days apart. After a baseline visit, the subject will begin either a low-salt or high-salt diet, based upon randomization assignment to one of the two following dietary protocols: A) low-salt diet, washout, then high-salt diet; or B) high-salt diet, washout, then low-salt diet. Each dietary or washout period lasts for 7 days.	Dietary supplement: Low-Salt Diet; The low-salt diet (7 days) will consist of meals, snacks, and sodium free water provided by the study staff.; Dietary supplement: High-Salt Diet; The high-salt diet (7 days) consists of each subject's usual diet, supplemented each day with 2 bouillon broth packets, which will be provided to the subject by the study staff.
Other: Whites; 40 healthy white subjects will be enrolled and each will undergo study procedures at 4 separate visits, with each visit occurring 7-days apart. After a baseline visit, the subject will begin either a low-salt or high-salt diet, based upon randomization assignment to one of the two following dietary protocols: A) low-salt diet, washout, then high-salt diet; or B) high-salt diet, washout, then low-salt diet. Each dietary or washout period lasts for 7 days.	Dietary supplement: Low-Salt Diet; The low-salt diet (7 days) will consist of meals, snacks, and sodium free water provided by the study staff.; Dietary supplement: High-Salt Diet; The high-salt diet (7 days) consists of each subject's usual diet, supplemented each day with 2 bouillon broth packets, which will be provided to the subject by the study staff.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The difference in circulating NT-proANP levels in response to low and high dietary salt.	4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tissue sodium content	Measured by sodium MRI	4 years
Blood pressure		4 years
Salt-sensitive hypertension	Measured by change in mean arterial pressure	4 years
Urinary sodium excretion	Measured from 24 hour urine collection	4 years
Myocardial early relaxation velocities	Measured from Echocardiography as tissue Doppler e'	4 years
Plasma renin	Physiological parameter	4 years
Serum aldosterone	Physiological parameter	4 years

Collaborators and Investigators

• Sponsor: Vanderbilt University
• Investigators: Principal Investigator: Deepak K Gupta, MD, Vanderbilt Cardiovascular Medicine

Publications and helpful links

General Publications

• Gupta DK, de Lemos JA, Ayers CR, Berry JD, Wang TJ. Racial Differences in Natriuretic Peptide Levels: The Dallas Heart Study. JACC Heart Fail. 2015 Jul;3(7):513-519. doi: 10.1016/j.jchf.2015.02.008. Epub 2015 Jun 10.
• Gupta DK, Claggett B, Wells Q, Cheng S, Li M, Maruthur N, Selvin E, Coresh J, Konety S, Butler KR, Mosley T, Boerwinkle E, Hoogeveen R, Ballantyne CM, Solomon SD. Racial differences in circulating natriuretic peptide levels: the atherosclerosis risk in communities study. J Am Heart Assoc. 2015 May 21;4(5):e001831. doi: 10.1161/JAHA.115.001831.

Study record dates

Study Major Dates

• Study Start (Actual): July 22, 2016
• Primary Completion (Actual): May 20, 2021
• Study Completion (Actual): May 20, 2021

Study Registration Dates

• First Submitted: March 29, 2016
• First Submitted That Met QC Criteria: March 31, 2016
• First Posted (Estimate): April 6, 2016

Study Record Updates

• Last Update Posted (Actual): November 9, 2022
• Last Update Submitted That Met QC Criteria: November 8, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Prehypertension
• Other Study ID Numbers: 151943

Plan for Individual participant data (IPD)

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