Racial Differences in Serum Sodium and Blood Pressure Regulation

Study Overview
=================
Brief Summary
-----------------
Nearly nine-in-ten Americans overconsume salt. Black individuals are more prone to salt-sensitive hypertension. The central goal of the study is to determine if dietary sodium influences blood vessel function and nervous system regulation of blood pressure differentially in black, compared to white individuals. These findings may help to explain why high dietary salt causes increases in blood pressure more frequently in black, compared to white individuals. A secondary goal of this project is to also determine the role of lifestyle factors (i.e., sleep, physical activity, and nutrition) on potential baseline racial differences in cardiovascular function.

Detailed Description
-----------------
The investigators aim to study racial differences in cardiovascular responses to high dietary sodium. An overwhelming majority of Americans consume more dietary sodium than what is recommended by the American Heart Association and the Dietary Guidelines for Americans. The investigators recently published data demonstrating that compared to white individuals, 1) black individuals have augmented increases in serum sodium concentration to a hypertonic saline infusion; and 2) exhibit higher blood pressure for a given serum sodium. In this proposal, the investigators will translate these findings by comprehensively assessing neurovascular responses to acute (single meal) high dietary sodium. The central hypothesis is that high dietary sodium influences sympathetic nerve activity similarly in black and white individuals; however, diminished vasodilator capacity and augmented sympathetic transduction (vasoconstrictor responses to sympathetic nerve bursts) contribute to exaggerated blood pressure dysregulation in black individuals. The investigators will also determine the role of lifestyle factors (i.e., sleep, physical activity, and nutrition) on potential baseline racial differences in cardiovascular function.

Official Title
-----------------
Racial Differences in Serum Sodium and Blood Pressure Regulation

Conditions
-----------------
Sodium Excess, Racial Disparities, Blood Pressure, Cardiovascular Risk Factor

Intervention / Treatment
-----------------
* Other: Acute Salt (sodium chloride)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Are between the ages of 19-75. Have blood pressure no higher than 150/90 mmHg. Have a BMI below 35 Kg/m2 (otherwise healthy) Free from metabolic disease (diabetes or renal disease), pulmonary disorders (e.g., COPD & cystic fibrosis), and cardiovascular disease (peripheral vascular, cardiac, or cerebrovascular). Do not have any precluding medical issues that prevent participants from exercising (i.e., cardiovascular issues, or muscle/joint issues including painful arthritis) or giving blood (e.g., blood thinners). Are not currently smoking, using smokeless tobacco, nor smoked within the past 12 months. Exclusion Criteria: High blood pressure - greater the 150/90 mmHg Low blood pressure - less than 90/50 mmHg History of cardiovascular disease History of cancer History of diabetes History of kidney disease Obesity (BMI > 30 kg/m2) Smoking or tobacco use Current pregnancy Nursing mothers Communication barriers

Ages Eligible for Study
-----------------
Minimum Age: 19 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: The intervention is to provide subjects with either a low sodium meal (140 mg sodium) and a high sodium meal (2500 mg sodium), in a randomized order.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High Sodium Meal (2500 mg sodium)<br>Participants will have sympathetic nerve activity, vascular function, blood pressure and blood samples (from intravenous catheters) assessed before and after a high sodium meal (2500 mg sodium). | Other: Acute Salt (sodium chloride)<br>* Varied amounts of salt (sodium chloride) will be added to a very low sodium soup to determine the effects of a single high sodium meal on measures of vascular function and autonomic regulation of blood pressure<br>|
| Placebo Comparator: Low Sodium Meal (140 mg sodium)<br>Participants will have sympathetic nerve activity, vascular function, blood pressure and blood samples (from intravenous catheters) assessed before and after a low sodium meal (140 mg sodium) which will serve as the control condition to demonstrate whether or not observed changes are due to high sodium or occur irrespective of sodium in the postprandial state. | Other: Acute Salt (sodium chloride)<br>* Varied amounts of salt (sodium chloride) will be added to a very low sodium soup to determine the effects of a single high sodium meal on measures of vascular function and autonomic regulation of blood pressure<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in muscle sympathetic nerve activity (MSNA) and sympathetic transduction | The investigators will directly record MSNA using an active tungsten microelectrode inserted into a nerve near the fibular head or popliteal fossa using standard microneurography techniques. The raw signal will be amplified, band-pass filtered, rectified, and integrated using a nerve traffic analyzer. The presence of MSNA will be confirmed by a pulse-synchronous signal that responds to an end-expiratory breath-hold and stimulation of muscle (tendon tapping), but not skin afferents (gentle skin stroke and/or startle stimulus). MSNA will be expressed as bursts per minute and per 100 cardiac cycles. Further, the investigators will measure common femoral artery blood flow using ultrasound and mean arterial pressure using photoplethysmography. This will allow determination of sympathetic transduction (the vasoconstrictor and pressor effects of MSNA) expressed as changes in blood pressure (mmHg) or changes in vascular conductance (ml blood flow/mmHg). | Before and one hour after soup, both conditions (high- and low-salt) | 
| Changes in flow-mediated dilation (FMD) | Flow-mediated vasodilation will be assessed using continuous measures of brachial artery diameter and velocity via duplex Doppler ultrasound (Hitachi Arietta 70). The brachial artery will be imaged in the longitudinal plane proximal to the medial epicondyle using a high-frequency (6-12 MHz) linear-array probe. The ultrasound probe will be stabilized using a custom-built clamp. Shear rate (sec-1) will be calculated as [(blood flow velocity (cm*s-1) *4)/blood vessel diameter (mm)] The image will be recorded throughout a 60-s baseline, a 300-s ischemic stimulus (250 mmHg), and 180 seconds post deflation. FMD will be expressed as % dilation (final diameter-baseline diameter/baseline diameter x 100) and also normalized to the shear stimulus. Allometric scaling will be used if appropriate, including if there are baseline differences in artery diameter by race or condition. | Before, 30 minutes, and one hour after soup, both conditions (high- and low- salt) | 
| Changes in indices of arterial stiffness | The investigators will use the SphygmoCor XCEL system to assess pulse wave analysis (PWA) and pulse wave velocity (PWV). A high-fidelity strain-gauge transducer is used to obtain the pressure waveform at the carotid and radial pulse. Distances from the carotid artery sampling site to the femoral artery (upper leg instrumented with a thigh cuff for oscillometric sphygmomanometry), and from the carotid artery to the suprasternal notch will be recorded. The investigators will also assess forward and reflective wave magnitudes. PWV will be expressed as cm/s and PWA will be expressed as % (calculated as augmentation pressure divided by the pulse pressure). | Before 30 minutes, and one hour after soup, both conditions (high- and low- salt) | 
| Changes in blood pressure reactivity | The investigators will measure systolic and diastolic pressure using photoplethysmography at the finger. Systolic and diastolic blood pressure will be assessed at rest and during handgrip exercise. Blood pressure reactivity will be expressed as a change in pressure (mmHg) from baseline to a predetermined time during the stressor (e.g., minute one average and minute two average). | Before and one hour after soup, both conditions (high- and low- salt) | 
| Changes in blood biomarkers of nitric oxide bioavailability | The investigators will measure nitric oxide metabolites (nitrate and nitrite nanomolar concentration). | Before, 30 minutes, and one hour after soup, both conditions (high- and low- salt) | 
| Changes in circulating reactive oxygen species | We will use electron paramagnetic resonance to measure reactive oxygen species (spectra units) in whole blood samples treated with a spin probe. | Before, 30 minutes, and one hour after soup, both conditions (high- and low- salt) | 
| Changes in circulating inflammatory cytokines | We will measure inflammatory markers (nano- or picograms per deciliter) via enzym linked immunoabsorbent assays. | Before, 30 minutes, and one hour after soup, both conditions (high- and low- salt) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective sleep duration and quality | Philips actiwatch spectrum will be used to quantify sleep duration. Participants will wear the watch units for 7 days. We will assess qualitative sleep scores and cross-check actigraphy wear times with a sleep diary. | Baseline (pre-intervention) | 
| Subjective Sleep duration and quality | We will use the Pittsburgh Sleep Quality Index to asses sleep duration and perceived sleep quality reflective of the one month period leading into the study. | Baseline (pre-intervention) | 
| Physical activity | Participants will wear an ActiGraph GT3X accelerometer for seven days to objectively quantify steps per day and metabolic equivalents per day. | Baseline (pre-intervention) | 
| Cardio-respiratory fitness | We will use indirect calorimetry to measure the participant's maximal oxygen consumption (VO2max) during incremental exercise on a treadmill. We will use a Parvo TrueOne metabolic cart and Woodway treadmill. | Baseline (pre-intervention) | 
| Mental health - social anxiety | We will administer the Liebowitz Social Anxiety Scale. The scale starts at 0 (none) and ends at 3 (severe) for 24 questions related to anxiety and avoidance, and a cumulative score is calculated. | Baseline (pre-intervention) | 
| Mental health - depression | We will administer the Beck's Depression Inventory. The scale starts at 0 and ends at 3 for 21 questions related to depression. | Baseline (pre-intervention) | 
| Habitual dietary intake | We will instruct participants to complete a diet log for 6 days which will be operationalized with Nutrition Data System for Research (NDSR). | Baseline (pre-intervention) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
blood pressure, racial disparities, cardiovascular health, physical fitness, sleep, dietary sodium, dietary salt, diet