Obesity, Cardiovascular Risk Factor, Salt; Excess
Conditions
Keywords
salt sensitive, blood pressure, obesity, magnetic resonance imaging
Brief summary
This study aims to assess the salt sensitive blood pressure response to dietary salt load compared with radiological markers of salt handling.
Detailed description
Hypertension is a major cause of heart disease, heart failure, and stroke. Hypertension, or high blood pressure, affects people differently and is related to the body's ability to maintain healthy circulation of salt. Some individuals may be affected by salt sensitive blood pressure (SSBP), when their blood pressure changes in response to dietary salt load. SSBP is a prevalent, independent risk factor for developing cardiovascular disease that preferentially affects black individuals. Current methods to assess SSBP require dietary salt loading over the course of days to weeks, and measurement of blood pressure following high salt diet and low salt diet. Such lengthy protocols are not feasible in a clinical setting to evaluate this risk factor for cardiovascular disease, and more importantly, these procedures provide incomplete information about mechanisms of salt sensitivity. Our knowledge regarding salt handling in the body is limited. While renal dysfunction is partly responsible for SSBP, recent research points to the role of lymphatic vascular clearance in regulating tissue salt storage and blood pressure control. To better understand these mechanisms in vivo, we have recently developed a noninvasive magnetic resonance (MR) lymphangiography method sensitive to lymphatic vasculature, and applied standardized MR protocols for measuring tissue sodium and fat storage in adults with impaired lymphatic clearance. We found evidence of lymph stasis and tissue salt deposition that correlated with local subcutaneous fat volume. Here, we will test whether similar lymphatic pathways are impaired in persons with SSBP, leading to tissue salt and fat storage, in comparison to the involvement of renal dysfunction in SSBP tissue profiles. The aims of this study are to improve our understanding of vascular mechanisms of human salt storage, and to provide standardized radiologic biomarkers sensitive to the SSBP phenotype. This study will test the primary hypothesis that the SSBP response is correlated with baseline tissue sodium storage, and elevated in persons with salt sensitivity. Secondary hypotheses will address whether the SSBP response is related to fat storage, lymphatic vascular function, renal vascular function, and impaired target organ responses to salt loading, including decreased urinary sodium excretion, and less suppression of plasma renin and serum aldosterone.
Interventions
DIETARY_SUPPLEMENTLow-salt diet
The low-salt diet (7 days) will consist of meals, snacks and water provided by Vanderbilt's metabolic kitchen.
DIETARY_SUPPLEMENTHigh-salt diet
The high-salt diet (7 days) consists of each subject's typical diet, supplemented each day with 2 bullion broth packets, which will be provided to the subject by the study staff.
Sponsors
Vanderbilt University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Identification as black race * Age between 18 and 55 years * Body mass index between 25 and \<35 kg/m2 * Normotensive or pre-hypertensive * Willing to adhere to study diets * Able to provide informed consent and communicate with study personnel
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, or use of hormone replacement therapy or oral contraceptive * Current steroid use * Contraindications to MRI * Active infection or open wounds on the top of the feet or hands
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Arterial Blood Pressure Following High-salt Diet and Low-salt Diet | Following completion of all dietary supplements and washout, in no less than 21 days. | Mean arterial pressure following high-salt diet and low-salt diet |
Countries
United States
Participant flow
Recruitment details
Black men and women 18-55 years old with BMI 25 to \<35 kg/m2 with BP\< 140/90 mmHg at screening were recruited as long as they had not used medications for cardiovascular disease, a history of hypertension or diabetes, use of blood pressure or anti-diabetic medications, prevalent renal disease, abnormal serum sodium or potassium. As well as not being a current or prior smoker, pregnant, using hormone replacement therapy, oral contraceptives, or steroids, or had contraindications to MRI.
Pre-assignment details
Participants went through a screening process with a physician to determine health and study qualifications. Once screening was complete, participants were assigned to either low-salt or high-salt diet study arm.
Participants by arm
| Arm | Count |
|---|---|
| Low- Then High-salt Diet 10 subjects will be enrolled and each will undergo study procedures at 4 separate visits. Subjects will be randomly assigned to this study arm, differing in the order of low and high salt diets. After a baseline visit to include a noninvasive MRI scan, the subject will begin this study diet: low-salt diet, then washout consisting of the subject's typical diet, then high-salt diet. Each dietary or washout period lasts for 7 days, and study visits will occur after each period.
Low-salt diet: The low-salt diet (7 days) will consist of meals, snacks and water provided by Vanderbilt's metabolic kitchen.
High-salt diet: The high-salt diet (7 days) consists of each subject's typical diet, supplemented each day with 2 bullion broth packets, which will be provided to the subject by the study staff. | 9 |
| High- Then Low-salt Diet 10 subjects will be enrolled and each will undergo study procedures at 4 separate visits. Subjects will be randomly assigned to this study arm, differing in the order of low and high salt diets. After a baseline visit to include a noninvasive MRI scan, the subject will begin this study diet: high-salt diet, then washout consisting of the subject's typical diet, then low-salt diet. Each dietary or washout period lasts for 7 days, and study visits will occur after each period.
Low-salt diet: The low-salt diet (7 days) will consist of meals, snacks and water provided by Vanderbilt's metabolic kitchen.
High-salt diet: The high-salt diet (7 days) consists of each subject's typical diet, supplemented each day with 2 bullion broth packets, which will be provided to the subject by the study staff. | 10 |
| Total | 19 |
Baseline characteristics
| Characteristic | Low- Then High-salt Diet | High- Then Low-salt Diet | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 10 Participants | 19 Participants |
| Age, Continuous | 25.4 years | 28.1 years | 26.8 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants | 10 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants | 10 Participants | 19 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 9 Participants | 10 Participants | 19 Participants |
| Sex: Female, Male Female | 4 Participants | 5 Participants | 9 Participants |
| Sex: Female, Male Male | 5 Participants | 5 Participants | 10 Participants |
| Tissue Sodium Content of the Leg | 14.84 mmol/L STANDARD_DEVIATION 1.5 | 14.33 mmol/L STANDARD_DEVIATION 3.06 | 14.60 mmol/L STANDARD_DEVIATION 2.61 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 19 | 0 / 19 |
| other Total, other adverse events | 1 / 19 | 0 / 19 |
| serious Total, serious adverse events | 0 / 19 | 0 / 19 |
Outcome results
Primary
Mean Arterial Blood Pressure Following High-salt Diet and Low-salt Diet
Mean arterial pressure following high-salt diet and low-salt diet
Time frame: Following completion of all dietary supplements and washout, in no less than 21 days.
Population: All Subjects received both a low salt diet and high salt diet. Data reported reflects measure of mean arterial blood pressure following high-salt diet and low-salt diet.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Salt Diet | Mean Arterial Blood Pressure Following High-salt Diet and Low-salt Diet | 83.3 mmHg | Standard Deviation 21.4 |
| High Salt Diet | Mean Arterial Blood Pressure Following High-salt Diet and Low-salt Diet | 89.5 mmHg | Standard Deviation 9.55 |