Salt-sensitivity of Blood Pressure
Conditions
Brief summary
The goal of this interventional study is to learn if elevated Na+ alters the gut microbiota and is associated with altered metabolism, inflammation and salt sensitivity of blood pressure (SSBP). The main questions it aims to answer are: * SSBP correlates with Na+-induced changes in gut microbiome composition * Na+-induced changes in the gut microbiome and SSBP are associated with altered metabolism and with immune cell activation * Microbiota from humans with SSBP induce inflammation and hypertension in germ-free mice. Researchers will quantify SSBP from 24-hour ambulatory BP monitoring in a randomized crossover design, using standardized one week low- and high-salt diets. Participants will: * Take high- and low-salt diet each for one-week * Complete three study visits, with each visit being 1 week apart * Complete a 72-hour dietary log
Detailed description
Salt-sensitivity of blood pressure (SSBP), quantified as the change in 24-hour ambulatory mean arterial pressure (MAP) from one week of high-salt to one week of low-salt diet, is an independent predictor of death due to cardiovascular events. SSBP affects nearly 50% of the hypertensive and 25% of the normotensive population. Strong evidence indicates that reducing sodium (Na+) intake decreases blood pressure and cardiovascular events, however the precise mechanisms of how dietary Na+ contributes to BP elevation and cardiovascular disease remain unclear. The gut is the first and largest location for Na+ absorption. Studies from the investigator's group and others suggest that gut microbiota contribute to salt-induced inflammation and hypertension. In preliminary cross-sectional analyses, the investigators found that elevated dietary Na+ alters the human and mouse gut microbiome, prompting an increase in Firmicutes and genus Prevotella bacteria. These alterations are associated with higher BP and altered metabolites in humans, and predispose mice to vascular inflammation and hypertension. However, there are limited data on the effect of Na+ intervention on gut microbiome composition and function, or on the contribution of microbiota to SSBP. Thus, the investigators propose deep phenotyping of adult subjects (N=50) enrolled into a SSBP challenge study, coupled with extensive mechanistic interrogation. Briefly, the investigators will quantify SSBP from 24-hour ambulatory BP monitoring in a randomized crossover design, using standardized one week low- and high-salt diets. The investigators will collect repeated stool, urine and blood samples to determine the relationships between gut microbiota, SSBP, microbial and host metabolism, and inflammation in humans, and will conduct mechanistic research using human cells and mice. The investigator's central hypothesis is that elevated Na+ alters the gut microbiota and is associated with altered metabolism, inflammation and SSBP. The specific aims are to test the hypotheses that 1) SSBP correlates with Na+-induced changes in gut microbiome composition; 2) Na+-induced changes in the gut microbiome and SSBP are associated with altered metabolism and with immune cell activation; and 3) Microbiota from humans with SSBP induce inflammation and hypertension in germ-free mice. The proposed study examines novel hypotheses regarding the relationship between the gut microbiome and SSBP and will allow for comprehensive interrogation of multiple mechanistic pathways. Successful completion of the aims will delineate the role of gut microbiota in SSBP, identify microbiota, metabolite and immune cell markers of SSBP, and could lead to more feasible and cost-effective microbiome-based therapy for SSBP.
Interventions
OTHERDietary sodium
To quantify salt sensitivity of blood pressure, each participant will consume a high-salt diet and a low-salt diet, with each diet lasting one week.
Sponsors
Vanderbilt University Medical Center
National Heart, Lung, and Blood Institute (NHLBI)
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
SINGLE (Outcomes Assessor)
Masking description
The study diets and diet orders are known to the participants and investigators. The outcomes assessors (blood pressure, gut microbiome, and inflammatory markers) will be masked to the study diets.
Eligibility
Sex/Gender
ALL
Age
50 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
1. Age ≥ 50 years and ≤ 70 years. 2. Omnivore. 3. Willing to adhere to the study protocol. 4. Able to provide written consent.
Exclusion criteria
1. Unwilling to make dietary changes or otherwise adhere to the study protocol. 2. Contraindications to high- or low-salt diet (e.g. heart, renal, or liver failure, postural orthostatic tachycardia syndrome) 3. Use of salt tabs, fludricortisone, or midodrine. 4. Contraindications to 24-hour ambulatory blood pressure monitoring, e.g. bilateral upper extremity lymphedema. 5. Medical contraindications to foods, e.g. celiac disease, nut allergy, egg allergy, etc. 6. Systolic blood pressure \< 90 or \> 160 mm Hg or diastolic blood pressure \< 50 or \> 100 mm Hg at screening 7. Current use of anti-hypertensive medications 8. Current use of oral steroids, daily NSAIDS, anti-inflammatory or immune modulating medications, probiotics, or antibiotics. 9. Rheumatologic condition (e.g. Lupus, Rheumatoid Arthritis, Psoriatic arthritis, Inflammatory Bowel Disease, Multiple Sclerosis). 10. Presence of acute or chronic medical conditions not generalizable to the general population (including eating disorders, cancer, severe mental illness, cognitive impairment, pregnancy or lactation).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Salt sensitivity of blood pressure | 2 weeks | Mean arterial pressure from 24 hour ambulatory pressure monitoring, calculated as MAP (high-salt) - MAP (low-salt) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Prevotella | 2 weeks | The difference in abundance of Prevotella bacteria in stool samples between the high and low salt diet weeks |
| Firmicutes | 2 weeks | The difference in abundance of Firmicutes bacteria in stool samples between the high and low salt diet weeks |
| Tumor necrosis factor alpha (TNF alpha) | 2 weeks | The difference in supernatant levels of TNFalpha from cultured peripheral bone marrow cells between the high and low-salt diet weeks |
Countries
United States
Outcome results
None listed