Psychological Stress, and Circadian Patterns of Sodium Excretion and Blood Pressure
Phase: NA
Conditions: Blood Pressure, Psychological Stress
Sponsor: Columbia University

Stress, Salt Excretion, and Nighttime Blood Pressure  
NCT03636490 
Last IRB approval date: 01/07/2025 
 
 

 
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Study Title: Stress, Salt Excretion, and Nighttime Blood Pressure (SABRE) 
Principal Investigator: Daichi Shimbo, MD 
IRB Number: AAAS0154 
 
1. Study Purpose and Rationale  
     Blood pressure (BP) has a diurnal rhythm; it is normally highest during the daytime period and lowest 
during the nighttime period (BP dipping). The diurnal pattern of BP over a 24-hour period can be 
assessed using ambulatory BP monitoring (ABPM).  Evidence indicates that an abnormal diurnal pattern 
of BP on ABPM, defined by reduced BP dipping or elevated nighttime BP, is associated with an increased 
risk of cardiovascular disease (CVD) events.  
     Psychological stress occurs when an individual perceives that the environmental demands exceed 
his/her adaptive capacity.  An individual’s response to events that are representative of this overload, 
such as perceived stress and negative affect including anger, hostility, depression, vital exhaustion, and 
symptoms of posttraumatic stress disorder, are associated with reduced BP dipping and/or higher 
nighttime BP.  Exposure to environmental factors which tax an individual’s ability to cope, including 
lower socioeconomic status, job strain, and perceived racism, are also associated with reduced BP 
dipping and/or higher nighttime BP.  This study will examine the disruption of the normal diurnal 
pattern of sodium excretion by psychological stress as a novel biological mechanism underlying an 
abnormal diurnal pattern of BP. 
     During the daytime period, the normal response to sodium intake is increased BP, which leads to 
increased urinary sodium excretion.  Most of the sodium that a person consumes is excreted during the 
daytime period, and a minimum is excreted during the nighttime period. It has been hypothesized that 
when urinary sodium excretion does not occur during the daytime period, urinary sodium excretion is 
shifted toward the nighttime period.  Increased urinary sodium excretion at night is accompanied by an 
increase in nighttime BP which in turn facilitates sodium excretion.  
     Exposure to an acute stressor using a mental stress task normally increases urinary sodium excretion 
in the laboratory setting.  However, there is substantial variability between individuals in the degree of 
stress-induced sodium excretion.  Individuals with lower stress-induced sodium excretion who 
experience psychological stress during the daytime may exhibit a shift of urinary sodium excretion from 
the daytime to nighttime periods due to an inability to excrete additional sodium during the daytime.  
This abnormal diurnal pattern of urinary sodium excretion may, in turn, be associated with a smaller 
decline in BP from the daytime to nighttime periods, leading to reduced BP dipping and elevated 
nighttime BP. The overall goal of the proposed study is to examine the associations between 
psychological stress, the diurnal pattern of sodium excretion, and the diurnal pattern of BP. The aims of 
the study are: 
Primary Aim 1: To examine the association between urinary sodium excretion after provoked 
psychological stress and the diurnal pattern of sodium excretion. 
Primary Aim 2: To examine the association between the diurnal pattern of sodium excretion 
and the diurnal pattern of BP. 
     Two secondary or exploratory aims that will also be investigated: 
Secondary Aim: To examine whether the association between urinary sodium excretion after 
provoked stress and the diurnal pattern of sodium excretion is modified by ecological 
momentary levels of perceived stress, experienced during the daytime period.  

 
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Exploratory Aim: To determine the sociodemographic, behavioral, and psychological traits, 
chronic stress, and biological stress-related factors that are associated with lower stress-induced 
sodium excretion. Identification of these factors will help determine who is at risk for having a 
differential sodium excretion response to psychological stress.  
 
2. Study Design  
     The study will be conducted both in the laboratory and in the naturalistic environment with a multi-
ethnic sample of 211 adult community participants from upper Manhattan who do not have a history of 
CVD, diabetes, chronic kidney disease, difficulty with blood draws, or another major medical condition 
and are not taking antihypertensive medication.  During a Laboratory Visit, urinary sodium excretion in 
response to mental stress tasks will be examined.  Urinary volume, electrolytes, creatinine, and 
endothelin-1 will be measured at baseline, post-stress, and recovery; salivary cortisol will be measured 
at baseline and post-recovery; the urinary albumin-to-creatinine ratio will be measured at baseline; 
plasma angiotensin II and epinephrine/norepinephrine will be measured at baseline and post-stress, and 
a basic metabolic panel, a lipid panel, and a Hemoglobin A1c assessment will be used at the baseline 
only.  Blood pressure and heart rate will be measured continually during the Laboratory Visit (every five 
minutes) and for the following 24 hours (every 30 minutes). 
     In the naturalistic environment, during the 24-hour period following the Laboratory Visit, the diurnal 
pattern of sodium excretion (measured during the daytime and nighttime) will be assessed by measuring 
urine volume and the urine concentrations of electrolytes and creatinine. Heart rate will be monitored 
using ABPM and ecological momentary assessments (EMA) of perceived stress will be surveyed. 
     The study has high clinical significance for improving our understanding of how psychological stress, 
sodium excretion and its diurnal pattern, and the diurnal pattern of BP are linked, and has the potential 
for identifying a treatment target to reduce the CVD risk associated with reduced BP dipping.    
 
3. Study Procedures 
     a. Participant Engagement 
     Interested individuals will review an online information sheet and provide consent to participate in an 
electronic eligibility screen.  This form will provide the contact information of the primary investigator, 
clinical research coordinator, and IRB office to ensure that all questions about the study, form, and 
participant’s rights are answered before consent for screening is provided.  Consent must be provided 
before access to the eligibility screen is allowed. 
     Individuals who pass the initial eligibility screen will be asked to provide contact information so that 
they may be contacted by a research coordinator by phone or email using a participant-specified contact 
method and time. Participants who pass the initial screen will also be asked to provide their gender. This 
is done to ensure that gender distribution in recruitment and enrollment can adhere to the targeted 
proportions. During this contact, the coordinator will ensure that potential participants understand the 
study, are eligible to participate, and can communicate in English satisfactorily.  After all participant 
questions are answered and eligibility has been reconfirmed, an Enrollment Visit will be scheduled.  If 
the Enrollment Visit cannot be scheduled at this time, the research coordinator will contact the 
participant at another specified time to do so. When scheduling the Enrollment Visit, the coordinator 
will ask the participant not to smoke within one hour before the scheduled visit time.  
     For the Enrollment Visit, participants will come to the Shimbo Hypertension Lab (Tower 1) at the 
Columbia University Medical Center between 9 AM and 5 PM.  To start, the research coordinator will 
explain the study procedures to participants in detail.  The coordinator will then present the participant 
with a physical copy of the study consent form, review this form verbally, and answer any questions that 

 
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the participant may have.  A HIPAA Authorization form will also be provided to the participant.  The 
provision of consent on both forms is necessary for further study participation.  If consent is provided, 
demographic information will also be collected at this time. Participants will also be asked to provide a 
home address so coordinators can provide an estimation of transportation costs that can be reimbursed 
in future visits. Then, the clinical research coordinator will measure participant blood pressure three 
times with one-minute intervals between measurements.  Measurements will be made using an Omron 
HEM-907XL device.  These measurements will be used to ensure that participants are not in violation of 
the study’s eligibility criteria concerning hypertension.  The coordinator will also ensure that participants 
have readily available veins for blood draws during the Laboratory Visit.  A copy of blood pressure 
readings will be provided to participants.  Next, the “ISQ: Psychometric Evaluation” will be administered 
as a short survey to ensure that participants do not experience insomnia, another condition precluding 
participation in the study. If the participant does not meet eligibility criteria for either blood pressure or 
insomnia, then the participant is compensated and the visit will end.  
     If the participant remains eligible, then the “Life Events Checklist” and “PTSD Checklist” will be 
provided separate from the other measures to ensure that the completion of these two questionnaires 
does not alter stress felt during the Laboratory Visit. Stress- and demographic-related measures will be 
presented to participants using Qualtrics opened on a provided laptop, and the insomnia survey will be 
administered as a paper form. The participant’s weight, height, hip and waist circumference, gender, 
age, normal activity levels, and dietary limitations will then be recorded on a Bionutrition Center form.  
In addition, a list of foods provided by the Bionutrition Center will be provided and the participant asked 
whether they agree to eat all of the foods on the checklist.  This information will be recorded for 
research use and forwarded to the Bionutrition Center to prepare the meals and snacks that will be 
consumed in the three days prior to the Laboratory Visit. 
     Finally, the research coordinator will provide the participant with a home polysomnography device 
and instruct him or her in its use.  This tool is used to detect sleep apnea, a condition that will preclude 
participation in the study.  An instruction sheet will be provided to participants with the device for their 
reference.  This device will be used by the participant during the night after the Enrollment Visit.  
Collected data will be analyzed when the device is returned to the Shimbo Hypertension Lab (Tower 1) 
within 1 week.   
     The dates of the Pre-Laboratory and Laboratory Visits may be scheduled during the Enrollment Visit 
or via phone or email in the following days.  Within one week of the Enrollment Visit, the home 
polysomnography device must be returned to the clinical research coordinator.  After returning the 
device, participants will also be informed as to whether they are eligible to participate in the remainder 
of SABRE.  If eligible, the Pre-Laboratory and Laboratory Visits will be scheduled at this time.  Regardless 
of whether participants experience sleep apnea, they will be provided with a form that details their 
measured AHI (Apnea-Hypopnea Index) and the AHI cutoffs that represent mild, moderate, and severe 
obstructive sleep apnea.   
     If sleep apnea (mild, moderate or severe) is identified in a study participant, the participant will be 
informed that such a diagnosis warrants further evaluation and possible treatment by a physician.  The 
participant will also be provided with a summary of the assessment results upon request (a sample 
report is included for IRB review).  The participant will have the option to bring the report to a physician 
they already have a treatment relationship with or, if they do not have a primary care physician, then 
research staff will offer to refer the participant to a primary care physician at Columbia University 
Medical Center/Columbia Doctors. 
      If participants do not experience sleep apnea and are fully eligible for the study, he or she will then 
work with the clinical research coordinator to schedule the Pre-Laboratory and Laboratory Visits or 

 
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confirm the dates that were proposed at the Enrollment Visit.  Additionally, the clinical research 
coordinator will make the necessary preparations for these visits, including informing the Bionutrition 
Center about the need for prepared meals, scheduling an examination room in the Irving Institute for 
Clinical and Translational Research (CTSA), and preparing materials for the visit.   
     Within eight weeks of the Enrollment Visit, the Pre-Laboratory Visit will occur.  At this time, the 
participant will be provided with meals and snacks prepared by the Irving Institute Bionutrition Unit.  
These meals will be packed into a portable cooler for participant convenience. In addition, the 
participant will have been provided with the link to the SABRE Online Measures one week prior to the 
Pre-Laboratory Visit. The research coordinator will check in with the participant at this time to verify 
they have completed the questionnaire by this time and respond to any questions that may arise. These 
measures ask about different aspects of life and personality, and they may be completed at any time 
before the Pre-Laboratory Visit.   
     At the end of the Pre-Laboratory Visit, participants will be informed that fees associated with parking 
or transportation to their desired destination with the cooler of food can be reimbursed during the final 
visit, provided they pay in cash and keep the receipt.  
     Starting the morning after the Pre-Laboratory Visit, participants will be asked to eat only this specially 
prepared food for the next 3 days.  No additional foods or drinks may be consumed other than water, 
plain decaf or mint or chamomile tea without sugar, milk or other additives, and up to one cup, or 
approximately 8 fluid ounces, of black coffee/tea per day.  The meals and snacks consumed each day will 
contain the same total amount of salt. The diet that will be provided to participants is not a dietary 
intervention designed to lower the amount of sodium in a person’s diet, but rather to keep the amount 
of dietary sodium fixed during the study visits. As such, the amount of dietary sodium (as well as 
potassium) are considered to be a moderate amount, which is consistent with the average amount a US 
adult is taking. Please see 
https://www.ars.usda.gov/ARSUserFiles/80400530/pdf/1112/Table_1_NIN_GEN_11.pdf. The 
participant will eat this food for the three days following the Pre-Laboratory Visit and leading up to the 
Laboratory Visit.  The research assistant will contact him or her every day to make sure there are no 
issues. The Laboratory Visit will be scheduled 4 days after the Pre-Laboratory Visit.  For example, if the 
Pre-Laboratory Visit takes place on Thursday, the Laboratory Visit will take place on Monday.   
     For the Laboratory Visit, participants will come to the Shimbo Hypertension Lab (Tower 1) at the 
Columbia University Medical Center.  Appointments will be scheduled between 8 AM and 9 AM in the 
morning four days after the Pre-Laboratory Visit.  This visit should be attended in a fasting state (without 
eating or drinking anything more than small sips of water after midnight of the day before. Participants 
will also be asked to not exercise for 12 hours before the visit and to not smoke within the hour prior to 
the visit.  At 30 minutes before the appointment, the participant will be asked to drink 8 ounces of  
Poland Spring water that will be provided prior to the appointment.  
     The research coordinator will escort the participant to the adult outpatient unit of the Irving Institute 
for Clinical and Translational Research (CTSA) on PH-10 where the Laboratory Visit will be conducted.  
The participant will be seated in a comfortable chair in an examination room with a private bathroom 
for the entire laboratory session.  First, he/she will be asked to use the bathroom to void their bladder, if 
possible.  The participant will then return to the exam room chair and drink about one cup of bottled 
spring water.  At this time, the research coordinator will attach a SpaceLabs OnTrak Ambulatory Blood 
Pressure Monitor (ABPM) blood pressure cuff to his/her upper arm.  This device will automatically 
inflate and measure blood pressure every five minutes for the duration of the Laboratory Visit, excluding 
time spent in the bathroom and times when blood is drawn.  The participant will then rest by watching a 
movie for 30 minutes.  This movie will show ocean scenery and aquatic wildlife to relax patients before 

 
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blood, saliva, and urine are collected at the baseline time point.  No narration, camera motion, or 
potentially stressful events are used or shown in the video.  After this rest period, the participant will be 
asked about the level of stress he/she is feeling using a Visual Analog Scale (VAS).  A sample of saliva will 
be collected by the research coordinator.  The participant will again use the bathroom where he/she will 
be asked to urinate into a collection container.  He/she will return to the exam room chair and a blood 
sample of about 31.5 milliliters, or 7 teaspoons, will be drawn.  If the phlebotomist is not available to 
draw the participant’s blood within the exam room, participants will be escorted to the phlebotomist 
within the CTSA for this service. 
     Next, the participant will drink about one cup of bottled spring water.  During the next 10 minutes, a 
research assistant (separate from the research coordinator) known as the stress inducer will read a 
mental stress script and conduct two stress tests.  First, the participant will be shown a series of words 
for five minutes and a research coordinator will ask him/her to name the color of each (Stroop Color-
Word Conflict Task).  Then, for another five minutes, the participant will be asked to complete a mental 
arithmetic task, comprising of a series of subtractions and additions (Mental Arithmetic Task).  The 
stress inducer will adjust the difficulty of the task appropriate for each participant.  The stress inducer 
will ask the participant to work as quickly and accurately as possible for both tasks.  
     Immediately after the math task, the participant will be asked about the level of stress he/she is 
feeling using a VAS measurement.  Then, the participant will use the bathroom, where he/she will be 
asked to urinate into a collection container.  He/she will return to the exam room chair and another 
blood sample of about 24.5 milliliters, or 5.5 teaspoons, will be drawn.  If the phlebotomist is not 
available to draw the participant’s blood within the exam room, participants will be escorted to the 
phlebotomist within the CTSA for this service. 
     Next, the participant will drink about one cup of bottled spring water and remain inactive during for a 
post-stress recovery period.  During this time, participants will rest naturally, allowing for elevated heart 
rate, increased blood pressure, and other stress symptoms to recover.  Twenty minutes following the 
end of the stress induction, a saliva sample will be collected.  After 30 minutes of recovery, the 
participant will be asked about the level of stress he/she is feeling for a final time, using a VAS 
measurement. Then, he/she will use the bathroom and asked to urinate into a collection container one 
final time. 
     Before leaving the Laboratory Visit, the participant’s non-dominant arm will be fitted with a new 
standard ambulatory blood pressure monitor (ABPM).  A research coordinator will explain how to use 
the device, provide one detailed instruction sheet and one concise instruction sheet, and provide a 
paper form where the times at which participants fall asleep, wake up, take naps, and remove the 
device may be listed.  Participants will also receive a cooler containing two urine collection bottles, 
which are to be used following the Laboratory Visit.  The participant will also receive instructions on the 
two bottles for collecting daytime and nighttime urine, respectively, over the next 24 hours.  One, 
labelled Day, should be used during the day following the Laboratory Visit.  The other, labelled Night, 
should be used if the participant wakes up to urinate during the night and for the first instance of 
urination after waking up the next day. The participant will be instructed to continue their normal daily 
and nightly routines, but they must limit their alcohol intake to one drink during the 24 hour period. The 
Laboratory Visit may take up to 3 hours. 
     The clinical research coordinator will ensure that, at 5 random times throughout the day and evening, 
the participant will be prompted by text message to respond electronically to 5 short questions through 
Qualtrics.  The questions will ask about how participants feel in that moment. 

 
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     After 24 hours, participants will return the ABPM device, the cooler containing both urine collection 
bottles, and the cooler containing any remaining food from the diet to Shimbo Hypertension Lab (BB-
210 or Tower 1).  They will complete a final 5-question survey through Qualtrics, identical to the ones 
they received via text that will ask them about the emotions they were feeling that morning prior to the 
visit. Participants will be provided the option of having Lyft concierge rides coordinated for them while 
traveling with the cooler, our research team will coordinate this service. Alternatively, transportation 
may be provided at the discretion of the Principal Investigator on a case-by-case basis. Patient 
satisfaction surveys will be provided at this time if participants are interested in completing one.   
     b. Blood, Urine, and Saliva Analysis 
     During each Laboratory Visit, three samples of urine and two samples of saliva will be collected.  In 
addition, blood will be drawn twice.  On the following day, two additional samples of urine, one for the 
previous day and one for the previous night, will be returned to the Shimbo Hypertension Lab (Tower 1) 
by the participant. 
     Saliva will be collected using a salivettes tube and salivary cortisol will be measured at the baseline 
and recovery time points.  The first blood draw of 31.5 milliliters will be used to test for a basic 
metabolic panel (which includes glucose and creatinine), a lipid panel (including cholesterol, low density 
and high density lipoproteins, and triglycerides), Hemoglobin A1c, Angiotensin II, and Catecholamines. 
The second blood draw of 24.5 milliliters will be tested for Angiotensin II and Catecholamines.  An 
approximate total of 56 mL of blood will be collected.  The urine collected during the laboratory study 
will be tested for sodium, potassium, chloride, creatinine, Endothelin-1, and volume.  The Albumin to 
Creatinine ratio in urine will also be measured at the baseline time point.  Urine collected during the 
ambulatory session will also be tested for sodium, potassium, chloride, creatinine, and volume.  
 
   c. Providing Results to the Participant 
After completing the study, the participant will be given the following results: total cholesterol, low-
density lipoprotein, high-density lipoprotein, triglycerides, hemoglobin A1c, glucose, and creatinine. 
Please see attached SABRE Blood Draw Results_REPORTING TEMPLATE. The participant will also be 
provided the results from the ABPM. Please see ABPM REPORT_EXAMPLE and ABPM REPORTING 
TEMPLATE. The participant will be given the option to not receive these results (i.e. opt-out). The 
participant will be invited to share the results with their health care provider. If they do not have a 
health care provider, the research staff will offer to refer the participant to a primary care physician at 
Columbia University Medical Center/Columbia Doctors. 
 
4. Statistical Procedures 
Data Preparation: All variables will be reviewed for outliers and internally inconsistent values. Once a 
valid, final data set is compiled, variable distributions will be evaluated for non-normality and data 
transformations will be applied as needed. Winsorization may be employed to reduce the effect of 
extreme, but valid, observations on data analyses. Although transformed data will be used for primary 
inferential analyses, the description of data will feature the original (untransformed) metric for ease of 
interpretation.    
Missing Data: Given the reasons for missing data (i.e., laboratory error or equipment failure), missing 
data for our primary variables will likely conform to a “missing completely at random” (MCAR) pattern. 
However, we will use the less restrictive “missing at random” (MAR)-analytic techniques (e.g. mixed 
effects regression, multiple imputation) for the analyses. For those who are missing a small number of 
items used to construct a psychosocial scale, we will use the EM algorithm in SAS’ PROC MI procedure to 
estimate the expected scale score for these participants conditional on their responses to all the other 

 
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items; this is the best estimate, assuming MAR, of their scores. Although we anticipate few missing data 
for the primary variables (i.e. stress-induced sodium excretion, diurnal patterns of sodium excretion and 
BP) as 100% of the participants in the SABRE pilot study had complete data, we have conservatively 
allowed for approximately 5% (N=11) of the 211 enrolled participants to have some missing data. A 
minimum sample size of 200 participants without missing data will provide adequate power for testing 
our primary hypotheses. 
Fidelity Checks: VAS stress ratings will be collected before and after laboratory stress induction.  VAS 
stress ratings will be monitored during the conduct of the study to ensure that the manipulation (i.e. 
mental stress tasks) is having its intended effects. If the stress tasks are not having their intended 
effects, Dr. Shimbo will work with the research staff to bolster the dose of the experimental 
manipulation that is administered. The focus of these fidelity checks will be on the magnitude of the 
pre-/post-stressor change in VAS ratings rather than on the statistical significance of the effects (which 
may be limited by sample size). The research coordinator will be blinded to the VAS stress ratings. 
Analytical Approach for Each Aim: 
Primary Aim 1:  Standard regression analysis will be used. We will estimate the unadjusted relation of 
awake-to-sleep ratio of urinary sodium excretion rate to change in urinary sodium excretion rate with 
stress. Next, we have a priori selected the following covariates for adjustment in a multiple regression 
model: age, sex, race/ethnicity (non-Hispanic whites, non-Hispanic blacks, Hispanics, and other), and 
body mass index. Age, sex, and race/ethnicity are standard covariates in studies of hypertension given 
their well-known associations with BP. Body mass index is included as a covariate since it is associated 
with both lower stress-induced sodium excretion and lower day-to-night ratio of urinary sodium 
excretion rate. The statistical significance of the coefficient for the change in urinary sodium excretion 
rate with stress in this adjusted model will constitute the primary test of the hypothesis. Sensitivity 
analyses will be performed to assess whether the strength of the association changes when additional 
covariates are included. Higher clinic SBP/DBP and parental history of hypertension are associated with 
lower stress-induced sodium excretion. Fasting blood glucose and 24-hour creatinine clearance are 
associated with lower daytime-to-nighttime ratio of urinary sodium excretion rate. Each of these will be 
evaluated as candidate covariates by selecting those that are associated with the outcome (awake-to-
sleep ratio of urinary sodium excretion rate) at p<0.10. Finally, secondary analyses will use generalized 
additive models (GAM) to explore potential non-linearity of the relationship, using PROC GAM in SAS. 
Primary Aim 2: The same approach for Hypothesis 1 will be used for the analysis of this hypothesis. SBP 
dipping and DBP dipping will be the primary and secondary outcomes, respectively. The a priori 
covariates that will be included in adjusted models are: age, sex, race/ethnicity, body mass index, 24-
hour sodium excretion, 24-hour potassium excretion, 24-hour creatinine clearance, FENa, current 
smoking, alcohol consumption, and fasting blood glucose. In addition to age, sex, and race/ethnicity 
(which were chosen because they are standard covariates in hypertension studies), the other measures 
were chosen as covariates as they may confound the association between the diurnal pattern of sodium 
excretion and the diurnal pattern of BP. Sensitivity analyses will be performed after additional covariates 
are included in the adjusted model. Prior studies have suggested that physical activity and fasting 
glucose are associated with the diurnal pattern of BP. Each of these measures will be evaluated as 
candidate covariates using the same approach described above for Primary Aim 1.  
 
Sample Size and Minimum Detectable Effect Sizes for Primary Aims: The sample size for this study was 
selected to ensure 80% power to detect a bivariate/partial correlation between the primary predictor 
and outcome of r=0.20 or greater; this is conservative, but consistent with our preliminary data in which 
the correlation between the change in urinary sodium excretion rate with stress and awake-to-sleep 

 
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ratio of urinary sodium excretion rate (Primary Aim 1) was 0.25, and the correlation of awake-to-sleep 
ratio of urinary sodium excretion rate and SBP dipping (Primary Aim 2) was 0.30. The minimum sample 
size required to detect this effect size with power 80% is 194 with valid data for the three primary 
measures (change in urinary sodium excretion rate with stress, awake-to-sleep ratio of urinary sodium 
excretion, and SBP dipping). We are targeting a final minimum sample size with complete data of 200.   
Secondary Aim: The ecological stress level for the awake period during which participants’ sodium 
excretion is monitored will be defined as the mean perceived stress level across the Ecologic Momentary 
Assessment (EMA) reports. Ecological stress is conceptualized as a moderating variable. Controlling for 
the effects of this measure and stress-induced sodium excretion, we will test their multiplicative 
interaction term; an extension of the regression model used to test Primary Aim 1. A positive interaction 
effect would provide the first empirical evidence supporting the conclusion that the hypothesized 
tendency for those with lower stress-induced sodium excretion rate to have a lower daytime-to-
nighttime ratio of urinary sodium excretion rate is stronger among those who experience higher stress 
during the day of monitoring. Although a moderator is not required to be associated with the outcome, 
we will examine the association between mean perceived stress and daytime-to-nighttime ratio of 
urinary sodium excretion rate. In the SABRE pilot study, the correlation coefficient for this association 
was -0.42.  
Exploratory Aim: Univariable and multivariable linear regression analyses will be performed to assess 
which factors are independently associated with lower stress-induced sodium excretion. All models will 
adjust for age, sex, and race/ethnicity. Variables entered into subsequent multivariable regression 
models will include other social determinants (place of birth, years living in the US, primary language 
spoke in the home, education attainment, employment status, health insurance status, marital status, 
household income, household size, social cohesion and safety, social support), behavioral factors (body 
mass index, current smoking, alcohol consumption, physical activity, recreational drug use), 
psychological traits and other psychosocial constructs, chronic stress factors (related to work, marriage, 
finances, caregiving, discrimination; perceived stress; and childhood adversity), and biological stress 
measures (baseline angiotensin II, epinephrine and norepinephrine, BP, heart rate, endothelin-1, and 
cortisol; and change in these measures with stress). Given the large number of predictors being 
examined, we will apply a false discovery rate of 0.05 (rather than ignore the inflated risk of Type I 
errors or use the excessively conservative Bonferroni correction), and interpret the results as 
“hypothesis generating” rather than “confirmatory”. 
Additional Exploratory Analyses: Social determinants including place of birth, years living in the US, etc. 
will be evaluated as candidate covariates by selecting those that are associated with the outcomes in 
Primary Aims 1 and 2 at p<0.10. The analyses for Primary Aim 2 will be repeated using mean sleep SBP 
and mean sleep DBP instead of SBP dipping and DBP dipping, respectively. Some investigators consider 
mean sleep BP to also be a measure of the diurnal pattern of BP. The analyses for the Secondary Aim will 
be repeated using the average of the EMA reports for each negative affect (angry/hostile, 
aggravated/irritated, sad/blue/depressed, and anxious/tense/nervous) instead of perceived stress to 
determine whether negative affect moderates the association between lower stress-induced sodium 
excretion and an abnormal diurnal pattern of sodium excretion. This analysis will be repeated using a 
composite negative affect score derived by averaging the EMA reports of all 4 negative affect ratings. 
We will evaluate multiplicative interaction terms of sex and separately race/ethnicity with stress-
induced sodium excretion to test for group differences in its association with the diurnal pattern of 
sodium excretion and with the diurnal pattern of sodium excretion to test for group differences in its 
association with diurnal pattern of BP. 
 

 
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5. Risks  
There may be risks or discomforts associated with taking part in this study. 
There may be minimal discomfort during and after the Laboratory Visit due to the blood pressure arm 
cuffs that are used in clinical blood pressure measurements and ambulatory blood pressure monitoring.  
The discomfort is temporary and minor. The ambulatory monitor takes measurements every 30 
minutes.  This may also cause disturbances to sleep. 
Risk of Blood Draw 
The risks of having blood drawn are soreness and/or a black and blue mark at the site where the blood is 
drawn.  Sometimes, participants feel uncomfortable at the time of the blood draw. Occasionally, 
participants feel lightheaded or faint.  There is also a small risk of infection whenever blood is drawn.   
Risk from Sensitive Questions  
This research study involves psychological testing.  The questions being asked may be sensitive and 
personal in nature.  It is possible that answering some questions may cause stress.  Participants will be 
instructed to immediately inform the study coordinators if they become upset or anxious.  The study 
staff will then stop performing psychological testing.   
Risk of Breach of Confidentiality  
A risk of taking part in this study is the possibility of a loss of confidentiality.  Loss of confidentiality 
includes having personal information shared with someone who is not supposed to see or know about 
your information.  The study team plans to protect participant confidentiality. 
 
6. Benefits  
Participants will not receive personal (direct) benefit from taking part in this research study.  However, 
the information collected from this research may help others in the future.   
 
7. Alternatives  
Participants may choose not to take part in this research study. 
 
8. Data and Safety Monitoring  
The research team will monitor the study to prevent any risks or dangers that may occur and will 
appropriately report any adverse events according to IRB policy.  
     If a participant feels upset or experiences emotional distress, a member of the research team will be 
available to talk to them and discuss appropriate care.  He/she will be offered a period of rest from 
study activities, and he/she will also be reminded that participation may be discontinued willingly at any 
time. Further, should any psychological issues arise, clinical psychologists on staff at the Shimbo 
Hypertension Lab (BB-210 and Tower 1) will also be available to evaluate the participant. If the 
participant needs further attention, he/she will be escorted to the emergency room for further 
evaluation. If there is no immediate risk, the participant will remain until the end of the study visit and 
be discharged. Participants will then be referred to their primary care doctor and as appropriate, the 
Columbia University Psychiatry Referral Line for further management. 
     Participants will be provided with copies of their own blood pressure and apnea-hypopnea index 
(AHI) measurements after this data is collected at the Enrollment Visit or during the following night.   
     The average blood pressure reading will be accompanied by a group of recommendations from the 
American Heart Association regarding actions that should be taken for abnormal values.  If the average 
BP (systole ranges/diastole ranges) is high normal, or 120-139/80-90 mmHg, it will be recommended 
that participants ask a physician about lifestyle changes and be rechecked within a year.  If the average 

 
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BP is mildly elevated, or 140-159/90-99 mmHg, it will be recommended that participants meet with their 
doctors to confirm this reading and receive instruction within a month.  If the average BP is high, or 160-
179/100-109 mmHg, it will be recommended that participants meet with their doctors for a follow-up 
within a week.  If the average BP is very high, or 180-209/110-119 mmHg, it will be recommended that 
participants meet with their doctors for a follow-up within a week.  If the average BP is equal to or 
greater than 210/120, participants will be escorted to the emergency room for immediate care. 
     The measured AHI value will be accompanied by a list of AHI ranges that correspond to mild, 
moderate, or severe sleep apnea.  If the participant’s measured AHI falls outside of the normal range, 
the participant will be informed that such a diagnosis warrants further evaluation and possible 
treatment by a physician, and the form itself will reiterate that they inform their regular physician of 
these results and ask for further guidance.  If the participant does not have a primary care physician, 
then research staff will offer to refer the participant to a primary care physician at Columbia University 
Medical Center/Columbia Doctors for follow-up.