Natriuretic Peptides, Nocturnal Blood Pressure, Obesity
Conditions
Keywords
Diurnal Rhythm, Race
Brief summary
The purpose of the study to assess the diurnal rhythm in natriuretic peptide levels and its temporal relationship with nocturnal blood pressure in obese and African-American individuals as compared with lean and white individuals.
Detailed description
Obese and African-American individuals are at greater risk for cardiovascular morbidity and mortality than lean and white individuals. One of the key reasons for this health disparity is a higher risk of hypertension among obese and African-American individuals. The reasons for why these disparities develop are not well understood. Natriuretic peptides are hormones produced by the heart and have a wide range of favorable cardiovascular effects such as natriuresis (sodium excretion), vasodilation, and direct inhibition of the renin-angiotensin-aldosterone system. Human studies showed the existence of 24-hour (diurnal) variations in the circulating natriuretic peptide levels. Prior work from the investigators and others demonstrated that individuals with genetically-determined lower circulating natriuretic peptides levels have higher blood pressure and greater risk of hypertension. Further, the investigators have shown that obesity and African-American race are associated with lower natriuretic peptide levels, suggesting that relatively low natriuretic peptide levels may be a biologic determinant contributing to health disparities. Obese and African-American individuals have a greater prevalence of nocturnal hypertension \[nighttime blood pressure \>120/80 mmHg\], which is an independent risk factor for cardiovascular events. The underlying reasons for 24-hour variations in blood pressure are unknown. The investigators hypothesize that loss of the natural 24-hour rhythm of natriuretic peptide levels plays a role in the development of nocturnal hypertension in obese and African-American individuals. The aims of this study are: 1. to examine whether there is a presence of a 24-hour rhythm in natriuretic peptide levels among normotensive obese and African-American individuals and whether there is a difference in the rhythmicity of natriuretic peptide levels between obese and lean as well as in African-Americans and whites; 2. to examine whether there is an existence of a relationship between 24-hour variability of natriuretic peptide levels and 24-hour patterns of blood pressure and whether this relationship of rhythmicity of natriuretic peptide levels and nocturnal blood pressure differed in obese and lean individuals and by race.
Interventions
OTHERstandardized Study Diet
Standardized diet consisted with eucaloric meals with 4.5 gm of sodium per day for 5 days.
Sponsors
University of Alabama at Birmingham
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* Age 18 to 40 years * Blood pressure less than 140/90 * Body Mass Index between 18.5 to 25 kg/m2 (lean) or 30 to 45 kg/m2 (obese) * Self identified African-American or white individuals * Willingness to comply with the study diet * Provide informed consent
Exclusion criteria
* History of hypertension * History of cardiovascular, renal, or liver disease * Diabetes or use of glucose-lowering medications * Use of vasoactive or diuretic medications * Atrial fibrillation * Anemia (Hematocrit \<41%) * Abnormal serum sodium or potassium * Abnormal liver function tests (\>3x upper limit of normal) * Current smokers * Regular users of non-steroid anti-inflammatory medications
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma MRproANP | About 24 hours on the in-patient study visit day after consuming study meals for 5 days | Assess the diurnal rhythm in circulating MRproANP levels among obese individuals and compared it with lean individuals |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Acrophase Difference in Hours Between the MR-proANP and Systolic BP Rhythm | About 24 hours on the in-patient study visit day after consuming study meals for 5 days | Assess relationship between 24-hour variability of MRproANP levels and 24-hour patterns of blood pressure and whether this relationship of rhythmicity of MRproANP levels and nocturnal blood pressure differed in obese and lean individuals and by race |
Other
| Measure | Time frame | Description |
|---|---|---|
| Plasma MRproANP | About 24 hours on the in-patient study visit day after consuming study meals for 5 days | Assess the diurnal rhythm in circulating MRproANP levels among African-American individuals and compared it with white individuals |
Countries
United States
Participant flow
Pre-assignment details
A total of 42 participants agreed to participate in the study following the completion of the informed consent process and were assigned to each Arm/group. We had one study dropout and one participant was not able to complete the protocol. A total of 40 participants completed the study.
Participants by arm
| Arm | Count |
|---|---|
| Lean Healthy self-identified African-American and white lean participants will be screened. Study consent will be obtained, medical history and physical examination administered, and study eligibility determined based on the inclusion and exclusion criteria. Eligible subjects will meet a bio-nutritionist who will explain the 5 days of standardized diet at the screening visit and will review instructions for complying with the diet. If the subject agrees to adhere to the study diet, they will then be enrolled in the study (stratified by race).
standardized Study Diet: Standardized diet consisted with eucaloric meals with 4.5 gm of sodium per day for 5 days. | 18 |
| Obese Healthy self-identified African-American and white obese participants will be screened. Study consent will be obtained, medical history and physical examination administered, and study eligibility determined based on the inclusion and exclusion criteria. Eligible subjects will meet a bio-nutritionist who will explain the 5 days of standardized diet at the screening visit and will review instructions for complying with the diet. If the subject agrees to adhere to the study diet, they will then be enrolled in the study (stratified by race).
standardized Study Diet: Standardized diet consisted with eucaloric meals with 4.5 gm of sodium per day for 5 days. | 22 |
| Total | 40 |
Baseline characteristics
| Characteristic | Obese | Lean | Total |
|---|---|---|---|
| Age, Continuous | 33.0 years | 30.5 years | 31.0 years |
| Body Mass Index | 32.2 kg/m^2 | 24.3 kg/m^2 | 29.6 kg/m^2 |
| Diastolic Blood Pressure | 73.7 mmHg | 69.5 mmHg | 71.0 mmHg |
| Fasting Glucose | 91.5 mg/dL | 85.0 mg/dL | 87.5 mg/dL |
| Heart rate | 77.0 beats/min | 76.5 beats/min | 77.0 beats/min |
| Hematocrit | 41.0 % | 40.5 % | 41.0 % |
| Hematological Parameters Platelet, * 100,000/mm3 | 248.7 cells*10,000/mm^3 | 217.7 cells*10,000/mm^3 | 243.4 cells*10,000/mm^3 |
| Hematological Parameters RBC, * 1,000,000/mm3 | 4.7 cells*10,000/mm^3 | 4.7 cells*10,000/mm^3 | 4.7 cells*10,000/mm^3 |
| Hematological Parameters WBC, * 10,000/mm3 | 5.5 cells*10,000/mm^3 | 5.3 cells*10,000/mm^3 | 5.4 cells*10,000/mm^3 |
| Hemoglobin | 14.2 g/dL | 14.0 g/dL | 14.2 g/dL |
| Hip circumference | 111.4 cm | 97.3 cm | 106.1 cm |
| Liver Function Alanine transaminase (ALT) | 17.0 mg/dL | 13.5 mg/dL | 14.0 mg/dL |
| Liver Function Aspartate transaminase (AST) | 17.0 mg/dL | 17.0 mg/dL | 17.0 mg/dL |
| Liver Function Gamma-glutamyl transferase (GGT) | 22.5 mg/dL | 16.0 mg/dL | 20.0 mg/dL |
| Liver Function Total bilirubin | 0.5 mg/dL | 0.5 mg/dL | 0.5 mg/dL |
| Mean Corpuscular Hemoglobin Concentration (MCHC) | 34.0 g/dL | 34.0 g/dL | 34.0 g/dL |
| Mean Corpuscular Hemoglobin (MCH) | 31.0 pg | 30.0 pg | 30.0 pg |
| Mean Corpuscular Volume (MCV) | 89.0 fl | 87.5 fl | 88.0 fl |
| Mean Platelet Volume (MPV) | 8.0 fL | 9.0 fL | 9.0 fL |
| 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 | 16 Participants | 10 Participants | 26 Participants |
| Race (NIH/OMB) More than one race | 6 Participants | 8 Participants | 14 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 |
| Red Cell Distribution Width (RDW) | 13.3 % | 13.5 % | 13.5 % |
| Renal Function Blood Urea Nitrogen (BUN) | 12.0 mg/dL | 12.0 mg/dL | 12 mg/dL |
| Renal Function Serum Creatinine | 0.9 mg/dL | 0.9 mg/dL | 0.9 mg/dL |
| Serum Calcium | 9.6 mg/dL | 9.6 mg/dL | 9.6 mg/dL |
| Serum Electrolytes Bicarbonate, mEq/L | 26.0 mEq/L | 26.0 mEq/L | 26.0 mEq/L |
| Serum Electrolytes Chloride, mEq/L | 103.5 mEq/L | 102.5 mEq/L | 103.0 mEq/L |
| Serum Electrolytes Potassium, mEq/L | 4.2 mEq/L | 4.2 mEq/L | 4.2 mEq/L |
| Serum Electrolytes Sodium, mEq/L | 138.0 mEq/L | 137.5 mEq/L | 138.0 mEq/L |
| Sex: Female, Male Female | 12 Participants | 8 Participants | 20 Participants |
| Sex: Female, Male Male | 10 Participants | 10 Participants | 20 Participants |
| Systolic Blood Pressure | 116.5 mmHg | 110.7 mmHg | 116.2 mmHg |
| Waist circumference | 103.6 cm | 76.9 cm | 97.6 cm |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 22 |
| other Total, other adverse events | 0 / 18 | 0 / 22 |
| serious Total, serious adverse events | 0 / 18 | 0 / 22 |
Outcome results
Primary
Plasma MRproANP
Assess the diurnal rhythm in circulating MRproANP levels among obese individuals and compared it with lean individuals
Time frame: About 24 hours on the in-patient study visit day after consuming study meals for 5 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lean | Plasma MRproANP | 17.92 pmol/l |
| Obese | Plasma MRproANP | 15.51 pmol/l |
p-value: 0.003Regression (Cosinor Fit)
p-value: <0.001Regression, Linear
Secondary
Acrophase Difference in Hours Between the MR-proANP and Systolic BP Rhythm
Assess relationship between 24-hour variability of MRproANP levels and 24-hour patterns of blood pressure and whether this relationship of rhythmicity of MRproANP levels and nocturnal blood pressure differed in obese and lean individuals and by race
Time frame: About 24 hours on the in-patient study visit day after consuming study meals for 5 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lean | Acrophase Difference in Hours Between the MR-proANP and Systolic BP Rhythm | -0.7 Hours | Standard Error 0.03 |
| Obese | Acrophase Difference in Hours Between the MR-proANP and Systolic BP Rhythm | -4.9 Hours | Standard Error 0.05 |
Other Pre-specified
Plasma MRproANP
Assess the diurnal rhythm in circulating MRproANP levels among African-American individuals and compared it with white individuals
Time frame: About 24 hours on the in-patient study visit day after consuming study meals for 5 days
Population: The race-specific analysis was not done for this study