Clinical trial NCT03834168: The Diurnal Rhythm in Natriuretic Peptide Levels
Official title: The Diurnal Rhythm in Natriuretic Peptide Levels and Relationship With Nocturnal Blood Pressure
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Natriuretic Peptides
Obesity
Nocturnal Blood Pressure
Keywords: Diurnal Rhythm
Race
Lead sponsor: University of Alabama at Birmingham
Sponsor class: OTHER
First posted: 2019-02-07
Enrollment: 42
Sex: MALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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.

Eligibility criteria: 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

Primary outcomes:
measure: Plasma MRproANP
timeFrame: About 24 hours on the in-patient study visit day after consuming study meals for 5 days
Secondary outcomes:
measure: Acrophase Difference in Hours Between the MR-proANP and Systolic BP Rhythm
timeFrame: About 24 hours on the in-patient study visit day after consuming study meals for 5 days
Other outcomes:
measure: Plasma MRproANP
timeFrame: About 24 hours on the in-patient study visit day after consuming study meals for 5 days
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
Study officials:
affiliation: University of Alabama at Birmingham
name: Pankaj Arora, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Alabama at Birmingham
name: Orlando M Gutierrez, MMSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: Goetze JP, Jorgensen HL, Sennels HP, Fahrenkrug J. Diurnal plasma concentrations of natriuretic propeptides in healthy young males. Clin Chem. 2012 Apr;58(4):789-92. doi: 10.1373/clinchem.2011.178921. Epub 2012 Jan 26. No abstract available.
citation: Arora P, Reingold J, Baggish A, Guanaga DP, Wu C, Ghorbani A, Song Y, Chen-Tournaux A, Khan AM, Tainsh LT, Buys ES, Williams JS, Heublein DM, Burnett JC, Semigran MJ, Bloch KD, Scherrer-Crosbie M, Newton-Cheh C, Kaplan LM, Wang TJ. Weight loss, saline loading, and the natriuretic peptide system. J Am Heart Assoc. 2015 Jan 16;4(1):e001265. doi: 10.1161/JAHA.114.001265.
citation: Bajaj NS, Gutierrez OM, Arora G, Judd SE, Patel N, Bennett A, Prabhu SD, Howard G, Howard VJ, Cushman M, Arora P. Racial Differences in Plasma Levels of N-Terminal Pro-B-Type Natriuretic Peptide and Outcomes: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study. JAMA Cardiol. 2018 Jan 1;3(1):11-17. doi: 10.1001/jamacardio.2017.4207.
citation: Arora P, Wu C, Hamid T, Arora G, Agha O, Allen K, Tainsh RET, Hu D, Ryan RA, Domian IJ, Buys ES, Bloch DB, Prabhu SD, Bloch KD, Newton-Cheh C, Wang TJ. Acute Metabolic Influences on the Natriuretic Peptide System in Humans. J Am Coll Cardiol. 2016 Feb 23;67(7):804-812. doi: 10.1016/j.jacc.2015.11.049.
citation: Parcha V, Patel N, Gutierrez OM, Li P, Gamble KL, Musunuru K, Margulies KB, Cappola TP, Wang TJ, Arora G, Arora P. Chronobiology of Natriuretic Peptides and Blood Pressure in Lean and Obese Individuals. J Am Coll Cardiol. 2021 May 11;77(18):2291-2303. doi: 10.1016/j.jacc.2021.03.291.