Chronobiology of Natriuretic Peptides and Blood Pressure in Lean and Obese Individuals
Vibhu Parcha, Nirav Patel, Orlando M Gutierrez, Peng Li, Karen L Gamble, Kiran Musunuru, Kenneth B Margulies, Thomas P Cappola, Thomas J Wang, Garima Arora, Pankaj Arora, Vibhu Parcha, Nirav Patel, Orlando M Gutierrez, Peng Li, Karen L Gamble, Kiran Musunuru, Kenneth B Margulies, Thomas P Cappola, Thomas J Wang, Garima Arora, Pankaj Arora
Abstract
Background: Diurnal variation of natriuretic peptide (NP) levels and its relationship with 24-h blood pressure (BP) rhythm has not been established. Obese individuals have a relative NP deficiency and disturbed BP rhythmicity.
Objectives: This clinical trial evaluated the diurnal rhythmicity of NPs (B-type natriuretic peptide [BNP], mid-regional pro-atrial natriuretic peptide [MR-proANP], N-terminal pro-B-type natriuretic peptide [NT-proBNP]) and the relationship of NP rhythm with 24-h BP rhythm in healthy lean and obese individuals.
Methods: On the background of a standardized diet, healthy, normotensive, lean (body mass index 18.5 to 25 kg/m2) and obese (body mass index 30 to 45 kg/m2) individuals, age 18 to 40 years, underwent 24-h inpatient protocol involving ambulatory BP monitoring starting 24 h prior to the visit, controlled light intensity, and repeated blood draws for assessment of analytes. Cosinor analysis of normalized NP levels (normalized to 24-h mean value) was conducted to assess the diurnal NP rhythm and its relationship with systolic BP.
Results: Among 52 participants screened, 40 participants (18 lean, 22 obese; 50% women; 65% Black) completed the study. The median range spread (percentage difference between the minimum and maximum values) over 24 h for MR-proANP, BNP, and NT-proBNP levels was 72.0% (interquartile range [IQR]: 50.9% to 119.6%), 75.5% (IQR: 50.7% to 106.8%), and 135.0% (IQR: 66.3% to 270.4%), respectively. A cosine wave-shaped 24-h oscillation of normalized NP levels (BNP, MR-proANP, and NT-proBNP) was noted both in lean and obese individuals (prhythmicity <0.05 for all). A larger phase difference between MR-proANP BP rhythm (-4.9 h vs. -0.7 h) and BNP BP rhythm (-3.3 h vs. -0.9 h) was seen in obese compared with lean individuals.
Conclusions: This human physiological trial elucidates evidence of diurnal NP rhythmicity and the presence of an NP-BP rhythm axis. There exists a misalignment of the NP-BP diurnal rhythm in the obese, which may contribute to the disturbed diurnal BP pattern observed among obese individuals. (The Diurnal Rhythm in Natriuretic Peptide Levels; NCT03834168).
Keywords: blood pressure; diurnal rhythm; hypertension; natriuretic peptides; obesity.
Conflict of interest statement
Funding Support and Author Disclosures This research was partly supported by the National Center for Advancing Translational Research of the National Institutes of Health under award number UL1TR001417 to the University of Alabama at Birmingham Center for Clinical and Translational Science. Dr. Margulies has received research grant support from Sanofi-Aventis, Merck, Sharp, and Dohme, and GlaxoSmithKline; and has consulted for MyoKardia, Pfizer, and Luitpold Pharmaceuticals. Drs. Wang and P. Arora are named as coinventors on a patent application relating to the use of miRNAs for the treatment of hypertension and other disorders. Dr. P. Arora is supported by the National Institutes of Health Mentored Patient-Oriented Research Award 5K23HL146887-02. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
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Source: PubMed