Chronobiology of Natriuretic Peptides and Blood Pressure in Lean and Obese Individuals

• Published in: Journal of the American College of Cardiology Vol. 77; no. 18; pp. 2291 - 2303
• Main Authors: Parcha, Vibhu, Patel, Nirav, Gutierrez, Orlando M., Li, Peng, Gamble, Karen L., Musunuru, Kiran, Margulies, Kenneth B., Cappola, Thomas P., Wang, Thomas J., Arora, Garima, Arora, Pankaj
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 11.05.2021
• Subjects: Adolescent; Adult; blood pressure; Blood Pressure - physiology; Cardiovascular; Chronobiology Phenomena; diurnal rhythm; Female; Humans; hypertension; Male; natriuretic peptides; Natriuretic Peptides - blood; obesity; Obesity - blood; Obesity - physiopathology; Young Adult; blood pressure; natriuretic peptides; HTN; NT-proBNP; BNP; RAAS; MR-proANP; diurnal rhythm; hypertension; obesity; mid-regional pro-atrial natriuretic peptides; renin-angiotensin-aldosterone system; B-type natriuretic peptides; N-terminal pro-B-type-natriuretic peptides
• ISSN: 0735-1097; 1558-3597; 1558-3597
• DOI: 10.1016/j.jacc.2021.03.291

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. 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. 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. 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. 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) [Display omitted]