4.7 Article

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

Journal

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Volume 77, Issue 18, Pages 2291-2303

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/j.jacc.2021.03.291

Keywords

blood pressure; diurnal rhythm; hypertension; natriuretic peptides; obesity

Funding

  1. National Center for Advancing Translational Research of the National Institutes of Health [UL1TR001417]
  2. Sanofi-Aventis
  3. Merck
  4. Sharp, and Dohme
  5. GlaxoSmithKline
  6. National Institutes of Health Mentored Patient-Oriented Research Award [5K23HL146887-02]

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This clinical trial investigated the diurnal rhythmicity of natriuretic peptides in healthy lean and obese individuals, revealing a misalignment of the NP-BP diurnal rhythm in the obese population.
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/m(2)) 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. (C) 2021 by the American College of Cardiology Foundation.

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