Vibhu Parcha1, Nirav Patel2, Orlando M Gutierrez3, Peng Li4, Karen L Gamble5, Kiran Musunuru6, Kenneth B Margulies7, Thomas P Cappola7, Thomas J Wang8, Garima Arora9, Pankaj Arora10. 1. Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, Alabama, USA. Electronic address: https://twitter.com/vibhuparcha. 2. Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA. 3. Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA; Department of Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama, USA. 4. School of Nursing, University of Alabama at Birmingham, Birmingham, Alabama, USA. 5. Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Birmingham, Alabama, USA. 6. Cardiovascular Institute, Department of Medicine, Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA. Electronic address: https://twitter.com/kiranmusunuru. 7. Division of Cardiovascular Medicine, Department of Medicine, Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA. 8. Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA. Electronic address: https://twitter.com/thomasjwang1. 9. Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, Alabama, USA. Electronic address: https://twitter.com/GarimaAroraMD. 10. Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, Alabama, USA; Section of Cardiology, Birmingham Veterans Affairs Medical Center, Birmingham, Alabama, USA. Electronic address: parora@uabmc.edu.
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).
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).
Authors: Christopher Newton-Cheh; Martin G Larson; Ramachandran S Vasan; Daniel Levy; Kenneth D Bloch; Aarti Surti; Candace Guiducci; Sekar Kathiresan; Emelia J Benjamin; Joachim Struck; Nils G Morgenthaler; Andreas Bergmann; Stefan Blankenberg; Frank Kee; Peter Nilsson; Xiaoyan Yin; Leena Peltonen; Erkki Vartiainen; Veikko Salomaa; Joel N Hirschhorn; Olle Melander; Thomas J Wang Journal: Nat Genet Date: 2009-02-15 Impact factor: 38.330
Authors: Robert H Fagard; Hilde Celis; Lutgarde Thijs; Jan A Staessen; Denis L Clement; Marc L De Buyzere; Dirk A De Bacquer Journal: Hypertension Date: 2007-11-26 Impact factor: 10.190