Circadian misalignment increases cardiovascular disease risk factors in humans

Christopher J. Morris, Taylor E. Purvis, Kun Hu, and Frank A. J. L. Scheer
PNAS March 8, 2016 113 (10) E1402-E1411; first published February 8, 2016 https://doi.org/10.1073/pnas.1516953113

  1. Edited by Joseph S. Takahashi, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX, and approved January 6, 2016 (received for review August 25, 2015)

Significance

Shift work is a risk factor for hypertension, inflammation, and cardiovascular disease, even after controlling for traditional risk factors. Shift workers frequently undergo circadian misalignment (i.e., misalignment between the endogenous circadian system and 24-h environmental/behavioral cycles). This misalignment has been proposed to explain, in part, why shift work is a risk factor for hypertension, inflammation, and cardiovascular disease. However, the impact of circadian misalignment per se on 24-h blood pressure and inflammatory markers is poorly understood. We show—under highly controlled laboratory conditions—that short-term circadian misalignment increases 24-h blood pressure and inflammatory markers in healthy adults. Our findings may help explain why shift work increases hypertension, inflammation, and cardiovascular disease risk.

Abstract

Shift work is a risk factor for hypertension, inflammation, and cardiovascular disease. This increased risk cannot be fully explained by classic risk factors. One of the key features of shift workers is that their behavioral and environmental cycles are typically misaligned relative to their endogenous circadian system. However, there is little information on the impact of acute circadian misalignment on cardiovascular disease risk in humans. Here we show—by using two 8-d laboratory protocols—that short-term circadian misalignment (12-h inverted behavioral and environmental cycles for three days) adversely affects cardiovascular risk factors in healthy adults. Circadian misalignment increased 24-h systolic blood pressure (SBP) and diastolic blood pressure (DBP) by 3.0 mmHg and 1.5 mmHg, respectively. These results were primarily explained by an increase in blood pressure during sleep opportunities (SBP, +5.6 mmHg; DBP, +1.9 mmHg) and, to a lesser extent, by raised blood pressure during wake periods (SBP, +1.6 mmHg; DBP, +1.4 mmHg). Circadian misalignment decreased wake cardiac vagal modulation by 8–15%, as determined by heart rate variability analysis, and decreased 24-h urinary epinephrine excretion rate by 7%, without a significant effect on 24-h urinary norepinephrine excretion rate. Circadian misalignment increased 24-h serum interleukin-6, C-reactive protein, resistin, and tumor necrosis factor-α levels by 3–29%. We demonstrate that circadian misalignment per se increases blood pressure and inflammatory markers. Our findings may help explain why shift work increases hypertension, inflammation, and cardiovascular disease risk.

Footnotes

  • ↵1To whom correspondence may be addressed. Email: christopher-morris{at}hotmail.co.uk or fscheer{at}rics.bwh.harvard.edu.

  • Author contributions: C.J.M. and F.A.J.L.S. designed research; C.J.M. and F.A.J.L.S. performed research; C.J.M., T.E.P., K.H., and F.A.J.L.S. analyzed data; and C.J.M. and F.A.J.L.S. wrote the paper.

  • The authors declare no conflict of interest.

  • This article is a PNAS Direct Submission.

  • See Commentary on page 2558.

  • This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1516953113/-/DCSupplemental.

  1. Christopher J. Morrisa,b,1,
  2. Taylor E. Purvisa,
  3. Kun Hua,b, and
  4. Frank A. J. L. Scheera,b,1
  1. aMedical Chronobiology Program, Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women’s Hospital, Boston, MA 02115;
  2. bDivision of Sleep Medicine, Department of Medicine, Harvard Medical School, Boston, MA 02115

  1. Edited by Joseph S. Takahashi, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX, and approved January 6, 2016 (received for review August 25, 2015)

Significance

Shift work is a risk factor for hypertension, inflammation, and cardiovascular disease, even after controlling for traditional risk factors. Shift workers frequently undergo circadian misalignment (i.e., misalignment between the endogenous circadian system and 24-h environmental/behavioral cycles). This misalignment has been proposed to explain, in part, why shift work is a risk factor for hypertension, inflammation, and cardiovascular disease. However, the impact of circadian misalignment per se on 24-h blood pressure and inflammatory markers is poorly understood. We show—under highly controlled laboratory conditions—that short-term circadian misalignment increases 24-h blood pressure and inflammatory markers in healthy adults. Our findings may help explain why shift work increases hypertension, inflammation, and cardiovascular disease risk.

Abstract

Shift work is a risk factor for hypertension, inflammation, and cardiovascular disease. This increased risk cannot be fully explained by classic risk factors. One of the key features of shift workers is that their behavioral and environmental cycles are typically misaligned relative to their endogenous circadian system. However, there is little information on the impact of acute circadian misalignment on cardiovascular disease risk in humans. Here we show—by using two 8-d laboratory protocols—that short-term circadian misalignment (12-h inverted behavioral and environmental cycles for three days) adversely affects cardiovascular risk factors in healthy adults. Circadian misalignment increased 24-h systolic blood pressure (SBP) and diastolic blood pressure (DBP) by 3.0 mmHg and 1.5 mmHg, respectively. These results were primarily explained by an increase in blood pressure during sleep opportunities (SBP, +5.6 mmHg; DBP, +1.9 mmHg) and, to a lesser extent, by raised blood pressure during wake periods (SBP, +1.6 mmHg; DBP, +1.4 mmHg). Circadian misalignment decreased wake cardiac vagal modulation by 8–15%, as determined by heart rate variability analysis, and decreased 24-h urinary epinephrine excretion rate by 7%, without a significant effect on 24-h urinary norepinephrine excretion rate. Circadian misalignment increased 24-h serum interleukin-6, C-reactive protein, resistin, and tumor necrosis factor-α levels by 3–29%. We demonstrate that circadian misalignment per se increases blood pressure and inflammatory markers. Our findings may help explain why shift work increases hypertension, inflammation, and cardiovascular disease risk.

  • circadian misalignment
  • hypertension
  • inflammatory markers
  • night work
  • shift work

Footnotes

  • ↵1To whom correspondence may be addressed. Email: christopher-morris{at}hotmail.co.uk or fscheer{at}rics.bwh.harvard.edu.

  • Author contributions: C.J.M. and F.A.J.L.S. designed research; C.J.M. and F.A.J.L.S. performed research; C.J.M., T.E.P., K.H., and F.A.J.L.S. analyzed data; and C.J.M. and F.A.J.L.S. wrote the paper.

  • The authors declare no conflict of interest.

  • This article is a PNAS Direct Submission.

  • See Commentary on page 2558.

  • This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1516953113/-/DCSupplemental.

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Misalignment and cardiovascular disease risk
Christopher J. Morris, Taylor E. Purvis, Kun Hu, Frank A. J. L. Scheer
Proceedings of the National Academy of Sciences Mar 2016, 113 (10) E1402-E1411; DOI: 10.1073/pnas.1516953113
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