Circadian misalignment increases cardiovascular disease risk factors in humans

Proc Natl Acad Sci U S A. 2016 Mar 8;113(10):E1402-11. doi: 10.1073/pnas.1516953113. Epub 2016 Feb 8.

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.

Keywords: circadian misalignment; hypertension; inflammatory markers; night work; shift work.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Actigraphy
  • Adult
  • Blood Pressure / physiology
  • C-Reactive Protein / metabolism
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / physiopathology*
  • Circadian Rhythm / physiology*
  • Cross-Over Studies
  • Epinephrine / urine
  • Female
  • Heart Rate / physiology
  • Humans
  • Hypertension / blood
  • Hypertension / physiopathology
  • Interleukin-6 / blood
  • Male
  • Middle Aged
  • Polysomnography
  • Resistin / blood
  • Risk Factors
  • Sleep Disorders, Circadian Rhythm / blood
  • Sleep Disorders, Circadian Rhythm / physiopathology*
  • Time Factors
  • Tumor Necrosis Factor-alpha / blood
  • Work Schedule Tolerance / physiology*
  • Young Adult

Substances

  • Interleukin-6
  • Resistin
  • Tumor Necrosis Factor-alpha
  • C-Reactive Protein
  • Epinephrine