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

Internal circadian time affects glucose tolerance in shift workers. Separately, circadian misalignment reduces glucose tolerance in shift workers, providing a mechanism to help explain the increased diabetes risk in shift workers.

Shift work is a risk factor for inflammation, hypertension and cardiovascular disease. This increased risk cannot be fully explained by classic risk factors. Shift workers’ 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 shift workers, independent of differences in work stress, food quality and other factors that are likely to differ between night and day shifts. Thus, our objectives were to determine the independent effect of circadian misalignment on 24-h high-sensitivity C-reactive protein (hs-CRP; a marker of systemic inflammation) and blood pressure levels—cardiovascular disease risk factors—in chronic shift workers. Chronic shift workers undertook two 3-day laboratory protocols that simulated night work comprised of 12-hour inverted behavioral and environmental cycles (circadian misalignment) or simulated day work (circadian alignment), using a randomized, crossover design. Circadian misalignment increased 24-h hs-CRP by 11% (P<0.0001). Circadian misalignment increased 24-h systolic blood pressure (SBP) and diastolic blood pressure (DBP) by 1.4 mmHg and 0.8 mmHg, respectively (both P≤0.038). The misalignment-mediated increase in 24-h SBP was primarily explained by an increase in SBP during the wake period (+1.7 mmHg; P=0.017), whereas the misalignment-mediated increase in 24-h DBP was primarily explained by an increase in DBP during the sleep opportunity (+1.8 mmHg; P=0.005). Circadian misalignment per se increases hs-CRP and blood pressure in shift workers. This may help explain the increased inflammation, hypertension and cardiovascular disease risk in shift workers.

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the Yale Center of Sleep Medicine. All patients completed polysomnography (PSG) and multiple sleep latency test (MSLT), and a structured interview by an independent sleep specialist. Patients were administered a standardized 8-page questionnaire within 4 weeks of their narcolepsy diagnosis. Sixteen patients did not complete the questionnaire or had missing data, and were excluded. The study was approved by the Yale Institutional Review Board. QuestionnaireThe standardized questionnaire, in addition to other sleep disorder symptoms, sleep history and habits, current medications, and social, psychological, psychiatric, surgical, and Study Objectives: To examine the impact of gender in narcoleptic patients on timeliness of diagnosis, symptomology, and health and lifestyle impairment Methods: This is a cross-sectional study of 109 consecutive patients (68 women) with newly diagnosed narcolepsy with and without cataplexy, from a University sleep disorders center. Consecutive patients were administered an 8-page questionnaire at the time of their diagnosis regarding sleep habits, medications, and medical conditions, lifestyle impairments, as well as details regarding narcolepsy-related symptoms. Results: Men and women presented with remarkably similar narcolepsy related symptoms, yet women were more likely to be delayed in diagnosis; 85% of men were likely to be diagnosed by 16 years after symptom onset, compared to 28 years in women. More women were likely to remain undiagnosed at any given time point after symptom onset (hazard ratio for diagnosis of men compared to women 1.53; 95% CI 1.01-2.32; p = 0.04). Men and women reported similar degree of subjective sleepiness as measured by the Epworth Sleepiness Scale (mean 16.2 ± 4.5; p = 0.18), though women demonstrated signifi cantly more severe objective sleepiness on multiple sleep latency testing (MSLT) (mean sleep latency in women = 5.4 min (± 4.1), in men 7.4 min (± 3.5); p = 0.03). Despite being more objectively sleepy, women were less likely to report lifestyle impairments in the areas of personal relationships (71% men, 44% women, p = 0.01) and physical activity (36% men, 16% women, p = 0.02), but were also more likely to self-medicate with caffeine (63.4% men, 82.4% women; p = 0.03). Conclusions: Narcolepsy impacts men and women's health and lifestyle differently, and may cause delays diagnosis for women. Keywords: Narcolepsy, gender, sex, sleep, hypersomnia, diagnosis, women S C I E N T I F I C I N V E S T I G A T I O N SS leep disorders affect women and men differently. This is well described, for example, in sleep disordered breathing, insomnia, and restless leg syndrome. In these common sleep disorders, there are notable sex differences in disease prevalence, manifestation, health effects, and social consequences, 1-9 as well as sex-related discrepancies in diagnosis and health care delivery. 10 There is some evidence from animal models and genetic studies to suggest sex differences in the susceptibility and manifestation of narcolepsy.11-13 However, sex d...

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