Table 3.
Hazard ratios of all-cause, cardiometabolic, and other-cause mortality for modeled circadian rhythm metrics
| All-cause mortality | Cardiometabolic mortality | Other-cause mortality | |||||
|---|---|---|---|---|---|---|---|
| HR [95%CI] | P-value | HR [95%CI] | P-value | HR [95%CI] | P-value | ||
| Model 1 | Mean Amplitude | 0.93 [0.90 to 0.96]* | <0.0001 | 0.88 [0.82 to 0.95]* | 0.00021 | 0.95 [0.92 to 0.99]* | 0.006 |
| Min. Amplitude | 0.95 [0.92 to 0.98]* | 0.00035 | 0.87 [0.80 to 0.94]* | 0.00031 | 0.91 [0.88 to 0.95]* | <0.0001 | |
| Max. Amplitude | 0.90 [0.87 to 0.93]* | <0.0001 | 0.91 [0.85 to 0.96]* | 0.00078 | 0.96 [0.93 to 1.00]* | 0.017 | |
| Phase Variability | 1.01 [0.98 to 1.04] | 0.42 | 0.99 [0.94 to 1.05] | 0.4 | 1.02 [0.99 to 1.05] | 0.14 | |
| Mean phase | |||||||
| 0 to 20% | 1.30 [1.17 to 1.44]* | <0.0001 | 1.43 [1.14 to 1.79]* | 0.0011 | 1.27[ 1.12 to 1.42]* | <0.0001 | |
| 20 to 40% | 1.13 [1.02 to 1.27]* | 0.023 | 1.25 [0.98 to 1.59]* | 0.035 | 1.10 [0.97 to 1.24] | 0.071 | |
| 40 to 60% (ref.) | – | – | – | – | – | – | |
| 60 to 80% | 1.07 [0.96 to 1.20] | 0.22 | 1.21 [0.95 to 1.54] | 0.059 | 1.04 [0.92 to 1.18] | 0.26 | |
| 80 to 100% | 1.20 [1.07 to 1.34]* | 0.0016 | 1.19 [0.92 to 1.52] | 0.091 | 1.20 [1.05 to 1.36]* | 0.003 | |
| Model 2 | Mean Amplitude | 0.93 [0.90 to 0.96]* | <0.0001 | 0.88 [0.82 to 0.95]* | 0.00022 | 0.95 [0.91 to 0.99]* | 0.0034 |
| Min. Amplitude | 0.94 [0.91 to 0.97]* | <0.0001 | 0.88 [0.81 to 0.96]* | 0.0013 | 0.92 [0.88 to 0.96]* | <0.0001 | |
| Max. Amplitude | 0.90 [0.87 to 0.94]* | <0.0001 | 0.90 [0.85 to 0.96]* | 0.00045 | 0.96 [0.92 to 0.99]* | 0.0077 | |
| Phase variability | 1.01 [0.98 to 1.04] | 0.43 | 0.99 [0.94 to 1.05] | 0.4 | 1.02 [0.99 to 1.04] | 0.15 | |
| Mean phase | |||||||
| 0 to 20% | 1.21 [1.09 to 1.35]* | 0.00041 | 1.33 [1.06 to 1.68]* | 0.0079 | 1.18 [1.05 to 1.33]* | 0.0032 | |
| 20 to 40% | 1.11 [1.00 to 1.24] | 0.054 | 1.21 [0.95 to 1.54] | 0.06 | 1.08 [0.95 to 1.22] | 0.11 | |
| 40 to 60% (ref.) | – | – | – | – | – | – | |
| 60 to 80% | 1.08 [0.97 to 1.21] | 0.17 | 1.24 [0.97 to 1.57]* | 0.044 | 1.05 [0.92 to 1.19] | 0.24 | |
| 80 to 100% | 1.20 [1.07 to 1.35]* | 0.0014 | 1.20 [0.93 to 1.54] | 0.081 | 1.20 [1.05 to 1.37]* | 0.0029 | |
| Model 3 | Mean Amplitude | 0.96 [0.92 to 0.99]* | 0.0083 | 0.92 [0.86 to 0.98]* | 0.0076 | 0.97 [0.94 to 1.01] | 0.076 |
| Min. Amplitude | 0.96 [0.93 to 0.99]* | 0.0052 | 0.93 [0.86 to 1.01]* | 0.04 | 0.95 [0.91 to 0.99]* | 0.007 | |
| Max. Amplitude | 0.94 [0.91 to 0.98]* | 0.0011 | 0.92 [0.87 to 0.98]* | 0.0043 | 0.97 [0.94 to 1.01] | 0.056 | |
| Phase variability | 1.01 [0.98 to 1.03] | 0.56 | 0.99 [0.94 to 1.05] | 0.37 | 1.01 [0.98 to 1.04] | 0.19 | |
| Mean phase | |||||||
| 0 to 20% | 1.16 [1.04 to 1.29]* | 0.0066 | 1.27 [1.00 to 1.61]* | 0.023 | 1.14 [1.00 to 1.28]* | 0.021 | |
| 20 to 40% | 1.11 [0.99 to 1.24] | 0.065 | 1.20 [0.94 to 1.53] | 0.073 | 1.08 [0.95 to 1.22] | 0.12 | |
| 40 to 60% (ref.) | – | – | – | – | – | – | |
| 60 to 80% | 1.07 [0.96 to 1.20] | 0.22 | 1.22 [0.96 to 1.56] | 0.055 | 1.04 [0.92 to 1.18] | 0.26 | |
| 80 to 100% | 1.13 [1.00 to 1.26]* | 0.042 | 1.10 [0.85 to 1.41] | 0.24 | 1.13 [0.99 to 1.29]* | 0.031 | |
Hazard ratios represent difference in mortality hazard per SD increase in each circadian metric for mean, min., and max. amplitude, and phase variability. Hazard ratios for mean phase represent hazard of each percentile group relative to the 40 to 60% reference group, centered at the population mean phase (03:50). Phase ranges relative to sample mean for each percentile group were −12 to −1.16 h (0 to 20%), −1.16 to −0.40 h (20 to 40%), 0.40 to 1.16 h (60 to 80%), and 1.16 to 12 h (80 to 100%). Model 1 was adjusted for age, sex, ethnicity, and photoperiod; Model 2 was additionally adjusted for employment status, education, income, and deprivation; Model 3 was further adjusted for physical activity, smoking status, alcohol consumption, urbanicity, and social activity.
*P < 0.05.