Introduction
Methods
Study populations and calcium and vitamin D supplementation
Data collection, follow-up, and outcome ascertainment
Statistical analysis
Results
CaD Trial | Observational Study | |||||||
---|---|---|---|---|---|---|---|---|
All participants | No personal supplementsa
| Non-users of supplements | Calcium + Vitamin D | Calcium only | Vitamin D only | |||
Placebo | CaD | Placebo | CaD | |||||
Number of women | 18,106 | 18,176 | 7,584 | 7,718 | 23,561 | 15,476 | 5,941 | 1,914 |
Hip fracture | ||||||||
Cases | 199 | 175 | 80 | 68 | 212 | 158 | 55 | 26 |
Age-adjusted incidence (%)b
| 0.20 | 0.17 | 0.20 | 0.16 | 0.14 | 0.15 | 0.13 | 0.18 |
Total fracture | ||||||||
Cases | 2,158 | 2,102 | 870 | 872 | 3,172 | 2,344 | 834 | 290 |
Age-adjusted incidence (%)b
| 1.94 | 1.85 | 1.86 | 1.81 | 2.02 | 2.28 | 2.04 | 2.21 |
Myocardial infarction | ||||||||
Cases | 390 | 411 | 167 | 193 | 433 | 210 | 77 | 40 |
Age-adjusted incidence (%)b
| 0.34 | 0.37 | 0.37 | 0.42 | 0.28 | 0.19 | 0.18 | 0.29 |
Coronary heart disease | ||||||||
Cases | 475 | 499 | 211 | 229 | 545 | 252 | 95 | 50 |
Age-adjusted incidence (%)b
| 0.42 | 0.45 | 0.47 | 0.51 | 0.35 | 0.23 | 0.22 | 0.36 |
Total heart disease | ||||||||
Cases | 1,363 | 1,405 | 642 | 621 | 1,602 | 762 | 328 | 132 |
Age-adjusted incidence (%)b
| 1.24 | 1.28 | 1.44 | 1.39 | 1.05 | 0.71 | 0.77 | 0.97 |
Stroke | ||||||||
Cases | 377 | 362 | 162 | 184 | 471 | 253 | 91 | 38 |
Age-adjusted incidence (%)b
| 0.35 | 0.33 | 0.37 | 0.42 | 0.31 | 0.23 | 0.21 | 0.27 |
Total cardiovascular disease | ||||||||
Cases | 1,810 | 1,832 | 813 | 848 | 2,187 | 1,069 | 440 | 181 |
Age-adjusted incidence (%)b
| 1.69 | 1.70 | 1.86 | 1.94 | 1.45 | 1.01 | 1.04 | 1.34 |
Colorectal cancer | ||||||||
Cases | 154 | 168 | 77 | 66 | 174 | 88 | 35 | 9 |
Age-adjusted incidence (%)b
| 0.13 | 0.15 | 0.16 | 0.14 | 0.11 | 0.08 | 0.08 | 0.06 |
Breast cancer | ||||||||
Cases | 546 | 528 | 249 | 202 | 665 | 517 | 210 | 60 |
Age-adjusted incidence (%)b
| 0.45 | 0.43 | 0.48 | 0.38 | 0.40 | 0.48 | 0.49 | 0.43 |
Total invasive cancer | ||||||||
Cases | 1,411 | 1,366 | 617 | 553 | 1,701 | 1,187 | 474 | 153 |
Age-adjusted incidence (%)b
| 1.21 | 1.16 | 1.28 | 1.11 | 1.07 | 1.11 | 1.12 | 1.12 |
Death | ||||||||
Cases | 807 | 744 | 338 | 331 | 1,240 | 674 | 266 | 119 |
Age-adjusted incidence (%)b
| 0.72 | 0.67 | 0.75 | 0.72 | 0.78 | 0.61 | 0.61 | 0.84 |
Years since CaD initiation | CaD trial | Observational study | Combined trial and OS | |||||||
---|---|---|---|---|---|---|---|---|---|---|
All participants | No personal supplementsa
| All participants | No personal supplementsa
| |||||||
HR | 95 % CI | HR | 95 % CI | HR | 95 % CI | HR | 95 % CI | HR | 95 % CI | |
Hip fracture | ||||||||||
<2 |
0.75
| 0.44,1.26 |
1.12
| 0.52,2.42 |
1.41
| 0.44,4.57 |
0.81
| 0.49,1.31 |
1.15
| 0.58,2.30 |
2–5 |
1.01
| 0.73,1.40 |
1.00
| 0.61,1.65 |
1.22
| 0.71,2.10 |
1.03
| 0.77,1.39 |
1.04
| 0.68,1.57 |
>5 |
0.82
| 0.61,1.12 |
0.62
| 0.38,1.00 |
0.84
| 0.66,1.07 |
0.78
| 0.59,1.03 |
0.65
| 0.44,0.98 |
Trend testb
| 0.96 | 0.13 | 0.14 | 0.43 | 0.02 | |||||
HR in OS/HR in trialc
| 1.09 | 0.78,1.54 | 1.28 | 0.82,1.98 | ||||||
Overall HRd
|
0.88
| 0.71, 1.08 |
0.86
| 0.62, 1.20 |
0.88
| 0.70, 1.11 | ||||
Total fracture | ||||||||||
<2 |
0.96
| 0.86,1.08 |
0.91
| 0.76,1.10 |
0.89
| 0.61,1.31 |
0.95
| 0.85,1.06 |
0.90
| 0.76,1.06 |
2–5 |
0.94
| 0.86,1.03 |
0.97
| 0.84,1.12 |
1.05
| 0.91,1.22 |
0.95
| 0.87,1.03 |
0.98
| 0.87,1.11 |
>5 |
0.98
| 0.88,1.09 |
1.03
| 0.87,1.22 |
1.08
| 1.01,1.14 |
0.98
| 0.90,1.08 |
1.02
| 0.90,1.16 |
Trend testb
| 0.83 | 0.35 | 0.42 | 0.53 | 0.21 | |||||
HR in OS/HR in trialc
| 1.09 | 0.99,1.21 | 1.05 | 0.92,1.20 | ||||||
Overall HRd
|
0.96
| 0.90, 1.02 |
0.97
| 0.88, 1.07 |
1.07
| 1.01, 1.14 | ||||
Death | ||||||||||
<2 |
0.73
| 0.56,0.96 |
0.68
| 0.44,1.06 |
1.49
| 0.79,2.83 |
0.80
| 0.62,1.04 |
0.86
| 0.58,1.27 |
2–5 |
0.87
| 0.75,1.02 |
0.87
| 0.68,1.11 |
0.85
| 0.61,1.18 |
0.87
| 0.76,1.01 |
0.89
| 0.72,1.09 |
>5 |
1.01
| 0.87,1.18 |
1.12
| 0.89,1.40 |
0.95
| 0.85,1.06 |
0.99
| 0.86,1.13 |
1.04
| 0.86,1.26 |
Trend testb
| 0.03 | 0.03 | 0.71 | 0.09 | 0.17 | |||||
HR in OS/HR in trialc
| 0.97 | 0.82,1.15 | 0.92 | 0.74,1.14 | ||||||
Overall HRd
|
0.91
| 0.83, 1.01 |
0.95
| 0.81, 1.11 |
0.95
| 0.85, 1.06 |
Years since CaD initiation | CaD trial | Observational study | Combined trial and OS | |||||||
---|---|---|---|---|---|---|---|---|---|---|
All participants | No personal supplementsa
| All participants | No personal supplementsa
| |||||||
HR | 95 % CI | HR | 95 % CI | HR | 95 % CI | HR | 95 % CI | HR | 95 % CI | |
Myocardial infarction | ||||||||||
<2 |
1.19
| 0.89,1.59 |
1.30
| 0.86,1.97 |
0.56
| 0.14,2.27 |
1.15
| 0.87,1.51 |
1.21
| 0.82,1.78 |
2–5 |
0.97
| 0.78,1.21 |
1.04
| 0.74,1.47 |
1.04
| 0.66,1.63 |
1.00
| 0.82,1.23 |
1.11
| 0.82,1.49 |
>5 |
1.01
| 0.80,1.29 |
1.06
| 0.74,1.50 |
0.89
| 0.73,1.08 |
1.00
| 0.80,1.24 |
1.05
| 0.78,1.41 |
Trend testb
| 0.46 | 0.49 | 0.94 | 0.49 | 0.54 | |||||
HR in OS/HR in trialc
| 0.90 | 0.69,1.18 | 0.85 | 0.61,1.18 | ||||||
Overall HRd
|
1.03
| 0.90, 1.19 |
1.11
| 0.90, 1.37 |
0.90
| 0.75, 1.09 | ||||
Coronary heart diseasee
| ||||||||||
<2 |
1.10
| 0.85,1.43 |
1.02
| 0.69,1.49 |
0.49
| 0.12,2.00 |
1.07
| 0.83,1.38 |
0.97
| 0.67,1.38 |
2–5 |
0.96
| 0.79,1.18 |
1.06
| 0.78,1.45 |
1.00
| 0.66,1.63 |
1.00
| 0.83,1.20 |
1.10
| 0.84,1.44 |
>5 |
1.05
| 0.85,1.30 |
1.02
| 0.75,1.40 |
0.88
| 0.74,1.05 |
1.03
| 0.85,1.25 |
1.02
| 0.78,1.33 |
Trend testb
| 0.87 | 0.97 | 0.88 | 0.93 | 0.93 | |||||
HR in OS/HR in trialc
| 0.86 | 0.67,1.10 | 0.86 | 0.64,1.16 | ||||||
Overall HRd
|
1.03
| 0.90, 1.17 |
1.03
| 0.85, 1.25 |
0.88
| 0.74, 1.04 | ||||
Total heart diseasef
| ||||||||||
<2 |
1.05
| 0.90,1.21 |
1.00
| 0.80,1.24 |
0.86
| 0.50,1.46 |
1.04
| 0.90,1.20 |
0.99
| 0.81,1.21 |
2–5 |
1.00
| 0.89,1.12 |
1.05
| 0.88,1.26 |
0.93
| 0.73,1.17 |
1.02
| 0.91,1.13 |
1.05
| 0.90,1.23 |
>5 |
1.04
| 0.91,1.19 |
0.98
| 0.81,1.20 |
0.87
| 0.79,0.97 |
1.02
| 0.91,1.15 |
0.99
| 0.84,1.16 |
Trend testb
| 0.96 | 0.91 | 0.83 | 0.88 | 0.91 | |||||
HR in OS/HR in trialc
| 0.86 | 0.75,0.99 | 0.82 | 0.74,1.05 | ||||||
Overall HRd
|
1.02
| 0.95, 1.11 |
1.02
| 0.91, 1.14 |
0.87
| 0.79, 0.96 | ||||
Strokeg
| ||||||||||
<2 |
0.82
| 0.60,1.12 |
1.11
| 0.73,1.68 |
0.47
| 0.12,1.89 |
0.78
| 0.58,1.05 |
1.00
| 0.68,1.46 |
2–5 |
1.06
| 0.84,1.34 |
1.17
| 0.83,1.65 |
0.91
| 0.57,1.44 |
1.03
| 0.84,1.27 |
1.16
| 0.87,1.55 |
>5 |
0.92
| 0.73,1.17 |
1.09
| 0.79,1.52 |
0.93
| 0.77,1.11 |
0.98
| 0.80,1.20 |
1.17
| 0.90,1.54 |
Trend testb
| 0.71 | 0.93 | 0.43 | 0.37 | 0.53 | |||||
HR in OS/HR in trialc
| 0.96 | 0.75,1.23 | 0.81 | 0.60,1.09 | ||||||
Overall HRd
|
0.95
| 0.82, 1.10 |
1.12
| 0.90, 1.39 |
0.92
| 0.77, 1.09 | ||||
Total cardiovascular diseaseh
| ||||||||||
<2 |
0.97
| 0.85,1.11 |
1.02
| 0.84,1.23 |
0.87
| 0.55,1.35 |
0.97
| 0.86,1.10 |
1.02
| 0.85,1.21 |
2–5 |
0.99
| 0.89,1.10 |
1.03
| 0.89,1.21 |
0.91
| 0.74,1.11 |
1.01
| 0.92,1.10 |
1.04
| 0.91,1.19 |
>5 |
1.05
| 0.93,1.18 |
1.02
| 0.86,1.21 |
0.86
| 0.79,0.94 |
1.02
| 0.93,1.13 |
1.01
| 0.88,1.16 |
Trend testb
| 0.37 | 0.97 | 0.84 | 0.42 | 0.93 | |||||
HR in OS/HR in Trialc
| 0.85 | 0.75,0.96 | 0.85 | 0.73,0.99 | ||||||
Overall HRd
|
1.00
| 0.94, 1.07 |
1.03
| 0.93, 1.13 |
0.86
| 0.79, 0.94 |
Years since CaD initiation | CaD trial | Observational study | Combined trial and OS | |||||||
---|---|---|---|---|---|---|---|---|---|---|
All participants | No personal supplementsa
| All participants | No personal supplementsa
| |||||||
HR | 95 % CI | HR | 95 % CI | HR | 95 % CI | HR | 95 % CI | HR | 95 % CI | |
Colorectal cancer | ||||||||||
<2 |
0.89
| 0.57,1.38 |
0.71
| 0.35,1.44 |
0.94
| 0.23,3.87 |
0.92
| 0.60,1.40 |
0.75
| 0.39,1.45 |
2–5 |
1.00
| 0.71,1.41 |
0.75
| 0.45,1.24 |
0.80
| 0.39,1.65 |
1.02
| 0.74,1.41 |
0.78
| 0.50,1.21 |
>5 |
1.30
| 0.88,1.92 |
0.99
| 0.56,1.77 |
0.83
| 0.60,1.14 |
1.23
| 0.87,1.74 |
0.90
| 0.56,1.45 |
Trend testb
| 0.19 | 0.44 | 0.96 | 0.26 | 0.57 | |||||
HR in OS/HR in triald
| 0.69 | 0.45,1.07 | 0.94 | 0.55,1.59 | ||||||
Overall HRd
|
1.06
| 0.85, 1.32 |
0.81
| 0.58, 1.13 |
0.83
| 0.61, 1.12 | ||||
Breast cancer | ||||||||||
<2 |
1.00
| 0.79,1.27 |
0.98
| 0.68,1.42 |
0.90
| 0.44,1.83 |
0.97
| 0.78,1.22 |
0.88
| 0.64,1.22 |
2–5 |
0.98
| 0.82,1.18 |
0.75
| 0.56,1.00 |
1.05
| 0.78,1.41 |
0.95
| 0.81,1.12 |
0.75
| 0.59,0.95 |
>5 |
0.89
| 0.72,1.11 |
0.73
| 0.52,1.02 |
1.14
| 1.00,1.30 |
0.95
| 0.80,1.14 |
0.80
| 0.62,1.02 |
Trend testb
| 0.45 | 0.26 | 0.42 | 0.89 | 0.87 | |||||
HR in OS/HR in trialc
| 1.18 | 0.96,1.45 | 1.42 | 1.09,1.84 | ||||||
Overall HRd
|
0.96
| 0.85, 1.08 |
0.80
| 0.66, 0.96 |
1.12
| 0.99, 1.28 | ||||
Total invasive cancer | ||||||||||
<2 |
0.96
| 0.83,1.12 |
0.96
| 0.76,1.22 |
0.87
| 0.56,1.36 |
0.95
| 0.82,1.09 |
0.91
| 0.74,1.12 |
2–5 |
0.94
| 0.84,1.06 |
0.82
| 0.69,0.98 |
0.99
| 0.82,1.20 |
0.94
| 0.85.1.05 |
0.84
| 0.73,0.97 |
>5 |
0.99
| 0.87,1.13 |
0.89
| 0.73,1.09 |
1.04
| 0.95,1.13 |
0.99
| 0.89,1.11 |
0.90
| 0.77,1.05 |
Trend testb
| 0.77 | 0.73 | 0.31 | 0.48 | 0.72 | |||||
HR in OS/HR in triald
| 1.04 | 0.91,1.18 | 1.15 | 0.97,1.35 | ||||||
Overall HRd
|
0.96
| 0.89, 1.04 |
0.88
| 0.78, 0.98 |
1.03
| 0.95, 1.11 |
Years from Supplement Initiation | Calcium only | Vitamin D only | CaD | Calcium only | Vitamin D only | CaD | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
HR | 95 % CI | HR | 95 % CI | HR | 95 % CI | HR | 95 % CI | HR | 95 % CI | HR | 95 % CI | |
Hip fracture | Total fracture | |||||||||||
<2 |
2.85
| 0.67,12.12 |
2.51
| 0.34,18.60 |
1.41
| 0.44,4.57 |
0.69
| 0.37,1.29 |
1.53
| 0.82,2.86 |
0.89
| 0.61,1.31 |
2–5 |
0.60
| 0.19,1.89 |
1.44
| 0.45,4.56 |
1.22
| 0.71,2.10 |
0.93
| 0.75,1.16 |
1.19
| 0.88,1.61 |
1.05
| 0.91,1.22 |
>5 |
0.82
| 0.58,1.15 |
1.17
| 0.73,1.86 |
0.84
| 0.66,1.07 |
1.00
| 0.91,1.09 |
1.02
| 0.88,1.18 |
1.08
| 1.01,1.14 |
Trend testa
| 0.49 | 0.48 | 0.14 | 0.26 | 0.15 | 0.42 | ||||||
Overall HRb
|
0.82
| 0.59, 1.14 |
1.23
| 0.80, 1.88 |
0.88
| 0.70,1.11 |
0.99
| 0.91,1.07 |
1.06
| 0.93,1.20 |
1.07
| 1.01,1.14 |
Myocardial infarction | Coronary heart disease | |||||||||||
<2 |
0.85
| 0.21,3.48 |
1.72
| 0.42,7.06 |
0.56
| 0.14,2.27 |
0.77
| 0.19,3.13 |
1.59
| 0.39,6.48 |
0.49
| 0.12,2.00 |
2–5 |
0.87
| 0.44,1.69 |
1.28
| 0.57,2.89 |
1.04
| 0.66,1.63 |
0.96
| 0.54,1.72 |
1.07
| 0.48,2.41 |
1.00
| 0.66,1.53 |
>5 |
0.71
| 0.53,0.97 |
0.99
| 0.67,1.47 |
0.89
| 0.73,1.08 |
0.74
| 0.56,0.97 |
1.02
| 0.72,1.45 |
0.88
| 0.74,1.05 |
Trend testa
| 0.60 | 0.38 | 0.94 | 0.53 | 0.61 | 0.88 | ||||||
Overall HRb
|
0.74
| 0.56, 0.97 |
1.06
| 0.75, 1.51 |
0.90
| 0.75,1.09 |
0.74
| 0.58,0.95 |
1.04
| 0.76,1.43 |
0.88
| 0.74,1.04 |
Total heart disease | Stroke | |||||||||||
<2 |
1.07
| 0.57,2.00 |
1.32
| 0.59,2.96 |
0.86
| 0.50,1.46 |
0.84
| 0.21,3.41 | NAc
|
0.47
| 0.12,1.89 | |
2–5 |
1.05
| 0.78,1.42 |
0.83
| 0.51,1.36 |
0.93
| 0.73,1.17 |
1.04
| 0.58,1.86 |
0.77
| 0.29,2.07 |
0.91
| 0.57,1.44 |
>5 |
0.95
| 0.82,1.10 |
0.97
| 0.78,1.20 |
0.87
| 0.79,0.97 |
0.81
| 0.62,1.07 |
0.82
| 0.55,1.23 |
0.93
| 0.77,1.11 |
Trend testa
| 0.47 | 0.82 | 0.83 | 0.47 | 0.45 | 0.28 | ||||||
Overall HRb
|
0.95
| 0.83, 1.08 |
0.96
| 0.79, 1.16 |
0.87
| 0.79,0.96 |
0.84
| 0.66,1.07 |
0.80
| 0.55,1.15 |
0.92
| 0.77,1.09 |
TOTAL CARDIOVASCULAR DISEASE | COLORECTAL CANCER | |||||||||||
<2 |
0.99
| 0.57,1.72 |
1.09
| 0.52,2.30 |
0.87
| 0.55,1.35 |
1.03
| 0.14,7.47 | NAc
|
0.94
| 0.23,3.87 | |
2–5 |
1.02
| 0.78,1.32 |
0.90
| 0.60,1.34 |
0.91
| 0.74,1.11 |
1.05
| 0.42,2.58 |
0.95
| 0.23,3.88 |
0.80
| 0.39,1.65 |
>5 |
0.89
| 0.79,1.01 |
0.92
| 0.76,1.10 |
0.86
| 0.79,0.94 |
1.01
| 0.66,1.55 |
0.64
| 0.28,1.46 |
0.83
| 0.60,1.14 |
Trend testa
| 0.31 | 0.81 | 0.84 | 0.96 | 0.91 | 0.96 | ||||||
Overall HRb
|
0.89
| 0.80,1.60 |
0.92
| 0.78,1.09 |
0.86
| 0.79,0.94 |
1.02
| 0.69,1.51 |
0.67
| 0.33,1.36 |
0.83
| 0.61,1.12 |
Breast cancer | Total invasive cancer | |||||||||||
<2 |
0.44
| 0.11,1.76 |
1.74
| 0.55,5.48 |
0.90
| 0.44,1.83 |
0.43
| 0.18,1.04 |
0.95
| 0.39,2.30 |
0.87
| 0.56,1.36 |
2–5 |
1.15
| 0.76,1.72 |
1.18
| 0.85,2.71 |
1.05
| 0.78,1.41 |
1.13
| 0.88,1.46 |
0.81
| 0.51,1.29 |
0.99
| 0.82,1.20 |
>5 |
1.18
| 0.98,1.42 |
1.11
| 0.62,1.23 |
1.14
| 1.00,1.30 |
1.12
| 0.99,1.26 |
1.05
| 0.87,1.28 |
1.04
| 0.95,1.13 |
Trend testa
| 0.30 | 0.07 | 0.42 | 0.18 | 0.40 | 0.31 | ||||||
Overall HRb
|
1.15
| 0.97,1.37 |
1.01
| 0.75,1.34 |
1.12
| 0.99.1.28 |
1.10
| 0.98,1.22 |
1.01
| 0.85,1.20 |
1.03
| 0.95,1.11 |
Death | ||||||||||||
<2 |
0.32
| 0.05,2.31 |
1.31
| 0.32,5.31 |
1.49
| 0.79,2.83 | ||||||
2–5 |
1.05
| 0.69,1.60 |
0.78
| 0.39,1.57 |
0.85
| 0.61,1.18 | ||||||
>5 |
0.93
| 0.80,1.09 |
1.09
| 0.87,1.35 |
0.95
| 0.85,1.06 | ||||||
Trend testa
| 0.81 | 0.60 | 0.71 | |||||||||
Overall HRb
|
0.94
| 0.81,1.09 |
1.06
| 0.86,1.30 |
0.95
| 0.85,1.06 |
Duration of CaD supplementation | All participants | No personal supplements | All participants | No personal supplements | ||||
---|---|---|---|---|---|---|---|---|
HR | 95 % CI | HR | 95 % CI | HR | 95 % CI | HR | 95 % CI | |
Hip fracture | Total fracture | |||||||
<2 |
0.62
| 0.33,1.15 |
0.88
| 0.32,2.43 |
0.95
| 0.83,1.08 |
0.87
| 0.70,1.06 |
2–5 |
0.83
| 0.50,1.37 |
0.66
| 0.28,1.52 |
0.90
| 0.79,1.03 |
0.91
| 0.73,1.13 |
>5 |
0.73
| 0.44,1.23 |
0.24
| 0.07,0.84 |
0.98
| 0.82,1.16 |
0.95
| 0.71,1.27 |
Trend testa
| 0.74 | 0.12 | 0.89 | 0.61 | ||||
Overall HRb
|
0.73
| 0.54, 1.00 |
0.55
| 0.32, 0.97 |
0.94
| 0.86, 1.02 |
0.90
| 0.78, 1.03 |
Myocardial infarction | Coronary heart disease | |||||||
<2 |
1.23
| 0.90,1.69 |
1.37
| 0.86,2.18 |
1.21
| 0.90,1.62 |
1.14
| 0.74,1.76 |
2–5 |
1.07
| 0.78,1.49 |
1.35
| 0.81,2.26 |
1.01
| 0.74,1.36 |
1.26
| 0.78,2.01 |
>5 |
0.82
| 0.55,1.21 |
0.78
| 0.43,1.41 |
0.88
| 0.61,1.26 |
0.82
| 0.47,1.41 |
Trend testa
| 0.12 | 0.17 | 0.17 | 0.40 | ||||
Overall HRb
|
1.06
| 0.87, 1.29 |
1.18
| 0.88, 1.59 |
1.04
| 0.87, 1.25 |
1.08
| 0.82, 1.42 |
Total heart disease | Stroke | |||||||
<2 |
1.06
| 0.89,1.25 |
1.05
| 0.82,1.34 |
0.81
| 0.57,1.14 |
1.01
| 0.63,1.64 |
2–5 |
1.01
| 0.85,1.19 |
1.00
| 0.77,1.31 |
1.19
| 0.85,1.67 |
1.73
| 0.99,3.01 |
>5 |
1.04
| 0.84,1.30 |
0.92
| 0.66,1.29 |
0.88
| 0.57,1.36 |
0.92
| 0.48,1.76 |
Trend testa
| 0.87 | 0.56 | 0.60 | 0.96 | ||||
Overall HRb
|
1.03
| 0.93, 1.15 |
1.00
| 0.86, 1.18 |
0.96
| 0.78, 1.19 |
1.18
| 0.86, 1.62 |
Total cardiovascular disease | Colorectal cancer | |||||||
<2 |
0.98
| 0.85,1.14 |
1.04
| 0.84,1.29 |
0.91
| 0.56,1.47 |
0.73
| 0.34,1.60 |
2–5 |
1.04
| 0.89,1.20 |
1.07
| 0.84,1.34 |
1.01
| 0.62,1.66 |
0.92
| 0.44,1.93 |
>5 |
1.06
| 0.88,1.29 |
0.98
| 0.73,1.31 |
1.10
| 0.59,2.07 |
0.71
| 0.27,1.88 |
Trend testa
| 0.49 | 0.77 | 0.63 | 0.98 | ||||
Overall HRb
|
1.02
| 0.93, 1.12 |
1.04
| 0.90, 1.19 |
0.99
| 0.73, 1.34 |
0.80
| 0.50, 1.27 |
Breast cancer | Total invasive cancer | |||||||
<2 |
0.96
| 0.73,1.27 |
0.90
| 0.58,1.39 |
0.97
| 0.82,1.14 |
0.94
| 0.71,1.23 |
2–5 |
0.85
| 0.66,1.10 |
0.60
| 0.39,0.92 |
0.86
| 0.74,1.02 |
0.70
| 0.53,0.92 |
>5 |
0.88
| 0.63,1.24 |
0.67
| 0.39,1.17 |
0.95
| 0.77,1.18 |
0.79
| 0.56,1.11 |
Trend testa
| 0.64 | 0.35 | 0.81 | 0.35 | ||||
Overall HRb
|
0.90
| 0.76, 1.06 |
0.71
| 0.55, 0.93 |
0.92
| 0.83, 1.02 |
0.80
| 0.68, 0.95 |
Death | ||||||||
<2 |
0.78
| 0.57,1.08 |
0.69
| 0.41,1.16 | ||||
2–5 |
0.81
| 0.63,1.04 |
0.82
| 0.54,1.26 | ||||
>5 |
1.06
| 0.80,1.41 |
1.02
| 0.65,1.59 | ||||
Trend testa
| 0.14 | 0.26 | ||||||
Overall HRb
|
0.88
| 0.75, 1.03 |
0.85
| 0.65, 1.11 |