Background
Methods
Study cohort and database
Enrolled participants and eligibility criteria
Identification of CRC, IBD, and IMIDs
Sample collection for FIT
Definition of variables
Laboratory measures | Limit values | |
---|---|---|
Male | Female | |
Blood haemoglobin, g/dL | ≥13 | ≥12 |
Serum creatinine, mg/dL | ≤1.5 | |
Serum total cholesterol, mg/dL | <200 | |
Serum triglyceride, mg/dL | <150 | |
Serum HDL-cholesterol, mg/dL | ≥60 | |
Serum LDL-cholesterol, mg/dL | <130 |
Statistical analysis
Results
Baseline characteristics of the FIT (+) and FIT (−) groups
Total cohort n=1,044,955 | FIT (−) n=815,361 | FIT (+) n=229,594 | p value | |
---|---|---|---|---|
Clinical parameter | ||||
Sex | <0.001 | |||
Male | 565,280 (54.1) | 436,092 (53.5) | 129,188 (56.3) | |
Female | 479,675 (45.9) | 379,269 (46.5) | 100,406 (43.7) | |
Age group at screening, years | <0.001 | |||
50–54 | 257,621 (24.7) | 194,292 (23.8) | 63,329 (27.6) | |
55–59 | 199,710 (19.1) | 152,024 (18.6) | 47,686 (20.8) | |
60–64 | 205,867 (19.7) | 158,717 (19.5) | 47,150 (20.5) | |
65–69 | 146,656 (14.0) | 114,319 (14.0) | 32,337 (14.1) | |
≥70 | 235,101 (22.5) | 196,009 (24.1) | 39,092 (17.0) | |
BMI, kg/m2 | 24.0 [22.1,26.0] | 24.0 [22.1,26.0] | 24.1 [22.2,26.1] | <0.001 |
Smoking status | <0.001 | |||
No | 754,426 (83.9) | 592,256 (84.0) | 162,170 (83.4) | |
Yes | 145,186 (16.1) | 112,858 (16.0) | 32,328 (16.6) | |
Alcohol drinking | <0.001 | |||
No | 709,427 (78.9) | 559,665 (79.4) | 149,762 (77.0) | |
Yes | 190,055 (21.1) | 145,337 (20.6) | 44,718 (23.0) | |
Exercise | <0.001 | |||
No | 297,913 (33.1) | 236,383 (33.5) | 61,530 (31.6) | |
Yes | 601,690 (66.9) | 468,718 (66.5) | 132,972 (68.4) | |
Insurance type | <0.001 | |||
Medical aid | 44,650 (4.3) | 35,631 (4.4) | 9,019 (3.9) | |
NHI | 100,265 (95.7) | 779,696 (95.6) | 220,569 (96.1) | |
Income status | <0.001 | |||
1st quantile | 208,136 (20.5) | 162,340 (20.5) | 45,796 (20.5) | |
2nd quantile | 145,115 (14.3) | 111,690 (14.1) | 33,425 (15.0) | |
3rd quantile | 170,324 (16.8) | 131,602 (16.6) | 38,722 (17.3) | |
4th quantile | 207,238 (20.4) | 161,637 (20.4) | 45,601 (20.4) | |
5th quantile | 285,505 (28.0) | 225,514 (28.4) | 59,991 (26.8) | |
Comorbidities | ||||
Hypertension | <0.001 | |||
No | 656,727 (87.8) | 518,754 (93.4) | 137,973 (92.5) | |
Yes | 47,872 (12.2) | 36,644 (6.6) | 11,228 (7.5) | |
Diabetes | <0.001 | |||
No | 656,727 (93.2) | 518,754 (93.4) | 137,973 (92.5) | |
Yes | 47,872 (6.8) | 36,644 (6.6) | 11,228 (7.5) | |
Dyslipidaemia | <0.001 | |||
No | 501,128 (67.1) | 397,006 (67.5) | 104,122 (65.4) | |
Yes | 246,187 (32.9) | 191,200 (32.5) | 54,987 (34.6) | |
Laboratory measures | ||||
Blood haemoglobin, g/dL | 13.8 [12.8,14.9] | 13.8 [12.9,14.9] | 13.8 [12.8,14.8] | <0.001 |
Serum creatinine, mg/dL | 0.9 [0.7,1.0] | 0.9 [0.7,1.0] | 0.9 [0.8,1.0] | <0.001 |
Serum total cholesterol, mg/dL | 197 [172,223] | 196 [172,222] | 198 [173,224] | <0.001 |
Serum triglycerides, mg/dL | 116 [82,167] | 116 [82,167] | 116 [81,168] | 0.011 |
Serum HDL-cholesterol, mg/dL | 52 [44,62] | 52 [44,61] | 52 [44,62] | <0.001 |
Serum LDL-cholesterol, mg/dL | 116 [93,140] | 116 [93,140] | 117 [94,141] | <0.001 |
Incidence of IMIDs at follow-up after FIT
Groups | Total number (%) | IR (95% CI) | Adjusted IR (95% CI)a | ||||||
---|---|---|---|---|---|---|---|---|---|
RA | SLE | PsA | RA | SLE | PsA | RA | SLE | PsA | |
Overall | 7645 (0.73) | 208 (0.02) | 101 (0.01) | 9.56 (9.35, 9.78) | 0.26 (0.23, 0.30) | 0.13 (0.10, 0.15) | - | - | - |
FIT (−) group (Ref.) | 5734 (0.70) | 157 (0.02) | 79 (0.01) | 9.28 (9.04, 9.52) | 0.25 (0.22, 0.30) | 0.13 (0.10, 0.16) | 8.96 (8.21, 9.78) | 0.23 (0.19, 0.28) | 0.14 (0.06, 0.34) |
FIT (+) group | 1911 (0.83) | 51 (0.02) | 22 (0.01) | 10.52 (10.06, 11.00) | 0.28 (0.21, 0.37) | 0.12 (0.08, 0.18) | 10.11 (9.26, 11.03) | 0.20 (0.17, 0.25) | 0.09 (0.04, 0.21) |
p value | 0.929 | 0.944 | 0.969 | 0.057 | 0.374 | 0.493 |
Groups | Total number | IR (95% CI) | Adjusted IR (95% CI)a | ||||||
---|---|---|---|---|---|---|---|---|---|
<1 year | 1–5 years | ≥5 years | <1 year | 1–5 years | ≥5 years | <1 year | 1–5 years | ≥5 years | |
Overall (n=7645) | |||||||||
Overall | 1359 | 4173 | 2113 | 13.06 (12.38, 13.77) | 8.21 (7.97, 8.46) | 2.70 (2.59, 2.82) | - | - | - |
FIT (-) group (Ref.) | 1038 | 3113 | 1583 | 12.78 (12.03, 13.59) | 7.87 (7.59, 8.15) | 2.62 (2.50, 2.75) | 11.89 (10.56, 13.38) | 7.56 (6.85, 8.33) | 2.60 (2.37, 2.86) |
FIT (+) Group | 321 | 1060 | 530 | 14.02 (12.57, 15.64) | 9.43 (8.88, 10.01) | 2.97 (2.72, 3.23) | 13.27 (11.79, 14.93) | 8.88 (8.06, 9.80) | 2.92 (2.65, 3.21) |
p value | 0.948 | 0.898 | 0.931 | 0.196 | 0.022 | 0.094 | |||
Seropositive RA (n=3184) | |||||||||
Overall | 553 | 1715 | 916 | 5.31 (4.89, 5.77) | 3.37 (3.21, 3.53) | 1.17 (1.09, 1.24) | - | - | - |
FIT (−) group (Ref.) | 428 | 1287 | 698 | 5.27 (4.80, 5.80) | 3.25 (3.07, 3.43) | 1.15 (1.07, 1.24) | 4.94 (3.77, 6.47) | 3.16 (2.84, 3.52) | 1.15 (1.06, 1.25) |
FIT (+) Group | 125 | 428 | 218 | 5.46 (4.58, 6.51) | 3.80 (3.45, 4.18) | 1.21 (1.06, 1.39) | 5.44 (4.15, 7.13) | 3.64 (3.27, 4.06) | 1.20 (1.10, 1.31) |
p value | 0.980 | 0.912 | 0.970 | 0.622 | 0.069 | 0.457 | |||
Seronegative RA (n=4461) | |||||||||
Overall | 806 | 2458 | 1197 | 7.74 (7.23, 8.30) | 4.83 (4.64, 5.03) | 1.53 (1.44, 1.61) | - | - | - |
FIT (−) group (Ref.) | 610 | 1826 | 885 | 7.51 (6.94, 8.13) | 4.61 (4.40, 4.82) | 1.46 (1.37, 1.56) | 7.04 (6.01, 8.26) | 4.39 (3.91, 4.93) | 1.45 (1.27, 1.65) |
FIT (+) Group | 196 | 632 | 312 | 8.56 (7.44, 9.85) | 5.61 (5.19, 6.07) | 1.74 (1.56, 1.95) | 7.51 (6.40, 8.80) | 5.19 (4.62, 5.83) | 1.70 (1.49, 1.93) |
p value | 0.927 | 0.889 | 0.902 | 0.581 | 0.046 | 0.087 |
RA | SLE | PsA | |
---|---|---|---|
Male, years | |||
Age 50–54 | 6.05 (4.86, 7.53) | 0.13 (0.11, 0.15) | 0.16 (0.12, 0.21) |
Age 55–59 | 6.27 (5.06, 7.77) | 0.12 (0.1, 0.14) | 0.15 (0.12, 0.2) |
Age 60–64 | 6.98 (5.66, 8.61) | 0.12 (0.1, 0.14) | 0.13 (0.1, 0.18) |
Age 65–69 | 7.13 (5.79, 8.78) | 0.13 (0.11, 0.15) | 0.09 (0.07, 0.12) |
Age ≥70 | 5.72 (4.66, 7.03) | 0.11 (0.09, 0.13) | 0.14 (0.1, 0.18) |
Female, years | |||
Age 50–54 | 12.52 (10.21, 15.36) | 0.44 (0.38, 0.51) | 0.13 (0.1, 0.17) |
Age 55–59 | 12.98 (10.55, 15.97) | 0.4 (0.34, 0.46) | 0.12 (0.09, 0.16) |
Age 60–64 | 14.45 (11.69, 17.87) | 0.41 (0.35, 0.48) | 0.11 (0.08, 0.14) |
Age 65–69 | 14.76 (11.91, 18.29) | 0.44 (0.38, 0.51) | 0.07 (0.05, 0.09) |
Age ≥70 | 11.84 (9.52, 14.73) | 0.37 (0.32, 0.43) | 0.11 (0.08, 0.14) |
Clinical and laboratory factors associated with RA development
Univariable analysis | Multivariable analysis | |||
---|---|---|---|---|
HR (95% CI) | p value | HR (95% CI) | p value | |
FIT result | ||||
Positive | 1.15 (1.08, 1.22) | <0.001 | 1.16 (1.09, 1.24) | <0.001 |
Negative | Ref. | Ref. | ||
Sex | ||||
Male | Ref. | Ref. | ||
Female | 2.19 (2.07, 2.31) | <0.001 | 2.15 (2.01, 2.29) | <0.001 |
Age group at screening, years | ||||
50–54 | 1.24 (1.14, 1.35) | <0.001 | 1.23 (1.13, 1.34) | <0.001 |
55–59 | 1.19 (1.08, 1.30) | <0.001 | 1.22 (1.11, 1.34) | <0.001 |
60–64 | 1.26 (1.15, 1.37) | <0.001 | 1.28 (1.18, 1.40) | <0.001 |
65–69 | 1.25 (1.13, 1.38) | <0.001 | 1.29 (1.17, 1.42) | <0.001 |
≥70 | Ref. | Ref. | ||
BMI | 1.00 (0.99, 1.01) | 0.664 | 1.00 (0.99, 1.01) | 0.750 |
Smoking status | ||||
No | Ref. | Ref. | ||
Yes | 0.67 (0.62, 0.73) | <0.001 | 1.04 (0.94, 1.14) | 0.460 |
Alcohol drinking | ||||
No | Ref. | Ref. | ||
Yes | 0.61 (0.57, 0.66) | <0.001 | 0.87 (0.80, 0.95) | 0.001 |
Exercise | ||||
No | 1.05 (1, 10.12) | 0.068 | 1.02 (0.97, 1.08) | 0.444 |
Yes | Ref. | Ref. | ||
Insurance type | ||||
Medial aid | Ref. | Ref. | ||
NHI | 0.98 (0.69, 1.38) | 0.890 | 1.06 (0.75, 1.49) | 0.744 |
Hypertension | ||||
No | Ref. | Ref. | ||
Yes | 0.92 (0.84, 1.01) | 0.070 | 0.98 (0.9, 1.08) | 0.683 |
Diabetes | ||||
No | Ref. | Ref. | ||
Yes | 0.79 (0.69, 0.89) | <0.001 | 0.89 (0.78, 1.01) | 0.076 |
Dyslipidaemia | ||||
No | Ref. | Ref. | ||
Yes | 0.95 (0.89, 1.00) | 0.068 | 1.00 (0.91, 1.10) | 0.975 |
Blood haemoglobin <13 g/dL for male and <12 g/dL for female | ||||
No | Ref. | Ref. | ||
Yes | 1.62 (1.19, 2.21) | 0.002 | 1.14 (0.84, 1.55) | 0.406 |
Serum creatinine > 1.5 mg/dL | ||||
No | Ref. | Ref. | ||
Yes | 0.92 (0.73, 1.16) | 0.480 | 1.08 (0.86, 1.36) | 0.515 |
Serum total cholesterol ≥ 200 mg/dL | ||||
No | Ref. | Ref. | ||
Yes | 1.03 (0.96, 1.10) | 0.404 | 0.96 (0.86, 1.06) | 0.386 |
Serum triglyceride ≥ 150 mg/dL | ||||
No | Ref. | Ref. | ||
Yes | 0.85 (0.79, 0.92) | <0.001 | 0.93 (0.84, 1.02) | 0.129 |
Serum HDL-cholesterol < 60 mg/dL | ||||
No | Ref. | Ref. | ||
Yes | 0.95 (0.88, 1.03) | 0.248 | 1.10 (1.01, 1.21) | 0.031 |
Serum LDL-cholesterol ≥130 mg/dL | ||||
No | Ref. | Ref. | ||
Yes | 1.04 (0.97, 1.11) | 0.276 | 0.95 (0.86, 1.06) | 0.384 |
Comparison of the incidence of RA in the matched population
Total cohort n=437,250 | FIT (−) n=291,500a | FIT (+) n=145,750a | p value | SMD | |
---|---|---|---|---|---|
Clinical parameter | |||||
Sex | 0.227 | 0.0033 | |||
Male | 246,455 (56.4) | 164,490 (56.4) | 81,965 (56.2) | ||
Female | 190,795 (43.6) | 127,010 (43.6) | 63,785 (43.8) | ||
Age group at screening, years | 0.738 | <0.001 | |||
50–54 | 131,325 (30.0) | 87,635 (30.1) | 43,690 (30.0) | ||
55–59 | 92,338 (21.1) | 61,530 (21.1) | 30,808 (21.1) | ||
60–64 | 92,705 (21.2) | 61,699 (21.2) | 31,006 (21.3) | ||
65–69 | 57,884 (13.2) | 38,527 (13.2) | 19,357 (13.3) | ||
≥70 | 62,998 (14.4) | 42,109 (14.4) | 20,889 (14.3) | ||
BMI, kg/m2 | 24.1 [22.2, 26.1] | 24.1 [22.1, 26.1] | 24.1 [22.3, 26.1] | 0.896 | 0.003 |
Smoking status | 0.744 | 0.001 | |||
No | 367,195 (84.0) | 244,834 (84.0) | 122,361 (84.0) | ||
Yes | 70,055 (16.0) | 46,666 (16.0) | 23,389 (16.0) | ||
Alcohol drinking | 0.541 | 0.002 | |||
No | 340,638 (77.9) | 227,013 (77.9) | 113,625 (78.0) | ||
Yes | 96,612 (22.1) | 64,487 (22.1) | 32,125 (22.0) | ||
Exercise | 0.790 | <0.001 | |||
No | 134,288 (30.7) | 89,487 (30.7) | 44,801 (30.7) | ||
Yes | 302,962 (69.3) | 202,013 (69.3) | 100,949 (69.3) | ||
Insurance type | 0.223 | <0.001 | |||
Medical aid | 2,336 (0.5) | 1,585 (0.5) | 751 (0.5) | ||
NHI | 434,914 (99.5) | 289,915 (99.5) | 144,999 (99.5) | ||
Comorbidities | |||||
Hypertension | 0.657 | 0.001 | |||
No | 390,814 (89.4) | 260,500 (89.4) | 130,314 (89.4) | ||
Yes | 46,436 (10.6) | 31,000 (10.6) | 15,436 (10.6) | ||
Diabetes | 0.709 | 0.001 | |||
No | 410,481 (93.9) | 273,626 (93.9) | 136,855 (93.9) | ||
Yes | 26,769 (6.1) | 17,874 (6.1) | 8,895 (6.1) | ||
Dyslipidaemia | 0.402 | 0.003 | |||
No | 310,009 (70.9) | 206,554 (70.9) | 103,455 (71.0) | ||
Yes | 127,241 (29.1) | 84,946 (29.1) | 42,295 (29.0) | ||
Laboratory measures | |||||
Blood haemoglobin, g/dL | 13.8 [12.8,14.9] | 13.8 [12.8,14.9] | 13.8 [12.8,14.9] | 0.002 | 0.001 |
Serum creatinine, mg/dL | 0.9 [0.8,1.0] | 0.9 [0.8,1.0] | 0.9 [0.8,1.0] | <0.001 | 0.005 |
Serum total cholesterol, mg/dL | 198 [174,224] | 198 [174,224] | 198 [174,224] | 0.304 | 0.004 |
Serum triglycerides, mg/dL | 116 [81,167] | 116 [82,166] | 16 [81,167] | 0.318 | <0.001 |
Serum HDL-cholesterol, mg/dL | 52 [44,61] | 52 [44,61] | 52 [44,62] | <0.001 | <0.001 |
Serum LDL-cholesterol, mg/dL | 118 [95,142] | 118 [95,142] | 18 [95,142] | 0.058 | 0.003 |