Antihypertensive Drugs and the Risk of Cancer: A Nationwide Cohort Study
Abstract
:1. Introduction
2. Methods
2.1. Study Population
2.2. Definition of Cancer
2.3. Assessment of Antihypertensive Drug Use
2.4. Other Covariates
2.5. Data Source
2.6. Statistical Analysis
3. Results
3.1. Study Population
3.2. Cancer Risk by Antihypertensive Medication
3.3. Risk Trends by Duration of ARB Use and Subgroups
4. Discussion
Limitations
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Variable | All Users | ACEI | ARB | BB | CCB | Diuretics |
---|---|---|---|---|---|---|
Number, N | 70,549 | 4210 | 55,645 | 13,158 | 51,036 | 32,990 |
Number of overall cancers, N (%) | 4513 (6.4) | 362 (8.6) | 3294 (5.9) | 982 (7.5) | 3443 (6.8) | 2155 (6.5) |
Follow-up, years | 8.6 (6.7–10.8) | 10.7 (8.4–12.0) | 8.5 (6.7–10.7) | 10.0 (7.7–11.8) | 8.8 (6.9–11.0) | 9.1 (7.2–11.3) |
Drug exposure duration, years | - | 3.3 (1.8–5.6) | 5.5 (3.5–7.2) | 3.8 (2.1–6.4) | 5.3 (3.0–7.6) | 4.1 (2.2–6.2) |
Deaths, N (%) | 3025 (4.3) | 353 (8.4) | 2050 (3.7) | 741 (5.6) | 2333 (4.6) | 1542 (4.7) |
Age, years | 55.2 ± 9.2 | 57.0 ± 9.5 | 54.5 ± 9.0 | 55.4 ± 9.2 | 55.4 ± 9.2 | 55.4 ± 9.3 |
Male sex, N (%) | 42,990 (60.9) | 3001 (71.3) | 35,113 (63.1) | 8270 (62.9) | 31,668 (62.1) | 19,747 (59.9) |
BMI, kg/m2 | 24.9 ± 3.0 | 24.7 ± 3.0 | 25.1 ± 3.0 | 25.0 ± 3.1 | 25.0 ± 3.0 | 25.2 ± 3.1 |
SBP, mmHg | 139.7 ± 18.3 | 138.2 ± 19.6 | 140.5 ± 18.4 | 141.5 ± 21.1 | 141.8 ± 18.5 | 142.3 ± 19.0 |
Smoking, N (%) | ||||||
Current | 16,214 (23.0) | 1053 (25.0) | 13,525 (24.3) | 3249 (24.7) | 12,277 (24.1) | 7882 (23.9) |
Past smoker | 12,155 (17.2) | 712 (16.9) | 9872 (17.7) | 1979 (15.0) | 8509 (16.7) | 5050 (15.3) |
Never-smoker | 42,180 (59.8) | 2445 (58.1) | 32,248 (58.0) | 7930 (60.3) | 30,250 (59.3) | 20,058 (60.8) |
Alcohol, N (%) | ||||||
None | 35,575 (50.4) | 2181 (51.8) | 26,871 (48.3) | 6759 (51.4) | 24,965 (48.9) | 16,387 (49.7) |
1–2/week | 22,265 (31.6) | 1323 (31.4) | 18,146 (32.6) | 4109 (31.2) | 16,322 (32.0) | 10,370 (31.4) |
3–4/week | 8302 (11.8) | 431 (10.2) | 6969 (12.5) | 1484 (11.3) | 6308 (12.4) | 3978 (12.1) |
≥5/week | 4407 (6.3) | 275 (6.5) | 3659 (6.6) | 806 (6.1) | 3441 (6.7) | 2255 (6.8) |
Income, N (%) | ||||||
Low (1st-3rd deciles) | 17,221 (24.4) | 1000 (23.8) | 13,456 (24.2) | 3374 (25.6) | 12,635 (24.8) | 8444 (25.6) |
Middle (4th-7th deciles) | 23,982 (34.0) | 1458 (34.6) | 19,006 (34.2) | 4596 (34.9) | 17,676 (34.6) | 11,720 (35.5) |
High (8th-10th deciles) | 29,346 (41.6) | 1752 (41.6) | 23,183 (41.7) | 5188 (39.4) | 20,725 (40.6) | 12,826 (38.9) |
Comorbidities | ||||||
Diabetes, N (%) | 13,382 (19.0) | 1156 (27.5) | 10,854 (19.5) | 1996 (15.2) | 8172 (16.0) | 5573 (16.9) |
Heart failure, N (%) | 216 (0.3) | 29 (0.7) | 154 (0.3) | 57 (0.4) | 113 (0.2) | 86 (0.3) |
COPD, N (%) | 1704 (2.4) | 102 (2.4) | 1227 (2.2) | 270 (2.1) | 1127 (2.2) | 752 (2.3) |
Variable | Follow-Up (Person Years) | Cancer Incidence, N | Incident Rate (per 1000 Person Years) | Unadjusted | Age- and Sex-Adjusted | Fully Adjusted | ||||
---|---|---|---|---|---|---|---|---|---|---|
HR | 95% CI | HR | 95% CI | HR | 95% CI | |||||
ACEI | No | 566,817 | 4151 | 7.32 | 1.000 (reference) | 1.000 (reference) | 1.000 (reference) | |||
Yes | 41,995 | 362 | 8.62 | 1.148 | 1.031–1.277 | 1.022 | 0.918–1.138 | 1.016 | 0.912–1.132 | |
ARB | No | 130,144 | 1219 | 9.37 | 1.000 (reference) | 1.000 (reference) | 1.000 (reference) | |||
Yes | 478,668 | 3294 | 6.88 | 0.744 | 0.696–0.794 | 0.822 | 0.769–0.878 | 0.833 | 0.775–0.896 | |
BB | No | 483,462 | 3531 | 7.30 | 1.000 (reference) | 1.000 (reference) | 1.000 (reference) | |||
Yes | 125,350 | 982 | 7.83 | 1.055 | 0.983–1.132 | 1.033 | 0.962–1.109 | 1.03 | 0.958–1.107 | |
CCB | No | 158,876 | 1070 | 6.73 | 1.000 (reference) | 1.000 (reference) | 1.000 (reference) | |||
Yes | 449,937 | 3443 | 7.65 | 1.124 | 1.049–1.204 | 1.081 | 1.009–1.158 | 1.053 | 0.981–1.13 | |
Diuretics | No | 309,741 | 2358 | 7.61 | 1.000 (reference) | 1.000 (reference) | 1.000 (reference) | |||
Yes | 299,071 | 2155 | 7.21 | 0.936 | 0.883–0.992 | 0.92 | 0.868–0.976 | 0.957 | 0.898–1.019 |
Variable | Follow-Up (Person Years) | Cancer Incidence, N | Incident Rate (per 1000 Person Years) | Unadjusted | Age- and Sex-Adjusted | Fully Adjusted | ||||
---|---|---|---|---|---|---|---|---|---|---|
HR | 95% CI | HR | 95% CI | HR | 95% CI | |||||
Lung cancer | ||||||||||
ACEI | No | 581,613 | 509 | 0.88 | 1.000 (reference) | 1.000 (reference) | 1.000 (reference) | |||
Yes | 43,359 | 54 | 1.25 | 1.335 | 1.009–1.768 | 1.019 | 0.768–1.351 | 0.998 | 0.752–1.326 | |
ARB | No | 134,482 | 159 | 1.18 | 1.000 (reference) | 1.000 (reference) | 1.000 (reference) | |||
Yes | 490,490 | 404 | 0.82 | 0.716 | 0.595–0.861 | 0.843 | 0.699–1.015 | 0.86 | 0.705–1.049 | |
BB | No | 495,930 | 433 | 0.87 | 1.000 (reference) | 1.000 (reference) | 1.000 (reference) | |||
Yes | 129,042 | 130 | 1.01 | 1.1 | 0.904–1.339 | 1.046 | 0.859–1.274 | 1.053 | 0.861–1.288 | |
CCB | No | 162,677 | 117 | 0.72 | 1.000 (reference) | 1.000 (reference) | 1.000 (reference) | |||
Yes | 462,295 | 446 | 0.96 | 1.298 | 1.06–1.59 | 1.186 | 0.968–1.453 | 1.186 | 0.965–1.458 | |
Diuretics | No | 318,319 | 283 | 0.89 | 1.000 (reference) | 1.000 (reference) | 1.000 (reference) | |||
Yes | 306,652 | 280 | 0.91 | 0.993 | 0.843–1.171 | 0.964 | 0.817–1.137 | 1.019 | 0.853–1.216 | |
Colorectal cancer | ||||||||||
ACEI | No | 580,493 | 589 | 1.01 | 1.000 (reference) | 1.000 (reference) | 1.000 (reference) | |||
Yes | 43,172 | 61 | 1.41 | 1.332 | 1.021–1.737 | 1.105 | 0.847–1.442 | 1.118 | 0.858–1.456 | |
ARB | No | 134,149 | 176 | 1.31 | 1.000 (reference) | 1.000 (reference) | 1.000 (reference) | |||
Yes | 489,516 | 474 | 0.97 | 0.755 | 0.635–0.898 | 0.868 | 0.728–1.036 | 0.857 | 0.711–1.031 | |
BB | No | 494,933 | 502 | 1.01 | 1.000 (reference) | 1.000 (reference) | 1.000 (reference) | |||
Yes | 128,732 | 148 | 1.15 | 1.098 | 0.914–1.2318 | 1.062 | 0.884–1.276 | 1.029 | 0.856–1.236 | |
CCB | No | 162,441 | 133 | 0.82 | 1.000 (reference) | 1.000 (reference) | 1.000 (reference) | |||
Yes | 461,224 | 517 | 1.12 | 1.342 | 1.108–1.624 | 1.258 | 1.039–1.524 | 1.178 | 0.968–1.432 | |
Diuretics | No | 317,700 | 319 | 1.00 | 1.000 (reference) | 1.000 (reference) | 1.000 (reference) | |||
Yes | 305,965 | 331 | 1.08 | 1.056 | 0.906–1.23 | 1.033 | 0.886–1.204 | 1.031 | 0.877–1.213 | |
Hepatic cancer | ||||||||||
ACEI | No | 581,886 | 346 | 0.59 | 1.000 (reference) | 1.000 (reference) | 1.000 (reference) | |||
Yes | 43,403 | 28 | 0.65 | 1.029 | 0.704–1.504 | 0.833 | 0.568–1.223 | 0.795 | 0.542–1.605 | |
ARB | No | 134,553 | 108 | 0.80 | 1.000 (reference) | 1.000 (reference) | 1.000 (reference) | |||
Yes | 490,736 | 266 | 0.54 | 0.69 | 0.551–0.864 | 0.692 | 0.552–0.868 | 0.665 | 0.519–0.851 | |
BB | No | 496,177 | 292 | 0.59 | 1.000 (reference) | 1.000 (reference) | 1.000 (reference) | |||
Yes | 129,111 | 82 | 0.64 | 1.042 | 0.817–1.329 | 0.995 | 0.78–1.269 | 0.992 | 0.776–1.269 | |
CCB | No | 162,754 | 79 | 0.49 | 1.000 (reference) | 1.000 (reference) | 1.000 (reference) | |||
Yes | 462,535 | 295 | 0.64 | 1.286 | 1.002–1.65 | 1.205 | 0.939–1.547 | 1.184 | 0.918–1.528 | |
Diuretics | No | 318,441 | 197 | 0.62 | 1.000 (reference) | 1.000 (reference) | 1.000 (reference) | |||
Yes | 306,848 | 177 | 0.58 | 0.911 | 0.745–1.114 | 0.916 | 0.748–1.121 | 1.02 | 0.818–1.271 | |
Gastric cancer | ||||||||||
ACEI | No | 580,103 | 681 | 1.17 | 1.000 (reference) | 1.000 (reference) | 1.000 (reference) | |||
Yes | 43,157 | 74 | 1.71 | 1.427 | 1.123–1.812 | 1.151 | 0.904–1.466 | 1.16 | 0.91–1.479 | |
ARB | No | 133,969 | 217 | 1.62 | 1.000 (reference) | 1.000 (reference) | 1.000 (reference) | |||
Yes | 489,291 | 538 | 1.10 | 0.691 | 0.59–0.81 | 0.763 | 0.65–1.895 | 0.759 | 0.636–0.906 | |
BB | No | 494,612 | 597 | 1.21 | 1.000 (reference) | 1.000 (reference) | 1.000 (reference) | |||
Yes | 128,648 | 158 | 1.23 | 1 | 0.839–1.192 | 0.96 | 0.805–1.143 | 0.937 | 0.784–1.119 | |
CCB | No | 162,142 | 200 | 1.23 | 1.000 (reference) | 1.000 (reference) | 1.000 (reference) | |||
Yes | 461,118 | 555 | 1.20 | 0.963 | 0.819–1.132 | 0.897 | 0.763–1.055 | 0.823 | 0.694–0.976 | |
Diuretics | No | 317,323 | 407 | 1.28 | 1.000 (reference) | 1.000 (reference) | 1.000 (reference) | |||
Yes | 305,937 | 348 | 1.14 | 0.877 | 0.76–1.011 | 0.865 | 0.75–0.998 | 0.904 | 0.772–1.059 | |
Bladder cancer | ||||||||||
ACEI | No | 582,117 | 155 | 0.27 | 1.000 (reference) | 1.000 (reference) | 1.000 (reference) | |||
Yes | 43,386 | 18 | 0.41 | 1.49 | 0.914–2.429 | 1.096 | 0.671–1.79 | 1.078 | 0.65–1.788 | |
ARB | No | 134,664 | 46 | 0.34 | 1.000 (reference) | 1.000 (reference) | 1.000 (reference) | |||
Yes | 490,839 | 127 | 0.26 | 0.774 | 0.553–1.084 | 0.884 | 0.629–1.244 | 0.996 | 0.693–1.433 | |
BB | No | 496,417 | 122 | 0.25 | 1.000 (reference) | 1.000 (reference) | 1.000 (reference) | |||
Yes | 129,087 | 51 | 0.40 | 1.564 | 1.123–2.179 | 1.474 | 1.057–2.054 | 1.505 | 1.074–2.108 | |
CCB | No | 162,790 | 37 | 0.23 | 1.000 (reference) | 1.000 (reference) | 1.000 (reference) | |||
Yes | 462,714 | 136 | 0.29 | 1.269 | 0.882–1.826 | 1.151 | 0.8–1.657 | 1.135 | 0.78–1.651 | |
Diuretics | No | 318,566 | 95 | 0.30 | 1.000 (reference) | 1.000 (reference) | 1.000 (reference) | |||
Yes | 306,937 | 78 | 0.25 | 0.836 | 0.618–1.13 | 0.819 | 0.606–1.109 | 0.781 | 0.562–1.085 | |
Breast cancer | ||||||||||
ACEI | No | 581,459 | 267 | 0.46 | 1.000 (reference) | 1.000 (reference) | 1.000 (reference) | |||
Yes | 43,407 | 8 | 0.18 | 0.413 | 0.204–0.836 | 0.599 | 0.296–1.212 | 0.609 | 0.299–1.24 | |
ARB | No | 134,451 | 71 | 0.53 | 1.000 (reference) | 1.000 (reference) | 1.000 (reference) | |||
Yes | 490,416 | 204 | 0.42 | 0.792 | 0.604–1.038 | 0.936 | 0.713–1.229 | 1.05 | 0.777–1.418 | |
BB | No | 495,860 | 216 | 0.44 | 1.000 (reference) | 1.000 (reference) | 1.000 (reference) | |||
Yes | 129,007 | 59 | 0.46 | 1.08 | 0.809–1.442 | 1.154 | 0.865–1.541 | 1.203 | 0.895–1.617 | |
CCB | No | 162,611 | 67 | 0.41 | 1.000 (reference) | 1.000 (reference) | 1.000 (reference) | |||
Yes | 462,256 | 208 | 0.45 | 1.114 | 0.884–1.468 | 1.263 | 0.957–1.667 | 1.194 | 0.896–1.593 | |
Diuretics | No | 318,193 | 154 | 0.48 | 1.000 (reference) | 1.000 (reference) | 1.000 (reference) | |||
Yes | 306,674 | 121 | 0.39 | 0.834 | 0.657–1.058 | 0.799 | 0.63–1.014 | 0.747 | 0.575–0.972 | |
Prostate cancer | ||||||||||
ACEI | No | 581,622 | 298 | 0.51 | 1.000 (reference) | 1.000 (reference) | 1.000 (reference) | |||
Yes | 43,328 | 28 | 0.65 | 1.165 | 0.789–1.719 | 0.791 | 0.534–1.71 | 0.764 | 0.513–1.137 | |
ARB | No | 134,514 | 82 | 0.61 | 1.000 (reference) | 1.000 (reference) | 1.000 (reference) | |||
Yes | 490,436 | 244 | 0.50 | 0.84 | 0.654–1.08 | 0.954 | 0.739–1.232 | 0.974 | 0.741–1.279 | |
BB | No | 495,889 | 248 | 0.50 | 1.000 (reference) | 1.000 (reference) | 1.000 (reference) | |||
Yes | 129,060 | 78 | 0.60 | 1.144 | 0.888–1.474 | 1.057 | 0.82–1.362 | 1.099 | 0.848–1.425 | |
CCB | No | 162,608 | 88 | 0.54 | 1.000 (reference) | 1.000 (reference) | 1.000 (reference) | |||
Yes | 462,342 | 238 | 0.51 | 0.917 | 0.717–1.172 | 0.813 | 0.635–1.041 | 0.85 | 0.657–1.1 | |
Diuretics | No | 318,213 | 173 | 0.54 | 1.000 (reference) | 1.000 (reference) | 1.000 (reference) | |||
Yes | 306,737 | 153 | 0.50 | 0.883 | 0.712–1.096 | 0.865 | 0.697–1.074 | 0.892 | 0.707–1.125 | |
Pancreatic cancer | ||||||||||
ACEI | No | 582,672 | 90 | 0.15 | 1.000 (reference) | 1.000 (reference) | 1.000 (reference) | |||
Yes | 43,445 | 7 | 0.16 | 0.959 | 0.446–2.064 | 0.827 | 0.383–1.787 | 0.893 | 0.421–1.897 | |
ARB | No | 134,810 | 26 | 0.19 | 1.000 (reference) | 1.000 (reference) | 1.000 (reference) | |||
Yes | 491,306 | 71 | 0.14 | 0.774 | 0.493–1.226 | 0.865 | 0.55–1.361 | 0.771 | 0.474–1.254 | |
BB | No | 496,794 | 86 | 0.17 | 1.000 (reference) | 1.000 (reference) | 1.000 (reference) | |||
Yes | 129,323 | 11 | 0.09 | 0.459 | 0.246–0.857 | 0.448 | 0.24–0.837 | 0.447 | 0.243–0.822 | |
CCB | No | 162,924 | 19 | 0.12 | 1.000 (reference) | 1.000 (reference) | 1.000 (reference) | |||
Yes | 463,193 | 78 | 0.17 | 1.383 | 0.84–2.277 | 1.316 | 0.799–2.167 | 1.326 | 0.797–2.206 | |
Diuretics | No | 318,887 | 47 | 0.15 | 1.000 (reference) | 1.000 (reference) | 1.000 (reference) | |||
Yes | 307,230 | 50 | 0.16 | 1.057 | 0.712–1.571 | 1.039 | 0.699–1.545 | 1.189 | 0.774–1.827 | |
Kidney cancer | ||||||||||
ACEI | No | 582,302 | 110 | 0.19 | 1.000 (reference) | 1.000 (reference) | 1.000 (reference) | |||
Yes | 43,414 | 10 | 0.23 | 1.241 | 0.656–2.347 | 1.123 | 0.594–2.124 | 1.102 | 0.577–2.105 | |
ARB | No | 134,721 | 28 | 0.21 | 1.000 (reference) | 1.000 (reference) | 1.000 (reference) | |||
Yes | 490,995 | 92 | 0.19 | 0.909 | 0.595–1.389 | 0.881 | 0.576–1.347 | 0.846 | 0.534–1.339 | |
BB | No | 496,511 | 93 | 0.19 | 1.000 (reference) | 1.000 (reference) | 1.000 (reference) | |||
Yes | 129,205 | 27 | 0.21 | 1.135 | 0.737–1.749 | 1.111 | 0.721–1.712 | 1.084 | 0.692–1.698 | |
CCB | No | 162,840 | 25 | 0.15 | 1.000 (reference) | 1.000 (reference) | 1.000 (reference) | |||
Yes | 462,876 | 95 | 0.21 | 1.353 | 0.867–2.11 | 1.309 | 0.838–2.045 | 1.328 | 0.845–2.088 | |
Diuretics | No | 318,716 | 59 | 0.19 | 1.000 (reference) | 1.000 (reference) | 1.000 (reference) | |||
Yes | 307,000 | 61 | 0.20 | 1.089 | 0.762–1.556 | 1.099 | 0.769–1.57 | 1.127 | 0.766–1.658 |
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Cho, I.-J.; Shin, J.-H.; Jung, M.-H.; Kang, C.Y.; Hwang, J.; Kwon, C.H.; Kim, W.; Kim, D.-H.; Lee, C.J.; Kang, S.-H.; et al. Antihypertensive Drugs and the Risk of Cancer: A Nationwide Cohort Study. J. Clin. Med. 2021, 10, 771. https://doi.org/10.3390/jcm10040771
Cho I-J, Shin J-H, Jung M-H, Kang CY, Hwang J, Kwon CH, Kim W, Kim D-H, Lee CJ, Kang S-H, et al. Antihypertensive Drugs and the Risk of Cancer: A Nationwide Cohort Study. Journal of Clinical Medicine. 2021; 10(4):771. https://doi.org/10.3390/jcm10040771
Chicago/Turabian StyleCho, In-Jeong, Jeong-Hun Shin, Mi-Hyang Jung, Chae Young Kang, Jinseub Hwang, Chang Hee Kwon, Woohyeun Kim, Dae-Hee Kim, Chan Joo Lee, Si-Hyuck Kang, and et al. 2021. "Antihypertensive Drugs and the Risk of Cancer: A Nationwide Cohort Study" Journal of Clinical Medicine 10, no. 4: 771. https://doi.org/10.3390/jcm10040771
APA StyleCho, I.-J., Shin, J.-H., Jung, M.-H., Kang, C. Y., Hwang, J., Kwon, C. H., Kim, W., Kim, D.-H., Lee, C. J., Kang, S.-H., Lee, J.-H., Kim, H.-L., Kim, H. M., Cho, I., Lee, H.-Y., Chung, W.-J., Ihm, S.-H., Kim, K. I., Cho, E. J., ... Sung, K.-C. (2021). Antihypertensive Drugs and the Risk of Cancer: A Nationwide Cohort Study. Journal of Clinical Medicine, 10(4), 771. https://doi.org/10.3390/jcm10040771