The Association of Diabetic Retinopathy and Cardiovascular Disease: A 13-Year Nationwide Population-Based Cohort Study
Abstract
:1. Introduction
2. Materials and Methods
2.1. Sources of Data
2.2. Definitions of Primary Events
2.3. Statistical Analysis
3. Results
3.1. Demographics
3.2. Analysis of the Incidence of CVD
3.3. Adjusted Hazard Ratios of CVD among All Study Groups
3.4. Adjusted Hazard Ratios of CVD among the Diabetic Population
3.5. Stratified Analysis of CVD among All Study Groups
3.6. Stratified Analysis of CVD among the Diabetic Population
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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ICD-9 | Diagnosis | ICD-9 | Diagnosis |
---|---|---|---|
410.00–410.92 | Myocardial infarction | 402.91 | Unspecified hypertensive heart disease with congestive heart failure |
412 | Old myocardial infarction | 404.01 | Malignant hypertensive heart and renal disease with congestive heart failure |
414.00–414.05 | Coronary atherosclerosis | 404.03 | Malignant hypertensive heart and renal disease with congestive heart failure and renal failure |
414.2 | Chronic total occlusion of coronary artery | 404.11 | Benign hypertensive heart and renal disease with congestive heart failure |
414.3 | Coronary atherosclerosis due to lipid rich plaque | 404.13 | Benign hypertensive heart and renal disease with congestive heart failure and renal failure |
414.4 | Coronary atherosclerosis due to calcified coronary lesion | 404.91 | Unspecified hypertensive heart and renal disease with congestive heart failure |
414.8 | Other specified forms of chronic ischemic heart disease | 404.93 | Unspecified hypertensive heart and renal disease with congestive heart failure and renal failure |
414.9 | Chronic ischemic heart disease, unspecified | 425.4–425.9 | Cardiomyopathies |
398.91 | Rheumatic heart failure (congestive) | 428.0–428.9 | Congestive heart failure |
402.01 | Malignant hypertensive heart disease with congestive heart failure | 433.00–433.91 | Occlusion and stenosis of basilar artery |
402.11 | Benign hypertensive heart disease with congestive heart failure | 434.00–434.91 | Cerebral infarction, unspecified |
435.0~435.9 | Transient cerebral ischemia |
DM with DR n = 2644 | DM without DR n = 10,576 | Non-DM n = 10,576 | p-Value 1 | p-Value 2 | |
---|---|---|---|---|---|
Age | 1.0000 | 1.0000 | |||
< 40 | 175 (6.6%) | 700 (6.6%) | 700 (6.6%) | ||
40–59 | 1519 (57.5%) | 6076 (57.5%) | 6076 (57.5%) | ||
60–79 | 917 (34.7%) | 3668 (34.7%) | 3668 (34.7%) | ||
≥ 80 | 33 (1.3%) | 132 (1.3%) | 132 (1.3%) | ||
Gender | 1.0000 | 1.0000 | |||
Male | 1238 (46.8%) | 4952 (46.8%) | 4952 (46.8%) | ||
Female | 1406 (53.2%) | 5624 (53.2%) | 5624 (53.2%) | ||
Comorbidity | |||||
Hypertension | 1627 (61.5%) | 5994 (56.7%) | 2651 (25.1%) | <0.0001 | <0.0001 |
Hyperlipidemia | 1575 (59.6%) | 6299 (59.6%) | 1846 (17.5%) | <0.0001 | 1.0000 |
Dementia | 15 (0.6%) | 118 (1.1%) | 74 (0.7%) | 0.9131 | 0.0230 |
Chronic pulmonary disease | 566 (21.4%) | 2790 (26.4%) | 2049 (19.4%) | 0.0378 | <0.0001 |
Rheumatic disease | 64 (2.4%) | 340 (3.2%) | 267 (2.5%) | 1.0000 | 0.0676 |
Renal disease | 316 (12.0%) | 880 (8.3%) | 380 (3.6%) | <0.0001 | <0.0001 |
Hepatitis and liver cirrhosis | 766 (29.0%) | 4372 (41.3%) | 2069 (19.6%) | <0.0001 | <0.0001 |
Alcoholic liver disease | 58 (2.2%) | 350 (3.3%) | 96 (0.9%) | <0.0001 | 0.0060 |
Gout | 379 (14.3%) | 2317 (21.9%) | 1072 (10.1%) | <0.0001 | <0.0001 |
Atopic dermatitis | 74 (2.8%) | 396 (3.7%) | 336 (3.2%) | 0.6313 | 0.0377 |
ENT allergies | 403 (15.2%) | 2046 (19.4%) | 1782 (16.9%) | 0.0931 | <0.0001 |
Eye disease | |||||
Keratopathy | 280 (10.6%) | 714 (6.8%) | 640 (6.1%) | <0.0001 | <0.0001 |
Dry eye syndrome | 310 (11.7%) | 805 (7.6%) | 629 (6.0%) | <0.0001 | <0.0001 |
Uveitis | 144 (5.5%) | 101 (1.0%) | 75 (0.7%) | <0.0001 | <0.0001 |
Glaucoma | 213 (8.1%) | 306 (2.9%) | 221 (2.1%) | <0.0001 | <0.0001 |
Age-related macular degeneration | 130 (4.9%) | 106 (1.0%) | 98 (0.9%) | <0.0001 | <0.0001 |
Cataracts | 1417 (53.6%) | 1726 (16.3%) | 1267 (12.0%) | <0.0001 | <0.0001 |
Retinopathy after vitrectomy | 130 (4.9%) | 19 (0.2%) | 46 (0.4%) | <0.0001 | <0.0001 |
Concomitant drug | |||||
Systemic steroids | 587 (22.2%) | 2038 (19.3%) | 1483 (14.0%) | <0.0001 | 0.0015 |
Topical steroids | 1526 (57.7%) | 1655 (15.7%) | 1367 (12.9%) | <0.0001 | <0.0001 |
Antipsychotics | 166 (6.3%) | 515 (4.9%) | 285 (2.7%) | <0.0001 | 0.0067 |
Antiarrhythmics | 11 (0.4%) | 37 (0.4%) | 23 (0.2%) | 0.1428 | 1.0000 |
Hypolipidemics | 848 (32.1%) | 2558 (24.2%) | 390 (3.7%) | <0.0001 | <0.0001 |
Hypoglycemics | 1984 (75.0%) | 5105 (48.3%) | 185 (1.8%) | <0.0001 | <0.0001 |
Duration of DM (year) | - | 1.0000 | |||
0 | 0 (0.0%) | 0 (0.0%) | 10,576 (100.0%) | ||
<2 | 1311 (49.6%) | 5244 (49.6%) | 0 (0.0%) | ||
2–5 | 749 (28.3%) | 2996 (28.3%) | 0 (0.0%) | ||
≥5 | 584 (22.1%) | 2336 (22.1%) | 0 (0.0%) | ||
Type of retinopathy | - | - | |||
Non-retinopathic | 0 (0.0%) | 10,576 (100.0%) | 0 (0.0%) | ||
NPDR | 1326 (50.2%) | 0 (0.0%) | 0 (0.0%) | ||
PDR | 1318 (49.9%) | 0 (0.0%) | 0 (0.0%) |
DM with DR n = 2644 | DM without DR n = 10,576 | Non-DM n = 10,576 | |
---|---|---|---|
Observed person-months | 136,873 | 571,430 | 627,706 |
Newly diagnosed CVD | 611 | 1873 | 1009 |
Incidence * (95% C.I.) | 44.64 (41.24–48.32) | 32.78 (31.33–34.30) | 16.07 (15.11–17.10) |
Crude relative risk (95% C.I.) | 2.750 (2.487–3.040) | 2.026 (1.876–2.187) | (Reference) |
Bonferroni adjusted relative risk (95% C.I.) | 2.750 (2.433–3.109) | 2.026 (1.845–2.225) | (Reference) |
Variable | aHR (95% C.I.) |
---|---|
Studied group | |
Non-DM vs. DM | 0.573 (0.524–0.627) * |
DM with DR vs. DM without DR | 1.215 (1.093–1.350) * |
Age (reference: 40–59) | |
<40 | 0.569 (0.463–0.700) * |
60–79 | 1.616 (1.499–1.743) * |
≥80 | 2.220 (1.745–2.823) * |
Sex (reference: female) | |
Male | 1.279 (1.194–1.372) * |
Comorbidity | |
Hypertension | 1.761 (1.633–1.900) * |
Hyperlipidemia | 0.983 (0.907–1.065) |
Dementia | 1.547 (1.182–2.024) * |
Chronic pulmonary disease | 1.177 (1.089–1.273) * |
Rheumatic disease | 1.184 (0.988–1.419) |
Renal disease | 1.251 (1.118–1.401) * |
Hepatitis and liver cirrhosis | 0.880 (0.815–0.950) * |
Alcoholic liver disease | 1.109 (0.870–1.413) |
Gout | 1.057 (0.968–1.154) |
Atopic dermatitis | 1.005 (0.834–1.212) |
ENT allergies | 0.939 (0.856–1.030) |
Eye disease | |
Keratopathy | 0.935 (0.816–1.072) |
Dry eye syndrome | 0.989 (0.868–1.126) |
Uveitis | 1.063 (0.819–1.379) |
Glaucoma | 1.023 (0.864–1.211) |
Age-related macular degeneration | 0.925 (0.721–1.188) |
Cataracts | 1.154 (1.053–1.265) * |
Retinopathy after vitrectomy | 1.136 (0.838–1.540) |
Concomitant medication | |
Systemic steroids | 1.204 (1.109–1.307) * |
Topical steroids | 1.115 (1.022–1.216) * |
Antipsychotics | 1.316 (1.138–1.521) * |
Antiarrhythmics | 2.491 (1.633–3.801) * |
Hypolipidemics | 1.069(0.974–1.174) |
Hypoglycemics | 0.878 (0.809–0.952) * |
Variable | aHR (95% C.I.) |
---|---|
Duration of diabetes (year) (reference: <2) | |
2–5 | 0.788 (0.717–0.866) * |
≥5 | 0.779 (0.690–0.879) * |
Type of retinopathy | |
NPDR vs. DM without DR | 0.940 (0.816–1.084) |
PDR vs. DM without DR | 1.612 (1.403–1.851) * |
Age (reference: 40–59) | |
<40 | 0.605 (0.482–0.759) * |
60–79 | 1.549 (1.416–1.694) * |
≥80 | 2.056 (1.535–2.753) * |
Sex (reference: female) | |
Male | 1.311 (1.207–1.424) * |
Comorbidity | |
Hypertension | 1.607 (1.471–1.755) * |
Hyperlipidemia | 0.933 (0.853–1.021) |
Dementia | 1.371 (0.983–1.912) |
Chronic pulmonary disease | 1.142 (1.04–1.253) * |
Rheumatic disease | 1.158 (0.934–1.437) |
Renal disease | 1.283 (1.133–1.454) * |
Hepatitis and liver cirrhosis | 0.846 (0.774–0.924) * |
Alcoholic liver disease | 1.041 (0.794–1.365) |
Gout | 1.034 (0.935–1.143) |
Atopic dermatitis | 0.963 (0.766–1.209) |
ENT allergies | 0.978 (0.877–1.091) |
Eye disease | |
Keratopathy | 0.921 (0.784–1.083) |
Dry eye syndrome | 0.998 (0.859–1.161) |
Uveitis | 0.995 (0.751–1.318) |
Glaucoma | 0.951 (0.783–1.156) |
Age-related macular degeneration | 0.809 (0.604–1.086) |
Cataracts | 1.181 (1.064–1.312) * |
Retinopathy after vitrectomy | 0.823 (0.583–1.16) |
Concomitant medication | |
Systemic steroids | 1.194 (1.085–1.314) * |
Topical steroids | 1.044 (0.941–1.158) |
Antipsychotics | 1.298 (1.104–1.527) * |
Antiarrhythmics | 2.072 (1.239–3.465) * |
Hypolipidemics | 1.081 (0.979–1.193) |
Hypoglycemics | 0.882 (0.812–0.959) * |
Bonferroni Adjusted aHR (95% C.I.) | |||
---|---|---|---|
Stratification | DM with DR | Non-DM | DM without DR |
Any cerebrovascular or cardiovascular diseases | 1.215 (1.068–1.382) | 0.573 (0.514–0.639) | Reference |
Ischemic heart disease | 1.194 (1.004–1.421) | 0.614 (0.531–0.710) | Reference |
Congestive heart failure | 1.915 (1.376–2.665) | 0.642 (0.464–0.889) | Reference |
Ischemic stroke | 2.003 (1.331–3.015) | 0.675 (0.462–0.986) | Reference |
Bonferroni Adjusted aHR (95% C.I.) | |||
---|---|---|---|
Stratification | DM Group | NPDR | PDR |
Any CVD | Reference | 0.940 (0.790–1.118) | 1.612 (1.361–1.909) |
Ischemic heart disease | Reference | 0.965 (0.765–1.218) | 1.545 (1.231–1.939) |
Congestive heart failure | Reference | 0.982 (0.592–1.628) | 3.482 (2.334–5.195) |
Ischemic stroke | Reference | 1.395 (0.785–2.479) | 3.802 (2.261–6.394) |
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Hsu, C.-Y.; Lee, C.-M.; Chou, K.-Y.; Lee, C.-Y.; Chen, H.-C.; Chiou, J.-Y.; Hsu, M.-Y. The Association of Diabetic Retinopathy and Cardiovascular Disease: A 13-Year Nationwide Population-Based Cohort Study. Int. J. Environ. Res. Public Health 2021, 18, 8106. https://doi.org/10.3390/ijerph18158106
Hsu C-Y, Lee C-M, Chou K-Y, Lee C-Y, Chen H-C, Chiou J-Y, Hsu M-Y. The Association of Diabetic Retinopathy and Cardiovascular Disease: A 13-Year Nationwide Population-Based Cohort Study. International Journal of Environmental Research and Public Health. 2021; 18(15):8106. https://doi.org/10.3390/ijerph18158106
Chicago/Turabian StyleHsu, Chin-Yuan, Chee-Ming Lee, Kuan-Yu Chou, Chia-Yi Lee, Hung-Chi Chen, Jeng-Yuan Chiou, and Min-Yen Hsu. 2021. "The Association of Diabetic Retinopathy and Cardiovascular Disease: A 13-Year Nationwide Population-Based Cohort Study" International Journal of Environmental Research and Public Health 18, no. 15: 8106. https://doi.org/10.3390/ijerph18158106