Abstract
To describe the incidence of benign prostatic hyperplasia (BPH) after a diagnosis of carpal tunnel syndrome or trigger finger. We performed a retrospective study on national health registry comparing the incidence of BPH between a cohort of 9720 study patients and a comparison cohort of 38,880 control individuals. The crude hazard ratio (HR) and the adjusted HR were estimated by the univariable and the multivariable Cox proportional hazard model, respectively. The risks of BPH in different age groups and patients with or without comorbidities were also investigated. The cumulative incidence curves were obtained by the Kaplan–Meier method and assessed by the Log-rank test. Compared to the control cohort, patients with carpal tunnel syndrome increased the risk of BPH by 1.36 times (95% confidence intervals [CI] = 1.29, 1.43). Patients only diagnosed with trigger finger raised the risk of BPH by 1.31 times (95% CI = 1.22, 1.40). The HR of BPH for patients with both carpal tunnel syndrome and trigger finger relative to the controls was 1.43 (95% CI = 1.33, 1.54). We concluded that the likelihood of developing BPH was increased in patients with carpal tunnel syndrome or trigger finger.
Keywords: benign prostatic hyperplasia, carpal tunnel syndrome, trigger finger
1. Introduction
Carpal tunnel syndrome or trigger finger, once thought to be a localized musculoskeletal and neurologic disorder, was proposed to be associated with systemic disease recently.[1–4] Benign prostatic hyperplasia (BPH), a common encountering disorder in elder man, is increasing recognized as a health burden because of increasing incidence and prevalence.[5,6] To our knowledge, there is no research on the relationship between them. The novelty of the current study should be highlighted because it is important to understand why this relationship is useful for science and for the medical context. Indeed, several possible factors link between these 2 entities were proposed.[1–9] It would appear novel and interesting to examine whether there is increased risk of BPH among men with carpal tunnel syndrome or trigger finger. By using data retrieved from the ICD-9 hospitalizations coding system in a Taiwan population, this study was conducted to compare the rate of onset of BPH in individuals with carpal tunnel syndrome or trigger finger as compared with controls from general population.
2. Methods
2.1. Data source
This cohort study utilized the data from the Nation Health Insurance Research Database. It contains medical information of over 99% of Taiwan’s resident since 1995. We analyzed the Longitudinal Health Insurance Database, a subset data of Nation Health Insurance Research Database, which included the outpatients and admission records, medications history and treatments received of one million insureds.[10–12] This study was approved by the Institutional Review Board of China Medical University Hospital Research Ethics Committee CMUH104-REC2-115(CR-7).
2.2. Study population
Male subjects with disease code, which follows the International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM), of 354.0 for 2 or more outpatient records or one in-patient record were carpal tunnel syndrome patients. Male subjects with ICD-9-CM code 727.03 were the trigger finger patients. Carpal tunnel syndrome or trigger finger patients diagnosed between 2000 and 2012 consisted of the case group of this study. Those who were free of carpal tunnel syndrome or trigger finger were the controls in this study. We excluded female patients, the patients diagnosed with BPH before entering the study or patients aged below twenty years. One study-patient was matched by 4 controls with corresponding age and the year of entry.
2.3. Main outcome and comorbidities
The primary outcome of this study was the occurrence of BPH (ICD-9-CM code 600.0). Patients who withdrew from the study or die were considered as censored. The related comorbidities including diabetes (ICD-9-CM code 250), hypertension (ICD-9-CM code 401–405), hyperlipidemia (ICD-9-CM code 272),coronary artery disease (ICD-9-CM code 410–414), heart failure (ICD-9-CM code 428), chronic obstructive pulmonary disease (COPD) (ICD-9-CM 491, 492, 496), chronic kidney disease (ICD-9-CM 585), hyperthyroidism (ICD-9-CM 242), sleep disorders (ICD-9-CM 307.4 and 780.5), gout (ICD-9-CM 274), osteoporosis (ICD-9-CM 733), depression (ICD-9-CM 296.2, 296.3, 300.4, 311), rheumatoid arthritis (ICD-9-CM 714), and osteoarthritis (ICD-9-CM 715) were the potential confounders.
2.4. Statistical analysis
The distributions of age and comorbidities in the case cohort and control cohort were examined by the chi-square test. The difference of the mean ages between the 2 cohorts was compared by the T test. The incidence rate was the number of events in 10,000 person-year. The crude hazard ratio (HR) and the adjusted HR were estimated by the univariable and the multivariable Cox proportional hazard model, respectively.
The risks of BPH in different age groups and patients with or without comorbidities were also investigated. The cumulative incidence curves were obtained by the Kaplan–Meier method and assessed by the Log-rank test. The statistical software SAS (version 9.1; SAS Institute, Cary, NC) was applied to perform the analysis. A 2-tail P value less than .05 was set as the significant level.
3. Result
Between 2000 and 2012, 9720 males were defined as patients with carpal tunnel syndrome or trigger finger. The average follow-up time of the case patients was 6.72 (±3.70) years. As shown as Table 1, 47.1% of them were aged from 20 to 49 years and the mean of age was 51.5 (±13.8) years. Patients in the case cohort were more likely to have comorbidities. The most 3 common comorbidities were hypertension (40.9%), hyperlipidemia (33.6%), and osteoarthritis (32.4%).
Table 1.
Characteristics between patients with carpal tunnel syndrome or trigger finger and patients without carpal tunnel syndrome or trigger finger.
| Carpal tunnel syndrome or trigger finger | P value | ||||
|---|---|---|---|---|---|
| Yes (N = 9720) | No (N = 38,880) | ||||
| n | % | n | % | ||
| Age, yr | .99 | ||||
| ≤49 | 4577 | 47.1 | 18,308 | 47.1 | |
| 50–64 | 3411 | 35.1 | 13,644 | 35.1 | |
| ≥65 | 1732 | 17.8 | 6928 | 17.8 | |
| Mean (SD) * | 51.5 | 13.8 | 51.0 | 14.2 | .002 |
| Comorbidity | |||||
| Diabetes | 927 | 9.54 | 2418 | 6.22 | <.001 |
| Hypertension | 3971 | 40.9 | 11,070 | 28.5 | <.001 |
| Hyperlipidemia | 3266 | 33.6 | 7906 | 20.3 | <.001 |
| Coronary artery disease | 2175 | 22.4 | 5374 | 13.8 | <.001 |
| Heart failure | 373 | 3.84 | 935 | 2.40 | <.001 |
| Chronic obstructive pulmonary disease | 1680 | 17.3 | 4688 | 12.1 | <.001 |
| Chronic kidney disease | 259 | 2.66 | 658 | 1.69 | <.001 |
| Hyperthyroidism | 141 | 1.45 | 376 | 0.97 | <.001 |
| Sleep disorders | 2471 | 25.4 | 6084 | 15.7 | <.001 |
| Gout | 2462 | 25.3 | 5636 | 14.5 | <.001 |
| Osteoporosis | 499 | 5.13 | 1133 | 2.91 | <.001 |
| Depression | 620 | 6.38 | 1490 | 3.83 | <.001 |
| Rheumatoid arthritis | 12 | 0.12 | 32 | 0.08 | .23 |
| Osteoarthritis | 3149 | 32.4 | 5948 | 15.3 | <.001 |
Chi-square test.
SD = standard deviation.
T test.
Table 2 presents the risk factors for BPH. Compared to the control cohort, patients with carpal tunnel syndrome increased the risk of BPH by 1.36 times (95% confidence intervals [CI] = 1.29, 1.43). Patients only diagnosed with trigger finger raised the risk of BPH by 1.31 times (95% CI = 1.22, 1.40). The HR of BPH for patients with both carpal tunnel syndrome and trigger finger relative to the controls was 1.43 (95% CI = 1.33, 1.54). Figure 1 shows that the cumulative incidence curve of BPH was higher in the case cohort than in the control cohort during the whole study period (Log-rank test with P value < .001).
Table 2.
The incidence (per 10,000 PY) and risk factors for BPH.
| Variable | Event | PY | Rate† | Crude HR (95% CI) | Adjusted HR‡ (95% CI) |
|---|---|---|---|---|---|
| Carpal tunnel syndrome or trigger finger | |||||
| No | 5182 | 239,001 | 21.7 | 1.00 | 1.00 |
| Carpal tunnel syndrome | 1141 | 37,017 | 30.8 | 1.42 (1.33, 1.52)*** | 1.36 (1.29, 1.43)*** |
| Trigger finger | 831 | 20,232 | 41.1 | 1.91 (1.77, 2.05)*** | 1.31 (1.22, 1.40)*** |
| Both | 1972 | 57,249 | 34.5 | 1.59 (1.51, 1.68)*** | 1.43 (1.33, 1.54)*** |
| Age, yr | |||||
| ≤49 | 1047 | 156,719 | 6.68 | 1.00 | 1.00 |
| 50–64 | 2917 | 97,829 | 29.8 | 4.58 (4.27, 4.92)*** | 3.83 (3.56, 4.12)*** |
| ≥65 | 3190 | 41,703 | 76.5 | 12.0 (11.2, 12.9)*** | 8.07 (7.47, 8.73)*** |
| Comorbidity | |||||
| Diabetes | |||||
| No | 6241 | 279,580 | 22.3 | 1.00 | 1.00 |
| Yes | 913 | 16,670 | 54.8 | 2.49 (2.32, 2.67)*** | 1.08 (1.01, 1.16)*** |
| Hypertension | |||||
| No | 3363 | 217,577 | 15.5 | 1.00 | 1.00 |
| Yes | 3791 | 78,674 | 48.2 | 3.18 (3.04, 3.34)*** | 1.18 (1.11, 1.24)*** |
| Hyperlipidemia | |||||
| No | 4591 | 237,571 | 19.3 | 1.00 | 1.00 |
| Yes | 2563 | 58,680 | 43.7 | 2.30 (2.19, 2.41)*** | 1.18 (1.11, 1.25)*** |
| Coronary artery disease | |||||
| No | 4843 | 258,489 | 18.7 | 1.00 | 1.00 |
| Yes | 2311 | 37,762 | 61.2 | 3.33 (3.17, 3.50)*** | 1.23 (1.16, 1.30)*** |
| Heart failure | |||||
| No | 6755 | 291,041 | 23.2 | 1.00 | 1.00 |
| Yes | 399 | 5210 | 76.6 | 3.41 (3.08, 3.77)*** | 1.07 (0.96, 1.19) |
| COPD | |||||
| No | 5293 | 264,900 | 20.0 | 1.00 | 1.00 |
| Yes | 1861 | 31,351 | 59.4 | 3.04 (2.88, 3.20)*** | 1.30 (1.22, 1.37)*** |
| Chronic kidney disease | |||||
| No | 6947 | 292,314 | 23.8 | 1.00 | 1.00 |
| Yes | 207 | 3937 | 52.6 | 2.26 (1.97, 2.60)*** | 0.91 (0.79, 1.05) |
| Hyperthyroidism | |||||
| No | 7073 | 293,646 | 24.1 | 1.00 | 1.00 |
| Yes | 81 | 2604 | 31.1 | 1.31 (1.05, 1.63)* | 1.04 (0.83, 1.29) |
| Sleep disorders | |||||
| No | 5347 | 254,610 | 21.0 | 1.00 | 1.00 |
| Yes | 1807 | 41,641 | 43.4 | 2.12 (2.01, 2.24)*** | 1.32 (1.25, 1.40)*** |
| Gout | |||||
| No | 5383 | 253,753 | 21.2 | 1.00 | 1.00 |
| Yes | 1771 | 42,497 | 41.7 | 2.00 (1.89, 2.11)*** | 1.15 (1.08, 1.22)*** |
| Osteoporosis | |||||
| No | 6688 | 288,526 | 23.2 | 1.00 | 1.00 |
| Yes | 466 | 7725 | 60.3 | 2.65 (2.41, 2.91)*** | 1.09 (0.99, 1.21) |
| Depression | |||||
| No | 6644 | 285,764 | 23.3 | 1.00 | 1.00 |
| Yes | 510 | 10,487 | 48.6 | 2.13 (1.94, 2.33)*** | 1.34 (1.22, 1.47)*** |
| Rheumatoid arthritis | |||||
| No | 7147 | 296,040 | 24.1 | 1.00 | 1.00 |
| Yes | 7 | 210 | 33.3 | 1.40 (0.67, 2.94) | 0.71 (0.34, 1.50) |
| Osteoarthritis | |||||
| No | 4715 | 251,027 | 18.8 | 1.00 | 1.00 |
| Yes | 2439 | 45,223 | 53.9 | 2.95 (2.81, 3.10)*** | 1.31 (1.24, 1.39)*** |
BPH = benign prostatic hyperplasia, CI = confidence intervals, COPD = chronic obstructive pulmonary disease, HR = hazard ratios, PY = person-years.
Rate, incidence rate, per 10,000 PY.
Adjusted HR multivariable analysis including age, and comorbidities of diabetes, hypertension, hyperlipidemia, coronary artery disease, heart failure, COPD, chronic kidney disease, hyperthyroidism, sleep disorders, gout, osteoporosis, depression, rheumatoid arthritis, osteoarthritis.
P < .05.
P < .001.
Figure 1.
Cumulative incidence of benign prostatic hyperplasia compared between patients with and without carpal tunnel syndrome or trigger finger using the Kaplan–Meier method.
The relationship between carpal tunnel syndrome or trigger finger and BPH in different subgroups was illustrated in Table 3. The adjusted HR of BPH for case cohort compared to the control cohort was the highest in patients aged under 49 years (1.48, 95% CI = 1.29, 1.70), followed by patients aged 50 to 64 years (1.39, 95% CI = 1.27, 1.51) and the lowest was among patients with age d ≥ 65 years (1.23, 95% CI = 1.13, 1.34). Among subjects without any comorbidities, case patients increase the hazard of having BPH by 1.59 folds (95% CI = 1.36, 1.86). Patients with any one of the comorbidities in the case cohort were more likely to develop BPH (adjusted HR = 1.44; 95% CI = 1.36, 1.52).
Table 3.
Incidence and hazard ratio of BPH between patients with carpal tunnel syndrome or trigger finger and without carpal tunnel syndrome or trigger finger.
| Outcome | Carpal tunnel syndrome or trigger finger | Crude HR (95% CI) | Adjusted HR‡ (95% CI) | |||||
|---|---|---|---|---|---|---|---|---|
| Yes | No | |||||||
| Event | PY | Rate† | Event | PY | Rate† | |||
| Age, yr | ||||||||
| ≤49 | 345 | 30,925 | 11.2 | 702 | 125,794 | 5.58 | 2.01 (1.77, 2.29)*** | 1.48 (1.29, 1.70)*** |
| 50–64 | 827 | 18,535 | 44.6 | 2090 | 79,293 | 26.4 | 1.71 (1.58, 1.85)*** | 1.39 (1.27, 1.51)*** |
| ≥65 | 800 | 7789 | 102.7 | 2390 | 33,914 | 70.5 | 1.47 (1.35, 1.59)*** | 1.23 (1.13, 1.34)*** |
| Comorbidity§ | ||||||||
| No | 185 | 16,068 | 11.5 | 1181 | 122,798 | 9.62 | 1.20 (1.02, 1.40)* | 1.59 (1.36, 1.86)*** |
| Yes | 1787 | 41,182 | 43.4 | 4001 | 116,204 | 34.4 | 1.26 (1.19, 1.33)*** | 1.44 (1.36, 1.52)*** |
CI = confidence intervals, HR = hazard ratios, PY = person-years.
Rate, incidence rate per 10,000 person-years.
‡Adjusted HR multivariable analysis including age, and comorbidities of diabetes, hypertension, hyperlipidemia, coronary artery disease, heart failure, chronic obstructive pulmonary disease, chronic kidney disease, hyperthyroidism, sleep disorders, gout, osteoporosis, depression, rheumatoid arthritis, and osteoarthritis.
Comorbidity: Patients with any one of the comorbidities (including diabetes, hypertension, hyperlipidemia, coronary artery disease, heart failure, chronic obstructive pulmonary disease, chronic kidney disease, hyperthyroidism, sleep disorders, gout, osteoporosis, depression, rheumatoid arthritis, and osteoarthritis) were classified as the comorbidity group.
P < .05.
P < .001.
4. Discussion
The authors retrospectively evaluated the risk of new onset BPH in patients with carpal tunnel syndrome or trigger finger, by analyzing a great national database in Taiwan. Diseases were coded according to the ICD-9-CM classification. Main findings are the increase in BPH risk in patients with carpal tunnel syndrome or trigger finger. Furthermore, high incidence of BPH was pointed out not only in the early stages but also a more prolonged follow-up, making this being new and original information.
In this study, if we look at Table 1, we can appreciate that the patients with carpal tunnel syndrome or trigger finger have higher incidence of medical comorbidities which were all very well-known risk factors for BPH onset. Briefly, the study group is a vastly different “substrate” from the comparison clearly. Some might argue that the finding of this study is that a cohort of patients with known risk factors for BPH, and that underwent carpal tunnel syndrome or trigger finger, are more likely to develop BPH than a cohort of controls. However, after accounting for the confounders which were risk factors for BPH, the association was even greater among those without comorbidity, affirming that the effect of comorbidity on this association was minimized and shared risk factors probably were not major known contributor to BPH, which probably can add some to current knowledge.
Although it is difficult for the association studies to provide adequate biological background to understand what exactly those patients had and why.[13] This study, rather only reporting an association, is more impactful since we moved beyond to include a hypothesis on mechanism and consideration of clinical impact. Possible mechanisms leading to BPH in carpal tunnel syndrome or trigger finger, this is surely multifactorial and are likely different in various pathophysiologic condition. Enhanced atherosclerotic process, impaired endothelial function, imbalance of autonomic system, stress reaction, and augmentation of systemic inflammatory response are possible contributors.[14–22]
Additionally, it is probable that increased systemic inflammation (but not CTS per si) is linked with increased risk of BPH. There are studies demonstrating increased risk of CTS in individuals who suffer from rheumatoid arthritis and osteoarthritis, known as inflammatory diseases.[23,24] However, the association remained even after incorporating the covariates including rheumatoid arthritis and osteoarthritis into the adjustment model, further emphasizing that our finding is solid and true. A clear discussion of practical applications in the medical context of this study is clear since our observations suggest that carpal tunnel syndrome or trigger finger should be considered as early as possible (as to anticipate a diagnosis of BPH) in men. However, based upon the design of the association research, it should be very cautious while interpreting our conclusion for avoiding something deterministic.
5. Limitations
First, ICD-9 classification can lead to inaccurate actual adjudication, which could generate misleading findings. Moreover, the use of ICD-9 codes alone does not represent the degree of critical illness of the patients. Additionally, carpal tunnel syndrome or trigger finger patients are highly checked, they receive frequent medical intervention. Thus, it may well be that there is a certain degree of underdiagnoses in non-carpal tunnel syndrome or trigger finger patients that is indeterminate and difficult to account for, and a higher chance of appropriate diagnosis in case groups. Finally, the major weakness of this study is the associative nature of the findings. While the large, inclusive Taiwan National Health Insurance program allows impressive adjustment for multiple variables. Residual confounding variables remained, and the burden and severity of the covariates were not accounted for in the analysis.
6. Conclusions
Increased risk of BPH in subjects with carpal tunnel syndrome or trigger finger is probably a novel finding since no body of evidence exists on this. The interpretation of our study should be very cautious due to certain limitations of the study.
Acknowledgments
We are grateful to Health Data Science Center, China Medical University Hospital for providing administrative, technical, and funding support.
Footnotes
This study is supported in part by Taiwan Ministry of Health and Welfare Clinical Trial Center (MOHW110-TDU-B-212-124004), China Medical University (CMU110-AWARD-01), and China Medical University Hospital (DMR-HHC-110-4; DMR-111-105). The funders had no role in the study design, data collection and analysis, the decision to publish, or preparation of the manuscript. No additional external funding was received for this study.
The authors have no conflicts of interest to disclose.
The datasets generated during and/or analyzed during the current study are not publicly available, but are available from the corresponding author on reasonable request.
How to cite this article: Hu W-S, Lin C-L. Carpal tunnel syndrome and trigger finger as related to benign prostatic hyperplasia: A retrospective nationwide cohort investigation. Medicine 2022;101:36(e30437).
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