Medicine
®
OBSERVATIONAL STUDY
Association Between Colonic Diverticulosis and Erectile Dysfunction A Nationwide Population-Based Study Chia-Chang Chen, MD, MSc, Jiann-Sheng Su, MD, Hong-Zen Yeh, MD, Chi-Sen Chang, MD, PhD, Yen-Chun Peng, MD, Chih-Wei Tseng, MD, Yu-Tso Chen, MD, Cheng-Li Lin, MSc, and Chia-Hung Kao, MD
Abstract: We investigated whether colonic diverticulosis (CD) is associated with an increased risk of the subsequent development of erectile dysfunction (ED). We identified 2879 patients, diagnosed with CD between 1998 and 2011 from the Taiwan National Health Insurance Research Database as the study cohort. Patients in a comparison cohort were frequencymatched with those in the CD cohort at a ratio of 1:4, frequency matched according to age (in 5-year bands) and year of CD diagnosis. The patients were followed-up until ED development, withdrawal from the National Health Insurance system, or the end of 2011. For both cohorts, the overall and age-specific incidence density rates of ED Editor: Somchai Amornyotin. Received: July 28, 2015; revised: September 21, 2015; accepted: September 24, 2015. From the Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan (C-CC, H-ZY, C-SC, Y-CP); Division of Gastroenterology and Hepatology, Kuang Tien General Hospital, Taichung, Taiwan (J-SS); Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung, Taiwan (C-WT); Division of Gastroenterology and Hepatology, Department of Internal Medicine, Feng Yuan Hospital Ministry of Health and Welfare, Taichung, Taiwan (Y-TC); Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan (C-LL); College of Medicine, China Medical University, Taichung, Taiwan (C-LL); Graduate Institute of Clinical Medical Science and School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan (C-HK); and Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung, Taiwan (C-HK). Correspondence: Chia-Hung Kao, Graduate Institute of Clinical Medical Science, College of Medicine, China Medical University, No. 2, YuhDer Road, Taichung, Taiwan (e-mail: [email protected]). Author contributions: All authors have contributed substantially to, and are in agreement with the content of, the manuscript—conception/design: Chia-Chang Chen, Chia-Hung Kao; provision of study materials: ChiaHung Kao; collection and/or assembly of data: all authors; data analysis and interpretation: all authors; manuscript preparation: all authors; final approval of manuscript: all authors. Funding: this study is supported, in part, by Taiwan Ministry of Health and Welfare Clinical Trial and Research Center of Excellence (MOHW104TDU-B-212-113002); China Medical University Hospital, Academia Sinica Taiwan Biobank, Stroke Biosignature Project (BM104010092); NRPB Stroke Clinical Trial Consortium (MOST 103-2325-B-039 -006); Tseng-Lien Lin Foundation, Taichung, Taiwan; Taiwan Brain Disease Foundation, Taipei, Taiwan; Katsuzo and Kiyo Aoshima Memorial Funds, Japan; and CMU under the Aim for Top University Plan of the Ministry of Education, Taiwan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding received for this study. The authors have no conflicts of interest to disclose. Copyright # 2015 Wolters Kluwer Health, Inc. All rights reserved. This is an open access article distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0, where it is permissible to download, share and reproduce the work in any medium, provided it is properly cited. The work cannot be changed in any way or used commercially. ISSN: 0025-7974 DOI: 10.1097/MD.0000000000002042
Medicine
Volume 94, Number 47, November 2015
(per 1000 person-years) were calculated. The effects of age, CD, and other comorbidities on the risk of ED development were examined using Cox proportional hazards regression models. The average follow-up durations were 4.76 years and 4.97 years for the CD patients and comparison cohorts, respectively. The overall incidence of ED was 1.70-fold higher in the CD cohort than in the comparison cohort (2.92 and 1.71 per 1000 person-years, respectively). Colonic diverticulosis was an independent risk factor for subsequent ED development (adjusted HR [aHR] ¼ 1.56, 95% confidence interval ¼ 1.07–2.28) in a multivariate Cox proportional hazards regression model. In this large retrospective cohort study, CD was associated with future ED development. Additional studies are required for validating our results. (Medicine 94(47):e2042) Abbreviations: CAD = coronary artery disease, CD = colonic diverticulosis, CIs = confidence intervals, CKD = chronic kidney disease, COPD = chronic obstructive pulmonary disease, ED = erectile dysfunction, HRs = hazard ratios, IBS = irritable bowel syndrome, ICD-9-CM = International Classification of Diseases, Ninth Revision, Clinical Modification, IRB = Institutional Review Board, NHI = Taiwan’s National Health Insurance, NHIRD = National Health Insurance Research Database, NHRI = National Health Research Institute, SUDD = symptomatic uncomplicated diverticular disease.
INTRODUCTION
C
olonic diverticulosis (CD) is the herniation of the colonic mucosa through the circular muscle layer at various points. The underlying pathological mechanisms that cause the formation of colonic diverticula remain unknown.1 The prevalence of CD is estimated 13.5% in Taiwan and even higher in older people (up to 71.4% for age > 80 years in USA).2,3 The common complications of CD include abdominal pain, diverticulitis, peritonitis, obstruction, fistulization, or abscess formation.4,5 In addition to these recurrent acute complications and chronic abdominal pain, model theories suggested that CD can cause some chronic disease and effect qualities of life.6 Chronic inflammation and microbiome shifts are potential etiologic factors for CD.7 –11 Chronic inflammation plays a role in the pathogenesis of cardiovascular disease, venous thromboembolism, and arterial atherosclerosis.12 Therefore, CD may increase relevant diseases associated with this condition. For example, CD was recently found to increase the risk of arterial and venous thromboembolic events.13 Erectile dysfunction (ED) is a consistent or recurrent inability to obtain or maintain penile erection sufficient for sexual activity. The prevalence of ED increases with age and www.md-journal.com |
1
Medicine
Chen et al
can reach 20% to 40% for men in their 60 s.14 Evidence has shown that ED is associated with cardiovascular disease and coronary artery disease (CAD).15,16 Erectile dysfunction was considered a predictor of silent CAD in diabetic populations.17 Studies also found that ED became evident before angina symptoms18 and preceded CAD by an average of 2 to 3 years.19 Subclinical endothelial dysfunction and low-grade inflammation may be the underlying pathogenesis of ED.20 Colonic diverticulosis was closely linked to chronic inflammation and thromboembolism which were important etiological factors of ED. It is possible that CD can increase ED. So we conducted a large population-based cohort study to see if CD was associated with ED.
METHOD Data Source The National Health Insurance Research Database (NHIRD) is derived from the mandatory single-payer National Health Insurance (NHI) program initiated by the Taiwan government in 1995. By 2014, >24 million people, representing 99% of the population of Taiwan, were covered by the NHI program.21 In this study, we analyzed data from the Longitudinal Health Insurance Database 2000, a subset of the NHIRD that contains the data of 1,000,000 randomly sampled patients, who were traced retrospectively to 1996 and followed-up to 2011. The National Health Research Institute (NHRI) has confirmed these random samples as representative of the general population of Taiwan. The NHRI safeguards the privacy of patients and provides data to researchers after ethical approval has been obtained. This retrospective study was approved to fulfill the condition for exemption by the Institutional Review Board (IRB) of China Medical University (CMUH-104-REC2-115). The IRB also specifically waived the consent requirement.
Sampled Participants Male patients, aged 20 years and older and newly diagnosed with CD (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] codes 562.10, 562.11, 562.12, 562.13) from 1998 to 2011, were identified as the CD cohort. The date of CD diagnosis was considered the index date. Patients with a history of ED (ICD-9-CM codes 302.72, 607.84) diagnosed before the index date, with missing information, and aged
®
OBSERVATIONAL STUDY
Association Between Colonic Diverticulosis and Erectile Dysfunction A Nationwide Population-Based Study Chia-Chang Chen, MD, MSc, Jiann-Sheng Su, MD, Hong-Zen Yeh, MD, Chi-Sen Chang, MD, PhD, Yen-Chun Peng, MD, Chih-Wei Tseng, MD, Yu-Tso Chen, MD, Cheng-Li Lin, MSc, and Chia-Hung Kao, MD
Abstract: We investigated whether colonic diverticulosis (CD) is associated with an increased risk of the subsequent development of erectile dysfunction (ED). We identified 2879 patients, diagnosed with CD between 1998 and 2011 from the Taiwan National Health Insurance Research Database as the study cohort. Patients in a comparison cohort were frequencymatched with those in the CD cohort at a ratio of 1:4, frequency matched according to age (in 5-year bands) and year of CD diagnosis. The patients were followed-up until ED development, withdrawal from the National Health Insurance system, or the end of 2011. For both cohorts, the overall and age-specific incidence density rates of ED Editor: Somchai Amornyotin. Received: July 28, 2015; revised: September 21, 2015; accepted: September 24, 2015. From the Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan (C-CC, H-ZY, C-SC, Y-CP); Division of Gastroenterology and Hepatology, Kuang Tien General Hospital, Taichung, Taiwan (J-SS); Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung, Taiwan (C-WT); Division of Gastroenterology and Hepatology, Department of Internal Medicine, Feng Yuan Hospital Ministry of Health and Welfare, Taichung, Taiwan (Y-TC); Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan (C-LL); College of Medicine, China Medical University, Taichung, Taiwan (C-LL); Graduate Institute of Clinical Medical Science and School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan (C-HK); and Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung, Taiwan (C-HK). Correspondence: Chia-Hung Kao, Graduate Institute of Clinical Medical Science, College of Medicine, China Medical University, No. 2, YuhDer Road, Taichung, Taiwan (e-mail: [email protected]). Author contributions: All authors have contributed substantially to, and are in agreement with the content of, the manuscript—conception/design: Chia-Chang Chen, Chia-Hung Kao; provision of study materials: ChiaHung Kao; collection and/or assembly of data: all authors; data analysis and interpretation: all authors; manuscript preparation: all authors; final approval of manuscript: all authors. Funding: this study is supported, in part, by Taiwan Ministry of Health and Welfare Clinical Trial and Research Center of Excellence (MOHW104TDU-B-212-113002); China Medical University Hospital, Academia Sinica Taiwan Biobank, Stroke Biosignature Project (BM104010092); NRPB Stroke Clinical Trial Consortium (MOST 103-2325-B-039 -006); Tseng-Lien Lin Foundation, Taichung, Taiwan; Taiwan Brain Disease Foundation, Taipei, Taiwan; Katsuzo and Kiyo Aoshima Memorial Funds, Japan; and CMU under the Aim for Top University Plan of the Ministry of Education, Taiwan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding received for this study. The authors have no conflicts of interest to disclose. Copyright # 2015 Wolters Kluwer Health, Inc. All rights reserved. This is an open access article distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0, where it is permissible to download, share and reproduce the work in any medium, provided it is properly cited. The work cannot be changed in any way or used commercially. ISSN: 0025-7974 DOI: 10.1097/MD.0000000000002042
Medicine
Volume 94, Number 47, November 2015
(per 1000 person-years) were calculated. The effects of age, CD, and other comorbidities on the risk of ED development were examined using Cox proportional hazards regression models. The average follow-up durations were 4.76 years and 4.97 years for the CD patients and comparison cohorts, respectively. The overall incidence of ED was 1.70-fold higher in the CD cohort than in the comparison cohort (2.92 and 1.71 per 1000 person-years, respectively). Colonic diverticulosis was an independent risk factor for subsequent ED development (adjusted HR [aHR] ¼ 1.56, 95% confidence interval ¼ 1.07–2.28) in a multivariate Cox proportional hazards regression model. In this large retrospective cohort study, CD was associated with future ED development. Additional studies are required for validating our results. (Medicine 94(47):e2042) Abbreviations: CAD = coronary artery disease, CD = colonic diverticulosis, CIs = confidence intervals, CKD = chronic kidney disease, COPD = chronic obstructive pulmonary disease, ED = erectile dysfunction, HRs = hazard ratios, IBS = irritable bowel syndrome, ICD-9-CM = International Classification of Diseases, Ninth Revision, Clinical Modification, IRB = Institutional Review Board, NHI = Taiwan’s National Health Insurance, NHIRD = National Health Insurance Research Database, NHRI = National Health Research Institute, SUDD = symptomatic uncomplicated diverticular disease.
INTRODUCTION
C
olonic diverticulosis (CD) is the herniation of the colonic mucosa through the circular muscle layer at various points. The underlying pathological mechanisms that cause the formation of colonic diverticula remain unknown.1 The prevalence of CD is estimated 13.5% in Taiwan and even higher in older people (up to 71.4% for age > 80 years in USA).2,3 The common complications of CD include abdominal pain, diverticulitis, peritonitis, obstruction, fistulization, or abscess formation.4,5 In addition to these recurrent acute complications and chronic abdominal pain, model theories suggested that CD can cause some chronic disease and effect qualities of life.6 Chronic inflammation and microbiome shifts are potential etiologic factors for CD.7 –11 Chronic inflammation plays a role in the pathogenesis of cardiovascular disease, venous thromboembolism, and arterial atherosclerosis.12 Therefore, CD may increase relevant diseases associated with this condition. For example, CD was recently found to increase the risk of arterial and venous thromboembolic events.13 Erectile dysfunction (ED) is a consistent or recurrent inability to obtain or maintain penile erection sufficient for sexual activity. The prevalence of ED increases with age and www.md-journal.com |
1
Medicine
Chen et al
can reach 20% to 40% for men in their 60 s.14 Evidence has shown that ED is associated with cardiovascular disease and coronary artery disease (CAD).15,16 Erectile dysfunction was considered a predictor of silent CAD in diabetic populations.17 Studies also found that ED became evident before angina symptoms18 and preceded CAD by an average of 2 to 3 years.19 Subclinical endothelial dysfunction and low-grade inflammation may be the underlying pathogenesis of ED.20 Colonic diverticulosis was closely linked to chronic inflammation and thromboembolism which were important etiological factors of ED. It is possible that CD can increase ED. So we conducted a large population-based cohort study to see if CD was associated with ED.
METHOD Data Source The National Health Insurance Research Database (NHIRD) is derived from the mandatory single-payer National Health Insurance (NHI) program initiated by the Taiwan government in 1995. By 2014, >24 million people, representing 99% of the population of Taiwan, were covered by the NHI program.21 In this study, we analyzed data from the Longitudinal Health Insurance Database 2000, a subset of the NHIRD that contains the data of 1,000,000 randomly sampled patients, who were traced retrospectively to 1996 and followed-up to 2011. The National Health Research Institute (NHRI) has confirmed these random samples as representative of the general population of Taiwan. The NHRI safeguards the privacy of patients and provides data to researchers after ethical approval has been obtained. This retrospective study was approved to fulfill the condition for exemption by the Institutional Review Board (IRB) of China Medical University (CMUH-104-REC2-115). The IRB also specifically waived the consent requirement.
Sampled Participants Male patients, aged 20 years and older and newly diagnosed with CD (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] codes 562.10, 562.11, 562.12, 562.13) from 1998 to 2011, were identified as the CD cohort. The date of CD diagnosis was considered the index date. Patients with a history of ED (ICD-9-CM codes 302.72, 607.84) diagnosed before the index date, with missing information, and aged
