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Gut and Liver is an international journal of gastroenterology, focusing on the gastrointestinal tract, liver, biliary tree, pancreas, motility, and neurogastroenterology. Gut atnd Liver delivers up-to-date, authoritative papers on both clinical and research-based topics in gastroenterology. The Journal publishes original articles, case reports, brief communications, letters to the editor and invited review articles in the field of gastroenterology. The Journal is operated by internationally renowned editorial boards and designed to provide a global opportunity to promote academic developments in the field of gastroenterology and hepatology. +MORE
Yong Chan Lee |
Professor of Medicine Director, Gastrointestinal Research Laboratory Veterans Affairs Medical Center, Univ. California San Francisco San Francisco, USA |
Jong Pil Im | Seoul National University College of Medicine, Seoul, Korea |
Robert S. Bresalier | University of Texas M. D. Anderson Cancer Center, Houston, USA |
Steven H. Itzkowitz | Mount Sinai Medical Center, NY, USA |
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Young-Il Kim1 , Young Ae Kim2
, Jang Won Lee3
, Hak Jin Kim4
, Su-Hyun Kim5
, Sang Gyun Kim6
, Jin Il Kim7
, Jae J. Kim8
, Il Ju Choi1
Correspondence to: Il Ju Choi
Center for Gastric Cancer, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang 10408, Korea
Tel: +82-31-920-2282, Fax: +82-31-920-2799, E-mail: cij1224@ncc.re.kr
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Gut Liver 2020;14(1):47-56. https://doi.org/10.5009/gnl18510
Published online July 24, 2019, Published date January 15, 2020
Copyright © Gut and Liver.
A meta-analysis of randomized trials performed in healthy asymptomatic individuals suggested that overall mortality may increase after From the database of the Korean National Health Insurance Sample Cohort, we selected 198,487 patients treated for hypertension between 2002 and 2010. Those who received During a median follow-up period of 4.8 years, death from any cause was reported in 4.1% of the patients in the Background/Aims
Methods
Results
Conclusions
Keywords: Helicobacter pylori, Mortality, Hypertension
Hypertension is an important risk factor for death from cardiovascular and cerebrovascular diseases.13 Thus, we selected patients with hypertension from the database of the Korean National Health Insurance population-based sample cohort. In the present study, we investigated if
This study is a retrospective population-based cohort study using the Korean National Health Insurance Service-National Sample Cohort database. This study was approved by the Institutional Review Board of the National Cancer Center, Korea (IRB number: NCC2016-0043) and informed consent requirements for the individuals in the database were waived.
We selected a study population from the database,14 which is a population-based sample cohort established to provide representative and useful health insurance and health examination data to public health researchers and policymakers. To summarize this cohort, approximately one million subjects (2.2% of the total eligible population) were randomly sampled from the 2002 Korean National Health Insurance database and followed up until 2013. This database has been well-validated and increasingly used for epidemiological and health policy studies for general Korean populations.15,16
The database includes participants’ insurance eligibility, medical treatments, medical care institutions, and general health examinations data. In the insurance eligibility database, variables include the participant’s identity and socioeconomic information (gender, residential area, type of health insurance, level of income, birth, and death). The medical treatment database contains the participant’s medical treatment bills, bill details, details of disease, and prescriptions. The general health examination database includes major health exam results and information about lifestyles and behaviors from questionnaires.14 To identify subjects’ diagnosis and cause of mortality, disease codes from the International Classification of Diseases (ICD) 10th revision were used.17
We selected patients with hypertension from the database. Patients who were aged ≥20 years, diagnosed with hypertension (ICD-10 code, I10) between 2002 and 2010, and had been prescribed at least a one anti-hypertensive drug were included in our study as patients with hypertension.
The prescription of
Patients in the
Of the patients in the
To define the starting time of observation periods for study outcomes in the nontreatment cohort, the corresponding date of
The primary outcome was overall mortality, defined as a death from any cause occurring from 6 months after the starting time of the observation period. Secondary outcomes included cancer-specific mortality, cardiovascular disease-specific mortality, and cerebrovascular-specific mortality occurring from 6 months after the starting time of the observation period. The disease codes describing the cause of death in the database were identified to define disease-specific mortalities, and disease codes were ICD-10 code C00-97 for cancers, I20–I25 for cardiovascular diseases, and I60–I66 for cerebrovascular diseases (Supplementary Table 1).
Descriptive analyses were performed to compare patients’ baseline characteristics between the
Kaplan-Meier curves with log-rank test were performed for the comparisons of overall mortality and cause-specific mortalities between
The study flow is presented in Fig. 1. A total of 198,487 patients were diagnosed with hypertension and prescribed hypertension medication at least once. Of these, 9,552 patients were prescribed
In the
During the observation periods until December 2013 (median, 4.8 years; interquartile range, 2.6 to 7.3 years; 85,078 person-years), death occurred in 837 patients (5.0%); 229 patients (4.1%) in the
Table 3 shows the incidence risks of diseases related to common cause of deaths, including cancer, cardiovascular, and cerebrovascular diseases, according to
The mortality risk due to cerebrovascular disease was significantly lower in the
In this retrospective population-based cohort study, we investigated the effects of
The recent European guideline stated that
Clarithromycin is often included in several
Recent retrospective cohort studies reported inconsistent results for the association between clarithromycin-containing
Antibiotic treatment can cause dysbiosis and may alter the beneficial roles of gut microbiota in the modulation of carcinogenesis, response to cancer treatment including chemotherapy, immunotherapy and radiotherapy, and treatment-related toxicities.10,11 Repeated macrolide antibiotic exposure was significantly associated with increased risks of lung, gastric, biliary, and kidney cancer.12 Our recent randomized trial also showed that the
Two recent meta-analyses reported inconsistent results regarding the association between
Our study has several limitations associated with an observational study of a retrospective cohort study design. First, our study population was hypertension patients and our results might not be applicable to the general population with no cardiovascular risk. Second, the ICD-10 disease codes for hypertension were used for selection of the study population from the database, and possible upcoding for hypertension diagnosis could not be completely excluded. However, to reduce the possibility, we only selected patients who had a prescription for an anti-hypertensive drug. Third, our analysis was based on the prescription of
In conclusion,
No potential conflict of interest relevant to this article was reported.
This research was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HC15C1077). This study used the Korean National Health Insurance Service-National Sample Cohort database (NHIS-2016-2-191) provided by the National Health Insurance Service.
Interpretation of the data: Y.I.K., Y.A.K., I.J.C. Drafting of the article: Y.I.K., I.J.C. Statistical analysis: Y.A.K., J.W.L. Conception and design of study: I.J.C. Critical revision for important intellectual content and final approval of the manuscript: Y.I.K., Y.A.K., J.W.L., H.J.K., S.H.K., S.G.K., J.I.K., J.J.K., I.J.C.
Baseline Characteristics of the Study Population
Characteristic | Nontreatment cohort (n=11,082) | p-value | |
---|---|---|---|
Age, yr | 1.00 | ||
20–29 | 41 (0.7) | 82 (0.7) | |
30–39 | 424 (7.7) | 848 (7.7) | |
40–49 | 1,526 (27.5) | 3,052 (27.5) | |
50–59 | 1,968 (35.5) | 3,936 (35.5) | |
60–69 | 1,297 (23.4) | 2,594 (23.4) | |
70–79 | 268 (4.8) | 536 (4.8) | |
≥80 | 17 (0.3) | 34 (0.3) | |
Sex | 1.00 | ||
Male | 3,059 (55.2) | 6,118 (55.2) | |
Female | 2,482 (44.8) | 4,964 (44.8) | |
Residential area | <0.001 | ||
Metropolitan | 2,745 (49.5) | 5,180 (46.7) | |
Small city or rural | 2,796 (50.5) | 5,902 (53.3) | |
Economic status level, % | <0.001 | ||
0–50 | 2,060 (37.2) | 4,452 (40.2) | |
51–100 | 3,481 (62.8) | 6,630 (59.8) | |
Smoking | <0.001 | ||
Never smoker | 2,574 (46.5) | 4,652 (42.0) | |
Ex-smoker | 520 (9.4) | 844 (7.6) | |
Current smoker | 1,045 (18.9) | 1,520 (13.7) | |
Missing | 1,402 (25.3) | 4,066 (36.7) | |
Alcohol drinking | 0.863 | ||
Never drinking | 2,383 (43.0) | 4,002 (36.1) | |
1–2 times/wk | 1,245 (22.5) | 2,127 (19.2) | |
3–4 times/wk | 414 (7.5) | 733 (6.6) | |
5–7 times/wk | 245 (4.4) | 425 (3.8) | |
Missing | 1,254 (22.6) | 3,795 (34.2) | |
Body mass index, kg/m2 | 0.204 | ||
≤18.5 | 46 (0.8) | 95 (0.9) | |
18.6–22.9 | 1,065 (19.2) | 1,845 (16.6) | |
23.0–24.9 | 1,208 (21.8) | 1,934 (17.5) | |
≥25.0 | 2,051 (37.0) | 3,556 (32.1) | |
Missing | 1,171 (21.1) | 3,652 (33.0) | |
CCI score at the time of hypertension diagnosis | 1.00 | ||
0 | 2,955 (53.3) | 5,910 (53.3) | |
1 | 866 (15.6) | 1,732 (15.6) | |
≥2 | 1,720 (31.0) | 3,440 (31.0) | |
Aspirin use* | 0.21 | ||
No | 4,386 (79.2) | 8,864 (80.0) | |
Yes | 1,155 (20,8) | 2,218 (20.0) | |
Statin use* | <0.001 | ||
No | 4,513 (81.4) | 9,434 (85.1) | |
Yes | 1,028 (18.6) | 1,648 (14.9) | |
PPI-clarithromycin containing triple therapy | 5,342 (96.4) | - | |
Bismuth-containing quadruple therapy | 72 (1.3) | - | |
Both | 127 (2.3) | - | |
Follow-up period, yr | 4.8 (2.6–7.4) | 4.8 (2.6–7.3) | 0.216 |
Data are presented number (%) or median (interquartile range).
Risk Factors Associated with Overall Mortality
Risk factor | No. | Univariate analysis* | Multivariate analysis*,† | ||
---|---|---|---|---|---|
Unadjusted HR (95% CI) | p-value | Adjusted HR (95% CI) | p-value | ||
Age, yr | <0.001 | <0.001 | |||
<60 | 11,877 | 1.00 | 1.00 | ||
≥60 | 4,746 | 3.99 (3.46–4.59) | 4.02 (3.05–4.64) | ||
Sex | <0.001 | <0.001 | |||
Female | 9,177 | 1.00 | 1.00 | ||
Male | 7,446 | 1.60 (1.39–1.84) | 1.75 (1.52–2.02) | ||
Economic status level, % | <0.001 | <0.001 | |||
0–50 | 6,512 | 1.00 | 1.00 | ||
51–100 | 10,111 | 0.75 (0.66–0.86) | 0.76 (0.66–0.87) | ||
Residential area | 0.003 | 0.064 | |||
Metropolitan | 7,925 | 1.00 | 1.00 | ||
Small city or rural | 8,698 | 1.23 (1.07–1.41) | 1.14 (0.99–1.31) | ||
CCI score | |||||
0 | 8,658 | 1.00 | 1.00 | ||
1 | 2,952 | 1.37 (1.13–1.66) | 0.001 | 1.27 (1.04–1.54) | 0.018 |
≥2 | 5,040 | 1.82 (1.56–2.11) | <0.001 | 1.80 (1.55–2.10) | <0.001 |
<0.001 | <0.001 | ||||
No | 11,082 | 1.00 | 1.00 | ||
Yes | 5,541 | 0.74 (0.64–0.86) | 0.70 (0.60–0.82) | ||
Aspirin use | 0.922 | 0.16 | |||
No | 13,250 | 1.00 | 1.00 | ||
Yes | 3,373 | 1.01 (0.85–1.19) | 0.88 (0.75–1.05) | ||
Statin use | 0.094 | 0.097 | |||
No | 13,947 | 1.00 | 1.00 | ||
Yes | 2,676 | 0.83 (0.67–1.03) | 0.83 (0.66–1.03) |
HR, hazard ratio; CI, confidence interval; CCI, Charlson comorbidity index;
†Covariates for multivariate analysis were age, sex, economic status, residential area, CCI score,
Risk of Incidence for Cardiovascular Diseases, Cerebrovascular Diseases, and Cancer Stratified by
Incidence, no. (%) | Risk of incidence for | |||||
---|---|---|---|---|---|---|
Control group (n=11,082) | Unadjusted HR (95% CI) | p-value | Adjusted HR (95% CI) | p-value | ||
Cardiovascular disease | 714 (12.9) | 1,232 (11.1) | 1.18 (1.07–1.29) | <0.001 | 1.13 (1.03–1.24) | 0.01 |
Cerebrovascular disease | 408 (7.4) | 814 (7.3) | 1.00 (0.89–1.13) | 0.962 | 0.98 (0.87–1.11) | 0.657 |
Overall cancers | 429 (7.7) | 737 (6.7) | 1.18 (1.04–1.32) | 0.008 | 1.14 (1.01–1.28) | 0.035 |
Stomach cancer | 54 (1.0) | 87 (0.8) | 1.24 (0.89–1.75) | 0.209 | 1.26 (0.90–1.78) | 0.182 |
Non-stomach cancer | 381 (6.9) | 659 (6.0) | 1.17 (1.03–1.32) | 0.017 | 1.12 (0.99–1.27) | 0.078 |
Oral cancer | 15 (0.3) | 19 (0.2) | 1.58 (0.80–3.11) | 0.185 | 1.60 (0.81–3.18) | 0.175 |
Esophageal cancer | 3 (0.1) | 7 (0.1) | 0.86 (0.22–3.31) | 0.823 | 0.82 (0.21–3.20) | 0.771 |
Colorectal cancer | 67 (1.2) | 95 (0.9) | 1.42 (1.04–1.93) | 0.03 | 1.39 (1.01–1.90) | 0.043 |
Liver cancer | 48 (0.9) | 101 (0.9) | 0.95 (0.67–1.34) | 0.774 | 0.83 (0.59–1.18) | 0.295 |
Biliary tract cancer | 5 (0.1) | 17 (0.2) | 0.59 (0.22–1.59) | 0.297 | 0.59 (0.22–1.61) | 0.302 |
Pancreatic cancer | 21 (0.4) | 31 (0.3) | 1.36 (0.78–2.36) | 0.282 | 1.25 (0.71–2.19) | 0.435 |
Lung cancer | 34 (0.6) | 67 (0.6) | 1.02 (0.67–1.53) | 0.942 | 0.99 (0.65–1.49) | 0.942 |
Breast cancer | 12 (0.2) | 24 (0.2) | 1.00 (0.50–2.00) | 1.000 | 0.98 (0.49–1.97) | 0.956 |
Prostate cancer | 58 (1.0) | 101 (0.9) | 1.15 (0.83–1.59) | 0.397 | 1.13 (0.81–1.56) | 0.472 |
Bladder cancer | 6 (0.1) | 17 (0.2) | 0.71 (0.28–1.79) | 0.462 | 0.70 (0.27–1.79) | 0.456 |
Thyroid cancer | 42 (0.7) | 53 (0.5) | 1.59 (1.06–2.38) | 0.025 | 1.54 (1.03–2.32) | 0.037 |
Brain, CNS cancer | 3 (0.1) | 6 (0.1) | 1.00 (0.25–4.00) | 1.000 | 0.87 (0.22–3.50) | 0.841 |
Non-Hodgkin lymphoma | 3 (0.1) | 4 (0.04) | 1.50 (0.34–6.70) | 0.595 | 1.39 (0.31–6.30) | 0.667 |
Leukemia | 5 (0.1) | 3 (0.03) | 3.34 (0.80–13.97) | 0.099 | 3.51 (0.83–14.89) | 0.089 |
Risk of Cause-Specific Mortality Stratified by
Death, No. (%) | Risk of mortality for | |||||
---|---|---|---|---|---|---|
Control group (n=11,082) | Unadjusted HR (95% CI) | p-value | Adjusted HR (95% CI) | p-value | ||
Overall | 229 (4.13) | 608 (5.49) | ||||
Cardiovascular disease | 18 (0.32) | 34 (0.31) | 1.06 (0.60–1.88) | 0.842 | 0.96 (0.54–1.71) | 0.896 |
Cerebrovascular disease | 15 (0.27) | 66 (0.60) | 0.45 (0.26–0.79) | 0.006 | 0.46 (0.26–0.81) | 0.007 |
Overall cancers | 68 (1.23) | 170 (1.53) | 0.80 (0.60–1.06) | 0.112 | 0.76 (0.57–1.01) | 0.058 |
Stomach cancer | 6 (0.11) | 10 (0.09) | 1.20 (0.44–3.30) | 0.724 | 1.21 (0.44–3.38) | 0.71 |
Non-stomach cancer | 62 (1.12) | 160 (1.44) | 0.77 (0.58–1.03) | 0.083 | 0.73 (0.55–0.99) | 0.04 |
Oral cancer | 0 | 2 (0.02) | NA | NA | ||
Esophageal cancer | 2 (0.04) | 3 (0.03) | NA | NA | ||
Colorectal cancer | 5 (0.09) | 17 (0.15) | 0.59 (0.22–1.59) | 0.297 | 0.60 (0.22–1.64) | 0.319 |
Liver cancer | 12 (0.22) | 45 (0.41) | 0.53 (0.28–1.01) | 0.052 | 0.48 (0.25–0.91) | 0.024 |
Biliary tract cancer | 5 (0.09) | 13 (0.12) | 0.77 (0.27–2.16) | 0.618 | 0.79 (0.28–2.22) | 0.65 |
Pancreatic cancer | 5 (0.09) | 13 (0.12) | 0.77 (0.27–2.16) | 0.618 | 0.67 (0.24–1.91) | 0.456 |
Lung cancer | 15 (0.27) | 32 (0.29) | 0.94 (0.51–1.73) | 0.836 | 0.95 (0.51–1.75) | 0.857 |
Breast cancer | 0 | 1 (0.01) | NA | NA | ||
Prostate cancer | 0 | 4 (0.04) | NA | NA | ||
Bladder cancer | 0 | 7 (0.06) | NA | NA | ||
Thyroid cancer | 1 (0.02) | 0 | NA | NA | ||
Brain, CNS cancer | 0 | 1 (0.01) | NA | NA | ||
Non-Hodgkin lymphoma | 1 (0.02) | 3 (0.03) | NA | NA | ||
Leukemia | 3 (0.05) | 1 (0.01) | NA | NA |
Gut and Liver 2020; 14(1): 47-56
Published online January 15, 2020 https://doi.org/10.5009/gnl18510
Copyright © Gut and Liver.
Young-Il Kim1 , Young Ae Kim2
, Jang Won Lee3
, Hak Jin Kim4
, Su-Hyun Kim5
, Sang Gyun Kim6
, Jin Il Kim7
, Jae J. Kim8
, Il Ju Choi1
1Center for Gastric Cancer and 2Cancer Survivorship Branch, National Cancer Control Institute, National Cancer Center, Goyang, 3College of Korean Medicine, Dongguk University, Gyeongju, 4Department of Cardiology, Center for Clinical Specialty, National Cancer Center, 5Department of Neurology, Research Institute and Hospital, National Cancer Center, Goyang, 6Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 7Department of Internal Medicine, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, and 8Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
Correspondence to:Il Ju Choi
Center for Gastric Cancer, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang 10408, Korea
Tel: +82-31-920-2282, Fax: +82-31-920-2799, E-mail: cij1224@ncc.re.kr
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
A meta-analysis of randomized trials performed in healthy asymptomatic individuals suggested that overall mortality may increase after From the database of the Korean National Health Insurance Sample Cohort, we selected 198,487 patients treated for hypertension between 2002 and 2010. Those who received During a median follow-up period of 4.8 years, death from any cause was reported in 4.1% of the patients in the Background/Aims
Methods
Results
Conclusions
Keywords: Helicobacter pylori, Mortality, Hypertension
Hypertension is an important risk factor for death from cardiovascular and cerebrovascular diseases.13 Thus, we selected patients with hypertension from the database of the Korean National Health Insurance population-based sample cohort. In the present study, we investigated if
This study is a retrospective population-based cohort study using the Korean National Health Insurance Service-National Sample Cohort database. This study was approved by the Institutional Review Board of the National Cancer Center, Korea (IRB number: NCC2016-0043) and informed consent requirements for the individuals in the database were waived.
We selected a study population from the database,14 which is a population-based sample cohort established to provide representative and useful health insurance and health examination data to public health researchers and policymakers. To summarize this cohort, approximately one million subjects (2.2% of the total eligible population) were randomly sampled from the 2002 Korean National Health Insurance database and followed up until 2013. This database has been well-validated and increasingly used for epidemiological and health policy studies for general Korean populations.15,16
The database includes participants’ insurance eligibility, medical treatments, medical care institutions, and general health examinations data. In the insurance eligibility database, variables include the participant’s identity and socioeconomic information (gender, residential area, type of health insurance, level of income, birth, and death). The medical treatment database contains the participant’s medical treatment bills, bill details, details of disease, and prescriptions. The general health examination database includes major health exam results and information about lifestyles and behaviors from questionnaires.14 To identify subjects’ diagnosis and cause of mortality, disease codes from the International Classification of Diseases (ICD) 10th revision were used.17
We selected patients with hypertension from the database. Patients who were aged ≥20 years, diagnosed with hypertension (ICD-10 code, I10) between 2002 and 2010, and had been prescribed at least a one anti-hypertensive drug were included in our study as patients with hypertension.
The prescription of
Patients in the
Of the patients in the
To define the starting time of observation periods for study outcomes in the nontreatment cohort, the corresponding date of
The primary outcome was overall mortality, defined as a death from any cause occurring from 6 months after the starting time of the observation period. Secondary outcomes included cancer-specific mortality, cardiovascular disease-specific mortality, and cerebrovascular-specific mortality occurring from 6 months after the starting time of the observation period. The disease codes describing the cause of death in the database were identified to define disease-specific mortalities, and disease codes were ICD-10 code C00-97 for cancers, I20–I25 for cardiovascular diseases, and I60–I66 for cerebrovascular diseases (Supplementary Table 1).
Descriptive analyses were performed to compare patients’ baseline characteristics between the
Kaplan-Meier curves with log-rank test were performed for the comparisons of overall mortality and cause-specific mortalities between
The study flow is presented in Fig. 1. A total of 198,487 patients were diagnosed with hypertension and prescribed hypertension medication at least once. Of these, 9,552 patients were prescribed
In the
During the observation periods until December 2013 (median, 4.8 years; interquartile range, 2.6 to 7.3 years; 85,078 person-years), death occurred in 837 patients (5.0%); 229 patients (4.1%) in the
Table 3 shows the incidence risks of diseases related to common cause of deaths, including cancer, cardiovascular, and cerebrovascular diseases, according to
The mortality risk due to cerebrovascular disease was significantly lower in the
In this retrospective population-based cohort study, we investigated the effects of
The recent European guideline stated that
Clarithromycin is often included in several
Recent retrospective cohort studies reported inconsistent results for the association between clarithromycin-containing
Antibiotic treatment can cause dysbiosis and may alter the beneficial roles of gut microbiota in the modulation of carcinogenesis, response to cancer treatment including chemotherapy, immunotherapy and radiotherapy, and treatment-related toxicities.10,11 Repeated macrolide antibiotic exposure was significantly associated with increased risks of lung, gastric, biliary, and kidney cancer.12 Our recent randomized trial also showed that the
Two recent meta-analyses reported inconsistent results regarding the association between
Our study has several limitations associated with an observational study of a retrospective cohort study design. First, our study population was hypertension patients and our results might not be applicable to the general population with no cardiovascular risk. Second, the ICD-10 disease codes for hypertension were used for selection of the study population from the database, and possible upcoding for hypertension diagnosis could not be completely excluded. However, to reduce the possibility, we only selected patients who had a prescription for an anti-hypertensive drug. Third, our analysis was based on the prescription of
In conclusion,
No potential conflict of interest relevant to this article was reported.
This research was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HC15C1077). This study used the Korean National Health Insurance Service-National Sample Cohort database (NHIS-2016-2-191) provided by the National Health Insurance Service.
Interpretation of the data: Y.I.K., Y.A.K., I.J.C. Drafting of the article: Y.I.K., I.J.C. Statistical analysis: Y.A.K., J.W.L. Conception and design of study: I.J.C. Critical revision for important intellectual content and final approval of the manuscript: Y.I.K., Y.A.K., J.W.L., H.J.K., S.H.K., S.G.K., J.I.K., J.J.K., I.J.C.
Table 1 Baseline Characteristics of the Study Population
Characteristic | Nontreatment cohort (n=11,082) | p-value | |
---|---|---|---|
Age, yr | 1.00 | ||
20–29 | 41 (0.7) | 82 (0.7) | |
30–39 | 424 (7.7) | 848 (7.7) | |
40–49 | 1,526 (27.5) | 3,052 (27.5) | |
50–59 | 1,968 (35.5) | 3,936 (35.5) | |
60–69 | 1,297 (23.4) | 2,594 (23.4) | |
70–79 | 268 (4.8) | 536 (4.8) | |
≥80 | 17 (0.3) | 34 (0.3) | |
Sex | 1.00 | ||
Male | 3,059 (55.2) | 6,118 (55.2) | |
Female | 2,482 (44.8) | 4,964 (44.8) | |
Residential area | <0.001 | ||
Metropolitan | 2,745 (49.5) | 5,180 (46.7) | |
Small city or rural | 2,796 (50.5) | 5,902 (53.3) | |
Economic status level, % | <0.001 | ||
0–50 | 2,060 (37.2) | 4,452 (40.2) | |
51–100 | 3,481 (62.8) | 6,630 (59.8) | |
Smoking | <0.001 | ||
Never smoker | 2,574 (46.5) | 4,652 (42.0) | |
Ex-smoker | 520 (9.4) | 844 (7.6) | |
Current smoker | 1,045 (18.9) | 1,520 (13.7) | |
Missing | 1,402 (25.3) | 4,066 (36.7) | |
Alcohol drinking | 0.863 | ||
Never drinking | 2,383 (43.0) | 4,002 (36.1) | |
1–2 times/wk | 1,245 (22.5) | 2,127 (19.2) | |
3–4 times/wk | 414 (7.5) | 733 (6.6) | |
5–7 times/wk | 245 (4.4) | 425 (3.8) | |
Missing | 1,254 (22.6) | 3,795 (34.2) | |
Body mass index, kg/m2 | 0.204 | ||
≤18.5 | 46 (0.8) | 95 (0.9) | |
18.6–22.9 | 1,065 (19.2) | 1,845 (16.6) | |
23.0–24.9 | 1,208 (21.8) | 1,934 (17.5) | |
≥25.0 | 2,051 (37.0) | 3,556 (32.1) | |
Missing | 1,171 (21.1) | 3,652 (33.0) | |
CCI score at the time of hypertension diagnosis | 1.00 | ||
0 | 2,955 (53.3) | 5,910 (53.3) | |
1 | 866 (15.6) | 1,732 (15.6) | |
≥2 | 1,720 (31.0) | 3,440 (31.0) | |
Aspirin use* | 0.21 | ||
No | 4,386 (79.2) | 8,864 (80.0) | |
Yes | 1,155 (20,8) | 2,218 (20.0) | |
Statin use* | <0.001 | ||
No | 4,513 (81.4) | 9,434 (85.1) | |
Yes | 1,028 (18.6) | 1,648 (14.9) | |
PPI-clarithromycin containing triple therapy | 5,342 (96.4) | - | |
Bismuth-containing quadruple therapy | 72 (1.3) | - | |
Both | 127 (2.3) | - | |
Follow-up period, yr | 4.8 (2.6–7.4) | 4.8 (2.6–7.3) | 0.216 |
Data are presented number (%) or median (interquartile range).
Table 2 Risk Factors Associated with Overall Mortality
Risk factor | No. | Univariate analysis* | Multivariate analysis*,† | ||
---|---|---|---|---|---|
Unadjusted HR (95% CI) | p-value | Adjusted HR (95% CI) | p-value | ||
Age, yr | <0.001 | <0.001 | |||
<60 | 11,877 | 1.00 | 1.00 | ||
≥60 | 4,746 | 3.99 (3.46–4.59) | 4.02 (3.05–4.64) | ||
Sex | <0.001 | <0.001 | |||
Female | 9,177 | 1.00 | 1.00 | ||
Male | 7,446 | 1.60 (1.39–1.84) | 1.75 (1.52–2.02) | ||
Economic status level, % | <0.001 | <0.001 | |||
0–50 | 6,512 | 1.00 | 1.00 | ||
51–100 | 10,111 | 0.75 (0.66–0.86) | 0.76 (0.66–0.87) | ||
Residential area | 0.003 | 0.064 | |||
Metropolitan | 7,925 | 1.00 | 1.00 | ||
Small city or rural | 8,698 | 1.23 (1.07–1.41) | 1.14 (0.99–1.31) | ||
CCI score | |||||
0 | 8,658 | 1.00 | 1.00 | ||
1 | 2,952 | 1.37 (1.13–1.66) | 0.001 | 1.27 (1.04–1.54) | 0.018 |
≥2 | 5,040 | 1.82 (1.56–2.11) | <0.001 | 1.80 (1.55–2.10) | <0.001 |
<0.001 | <0.001 | ||||
No | 11,082 | 1.00 | 1.00 | ||
Yes | 5,541 | 0.74 (0.64–0.86) | 0.70 (0.60–0.82) | ||
Aspirin use | 0.922 | 0.16 | |||
No | 13,250 | 1.00 | 1.00 | ||
Yes | 3,373 | 1.01 (0.85–1.19) | 0.88 (0.75–1.05) | ||
Statin use | 0.094 | 0.097 | |||
No | 13,947 | 1.00 | 1.00 | ||
Yes | 2,676 | 0.83 (0.67–1.03) | 0.83 (0.66–1.03) |
HR, hazard ratio; CI, confidence interval; CCI, Charlson comorbidity index;
†Covariates for multivariate analysis were age, sex, economic status, residential area, CCI score,
Table 3 Risk of Incidence for Cardiovascular Diseases, Cerebrovascular Diseases, and Cancer Stratified by
Incidence, no. (%) | Risk of incidence for | |||||
---|---|---|---|---|---|---|
Control group (n=11,082) | Unadjusted HR (95% CI) | p-value | Adjusted HR (95% CI) | p-value | ||
Cardiovascular disease | 714 (12.9) | 1,232 (11.1) | 1.18 (1.07–1.29) | <0.001 | 1.13 (1.03–1.24) | 0.01 |
Cerebrovascular disease | 408 (7.4) | 814 (7.3) | 1.00 (0.89–1.13) | 0.962 | 0.98 (0.87–1.11) | 0.657 |
Overall cancers | 429 (7.7) | 737 (6.7) | 1.18 (1.04–1.32) | 0.008 | 1.14 (1.01–1.28) | 0.035 |
Stomach cancer | 54 (1.0) | 87 (0.8) | 1.24 (0.89–1.75) | 0.209 | 1.26 (0.90–1.78) | 0.182 |
Non-stomach cancer | 381 (6.9) | 659 (6.0) | 1.17 (1.03–1.32) | 0.017 | 1.12 (0.99–1.27) | 0.078 |
Oral cancer | 15 (0.3) | 19 (0.2) | 1.58 (0.80–3.11) | 0.185 | 1.60 (0.81–3.18) | 0.175 |
Esophageal cancer | 3 (0.1) | 7 (0.1) | 0.86 (0.22–3.31) | 0.823 | 0.82 (0.21–3.20) | 0.771 |
Colorectal cancer | 67 (1.2) | 95 (0.9) | 1.42 (1.04–1.93) | 0.03 | 1.39 (1.01–1.90) | 0.043 |
Liver cancer | 48 (0.9) | 101 (0.9) | 0.95 (0.67–1.34) | 0.774 | 0.83 (0.59–1.18) | 0.295 |
Biliary tract cancer | 5 (0.1) | 17 (0.2) | 0.59 (0.22–1.59) | 0.297 | 0.59 (0.22–1.61) | 0.302 |
Pancreatic cancer | 21 (0.4) | 31 (0.3) | 1.36 (0.78–2.36) | 0.282 | 1.25 (0.71–2.19) | 0.435 |
Lung cancer | 34 (0.6) | 67 (0.6) | 1.02 (0.67–1.53) | 0.942 | 0.99 (0.65–1.49) | 0.942 |
Breast cancer | 12 (0.2) | 24 (0.2) | 1.00 (0.50–2.00) | 1.000 | 0.98 (0.49–1.97) | 0.956 |
Prostate cancer | 58 (1.0) | 101 (0.9) | 1.15 (0.83–1.59) | 0.397 | 1.13 (0.81–1.56) | 0.472 |
Bladder cancer | 6 (0.1) | 17 (0.2) | 0.71 (0.28–1.79) | 0.462 | 0.70 (0.27–1.79) | 0.456 |
Thyroid cancer | 42 (0.7) | 53 (0.5) | 1.59 (1.06–2.38) | 0.025 | 1.54 (1.03–2.32) | 0.037 |
Brain, CNS cancer | 3 (0.1) | 6 (0.1) | 1.00 (0.25–4.00) | 1.000 | 0.87 (0.22–3.50) | 0.841 |
Non-Hodgkin lymphoma | 3 (0.1) | 4 (0.04) | 1.50 (0.34–6.70) | 0.595 | 1.39 (0.31–6.30) | 0.667 |
Leukemia | 5 (0.1) | 3 (0.03) | 3.34 (0.80–13.97) | 0.099 | 3.51 (0.83–14.89) | 0.089 |
Table 4 Risk of Cause-Specific Mortality Stratified by
Death, No. (%) | Risk of mortality for | |||||
---|---|---|---|---|---|---|
Control group (n=11,082) | Unadjusted HR (95% CI) | p-value | Adjusted HR (95% CI) | p-value | ||
Overall | 229 (4.13) | 608 (5.49) | ||||
Cardiovascular disease | 18 (0.32) | 34 (0.31) | 1.06 (0.60–1.88) | 0.842 | 0.96 (0.54–1.71) | 0.896 |
Cerebrovascular disease | 15 (0.27) | 66 (0.60) | 0.45 (0.26–0.79) | 0.006 | 0.46 (0.26–0.81) | 0.007 |
Overall cancers | 68 (1.23) | 170 (1.53) | 0.80 (0.60–1.06) | 0.112 | 0.76 (0.57–1.01) | 0.058 |
Stomach cancer | 6 (0.11) | 10 (0.09) | 1.20 (0.44–3.30) | 0.724 | 1.21 (0.44–3.38) | 0.71 |
Non-stomach cancer | 62 (1.12) | 160 (1.44) | 0.77 (0.58–1.03) | 0.083 | 0.73 (0.55–0.99) | 0.04 |
Oral cancer | 0 | 2 (0.02) | NA | NA | ||
Esophageal cancer | 2 (0.04) | 3 (0.03) | NA | NA | ||
Colorectal cancer | 5 (0.09) | 17 (0.15) | 0.59 (0.22–1.59) | 0.297 | 0.60 (0.22–1.64) | 0.319 |
Liver cancer | 12 (0.22) | 45 (0.41) | 0.53 (0.28–1.01) | 0.052 | 0.48 (0.25–0.91) | 0.024 |
Biliary tract cancer | 5 (0.09) | 13 (0.12) | 0.77 (0.27–2.16) | 0.618 | 0.79 (0.28–2.22) | 0.65 |
Pancreatic cancer | 5 (0.09) | 13 (0.12) | 0.77 (0.27–2.16) | 0.618 | 0.67 (0.24–1.91) | 0.456 |
Lung cancer | 15 (0.27) | 32 (0.29) | 0.94 (0.51–1.73) | 0.836 | 0.95 (0.51–1.75) | 0.857 |
Breast cancer | 0 | 1 (0.01) | NA | NA | ||
Prostate cancer | 0 | 4 (0.04) | NA | NA | ||
Bladder cancer | 0 | 7 (0.06) | NA | NA | ||
Thyroid cancer | 1 (0.02) | 0 | NA | NA | ||
Brain, CNS cancer | 0 | 1 (0.01) | NA | NA | ||
Non-Hodgkin lymphoma | 1 (0.02) | 3 (0.03) | NA | NA | ||
Leukemia | 3 (0.05) | 1 (0.01) | NA | NA |