Associations of cholecystectomy with metabolic health changes and incident cardiovascular disease: a retrospective cohort study.

Although some studies conducted about the risk of cholecystectomy and cardiovascular disease, there was a limit to explaining the relationship. We investigated the short-term and long-term relationship between cholecystectomy and cardiovascular disease, and evidence using the elements of the metabolic index as an intermediate step. It was a retrospective cohort study and we used the National Health Insurance Service database of South Korea between 2002 and 2015. Finally, 5,210 patients who underwent cholecystectomy and 49,457 at 1:10 age and gender-matched controls of subjects were collected. The main results was estimated by Multivariate Cox proportional hazard regression to calculate the hazard ratio (HR) with 95% confidence interval (CI) for risk of cardiovascular disease after cholecystectomy. Regarding short-term effects of cholecystectomy, increased risk of cardiovascular disease (aHR 1.35, 95% CI 1.15-1.58) and coronary heart disease (aHR 1.77, 95% CI 1.44-2.16) were similarly seen within 2 years of surgery. When analyzing the change in metabolic risk factors, cholecystectomy was associated with a change in systolic blood pressure (adjusted mean [aMean]: 1.51, 95% CI: [- 1.50 to - 4.51]), total cholesterol (aMean - 14.14, [- 20.33 to 7.95]) and body mass index (aMean - 0.13, [- 0.37 to 0.11]). Cholecystectomy patients had elevated risk of cardiovascular disease in the short-term, possibly due to the characteristics of the patient before surgery. The association of cholecystectomy and cardiovascular disease has decreased after 2 years in patients who underwent cholecystectomy, suggesting that because of improvement of metabolic health, cholecystectomy-associated elevation of cardiovascular disease risk may be ameliorated 2 years after cholecystectomy.

Cardiovascular Benefit of Statin Use Against Air Pollutant Exposure in Older Adults.

BACKGROUND AND AIMS: Little is known about the cardiovascular benefit of statin use against ambient air pollution among older adults who are at higher risk of cardiovascular disease (CVD) potentially owing to age-related declines in cardiovascular functions along with other risk factors. METHODS AND RESULTS: This retrospective, population-based cohort study consisted of adults aged 60 years and older free of CVD at baseline identified from the National Health Insurance Service (NHIS) database linked to the National Ambient Air Monitoring Information System (NAMIS) for average daily exposure to PM10 and PM2.5 in 2015 in the major metropolitan areas in the Republic of Korea. Follow-up period began on January 1, 2016 and lasted until December 31, 2021. Cox proportional hazards model was used to evaluate association of cardiovascular benefit with statin use against different levels of air pollutant exposure. Of 1,229,444 participants aged 60 years and older (mean age, 67.4; 37.7% male), 377,076 (30.7%) were identified as statin-users. During 11,963,322 person-years (PY) of follow-up, a total of 86,018 incident stroke events occurred (719.0 events per 100,000 PYs). Compared to statin non-user exposed to high level of PM10 (>50 µg/m3) and PM2.5 (>25 µg/m3), statin users had 20% (adjusted hazard ratio [HR], 0.80; 95% confidence intervals [CI], 0.75 to 0.85) and 17% (adjusted HR, 0.80; 95% CI, 0.80 to 0.86) lower adjusted risk of incident stroke for PM10 and PM2.5, respectively. Similar risk reduction for incident CVD was also found among statin-users exposed to low or moderate level of PM10 (≤50 µg/m3) and PM2.5 (≤25 µg/m3) exposure. CONCLUSION: Among adults aged 60 years and older with high and low or moderate levels of exposure to PM10 and PM2.5, statin use was associated with a significantly lower risk of stroke.

In a retrospective cohort study of older adults exposed to high and low or moderate levels of PM10 and PM2.5, statin use was associated with a significantly lower risk of incident stroke.

Association Between Antibiotic Exposure and Thyroid Cancer: A Nationwide Cohort Study in South Korea.

Background: Although recent studies have introduced antibiotics as a potential risk factor for thyroid cancer, further studies are necessary. We examined the association between long-term antibiotic usage and thyroid cancer risk. Methods: This nationwide cohort study investigated 9,804,481 individuals aged 20 years or older who participated in health screening (2005-2006) with follow-up ending on December 31, 2019, using the Korean National Health Insurance Service database. Multivariable Cox proportional hazards regression was used to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for thyroid cancer risk according to the cumulative days of antibiotic prescription and the number of antibiotic classes, respectively. A 1:1 propensity score (PS) matching was also performed for analysis. Results: Compared with nonusers of antibiotics, participants prescribed ≥365 days of antibiotics showed an increased risk of thyroid cancer (aHR, 1.71; CI, 1.66-1.78) after adjusting for covariates including age, smoking status, comorbidities including thyroid-related diseases, and the number of head and neck computed tomography scans. Participants prescribed ≥365 days of antibiotics also had a significantly increased risk of thyroid cancer (aHR, 1.37; CI, 1.34-1.40) compared with participants prescribed 1-14 days of antibiotics. Association remained significant in the 1:1 PS-matched cohort. Moreover, compared with nonusers of antibiotics, the 5 or more antibiotic class user group had a higher thyroid cancer risk (aHR, 1.71; CI, 1.65-1.78). Conclusions: Long-term antibiotic prescriptions and an increasing number of antibiotic classes may be associated with a higher risk of thyroid cancer in a duration-dependent manner. The effects of long-term antibiotic exposure on thyroid cancer should be further investigated.

Association between antibiotic use and subsequent risk of prostate cancer: A retrospective cohort study in South Korea.

OBJECTIVES: Several studies suggest that antibiotic use may affect overall cancer incidence, but the association between antibiotics and prostate cancer is still unclear. This retrospective cohort study aimed to assess the association between antibiotics and the risk of prostate cancer. METHODS: A population-based retrospective cohort study was conducted using the Korean National Health Insurance Service (NHIS) database. 1 032 397 individuals were followed up from January 1, 2007, to December 31, 2019. Multivariable Cox hazards regression was utilized to calculate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for the risk of prostate cancer according to accumulative days of antibiotic use and the number of antibiotic classes used from 2002 to 2006. RESULTS: Individuals who used antibiotics for 180 or more days had a higher risk of prostate cancer (aHR, 1.46; 95% CI, 1.11-1.91) than those who did not use antibiotics. Also, individuals who used four or more kinds of antibiotics had a higher risk of prostate cancer (aHR, 1.18; 95% CI, 1.07-1.30) than antibiotic non-users. An overall trend was observed among participants who underwent health examinations. CONCLUSIONS: Our findings suggest that long-term use of antibiotics may affect prostate cancer incidence. Further studies are needed to improve understanding of the association between antibiotic use and prostate cancer incidence.

Association between antibiotics and asthma risk among adults aged over 40 years: a nationally representative retrospective cohort study.

INTRODUCTION: Several studies have reported that exposure to antibiotics can lead to asthma during early childhood. However, the association between antibiotic use and risk of asthma in the adult population remains unclear. This study aimed to investigate the association between antibiotic use and asthma in adults. METHODS: We used data from the National Health Insurance Service (NHIS)-Health Screening Cohort, which included participants aged ≥40 years who had health screening examination data in 2005-2006. A total of 248 961 participants with a mean age of 55.43 years were enrolled in this retrospective cohort study. To evaluate antibiotic exposure from the NHIS database for 5 years (2002-2006), cumulative usage and multiclass prescriptions were identified, respectively. During the follow-up period (2007-2019), 42 452 patients were diagnosed with asthma. A multivariate Cox proportional hazard regression model was used to assess the association between antibiotic use and newly diagnosed asthma. RESULTS: Participants with antibiotic use for ≥91 days showed a higher risk of asthma (adjusted HR (aHR) 1.84, 95% CI 1.72 to 1.96) compared with participants who did not use antibiotics (n=38 450), with a duration-dependent association (ptrend<0.001). Furthermore, ≥4 antibiotic class user group had an increased risk of asthma (aHR 1.44, 95% CI 1.39 to 1.49) compared with one class of antibiotic use (n=64 698). Also, one class of antibiotic use had a higher risk of asthma (aHR 1.21, 95% CI 1.17 to 1.26) compared with non-users, and it also showed a duration-dependent relationship in all classes, including 1, 2, 3 and ≥4 class group (ptrend<0.001). The duration-response relationship between antibiotic use and increased risk of asthma remained in our sensitivity analyses with the washout and shifting of the index date. CONCLUSIONS: The duration-response pattern observed in antibiotic use and asthma may suggest the implication of proper antibiotic use and management in adults.

Changes in total cholesterol level and cardiovascular disease risk among type 2 diabetes patients.

Despite many diabetic patients having hypercholesterolemia, the association of total cholesterol (TC) levels with CVD risk in type 2 diabetes (T2D) patients is unclear. Diagnosis of type 2 diabetes often leads to changes in total cholesterol (TC) levels. Thus, we examined whether changes in TC levels from pre- to post-diagnosis of T2D were associated with CVD risk. From the National Health Insurance Service Cohort, 23,821 individuals diagnosed with T2D from 2003 to 2012 were followed-up for non-fatal CVD incidence through 2015. Two measurements of TC, 2 years before and after T2D diagnosis, were classified into 3 levels (low, middle, high) to define changes in cholesterol levels. Cox proportional hazards regression was performed to estimate adjusted hazards ratios (aHRs) and 95% confidence intervals (CIs) for the associations between changes in cholesterol levels and CVD risk. Subgroup analyses were performed by use of lipid-lowering drugs. Compared with low-low, aHR of CVD was 1.31 [1.10-1.56] for low-middle and 1.80 [1.15-2.83] for low-high. Compared with middle-middle, aHR of CVD was 1.10 [0.92-1.31] for middle-high but 0.83 [0.73-0.94] for middle-low. Compared with high-high, aHR of CVD was 0.68 [0.56-0.83] for high-middle and 0.65 [0.49-0.86] for high-low. The associations were observed regardless of use of lipid-lowering drugs. For diabetic patients, management of TC levels may be important to lower CVD risk.

Association of antibiotic use with risk of lung cancer: A nationwide cohort study.

BACKGROUND: Although recent studies indicated that antibiotics may be a risk factor for lung cancer, further understanding is needed. We investigated the association of long-term antibiotic exposure with lung cancer risk. METHODS: This population-based retrospective cohort study investigated 6,214,926 participants aged ≥ 40 years who underwent health screening examinations (2005-2006) from the Korean National Health Insurance Service database. The date of the final follow-up was December 31, 2019. Exposures were the cumulative days of antibiotics prescription and the number of antibiotics classes. The adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for lung cancer risk according to antibiotic use were assessed using multivariable Cox proportional hazards regression. RESULTS: Compared with the antibiotic non-user group, participants with ≥ 365 days of antibiotics prescribed had a significantly increased risk of lung cancer (aHR, 1.21; 95% CI, 1.16-1.26). Participants with ≥ 365 days of antibiotics prescribed also had a significantly increased risk of lung cancer (aHR, 1.21; 95% CI, 1.17-1.24) than 1-14 days of the antibiotic user group. The results were also consistent in competing risk analyses and adjusted Cox regression models that fitted restricted cubic spline. Compared with the antibiotic non-user group, ≥ 5 antibiotic classes prescribed group had a higher lung cancer risk (aHR, 1.15; 95% CI, 1.10-1.21). CONCLUSION: The long-term cumulative days of antibiotic use and the increasing number of antibiotics classes were associated with an increased risk of lung cancer in a clear duration-dependent manner after adjusting for various risk factors.

Association of hemoglobin variability with the risk of cardiovascular disease: a nationally representative retrospective cohort study from South Korea.

Hemoglobin variability is known to increase cardiovascular mortality in chronic kidney disease, but the association of hemoglobin variability with the risk of cardiovascular disease (CVD) in the general population is yet unclear. This retrospective cohort study based on 'the South Korean National Health Insurance Service database' consisted of 198,347 adults who went through all three health examinations. Hemoglobin variability is defined as the average successive variability of three separate hemoglobin values from each health screening period. Participants were followed up for 6 years to determine the risk of coronary heart disease and stroke. We used multivariate Cox proportional hazards regression to examine the adjusted hazard ratios for CVD according to hemoglobin variability. Per 1 unit increase of hemoglobin variability, the risk for CVD (aHR 1.06, 95% CI 1.02-1.09) and stroke (aHR 1.08, 95% CI 1.03-1.13) increased significantly. The risk-increasing trend was preserved in the low-to-moderate risk group of CVDs (aHR 1.07, 95% CI 1.02-1.11). This result suggests that subjects with high hemoglobin variability who would otherwise be categorized as having low-to-moderate CVD risk may have higher risk of CVD than those with low hemoglobin variability.

Association of Change in Smoking Status and Subsequent Weight Change with Risk of Nonalcoholic Fatty Liver Disease.

Background/Aims: Smoking is considered a risk factor for the development of nonalcoholic fatty liver disease (NAFLD). However, the association of a weight change after a change in smoking status and the risk of NAFLD remains undetermined. Methods: This study used the Korean National Health Insurance Service-National Sample Cohort. Based on the first (2009 to 2010) and second (2011 to 2012) health examination periods, 139,180 adults aged at least 40 years were divided into nonsmoking, smoking cessation, smoking relapse, and sustained smoking groups. NAFLD was operationally defined using the fatty liver index. The adjusted odds ratio (aOR) and 95% confidence interval (CI) were calculated using multivariable-adjusted logistic regression. Results: Compared to nonsmoking with no body mass index (BMI) change, the risk of NAFLD was significantly increased among subjects with BMI gain and nonsmoking (aOR, 4.07; 95% CI, 3.77 to 4.39), smoking cessation (aOR, 5.52; 95% CI, 4.12 to 7.40), smoking relapse (aOR, 7.51; 95% CI, 4.81 to 11.72), and sustained smoking (aOR, 6.65; 95% CI, 5.33 to 8.29), whereas the risk of NAFLD was reduced among participants with BMI loss in all smoking status groups. In addition, smoking cessation (aOR, 1.76; 95% CI, 1.35 to 2.29) and sustained smoking (aOR, 1.64; 95% CI, 1.39 to 1.94) were associated with higher risk of NAFLD among participants with no BMI change. The liver enzyme levels were higher among participants with smoking cessation and BMI gain. Conclusions: Monitoring and management of weight change after a change in smoking status may be a promising approach to reducing NAFLD.

Association between antibiotics and dementia risk: A retrospective cohort study.

Background: The possible relation between antibiotic exposure and the alteration of gut microbiota, which may affect dementia risk, has been revealed. However, the association between antibiotics and dementia incidence has rarely been studied. We aimed to determine the association between antibiotic exposure and the risk of dementia. Methods: This population-based retrospective cohort study used data from the National Health Insurance Service-Health Screening Cohort (NHIS-HEALS) in South Korea. Exposure was the cumulative days of antibiotic prescription from 2002 to 2005. Newly diagnosed overall dementia, Alzheimer's disease (AD), and vascular dementia (VD) were identified based on diagnostic codes and prescriptions for dementia-related drugs. The follow-up investigation was carried out from 1 January 2006 to 31 December 2013. The Cox proportional hazards regression was used to assess the association between cumulative antibiotic prescription days and dementia incidence. Results: A total of 313,161 participants were analyzed in this study. Compared to antibiotic non-users, the participants who used antibiotics for 91 or more days had an increased risk of overall dementia [adjusted hazard ratio (aHR), 1.44; 95% confidence interval (CI), 1.19-1.74], AD (aHR, 1.46; 95% CI, 1.17-1.81), and VD (aHR, 1.38; 95% CI, 0.83-2.30). Those who used five or more antibiotic classes had higher risks of overall dementia (aHR, 1.28; 95% CI, 1.00-1.66) and AD (aHR, 1.34; 95% CI, 1.00-1.78) than antibiotic non-users. Conclusion: Antibiotic exposure may increase the risk of dementia in a cumulative duration-dependent manner among adult participants. Future studies are needed to assess the causality between the long-term prescription of antibiotics and dementia risk.

Association of the presence of allergic disease with subsequent risk of liver cancer in a nationwide retrospective cohort among Koreans.

A number of studies have proposed an inverse association between allergic diseases and risk of cancer, but only a few studies have specifically investigated the risk of primary liver cancer, including hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). The aim of this study was to evaluate the association of allergic diseases with risk of primary liver cancer. We conducted a retrospective cohort study of the Korean National Health Insurance Service database consisted of 405,512 Korean adults ages 40 and above who underwent health screening before January 1st, 2005. All participants were followed up until the date of liver cancer, death, or December 31st, 2013, whichever happened earliest. Those who died before the index date or had pre-diagnosed cancer were excluded from the analyses. Cox proportional hazards regression was used to determine the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for risk of primary liver cancer according to the presence of allergic diseases, including atopic dermatitis, asthma, and allergic rhinitis. The aHR (95% CI) for overall liver cancer among allergic patients was 0.77 (0.68-0.87) compared to those without allergic disease. Allergic patients had significantly reduced risk of HCC (aHR, 0.72; 95% CI 0.62-0.85) but not ICC (aHR, 0.95; 95% CI 0.73-1.22). The presence of allergies was associated with significantly lower risk of liver cancer among patients whose systolic blood pressure is lower than 140 mmHg (aHR, 0.64; 95% CI 0.62-0.78 for overall liver cancer; aHR, 0.64; 95% CI 0.52-0.78 for HCC) but this effect was not observed among patients whose systolic blood pressure is higher than 140 mmHg (aHR, 0.91; 95% CI 0.71-1.18 for overall liver cancer; aHR, 0.91; 95% CI 0.71-1.18 for HCC) The aHR (95% CI) for overall liver cancer of allergic patients with and without chronic hepatitis virus infection were 0.60 (95% CI 0.44-0.81) and 0.77 (95% CI 0.64-0.93), respectively. In addition, allergic patients without cirrhosis showed significantly lower risk of overall liver cancer (aHR, 0.73; 95% CI 0.63-0.83). Patients with allergic diseases have significantly lower risk of primary liver cancer compared to those without allergic diseases, which supports the rationale for immunotherapy as an effective treatment for liver cancer.

Association between Proton Pump Inhibitor Use and Risk of Hepatocellular Carcinoma: A Korean Nationally Representative Cohort Study.

(1) Background: The association between proton pump inhibitor (PPI) use and hepatocellular carcinoma (HCC) has been controversial, especially in the general population. We aimed to determine the impact of PPI on HCC risk in participants without liver cirrhosis or chronic hepatitis virus infection. (2) Methods: We assessed 406,057 participants from the Korean National Health Insurance Service database who underwent health screening from 2003 to 2006. We evaluated exposure to PPI before the index date using a standardized daily defined dose (DDD) system. The association of proton pump inhibitor use with the risk of HCC was evaluated using multivariable-adjusted Cox proportional hazards regression. (3) Results: Compared with non-users, PPI use was not associated with the HCC risk in low (<30 DDDs; aHR, 1.07; 95% CI, 0.91−1.27), intermediate (30 ≤ PPI < 60 DDDs; aHR, 0.96; 95% CI, 0.73−1.26), and high (≥60 DDDs; aHR, 0.86; 95% CI, 0.63−1.17) PPI groups in the final adjustment model. In addition, risks of cirrhosis-associated HCC and non-cirrhosis-associated HCC were not significantly associated with PPI use. The results remained consistent after excluding events that occurred within 1, 2, and 3 years to exclude pre-existing conditions that may be associated with the development of HCC. We also found no PPI-associated increase in HCC risk among the selected population, such as those with obesity, older age, and chronic liver diseases. (4) Conclusions: PPI use may not be associated with HCC risk regardless of the amount. We call for future studies conducted in other regions to generalize our findings.

Association of antibiotics exposure within the first 2 years after birth with subsequent childhood type 1 diabetes.

PURPOSE: Antibiotics prescription in early life can cause dysbiosis, an imbalance of gut microbiota. We aimed to reveal the relationship between antibiotics exposure during the first 2 years after birth and type 1 diabetes risk in children under 8 years of age using a nationally representative data from South Korea. METHODS: The final study population consisted of 63,434 children from the National Health Insurance Service (NHIS) database from 2008 to 2015. The primary exposure of interest was antibiotics prescription in first 2 years after birth. The analysis was conducted with cumulative defined daily dose (cDDD; 0-29, 30-59, ≥ 60 cDDD), the number of antibiotics classes (0-3, 4, ≥5 classes), and age at first antibiotics prescription (0-119, 120-239, ≥ 240 days). Age, sex, household income, and overweight were considered as potential confounding covariates. RESULTS: Compared to those within the less than 30 cDDD, other groups that were prescribed more antibiotics did not have a significant difference in diabetes risk (aHR 0.86, 95% CI 0.37-2.02 in ≥ 60 cDDD). The number of antibiotics classes and age at first antibiotics prescriptions were also not associated with the risk of type 1 diabetes. The development of diabetes was not related to the cDDD, the number of antibiotics classes, and age at first antibiotics prescription according to subgroup analysis which was stratified by overweight. CONCLUSIONS: Antibiotics exposure within the first 2 years of life was not associated with subsequent diabetes risk. Future studies using a larger number of long-term follow-up data are needed.

Association of short-term particulate matter exposure with suicide death among major depressive disorder patients: a time-stratified case-crossover analysis.

There is growing evidence that suggests a potential association between particulate matter (PM) and suicide. However, it is unclear that PM exposure and suicide death among major depressive disorder (MDD) patients, a high-risk group for suicide. We aimed to assess the effect of short-term exposure to PM on the risk of suicide in MDD patients who are at high risk for suicide. We investigated the risk of suicide among 922,062 newly-diagnosed MDD patients from 2004 to 2017 within the Korean National Health Insurance Service (NHIS) database. We identified 3,051 suicide cases from January 1, 2015, to December 31, 2017, within the death statistics database of the Korean National Statistical Office. PMs with aerodynamic diameter less than 2.5 µm (PM2.5), less than 10 µm (PM10), and 2.5-10 µm (PM2.5-10) were considered, which were provided from the National Ambient Air Monitoring System in South Korea. Time-stratified case-crossover analysis was performed to investigate the association of particulate matter exposure to suicide events. The risk of suicide was significantly high upon the high level of exposure to PM2.5, PM2.5-10 (coarse particle) and PM10 on lag 1 (p for trend < 0.05). Short-term exposure to a high level of PM was associated with an elevated risk for suicide among MDD patients. There is a clear dose-response relationship between short-term PM exposures with suicide death among MDD patients. This result will be used as an essential basis for consideration when establishing an air pollution alarm system for reducing adverse health outcomes by PM.

Combined Associations of Physical Activity and Particulate Matter With Subsequent Cardiovascular Disease Risk Among 5-Year Cancer Survivors.

Background The combined associations of physical activity and particulate matter (PM) with subsequent cardiovascular disease (CVD) risk is yet unclear. Methods and Results The study population consisted of 18 846 cancer survivors who survived for at least 5 years after initial cancer diagnosis from the Korean National Health Insurance Service database. Average PM levels for 4 years were determined in administrative district areas, and moderate-to-vigorous physical activity (MVPA) information was acquired from health examination questionnaires. A multivariable Cox proportional hazards model was used to evaluate the risk for CVD. Among patients with low PM with particles ≤2.5 µm (PM2.5; (19.8-25.6 µg/m3) exposure, ≥5 times per week of MVPA was associated with lower CVD risk (adjusted hazard ratio [aHR], 0.77; 95% CI, 0.60-0.99) compared with 0 times per week of MVPA. Also, a higher level of MVPA frequency was associated with lower CVD risk (P for trend=0.028) among cancer survivors who were exposed to low PM2.5 levels. In contrast, ≥5 times per week of MVPA among patients with high PM2.5 (25.8-33.8 µg/m3) exposure was not associated with lower CVD risk (aHR, 0.98; 95% CI, 0.79-1.21). Compared with patients with low PM2.5 and MVPA ≥3 times per week, low PM2.5 and MVPA ≤2 times per week (aHR, 1.26; 95% CI, 1.03-1.55), high PM2.5 and MVPA ≥3 times per week (aHR, 1.34; 95% CI, 1.07-1.67), and high PM2.5 and MVPA ≤2 times per week (aHR, 1.38; 95% CI, 1.12-1.70) was associated with higher CVD risk. Conclusions Cancer survivors who engaged in MVPA ≥5 times per week benefited from lower CVD risk upon low PM2.5 exposure. High levels of PM2.5 exposure may attenuate the risk-reducing effects of MVPA on the risk of CVD.

Association of non-alcoholic fatty liver disease with incident dementia later in life among elder adults.

BACKGROUND/AIMS: Accumulating evidence suggests a link between non-alcoholic fatty liver disease (NAFLD) and brain health. However, population-based evidence on the association between NAFLD and dementia remains unclear. This study was conducted to determine the association between NAFLD and incident dementia. METHODS: The study population included 608,994 adults aged ≥60 years who underwent health examinations between 2009 and 2010. Data were collected from the Korean National Health Insurance Service database. NAFLD was assessed using the fatty liver index (FLI). A Cox proportional hazards regression model was used to determine the association between NAFLD and dementia. RESULTS: During the 6,495,352 person-years of follow-up, 48,538 participants (8.0%) developed incident dementia. The participants were classified into low (FLI <30), intermediate (FLI ≥30 and <60), and high (FLI ≥60) groups. In the overall study population, the FLI groups were associated with a risk of dementia (P for trend <0.001). After propensity score matching, a low FLI was associated with a reduced risk of dementia (adjusted hazard ration [aHR], 0.96; 95% confidence interval [CI], 0.93-0.98; P=0.002), whereas a high FLI (NAFLD) was associated with an increased risk of dementia (aHR, 1.05; 95% CI, 1.02-1.08; P=0.001). A higher risk of dementia in the high FLI group than in the intermediate FLI group was attributed to Alzheimer's disease (aHR, 1.04; 95% CI, 1.01-1.07; P=0.004) rather than vascular dementia (aHR, 0.94; 95% CI, 0.75-1.18; P=0.602). CONCLUSION: NAFLD was associated with an increased risk of dementia, which was attributed to an increased risk of Alzheimer's disease.

Association of physical activity with stroke among long-term colorectal cancer survivors.

PURPOSE: Cancer survivors are currently considered high-risk populations for cardiovascular disease. However, no studies have directly evaluated risks and benefits of physical activity for stroke among long-term colorectal cancer survivors. METHODS: This large-scale observational cohort study used data from the Korean National Health Insurance Service database. Newly diagnosed colorectal cancer patients diagnosed between 2006 and 2013 who survived at least 5 years were studied. The primary outcome was stroke, including ischemic stroke and hemorrhage stroke. All patients were followed up to the date of stroke, death, or December 2018, whichever occurred earliest. RESULTS: Of 20,674 colorectal cancer survivors with a median age of 64 years, stroke occurred in 601 patients (2.9%). Moderate-to-vigorous physical activity lowered stroke risk in 5-9 time/week group (adjusted hazard ratio [aHR], 0.72; 95% confidence interval [CI], 0.57-0.93; P=0.010), but not in ≥10 time/week group (aHR, 0.85; 95% CI, 0.62-1.17; P=0.327). Walking also lowered stroke risk in 4-5 time/week group (aHR, 0.75; 95% CI, 0.58-0.97; P=0.028), but not in ≥6 time/week group (aHR, 0.96; 95% CI, 0.78-1.18; P=0.707). In addition, benefits of physical activity were maximized when carried out both moderate-to-vigorous physical activity and walking with moderate frequency (aHR, 0.77; 95% CI, 0.60-0.97; P=0.027). CONCLUSIONS: Moderate frequency of moderate-to-vigorous physical activity (5-9 time/week) and walking (4-5 time/week) significantly lowers the risk of stroke, whereas high-frequency physical activity reduces the benefits of physical activity. IMPLICATIONS FOR CANCER SURVIVORS: Physical activity with moderate frequency is important in the prevention of stroke for long-term colorectal cancer survivors.

Metabolic Dysfunction-Associated Fatty Liver Disease Better Predicts Incident Cardiovascular Disease.

Background/Aims: Metabolic dysfunction (MD)-associated fatty liver disease is a new positive diagnostic criterion based on hepatic steatosis and MD. However, a comprehensive evaluation on the association of MD and hepatic steatosis with incident cardiovascular disease (CVD) has yet to be performed. Methods: This retrospective cohort study included 333,389 participants from the Korean National Health Insurance Service database who received a health examination between 2009 and 2010. Hepatic steatosis was defined using the Korean National Health and Nutrition Examination Survey-derived nonalcoholic fatty liver disease scoring system. Cox proportional hazards regression was adopted to determine the adjusted hazard ratio (aHR) with 95% confidence interval (CI) for CVD according to the presence of hepatic steatosis and MD, as well as the composite term. Results: This study included 179,437 men and 153,952 women with a median age of 57 years. Hepatic steatosis with MD (aHR, 2.00; 95% CI, 1.89 to 2.13) and without MD (aHR, 1.30; 95% CI, 1.10 to 1.54) significantly increased the risk of CVD compared to no steatosis without MD (reference). However, steatosis revealed no significant difference in the risk of CVD compared to no steatosis among participants with one MD (aHR, 1.09; 95% CI, 0.91 to 1.30). In participants with steatosis, the presence of one and ≥2 MDs had aHR values of 1.25 (95% CI, 0.87 to 1.79) and 1.71 (95% CI, 1.22 to 2.41), respectively, compared to no MD. Conclusions: Combined consideration of hepatic steatosis and MD was significantly associated with increased CVD risk and showed better predictive performance for CVD than hepatic steatosis or MD alone.