Evolutionary changes in metabolic dysfunction-associated steatotic liver disease and the risk of hepatocellular carcinoma: a nationwide cohort study.

Background/Aims: To determine the association between evolutionary changes in metabolic dysfunction-associated steatotic liver disease (MASLD) status and the risk of hepatocellular carcinoma (HCC) in a nationwide population-based cohort. Methods: Information on study participants were derived from the Korea National Health Insurance Service database. The study population consisted of 5,080,410 participants who underwent two consecutive biennial health screenings between 2009 and 2012. All participants were followed up until HCC, death, or 31 December 2020. Association of evolutionary changes in MASLD status as assessed by fatty liver index and cardiometabolic risk factors, including persistent non-MASLD, resolved MASLD, incident MASLD, and persistent MASLD, with HCC risk was evaluated using the multivariable-adjusted Cox proportional hazards regression. Results: Among the 5,080,410 participants with 39,910,331 person-years of follow-up, 4,801 participants developed HCC. The incidence of HCC in participants with resolved, incident, and persistent MASLD was approximately 2.2-, 2.3-, and 4.7-fold higher, respectively, than that in those with persistent non-MASLD among the Korean adult population. When stratifying the participants according to the evolutionary change in MASLD status, persistent (adjusted hazard ratio [aHR], 2.94; 95% confidence interval [CI], 2.68-3.21; P<0.001), incident (aHR, 1.85; 95% CI, 1.63-2.10; P<0.001), and resolved MASLD (aHR, 1.33; 95% CI, 1.18-1.50; P<0.001) had an increased risk of HCC than that of persistent non-MASLD. Conclusions: The evolutionary changes in MASLD were associated with the differential risk of HCC independent of metabolic risk factors and concomitant medications, providing additional information on the risk of HCC stratification in patients with MASLD.

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.

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 of post-smoking cessation changes in fasting serum glucose with changes in predicted fatty liver score.

Major post-cessation metabolic changes include weight gain and hyperglycemia. However, the association of post-cessation change in fasting serum glucose (FSG) with risk of fatty liver remains unclear. A total of 111,106 participants aged 40 and above who underwent health screening at least once in two examination periods were extracted from the Korean National Health Insurance Service-National Sample Cohort. Fatty liver status was evaluated using the Korean National Health and Nutrition Examination Survey nonalcoholic fatty liver disease (K-NAFLD) score. Linear and logistic regression were used to calculate the adjusted mean (aMean) and adjusted odds ratio (aOR) with 95% confidence intervals. Compared to stable (aMean 0.10; 95% CI 0.03-0.18) and decline (aMean - 0.60; 95% CI - 0.71 to 0.49) groups, FSG elevation (aMean 1.28; 95% CI 1.16-1.39) was associated with higher K-NAFLD score even within different body mass index change groups. Risk of fatty liver was significantly reduced among participants with stable (aOR 0.38; 95% CI 0.31-0.45) and declined (aOR 0.17; 95% CI 0.13-0.22) FSG levels after smoking cessation compared to FSG elevation group. This study suggests that quitters with elevated FSG are associated with higher NAFLD risk and may benefit from careful monitoring of FSG levels and management of other cardiovascular risk factors.

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 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 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.

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.

Changes in predicted lean body mass, appendicular skeletal muscle mass, and body fat mass and cardiovascular disease.

BACKGROUND: Little is known about the association of changes in two body components, muscle and fat mass, with the risk of cardiovascular disease (CVD) among young adults. We investigated the association of changes in predicted lean body mass index (LBMI), appendicular skeletal muscle mass index (ASMI), and body fat mass index (BFMI) with the development of CVD among young adults. METHODS: This nationwide, population-based cohort study included 3 727 738 young adults [2 406 046 (64.5%) men and 1 321 692 (35.5%) women] aged 20-39 years without a previous history of CVD who underwent two health screening examinations during 2009-2010 and 2011-2012. Using validated and robust prediction equations, we calculated the changes in predicted LBMI, ASMI, and BFMI from the first to the second examinations. RESULTS: The mean (SD) age was 32.2 (4.9) years, and 2 406 046 (64.5%) of the participants were men. A total of 23 344 CVD events were detected during 22 257 632 person-years of follow-up. Each 1 kg/m2 increase in predicted LBMI and ASMI change was associated with a reduced risk of CVD among men [adjusted hazard ratio (aHR): 0.86, 95% confidence interval (CI) 0.82-0.91; aHR: 0.76, 95% CI 0.69-0.82, respectively] and women (aHR: 0.77, 95% CI 0.63-0.95; aHR: 0.75, 95% CI 0.59-0.96). Each 1 kg/m2 increase in predicted BFMI change was associated with an increased risk of CVD among men (aHR: 1.16, 95% CI 1.10-1.22) and women (aHR: 1.32, 95% CI 1.06-1.65). In both sexes, decreases in predicted LBMI and ASMI were associated with greater CVD risk, and decreased predicted BFMI was associated with a reduced CVD risk. Those who maintained their BMI between -1 and +1 kg/m2 also had a decreased risk of CVD per 1 kg/m2 increase in predicted LBMI and ASMI change among men (aHR: 0.86, 95% CI 0.80-0.92; aHR: 0.85, 95% CI 0.76-0.95) and women (aHR: 0.62, 95% CI 0.47-0.83; aHR: 0.59, 95% CI 0.44-0.80) and had a greater risk of CVD per 1 kg/m2 increase in predicted BFMI change among men (aHR: 1.17, 95% CI 1.10-1.25) and women (aHR: 1.64, 95% CI 1.20-2.23). Regardless of changes in weight, such as from normal to obese or vice versa, these results were consistent. CONCLUSIONS: Among young adults, increased predicted muscle mass or decreased predicted fat mass were associated with a reduced risk of development of CVD. Decreased predicted muscle mass or increased predicted fat mass were associated with an elevated risk of development of CVD.

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.

Association between antibiotics use and diabetes incidence in a nationally representative retrospective cohort among Koreans.

Numerous studies have reported that antibiotics could lead to diabetes, even after adjusting for confounding variables. This study aimed to determine the causal relationship between antibiotics use and diabetes in a nationally representative cohort. This retrospective cohort study included adults aged 40 years or older who were enrolled in the Korean National Health Insurance Service-Health Screening Cohort. Antibiotic exposure was assessed from 2002 to 2005 and newly diagnosed diabetes mellitus was determined based on diagnostic codes and history of antidiabetic medication use from 2006 to 2015. Multivariate Cox proportional hazards model was used to assess the association between antibiotic use and diabetes incidence. The mean age of the 201,459 study subjects was 53.2 years. People who used antibiotics for 90 or more days had a higher risk of diabetes (adjusted hazard ratio [aHR] 1.16, 95% confidence interval [CI] 1.07-1.26) compared to non-users. Those who used five or more classes of antibiotics had a higher risk of diabetes than those who used one antibiotic class (aHR 1.14; 95% CI 1.06-1.23). The clear dose-dependent association between antibiotics and diabetes incidence supports the judicious use of antibiotics in the future.

Association of Short-Term Particulate Matter Exposure among 5-Year Cancer Survivors with Incident Cardiovascular Disease: A Time-Stratified Case-Crossover Study.

The association of short-term particulate matter concentration with cardiovascular disease (CVD) among cancer survivors is yet unclear. Using the National Health Insurance Service database from South Korea, the study population consisted of 22,864 5-year cancer survivors with CVD events during the period 2015-2018. Using a time-stratified case-crossover design, each case date (date of incident CVD) was matched with three or four referent dates, resulting in a total of 101,576 case and referent dates. The daily average particulate matter 10 (PM10), 2.5 (PM2.5), and 2.5-10 (PM2.5-10) on the day of case or referent date (lag0), 1-3 days before the case or referent date (lag1, lag2, and lag3), and the mean value 0-3 days before the case or referent date (lag0-3) were determined. Conditional logistic regression was conducted to calculate the adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for CVD according to quartiles of PM10, PM2.5, and PM2.5-10. Compared to the 1st (lowest) quartile of lag0-3 PM10, the 4th (highest) quartile of lag0-3 PM10 was associated with higher odds for CVD (aOR 1.13, 95% CI 1.06-1.21). The 4th quartiles of lag1 (aOR 1.12, 95% CI 1.06-1.19), lag2 (aOR 1.09, 95% CI 1.03-1.16), lag3 (aOR 1.06, 95% CI 1.00-1.12), and lag0-3 (aOR 1.11, 95% CI 1.05-1.18) PM2.5 were associated with higher odds for CVD compared to the respective 1st quartiles. Similarly, the 4th quartile of lag0-3 PM2.5-10 was associated with higher CVD events (aOR 1.11, 95% CI 1.03-1.19) compared to the 1st quartile. Short-term exposure to high levels of PM may be associated with increased CVD risk among cancer survivors.

Associations between alcohol consumption and cardiovascular disease among long-term survivors of colorectal cancer: a population-based, retrospective cohort study.

BACKGROUND: There is no evidence whether it is best to stop drinking alcohol at all or whether it is okay to drink a little in that light-to-moderate alcohol use was associated with low cardiovascular disease (CVD) compared to non-drinker among colorectal cancer (CRC) survivors, who are regarded as vulnerable to CVD. Therefore, we evaluated the association between alcohol consumption and incident CVD among long-term survivors of CRC. METHODS: This population-based, retrospective cohort study utilized data from the Korean National Insurance Service of 20,653 long-term survivors of CRC diagnosed between 2006 and 2012. Participants were followed up to the date of CVD, death, or December 31, 2018. All patients were categorized according to their daily alcohol consumption (g/day). The outcomes were incident CVD, including ischemic heart disease (IHD) and ischemic and hemorrhagic stroke, analyzed using the Cox proportional hazards regression after adjusting for cardiovascular risk factors and history of chemotherapy and radiotherapy. RESULTS: There was no association between alcohol consumption and incident CVD among long-term survivors of CRC. Additionally, hazardous alcohol consumption (≥ 40 g/day in male patients and ≥ 20 g/day in female patients) was associated with increased CVD, ischemic stroke, and hemorrhagic stroke (adjusted hazard ratio [95% confidence interval]: 1.51 [1.15-1.97], 1.60 [1.03-2.48], and 2.65 [1.25-5.62], respectively) compared with non-drinkers. CONCLUSION: No discernable protective association was found between alcohol consumption and incident CVD for even light-to-moderate drinking among long-term survivors of CRC. Alcohol consumption ≥40 g/day in male patients and ≥ 20 g/day in female patients was associated with an increased risk of stroke compared with non-drinkers. These novel results provide useful evidence when advising survivors of CRC regarding alcohol use.

Salivary flow rate and the risk of cognitive impairment among Korean elders: a cross-sectional study.

BACKGROUND: Salivary function has been suggested to be associated with cognitive impairment. However, the effect of salivary flow rate (SFR) on cognitive impairment remains unclear. This study aimed to investigate whether SFR is associated with cognitive impairment among Korean elders. METHODS: This cross-sectional study included 649 elders aged 65 and older in the Korean community-dwelling population. Cognitive impairment was assessed using the Mini-Mental Status Examination. Unstimulated SFR was measured and dichotomized. Denture status, age, sex, education level, smoking, drinking, diabetes, hypertension, and obesity were considered confounders. Multivariable logistic regression analysis was applied to assess the adjusted association. Stratified analysis by sex and denture status was performed to clarify the effect modification. RESULTS: Participants without cognitive impairment showed a higher SFR level than those with cognitive impairment (0.81 mL/min for non-cognitive impairment versus 0.52 mL/min for cognitive impairment, p < 0.001). After controlling for confounders, participants with low SFR (< 0.3 mL/min) were more likely to have cognitive impairment by 1.5 times than participants with normal SFR (odds ratio [OR] = 1.5, confidence interval [CI] = 1.05-2.10). The association of low SFR with cognitive impairment was higher in women and dentate participants: about 10% higher in women (OR = 1.63, CI = 1.07-2.50) and about 22% higher in dentate participants (OR = 1.82, CI = 1.41-2.90). CONCLUSIONS: Salivary flow rate is independently associated with cognitive impairment among Korean elders. The association was modified in females and dentate elders. Physicians and dentists should consider low SFR and cognitive impairment as a risk factor between them in clinics.

Development and validation of prediction equations for the assessment of muscle or fat mass using anthropometric measurements, serum creatinine level, and lifestyle factors among Korean adults.

BACKGROUND/OBJECTIVES: The measurement of body composition, including muscle and fat mass, remains challenging in large epidemiological studies due to time constraint and cost when using accurate modalities. Therefore, this study aimed to develop and validate prediction equations according to sex to measure lean body mass (LBM), appendicular skeletal muscle mass (ASM), and body fat mass (BFM) using anthropometric measurement, serum creatinine level, and lifestyle factors as independent variables and dual-energy X-ray absorptiometry as the reference method. SUBJECTS/METHODS: A sample of the Korean general adult population (men: 7,599; women: 10,009) from the Korean National Health and Nutrition Examination Survey 2008-2011 was included in this study. The participants were divided into the derivation and validation groups via a random number generator (with a ratio of 70:30). The prediction equations were developed using a series of multivariable linear regressions and validated using the Bland-Altman plot and intraclass correlation coefficient (ICC). RESULTS: The initial and practical equations that included age, height, weight, and waist circumference had a different predictive ability for LBM (men: R2 = 0.85, standard error of estimate [SEE] = 2.7 kg; women: R2 = 0.78, SEE = 2.2 kg), ASM (men: R2 = 0.81, SEE = 1.6 kg; women: R2 = 0.71, SEE = 1.2 kg), and BFM (men: R2 = 0.74, SEE = 2.7 kg; women: R2 = 0.83, SEE = 2.2 kg) according to sex. Compared with the first prediction equation, the addition of other factors, including serum creatinine level, physical activity, smoking status, and alcohol use, resulted in an R2 that is higher by 0.01 and SEE that is lower by 0.1. CONCLUSIONS: All equations had low bias, moderate agreement based on the Bland-Altman plot, and high ICC, and this result showed that these equations can be further applied to other epidemiologic studies.

Association between physical activity and subsequent cardiovascular disease among 5-year breast cancer survivors.

PURPOSE: To examine the association of physical activity among long-term breast cancer survivors on the occurrence of subsequent cardiovascular disease (CVD). METHODS: We investigated the risk of CVD among 39,775 breast cancer patients who were newly diagnosed in 2006 and survived until 2011 within the Korean National Health Insurance Service database. Patients were followed up from 5 years after breast cancer diagnosis to the date of CVD event, death, or December 31, 2018, whichever came earliest. Every 500 MET-mins/week correspond to 152, 125, and 62.5 min per week of light-, moderate-, and vigorous-intensity physical activity, respectively. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for CVD were calculated using Cox proportional hazards regression by physical activity levels. RESULTS: Compared with those with physical activity of 0 MET-min/week, those with 1-499 (aHR 0.82, 95% CI 0.69-0.98), 500-999 (aHR 0.75, 95% CI 0.63-0.90), and ≥ 1,000 (aHR 0.76, 95% CI 0.63-0.93) MET-min/week of PA had lower risk of CVD. Higher levels of PA were associated with lower risk of stroke (p for trend = 0.016). The benefits of PA on obese and overweight breast cancer survivors were smaller than those in normal weight survivors. The frequency of moderate-to-vigorous physical activity (MVPA) showed a reverse J-curve association with CVD, and the best benefit occurred in the 3-4 times MVPA per week group (aHR 0.59, 95% CI 0.46-0.74). CONCLUSIONS: The study showed that even small amounts of PA may be beneficial in potentially decreasing the risk of CVD, CHD, and stroke in breast cancer survivors. Our result will be useful to prescribe and delivery exercise among long-term breast cancer survivors.

Risk of coronary heart disease among cancer survivors with different prediagnosis body mass index.

Association between body mass index (BMI) and coronary heart disease (CHD) in cancer survivors is not clearly established. This study analyzed the prediagnosis BMI-CHD association by examining 13,500 cancer survivors identified from the National Health Insurance Service-Health Screening Cohort from January 1, 2004 to December 31, 2009 including the patients who were free of cardiovascular disease at enrollment. The Cox proportional hazards model (adjusted for socioeconomic, health behavior, health status, and medical characteristics) was used for calculating hazard ratios (HR) and 95% confidence intervals (95% CI) for CHD in each prediagnosis BMI category among cancer survivors. Compared to cancer survivors with a prediagnosis BMI between 18.5 and 22.9 kg/m2, those with a prediagnosis BMI of 23.0-24.9 kg/m2 and ≥ 25.0 kg/m2 had significantly higher CHD risk (HR = 1.51; 95% CI: 1.13-2.01 and HR = 1.38; 95% CI: 1.04-1.84, respectively). Cancer survivors with a low prediagnosis BMI (< 18.5 kg/m2) also had significantly higher CHD risk (HR = 1.97; 95% CI: 1.20-3.24) compared to those with a BMI of 18.5-22.9 kg/m2. Similar associations were found after stratifying analyses based on first cancer site and sociodemographic and medical characteristic subgroups. Our study suggests that prediagnosis underweight among patients with cancer is a predictor of CHD risk.

Association of weight change in young adulthood with subsequent risk of hepatocellular carcinoma: a national cohort study.

Risk of hepatocellular carcinoma (HCC) in young adults might be clinically overlooked for future HCC risk. Thus, we examined the association between weight change and future risk of developing HCC in young adults. We collected a nationwide and population-based cohort data of more than 2.2 million men and women aged between 20 and 39 who were without previous cancer diagnosis and underwent two consecutive biennial national health screening between 2002 and 2005 from the National Health Insurance Service database. The individuals were categorized as weight loss (≥5.0 kg and 2.0-4.9 kg), stable weight (weight gain or loss <2.0 kg), and weight gain (2.0-4.9 kg and ≥5.0 kg) and were followed-up for incident HCC from 1 January 2006 to 31 December 2018. During 12 years of follow-up, there were 2694 HCCs in men and 306 HCCs in women. In the multivariable Cox proportional hazards model adjusted for socioeconomic, health behavior, medical characteristics, and family history, weight gain of more than 5.0 kg and between 2.0 and 4.9 kg were associated with significantly increased risk in young men [hazard ratio (HR) 1.16, 95% confidence intervals (95% CI) 1.01-1.32] and young women (HR 1.34, 95% CI 1.01-1.77), respectively. Protective association of weight loss with HCC was not observed. The association of weight gain and HCC risk was stronger in young adults with underlying liver diseases compared to those without any liver disease (Pheterogeneity < 0.001). Weight gain during young adulthood should not be clinically overlooked for future HCC risk, especially among those with underlying liver diseases.

Estimating Risk of Cardiovascular Disease Among Long-Term Colorectal Cancer Survivors: A Nationwide Cohort Study.

BACKGROUND: Concerns about a growing number of colorectal cancer survivors have emerged regarding cardiovascular disease (CVD) risks. However, there is not yet a predictive tool that can estimate CVD risk and support the management of healthcare as well as disease prevention in terms of CVD risk among long-term colorectal cancer survivors. AIM: To develop predictive tools to estimate individualized overall and each subtype of CVD risk using a nationwide cohort in South Korea. METHODS AND RESULTS: A total of 4,709 newly diagnosed patients with colorectal cancer who survived at least 5 years in the National Health Insurance System were analyzed. Cox proportional hazard regression was used for the identification of independent risk factors for the derivation of predictive nomograms, which were validated in an independent cohort (n = 3,957). Age, fasting serum glucose, γ-glutamyl transpeptidase, Charlson comorbidity index, household income, body mass index, history of chemotherapy, cigarette smoking, and alcohol consumption were identified as independent risk factors for either overall CVD or each subtype of CVD subtype. Based on the identified independent risk factors, six independent nomograms for each CVD category were developed. Validation by an independent cohort demonstrated a good calibration with a median C-index of 0.687. According to the nomogram-derived median score, relative risks of 2.643, 1.821, 4.656, 2.629, 4.248, and 5.994 were found for overall CVD, ischemic heart disease, myocardial infarction, total stroke, ischemic stroke, and hemorrhage stroke in the validation cohort. CONCLUSIONS: The predictive tools were developed with satisfactory accuracy. The derived nomograms may support the estimation of overall and individual CVD risk for long-term colorectal cancer survivors.