Diabetic MAFLD is associated with increased risk of hepatocellular carcinoma and mortality in chronic viral hepatitis patients.

Metabolic dysfunction-associated fatty liver disease (MAFLD) can coexist with chronic viral hepatitis. MAFLD is a heterogeneous disease because the diagnostic criteria include various metabolic traits. We aimed to identify patients at high risk of poor long-term outcomes based on MAFLD subgroups in chronic viral hepatitis patients. We evaluated 63 273 chronic hepatitis B and C patients. Patient with a fatty liver index ≥30 was defined to have hepatic steatosis. MAFLD was defined as the presence of hepatic steatosis with any one of the following three conditions, overweight/obesity, type 2 diabetes or ≥2 metabolic risk factors. The prevalence of MAFLD was 38.4% (n = 24 290). During a median 8.8-year follow-up, 1839 HCCs and 2258 deaths were documented in MAFLD patients. Among MAFLD patients, diabetes could identify patients at high risk of HCC and mortality, whereas overweight/obesity and metabolic risk factors did not. Compared with non-MAFLD patients, risk of HCC and mortality was significantly higher in diabetic MAFLD patients (adjusted hazard ratio [aHR] = 1.34, 95% confidence interval [CI] = 1.26-1.43 for HCC; aHR = 1.15, 95% CI = 1.08-1.22 for mortality). Risk of HCC and mortality was significantly higher in diabetic MAFLD patients (aHR = 1.40, 95% CI = 1.26-1.55 for HCC; aHR = 1.77, 95% CI = 1.63-1.93 for mortality) compared with non-diabetic MAFLD patients. Diabetic MAFLD is associated with increased risk of HCC and mortality among chronic viral hepatitis patients. Our findings highlight the need for close surveillance and effective treatment for these high-risk patients to reduce HCC and mortality in patients with chronic viral hepatitis.

Risk of various cancers in adults with abdominal aortic aneurysms.

BACKGROUND: The cause of death for patients with an abdominal aortic aneurysm (AAA) can be related to the AAA itself. However, cancer-related mortality could also be a contributing factor. In the present study, we examined the hypothesis that an association exists between AAAs and certain cancers. METHODS: Information from 2009 to 2015 was extracted from the Korean National Health Insurance Service database. We included 14,920 participants with a new diagnosis of an AAA. Propensity score matching by age and sex with disease-free patients was used to select the control group of 44,760 participants. The primary end point of the present study was a new diagnosis of various cancers. RESULTS: The hazard ratio (HR) for cancer incidence was higher in the AAA group than in the control group for hepatoma, pancreatic cancer, and lung cancer (HR, 1.376, 1.429, and 1.394, respectively). In the case of leukemia, the HR for cancer occurrence was not significantly higher in the AAA group than in the control group. However, when stratified by surgery, the HR was significantly higher for the surgical group (HR, 3.355), especially for endovascular aneurysm repair (HR, 3.864). CONCLUSIONS: We found that AAAs are associated with an increased risk of cancer, in particular, hepatoma, pancreatic cancer, and lung cancer, even after adjusting for several comorbidities. Thus, continued follow-up is necessary for patients with an AAA to permit the early detection of the signs and symptoms of cancer.

High body weight variability is associated with increased risk of depression: a nationwide cohort study in South Korea.

BACKGROUND: Body weight variability (BWV) negatively affects the incidence and outcomes of various diseases, but the nature of the association between BWV and depression remains unclear. In this study, we aimed to test the hypothesis that BWV is associated with the risk of new-onset depression. METHODS: Data from a nationwide population-based cohort in the Korean National Health Insurance Service database were analyzed for 6 598 570 adults with no history of depression and reports of at least three health examinations. BWV was estimated using variability independent of the mean indices and divided into quartiles (Q1 lowest, Q4 highest BWV). Cox proportional hazard models were applied to assess the risk of depression according to the quartile of BWV. RESULTS: The incident rate for depression from Q1 to Q4 of BWV was 20.7, 20.3, 20.8, and 22.2 per 1000 person-years, respectively. BWV, especially high BWV, was associated with an increased risk of depression after adjusting for age, sex, smoking, alcohol consumption, physical activity, income, diabetes mellitus, hypertension, and dyslipidemia. The hazard ratio (HR) of new-onset depression was highest in Q4 relative to Q1 in the total population (HR 1.12, p < 0.0001) and was higher in women than in men (HR 1.72 v. 1.16, p < 0.0001). In stratified analyses, regardless of obesity or weight change status at baseline, the risk of depression was increased when bodyweight fluctuated highly during follow-up. CONCLUSIONS: High BWV was associated with an increased risk of depression. Further studies need to evaluate the role of high BWV with respect to the onset of depression.

Hormone Replacement Therapy and the Incidence of Nonarteritic Anterior Ischemic Optic Neuropathy: a Nationwide Population-Based Study (2009-2018).

PURPOSE: This study aimed to assess the association between hormone replacement therapy (HRT) and the prevalence of nonarteritic anterior ischemic optic neuropathy (NAION) in menopausal women using national data from the entire Korean population. METHODS: The health screening data of 1,381,605 women between 40 and 90 years of age collected by the National Health Insurance Service (NHIS) of Korea between January 1, 2009, and December 31, 2018, were retrospectively reviewed. Before data analysis, the potential cofounders were adjusted for among all participants. Based on HRT use and its duration (classified into four groups), the hazard ratio (HR) and 95% confidence interval (CI) of NAION development were calculated via a Cox proportional hazards regression analysis using the nonuser group as a reference. RESULTS: Overall, 7824 NAION diagnoses were made during the mean follow-up of 8.22 years (standard deviation: 1.09 years) in 1,381,605 post-menopausal women. NAION was more common in the HRT group than in the non-HRT group (HR [95% CI]: 1.268 [1.197-1.344]). Furthermore, the risk of NAION increased along with increased HRT duration (p < 0.0001). In the multivariate analysis, the adjusted HRs of the < 2-year HRT group, the 2-5-year HRT group, and the ≥ 5-year HRT group were 1.19 (95% CI: 1.10-1.28), 1.3 (95% CI: 1.17-1.45), and 1.473 (95% CI: 1.31-1.65), respectively. Compared to women younger than 65 years, the HR of HRT for NAION was significantly higher than that of women older than 65 years (p < 0.0001). CONCLUSION: Our population-based cohort study found that HRT was significantly associated with increased incidence of NAION. The incidence of NAION also increased with the duration of HRT.

Changes in general and central fatness are associated with hepatocellular carcinoma: A Korean nationwide longitudinal study.

We investigated the impact of short-term changes in general and central fatness on the risk of hepatocellular carcinoma (HCC) in a large, population-based cohort. We screened 7 221 479 subjects who underwent health examinations provided by the National Health Insurance Service of South Korea in 2009 and 2011. In total, 6 789 472 subjects were included in the final analysis. General fatness was defined as a body mass index (BMI) ≥25 kg/m2 , and central fatness was defined as a waist circumference (WC) ≥90 cm in men and ≥85 cm in women. Subjects were classified according to the change in body fatness between 2009 and 2011, as follows: (a) persistent no fatness as no fatness in both 2009 and 2011, (b) reversed fatness as fatness in 2009, but no fatness in 2011, (c) incident fatness as no fatness in 2009, but fatness in 2011 or (d) persistent fatness as fatness in both 2009 and 2011. During a median 6.4-year follow-up, we documented 9952 HCC cases. Compared to subjects with a persistent no general fatness, the risk of HCC significantly increased in those with incident (adjusted hazard ratio [aHR] = 1.10, 95% confidence interval [CI] = 1.01-1.20) and persistent (aHR = 1.28, 95% CI = 1.23-1.34) general fatness. Compared to subjects with persistent no central fatness, those with incident and persistent central fatness showed a significantly increased risk of HCC (aHR = 1.19, 95% CI = 1.11-1.27 and aHR = 1.33, 95% CI = 1.26-1.40, respectively). Taken together, these findings indicate the importance of strategies for preventing and reversing body fatness to reduce the incidence of HCC.

Nationwide cohort study: cholesterol level is inversely related with the risk of gastric cancer among postmenopausal women.

BACKGROUND: Recent studies showed inverse relationship between hypercholesterolemia and the risk of gastric cancer, especially among male. However evidence among female is inconsistent. We aimed to investigate the relationship between cholesterol level and the risk of gastric cancer among female according to menopausal status. METHODS: We analyzed the data from a population-based prospective cohort of female ≥ 30 years old who underwent cancer screening and general health screening provided by the Korean National Health Insurance Corporation in 2009. Under quartile stratification of the level of cholesterol components, we calculated the hazard ratio (HR) for gastric cancer incidence until 2018 for each level group according to the menopausal status at 2009. RESULTS: Among total 2,722,614 individuals, 17,649 gastric cancer cases developed after mean 8.26 years of follow-up (premenopausal 3746/1180666; postmenopausal 13,903/1541948). Total cholesterol, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) showed inverse relationship with the risk of gastric cancer among postmenopausal women (adjusted HR (95% confidence interval) for the highest quartile vs. lowest quartile and p-for-trend: 0.88 (0.84-0.92) and < 0.001 for total cholesterol; 0.89 (0.85-0.92) and < 0.001 for HDL-C; 0.92 (0.89-0.97) and 0.001 for LDL-C), whereas none showed statistically significant risk relationship among premenopausal women. Triglyceride was not independently related with gastric cancer risk among both pre- and postmenopausal women. CONCLUSIONS: Cholesterol levels, including total cholesterol, HDL-C, and LDL-C, are inversely related with the risk of gastric cancer among postmenopausal women, but not among premenopausal women.

Liver enzymes and risk of ocular motor cranial nerve palsy: a nationwide population-based study.

This study aimed to assess the associations between liver enzymes including γ-glutamyl transferase (GGT) and the development of ocular motor cranial nerve palsy (CNP) using the National Sample Cohort database from Korea's National Health Insurance Service. We analyzed data from 4,233,273 medical screening examinees aged 20 years or more in 2009. Study participants were followed up until December 31, 2018. A Cox proportional hazard regression analysis was performed for quartiles of liver enzymes to determine the linkage between each value and ocular motor CNP using quartile 1 as a reference after adjusting for potential confounders. A total of 5,807 (0.14%) patients developed ocular motor CNP during the follow-up period of 8.22 ± 0.94 years. The incidence of ocular motor CNP gradually increased as the GGT levels increased. The highest quartile of the GGT group had hazard ratio (HR) of 1.245 (95% confidence interval [CI], 1.136-1.365). Regarding alanine aminotransferase (ALT), the highest quartile of the ALT group had HR of 1.141 (95% CI, 1.049-1.241). However, the incidence of ocular motor CNP did not gradually increase as the ALT levels increased. The coexistence of the increased level of GGT, metabolic syndrome, and obesity showed a stronger association with ocular motor CNP development (HR, 1.331; 95% CI, 1.173, 1.511) compared to having a single factor or two factors. In conclusion, our population-based cohort study demonstrated a significant association between serum GGT level and the incidence of ocular motor CNP, suggesting that GGT could be a new clinical marker for predicting the occurrence of ocular motor CNP.

Increasing serum gamma-glutamyltransferase level accompanies a rapid increase in the incidence of endometrial cancer in Korea: A nationwide cohort study.

OBJECTIVE: This study aimed to determine the association of serum GGT levels with the risk of developing endometrial cancer. Women's obesity and menopausal status were also taken into account in our analysis. METHODS: We used a nationwide cohort to examine the association between serum GGT levels and endometrial cancer development in Korean women. Data were retrieved from the Korean National Health Insurance Service (NHIS) healthcare system. Women aged over 19 years who participated in the Korea National Health Screening Examination in 2009 and were not diagnosed with endometrial cancer 1-year post-examination were included in our study (n = 2,736,588). RESULTS: Obese (BMI, ≥25 kg/m2) women with increased GGT levels were at high risk of endometrial cancer (HR = 1.415, 95% CI: 1.236-1.621). Interestingly, in pre-menopausal women, high GGT level (Q4) was associated with the increased endometrial cancer risk only for obese women (HR = 1.482, 95% CI: 1.205-1.821). In post-menopausal women, only a high GGT level (Q4) was also associated with the increased cancer risk for obese women (HR = 1.313, 95% CI: 1.096-1.573). We observed a significant association between high GGT levels and increased risk of endometrial cancer in pre-menopausal women with abdominal obesity (WC, ≥85 cm) (HR = 1.647, 95% CI: 1.218-2.227). CONCLUSIONS: Increased GGT level is an independent risk factor of endometrial cancer, especially for post-menopausal women and obese pre-menopausal women. These results may suggest that serum GGT levels might be useful in the risk stratification of endometrial cancer. Adopting a healthy lifestyle for lowering serum GGT level is warranted, especially for women with a higher risk of developing endometrial cancer.

Proteinuria and risk of ocular motor cranial nerve palsy: a nationwide population-based study.

Understanding the association between dipstick-detected proteinuria and oculomotor cranial nerve palsy (CNP) could have significant implications for understanding the mechanism of CNP development and for developing preventive strategies against CNP development in patients with proteinuria. This study aimed to determine the relationship between dipstick-determined proteinuria and ocular motor CNP using National Sample Cohort (NSC) database from Korea's National Health Insurance Service (NHIS). A nationwide population-based cohort study was conducted using data from the NSC database of Korea's NHIS. These data were collected from 2009 to 2018. A one-year time lag was established to prevent a situation in which the causal link was inverted. Participants aged 20 years or more who were diagnosed with proteinuria in 2009 were included. Individuals with specific pre-existing CNP, missing data, and those who were newly diagnosed with CNP or who died within one year of being tested were excluded. The study population was classified into six groups according to the degree of proteinuria (negative, trace, or between 1 + and 4 +) based on the urine dipstick test. A Cox proportional hazard regression analysis was performed to determine the linkage between the degree of proteinuria and ocular motor CNP. A total of 5,807 (0.14% of subjects) with ocular motor CNP were assigned to the ocular motor CNP group and 4,047,205 subjects were assigned to the control group. After full adjustment of comorbidities, hazard ratios (HRs) for 1 + , 2 + , 3 + and 4 + proteinuria groups were 1.449 (95% confidence interval [CI] 1.244-1.687), 2.081 (1.707-2.538), 1.96 (1.322-2.904), and 3.011 (1.507-6.014), respectively, for developing ocular motor CNP compared to the proteinuria-negative group. In subgroup analysis, the HR of patients with proteinuria for the development of ocular motor CNP was higher in the younger age group (less than 40 years) (P = 0.0242) and the group with DM (P = 0.04). Our population-based cohort study demonstrated a significant association between proteinuria and the incidence of CNP, suggesting that urine protein level could be a new clinical marker for predicting the development of CNP.

Association between exercise and risk of fractures in new-onset type 2 diabetes: a retrospective cohort study.

In this population-based retrospective cohort study, exercising before and after the diagnosis of type 2 diabetes was significantly associated with lower risk of fractures. This result suggested that exercising might be effective in reducing fracture risk. PURPOSE: Patients with diabetes have a significantly higher risk of fractures. We aimed to investigate the association between exercise and fracture risk in new-onset type 2 diabetes. METHODS: This retrospective cohort study using the Korean National Health Insurance Service database included 170,148 patients with new-onset type 2 diabetes who underwent two cycles of health checkup between 2009-2012 and 2011-2014. The patients were classified into four groups (non-exercising, newly exercising, previously exercising, and continuously exercising) and followed up until the date of fracture, death, or December 31, 2018. Hip fractures, vertebral fractures, and any fractures were defined using diagnostic codes. RESULTS: The proportions of non-exercising, newly exercising, previously exercising, and continuously exercising patients were 65.1%, 15.7%, 10.9%, and 8.3%, respectively. Continuously exercising patients showed the lowest risk for fractures, followed by newly exercising patients using the non-exercising group as a reference. The adjusted hazard ratios (95% confidence intervals) for hip fracture, vertebral fracture, and any fracture were 0.69 (0.50-0.94), 0.73 (0.63-0.84), and 0.90 (0.83-0.97), respectively, in the continuously exercising group and 0.76 (0.61-0.95), 0.85 (0.76-0.94), and 0.93 (0.88-0.98) in the newly exercising group. The risk was lower in patients who lost less than 5% of their body weight than in those who lost 5% or more. CONCLUSION: Exercising was associated with lower risk of fractures in newly diagnosed diabetes. However, exercise accompanied by excessive weight loss may not have a significant association with a lower risk of fractures.

Two-Year Changes in Diabetic Kidney Disease Phenotype and the Risk of Heart Failure: A Nationwide Population-Based Study in Korea.

BACKGRUOUND: Diabetic kidney disease (DKD) is a risk factor for hospitalization for heart failure (HHF). DKD could be classified into four phenotypes by estimated glomerular filtration rate (eGFR, normal vs. low) and proteinuria (PU, negative vs. positive). Also, the phenotype often changes dynamically. This study examined HHF risk according to the DKD phenotype changes across 2-year assessments. METHODS: The study included 1,343,116 patients with type 2 diabetes mellitus (T2DM) from the Korean National Health Insurance Service database after excluding a very high-risk phenotype (eGFR <30 mL/min/1.73 m2) at baseline, who underwent two cycles of medical checkups between 2009 and 2014. From the baseline and 2-year eGFR and PU results, participants were divided into 10 DKD phenotypic change categories. RESULTS: During an average of 6.5 years of follow-up, 7,874 subjects developed HHF. The cumulative incidence of HHF from index date was highest in the eGFRlowPU- phenotype, followed by eGFRnorPU+ and eGFRnorPU-. Changes in DKD phenotype differently affect HHF risk. When the persistent eGFRnorPU- category was the reference, hazard ratios for HHF were 3.10 (95% confidence interval [CI], 2.73 to 3.52) in persistent eGFRnorPU+ and 1.86 (95% CI, 1.73 to 1.99) in persistent eGFRlowPU-. Among altered phenotypes, the category converted to eGFRlowPU+ showed the highest risk. In the normal eGFR category at the second examination, those who converted from PU- to PU+ showed a higher risk of HHF than those who converted from PU+ to PU-. CONCLUSION: Changes in DKD phenotype, particularly with the presence of PU, are more likely to reflect the risk of HHF, compared with DKD phenotype based on a single time point in patients with T2DM.

The effect of metabolic dysfunction-associated fatty liver disease and diabetic kidney disease on the risk of hospitalization of heart failure in type 2 diabetes: a retrospective cohort study.

BACKGROUND: Diabetes mellitus is a major risk factor for heart failure. A recent consensus statement recommended annual cardiac biomarker testing (e.g. natriuretic peptide or high-sensitivity cardiac troponin) for all patients with diabetes. We aimed to identify patients at a higher risk of hospitalization for heart failure among patients with type 2 diabetes to prioritize those who would require screening. METHODS: Overall, 1,189,113 patients who underwent two medical health checkup cycles (2009-2012 and 2011-2014) and had stable diabetic kidney disease (DKD) phenotype in the Korean National Health Insurance Service database were included in this study. After excluding those with concurrent proteinuria (PU) and reduced estimated glomerular filtration rate, three groups (no-DKD, PU+DKD, and PU-DKD) were identified. A fatty liver index of ≥ 60 was defined as metabolic dysfunction-associated fatty liver disease (MAFLD). Patients were followed up until December 2018 or until outcomes developed. The Cox proportional hazard model was used to compare the risk of hospitalization for heart failure across groups. RESULTS: During an average of 6.6 years of follow-up, 5781 patients developed hospitalization for heart failure. After adjusting for covariates, the risk of hospitalization for heart failure was highest in the PU+DKD group [HR 3.12, 95% CI (2.75-3.55)], followed by the PU-DKD group [HR 1.85, 95% CI (1.73-1.99)] using the no-DKD group as the reference category. The risk of hospitalization for heart failure was comparable regardless of MAFLD status in patients who already had DKD. However, in the no-DKD group, the risk of hospitalization for heart failure was 1.4 times higher in patients with MAFLD than in those without [HR 1.41, 95% CI (1.31-1.52)]. CONCLUSIONS: In lines with the international consensus statement, we suggest that annual cardiac biomarker testing should be conducted at least in patients with DKD and/or MAFLD.

Physical Activity Changes and the Risk of Incident Atrial Fibrillation in Patients With Type 2 Diabetes Mellitus: A Nationwide Longitudinal Follow-up Cohort Study of 1.8 Million Subjects.

OBJECTIVE: We investigated the association between alterations in regular physical activity (PA) and the risk of developing AF in patients with type 2 diabetes mellitus (T2DM) and the optimal PA range based on energy expenditure. RESEARCH DESIGN AND METHODS: In a nationwide database, subjects who underwent health examinations twice at a 2-year interval between 2009 and 2012 were studied. After 1,815,330 patients with T2DM who did not have a history of AF were identified, they were followed until 2018. Regular PA alterations over time were used to divide individuals into four groups: persistent nonexercisers (n = 1,181,837), new exercisers (n = 242,968), exercise dropouts (n = 225,124), and exercise maintainers (n = 165,401). RESULTS: During a mean follow-up period of 5.6 ± 1.3 years, 46,589 cases (2.6%) of new-onset AF occurred. Compared with the persistent nonexerciser group, both the exercise dropout group (adjusted hazard ratio [HR] 0.96, 95% CI 0.94-0.99) and new exerciser group (HR 0.95, 95% CI 0.93-0.98) had lower risks of incident AF. The exercise maintainer group showed the lowest risk (HR 0.91, 95% CI 0.89-0.94). When we stratified patients with T2DM according to energy expenditure, undergoing regular PA with ≥1,500 MET-min/week in new exercisers and ≥1,000 MET-min/week in exercise maintainers was associated with lower risks of incident AF than nonexercisers. CONCLUSIONS: In patients with T2DM, starting and maintaining regular PA were both associated with lower risk of incident AF. Optimal PA ranges based on energy expenditure, which were associated with lower risks of incident AF, can be defined.

Changes in Alcohol Consumption and Risk of Dementia in a Nationwide Cohort in South Korea.

Importance: The impact of serial changes in alcohol consumption on dementia risk has rarely been investigated to date. Objective: To investigate the association of comprehensive patterns of changes in alcohol consumption with the incidence of all-cause dementia, Alzheimer disease (AD), and vascular dementia (VaD). Design, Setting, and Participants: This is a retrospective cohort study. Data were obtained from the Korean National Health Insurance Service database. Adults aged 40 years and older underwent 2 health examinations in 2009 and 2011. The cohort was assessed until December 31, 2018, and statistical analysis was performed in December 2021. Exposures: Alcohol consumption level was categorized into none (0 g per day), mild (<15 g per day), moderate (15-29.9 g per day), and heavy (≥30 g per day) drinking. On the basis of changes in alcohol consumption level from 2009 to 2011, participants were categorized into the following groups: nondrinker, quitter, reducer, sustainer, and increaser. Main Outcomes and Measures: The primary outcome was newly diagnosed AD, VaD, or other dementia. Results: Among 3 933 382 participants (mean [SD] age, 55.0 [9.6] years; 2 037 948 men [51.8%]), during a mean (SD) follow-up of 6.3 (0.7) years, there were 100 282 cases of all-cause dementia, 79 982 cases of AD, and 11 085 cases of VaD. Compared with sustained nondrinking, sustained mild (adjusted hazard ratio [aHR], 0.79; 95% CI, 0.77-0.81) and moderate (aHR, 0.83; 95% CI, 0.79-0.88) drinking were associated with a decreased risk of all-cause dementia, whereas sustained heavy drinking was associated with an increased risk of all-cause dementia (aHR, 1.08; 95% CI, 1.03-1.12). Compared with sustained levels of drinking, reducing alcohol consumption from a heavy to a moderate level (aHR, 0.92; 95% CI, 0.86-0.99) and the initiation of mild alcohol consumption (aHR, 0.93; 95% CI, 0.90-0.96) were associated with a decreased risk of all-cause dementia. Increasers and quitters exhibited an increased risk of all-cause dementia compared with sustainers. The trends in AD and VaD remained consistent. Conclusions and Relevance: In this cohort study of a Korean population, decreased risk of dementia was associated with maintaining mild to moderate alcohol consumption, reducing alcohol consumption from a heavy to a moderate level, and the initiation of mild alcohol consumption, suggesting that the threshold of alcohol consumption for dementia risk reduction is low.

Smoking Cessation Reduces the Risk of Heart Failure: A Nationwide Cohort Study.

BACKGROUND: There is a lack of data for the incidence of heart failure (HF) according to changes in smoking behaviors. OBJECTIVES: The authors aimed to investigate the effects of smoking behavior change on development of HF. METHODS: In this population-based, retrospective cohort study using the Korean National Health Insurance System database, the authors identified 778,608 current smokers who participated in a health screening program in 2009 and in a follow-up screening in 2011. Participants were categorized into quitters, reducers I (≥50% reduction) and II (<50% reduction), sustainers, and increasers. RESULTS: During a median follow-up of 6.3 years, there were 23,329 HF events (4.8 per 1,000 person-years). Compared with sustainers, the risk of HF was increased among increasers (adjusted hazard ratio [aHR]: 1.06 [95% CI: 1.02-1.10]). By contrast, quitters had a reduced risk for HF (aHR: 0.86 [95% CI: 0.83-0.90]). Even heavy smokers who quit smoking had a lower risk for HF than those who sustained heavy smoking (aHR: 0.90 [95% CI: 0.85-0.95]). In reducers, the risk of HF was not reduced but rather increased slightly (≥50% reduction, aHR: 1.06 [95% CI: 1.01-1.11]; <50% reduction, aHR: 1.04 [95% CI: 1.00-1.08]). CONCLUSIONS: Current smokers who increased their smoking amount were associated with a higher risk for HF development compared to sustainers, whereas self-reported smoking cessation was associated with a lower risk of HF. There was no benefit from reduction in smoking amount. Self-reported smoking cessation should be reinforced whenever possible to prevent HF.

Association of reproductive factors with cardiovascular disease risk in pre-menopausal women: nationwide population-based cohort study.

BACKGROUND: Although the morbidity and mortality of cardiovascular diseases (CVD) are rising in young women, the risk factors of CVD among Korean pre-menopausal women have not been intensively investigated. AIMS: To determine how age at menarche and other female reproductive factors are associated with the risk of CVD in pre-menopausal women. METHODS AND RESULTS: A total of 1 088 992 pre-menopausal women who participated in health screening in 2009 were included. The study outcomes were myocardial infarction (MI) and ischaemic stroke. Cox proportional hazards regression analysis was conducted with adjustment of traditional CVD risk factors and reproductive factors. RESULTS: Mean age was 43.8 ± 5.3 years (98.9%, < 55 years), 3.5% were current smokers, and 1.2% were heavy drinkers. During a mean follow-up of 8.3years [9 032 685.9 person-years (PY)], there were 10 876 CVD events (1.0 per 1000 PY).With later menarche, the risk of CVD increased; ≤12 years [adjusted hazard ratio (HR) 1.04, 95% confidence interval 0.93-1.16], 13 years (reference), 14 years (1.06, 0.98-1.14), 15 years (1.15, 1.07-1.24), 16 years (1.23, 1.14-1.34), and ≥17 years (1.33, 1.24-1.44). Compared with non-users, oral contraceptives (OC) users (≥1 year) had an increased risk of CVD (1.11, 1.01-1.22) (P for trend = 0.007). CONCLUSIONS: Later menarche than the mean age at menarche (13 years old) and the use of OC (≥1 year) were associated with a higher risk of CVD, after adjusting for traditional cardiovascular risk factors. This study suggests that female reproductive factors could be unique risk factors for CVD in pre-menopausal women.

Association of Changes in Smoking Intensity With Risk of Dementia in Korea.

Importance: Several observational studies have reported that smoking cessation is associated with a lower risk of dementia. However, no studies have examined the association between change in smoking intensity and risk of dementia. Objective: To investigate the association between a change in smoking intensity, including smoking reduction and smoking cessation, and risk of all dementia. Design, Setting, and Participants: This cohort study used data from the National Health Insurance Service database of Korea. The cohort included participants 40 years or older who underwent biennial health examinations (2009 and 2011) and had current smoking status at the first health examination. The cohort was followed up until December 31, 2018, and statistical analysis was performed between July and December 2021. Exposures: Change in smoking intensity from baseline was defined operationally as follows: quitters (stopped smoking), reducers I (decreased number of cigarettes smoked per day by ≥50%), reducers II (decreased number of cigarettes smoked per day by 20%-50%), sustainers (maintained [decreased or increased] number of cigarettes smoked per day by less than 20%), or increasers (increased number of cigarettes smoked per day by ≥20%). Main Outcomes and Measures: The primary outcome was newly diagnosed dementia, which was identified by prescribed antidementia medications with concomitant International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnosis codes for dementia. Adjusted hazard ratios and 95% CIs were used to determine the association between change in smoking intensity and incidence of dementia, including Alzheimer disease (AD) and vascular dementia (VaD). Results: A total of 789 532 participants (756 469 males [95.8%]; mean [SD] age, 52.2 [8.5] years) were included. During a median (IQR) follow-up period of 6.3 (6.1-6.6) years, 11 912 dementia events, including 8800 AD and 1889 VaD events, were identified. Overall, participants in the quitter group had a significantly lower risk of all dementia (adjusted hazard ratio [aHR], 0.92; 95% CI, 0.87-0.97) compared with those in the sustainer group. Those in the reducer I (aHR, 1.25; 95% CI, 1.18-1.33) and increaser (aHR, 1.12; 95% CI, 1.06-1.18) groups had a significantly higher risk of all dementia compared with those in the sustainer group.The patterns for AD and VaD remained consistent with patterns for all dementia. Conclusions and Relevance: The results of this study showed that smoking cessation was associated with a lower risk of dementia compared with sustained smoking intensity, while smoking reduction was associated with a higher risk. Smoking cessation should be emphasized in efforts to reduce the disease burden of dementia.

Changes in smoking, alcohol consumption, and the risk of Parkinson's disease.

Objective: There have been no studies on the association between changes in smoking and alcohol consumption or combined changes in smoking and alcohol consumption frequencies and PD risk. To assess the influence of changes in smoking and alcohol consumption on the risk of Parkinson's disease (PD). Methods: National Health Insurance Service (NHIS) database between January 2009 to December 2011 was analyzed. A total of 3,931,741 patients were included. Study participants were followed up for the incidence of PD until December 2017. Results: Compared to the sustained non-smokers, sustained light smokers (adjusted hazard ratio [aHR] 0.80, 95% confidence interval [CI] 0.75-0.85), sustained moderate smokers (aHR 0.54, 95% CI 0.47-0.61), and sustained heavy smokers (aHR 0.49, 95% CI 0.44-0.55) had a lower risk of PD. Compared to those who sustained non-drinking, sustained light drinkers (aHR 0.85 95% CI 0.89-0.91), sustained moderate drinkers (aHR 0.68, 95% CI 0.60-0.78), and sustained heavy drinkers (aHR 0.77, 95% CI 0.68-0.87) showed decreased risk of PD. Among non-drinkers, those who started drinking to a light level were at decreased risk of PD (aHR 0.84, 95% CI 0.77-0.91). Among non-smoking and non-drinking participants, those who initiated smoking only (aHR 0.78, 95% CI 0.70-0.86), drinking only (aHR 0.77, 95% CI 0.68-0.87), and both smoking and drinking (aHR 0.69, 95% CI 0.58-0.82) showed decreased risk of PD. Conclusion: Smoking is associated with decreased risk of PD with a dose-response relationship. Alcohol consumption at a light level may also be associated with decreased risk of PD. Further studies are warranted to find the possible mechanisms for the protective effects of smoking and drinking on PD, which may present insights into the etiology of PD.

Physical activity and cardiovascular health in depression: Links between changes in physical activity and cardiovascular risk.

OBJECTIVE: To examine the association between changes in physical activity before and after a diagnosis of depression and risks of cardiovascular diseases (CVDs) and all-cause mortality. METHOD: A total of 1,282,160 patients with depression were included in the analyses. Subjects were divided into four groups (never, beginning, maintenance, and discontinuation) according to changes in physical activity before and after the diagnosis of depression. The occurrence of CVD including myocardial infarction (MI) and ischemic stroke and all-cause mortality were determined. RESULTS: The beginning group showed decreased risks of MI (adjusted hazard ratio [aHR]: 0.85; 95% confidence interval [CI]: 0.81-0.89), ischemic stroke (aHR: 0.89; 95% CI: 0.85-0.93), and all-cause mortality (aHR: 0.80; 95% CI: 0.77-0.82) than the never group. Compared to the maintenance group, the discontinuation group showed increased risks of MI (aHR: 1.15; 95% CI: 1.08-1.23), ischemic stroke (aHR: 1.13; 95% CI: 1.06-1.21), and all-cause mortality (aHR: 1.29; 95% CI: 1.23-1.35). CONCLUSIONS: Beginning regular physical activity after a diagnosis of depression was associated with a decreased cardiovascular risk. Discontinuing regular physical activity after a diagnosis of depression was associated with an increased cardiovascular risk.

Impairment of Quality of Life and Mental Health Status in Adult-Onset Atopic Dermatitis.

BACKGROUND: Patients with atopic dermatitis (AD) have an impaired quality of life (QoL). To our knowledge, impairments in mental health status and health-related QoL (HRQoL) have not yet been evaluated in adult-onset and child-onset AD in a large-scale study. OBJECTIVE: This study compared the mental health status and HRQoL (using the EuroQoL [EQ] five-dimensional [5D] questionnaire) in child-onset AD and adult-onset AD to those in normal controls. METHODS: We used nationwide, population-based, cross-sectional data from the Korean National Health and Nutrition Examination Survey conducted from 2008 to 2013. We performed multiple logistic regression analyses with adjustments for age, sex, body mass index, income, education level, drinking status, current smoking, regular exercise, diabetes mellitus, hypertension, and dyslipidemia, and analyzed odds ratios (OR) for factors associated with impaired QoL. RESULTS: The OR for strong psychological stress, depressed mood, and suicidal ideation were significantly increased in adult-onset AD patients compared to in normal controls. In addition, the OR (95% confidence interval [CI]) values for the EQ-5D questionnaire responses (for physical activity, self-control, daily activities, pain/discomfort, and anxiety/depression) were significantly high in adult-onset AD compared to in normal controls after adjustments for covariates. However, patients with child-onset AD showed a significantly increased OR (95% CI) only for problems in pain/discomfort in the EQ-5D questionnaire. CONCLUSION: Adult-onset AD patients suffer from impaired HRQoL and significant mental problems compared to normal controls. Dermatologists should focus not only on the clinical phenotype but also patients' psychological health status to ensure a better treatment outcome.