Gamma-glutamyl transferase and the risk of all-cause and disease-specific mortality in patients with diabetes: A nationwide cohort study.

BACKGROUND: There exists a paucity of data regarding whether gamma-glutamyl transferase is associated with disease-specific mortality in patients with type 2 diabetes mellitus. This study aimed to investigate the association of serum gamma-glutamyl transferase levels with all-cause and disease-specific mortality in patients with diabetes mellitus using a Korean nationwide health-screening database. METHODS: A total of 9 687 066 patients without viral hepatitis or liver cirrhosis who underwent health examination in 2009 were included. These patients were divided into four groups according to sex-specific quartiles of serum gamma-glutamyl transferase levels. RESULTS: During a median follow-up period of 8.1 years, 222 242 deaths were identified. The all-cause mortality rate increased as the serum gamma-glutamyl transferase levels became higher (highest quartile vs lowest quartile: hazard ratio [HR], 1.57; 95% confidence interval [CI], 1.55-1.59; p for trend <.001). Similar trends were observed for cardiovascular disease (HR, 1.57; 95% CI, 1.53-1.62), ischemic heart disease (HR, 1.40; 95% CI, 1.33-1.48), and stroke (HR, 1.72; 95% CI, 1.60-1.85) in the highest quartile, as compared with the lowest quartile (p for trend <.001). As the gamma-glutamyl transferase quartiles became higher, mortality rates related to cancer (HR, 1.56; 95% CI, 1.52-1.60), liver disease (HR, 9.42; 95% CI, 8.81-10.07), respiratory disease (HR, 1.55; 95% CI, 1.49-1.62), and infectious disease (HR, 1.73; 95% CI, 1.59-1.87) also increased in the highest quartile, compared with the lowest quartile (p for trend <.001). CONCLUSIONS: Serum gamma-glutamyl transferase levels may be useful for the risk assessment of all-cause and disease-specific mortality among patients with type 2 diabetes mellitus.

2023 Obesity Fact Sheet: Prevalence of Obesity and Abdominal Obesity in Adults, Adolescents, and Children in Korea from 2012 to 2021.

Background: The 2023 Obesity Fact Sheet aims to present an updated overview of obesity prevalence across all age groups, including children and adolescents. Methods: This study included individuals aged ≥20 years (n=16,941,423 in 2021) who underwent health checkups provided by the Korean National Health Insurance Service between 2012 and 2021. The prevalence of obesity and abdominal obesity was standardized by age and sex using data from the 2010 population and housing census. For children and adolescents (6 to 18 years) (n=884 in 2021), we used the Korea National Health and Nutrition Examination Survey (2012 to 2021), and obesity was defined by the corresponding sex- and age-specific body mass index percentile of 95th or greater based on the 2017 Korean National Growth Chart for Children and Adolescents. Results: The overall prevalence of obesity in 2021 is 38.4% (49.2% in men and 27.8% in women), which is a 1.27-fold increase from 30.2% in 2012. The prevalence of obesity has increased across all age groups, particularly among those aged 20, 30, and 80 years. The prevalence of class III obesity substantially increased from 0.35% (men) and 0.42% (women) in 2012 to 1.21% and 0.97% in 2021, with 3.46- and 2.31-fold increases, respectively. This increase was particularly pronounced in young adults. The prevalence of obesity in children and adolescents has surged from 9.7% in 2012 to 19.3% in 2021, with a greater increase among boys. Conclusion: Our study provides information on the current status of obesity prevalence based on the 2023 Obesity Fact Sheet, emphasizing the urgency of implementing timely strategies to reverse this increasing trend.

Associations between body weight change and incidence of major depressive disorder in patients with type 2 diabetes mellitus: a nationwide longitudinal follow-up cohort study of 1.1 million.

BACKGROUND: Comorbid depression substantially affects the management of glycemia and diabetes-related complications among patients with type 2 diabetes mellitus. In this study, we sought to determine the association between weight change over 4 years and depression risk among patients with type 2 diabetes mellitus. METHODS: This population-based retrospective cohort study from the National Health Insurance Services of Korea included 1 111 345 patients with type 2 diabetes who were divided into groups according to body weight change over 4 years. Body weight changes were compared with the preceding 4-year period (2005-2008). Depression was defined according to the International Classification of Diseases 10th revision code for depression (F32 and F33) on one or more inpatient or outpatient claims. RESULTS: During a median follow-up of 7.4 years, 244 081 cases of depression were identified. We observed a U-shaped association between body weight change and depression risk with a higher risk among both groups of weight loss (hazard ratio (HR) 1.17, 95% CI 1.15-1.19 for ⩾ -10%; HR 1.07, 95% CI 1.06-1.08 for -10 to -5%) and weight gain (HR 1.06, 95% CI 1.04-1.08 for ⩾10%; HR 1.02, 95% CI 1.01-1.04 for 5-10%) compared with the stable weight group (-5 to 5%). CONCLUSIONS: A U-shaped association between body weight change and depression risk was observed in this large nationwide cohort study. Our study suggests that patients with type 2 diabetes and weight change, either gain or loss, could be considered a high-risk group for depression.

Smoking Behavior Change and the Risk of Heart Failure in Patients With Type 2 Diabetes: Nationwide Retrospective Cohort Study.

BACKGROUND: Heart failure (HF) is one of the most common initial manifestations of cardiovascular disease in patients with type 2 diabetes. Although smoking is an independent risk factor for HF, there is a lack of data for the incidence of HF according to changes in smoking behaviors in patients with type 2 diabetes. OBJECTIVE: We aimed to examine the association between interval changes in smoking behavior and the risk of HF among patients with type 2 diabetes. METHODS: We conducted a retrospective cohort study using the National Health Insurance Service database. We identified 365,352 current smokers with type 2 diabetes who had 2 consecutive health screenings (2009-2012) and followed them until December 31, 2018, for the incident HF. Based on smoking behavior changes between 2 consecutive health screenings, participants were categorized into quitter, reducer I (≥50% reduction) and II (<50% reduction), sustainer (reference group), and increaser groups. RESULTS: During a median follow-up of 5.1 (IQR 4.0-6.1) years, there were 13,879 HF cases (7.8 per 1000 person-years). Compared to sustainers, smoking cessation was associated with lower risks of HF (adjusted hazard ratio [aHR] 0.90, 95% CI0.86-0.95), whereas increasers showed higher risks of HF than sustainers; heavy smokers who increased their level of smoking had a higher risk of HF (aHR 1.13, 95% CI 1.04-1.24). In the case of reducers, the risk of HF was not reduced but rather increased slightly (reducer I: aHR 1.14, 95% CI 1.08-1.21; reducer II: aHR 1.03, 95% CI 0.98-1.09). Consistent results were noted for subgroup analyses including type 2 diabetes severity, age, and sex. CONCLUSIONS: Smoking cessation was associated with a lower risk of HF among patients with type 2 diabetes, while increasing smoking amount was associated with a higher risk for HF than in those sustaining their smoking amount. There was no benefit from reduction in smoking amount.

Risk factors for early-onset lung cancer in Korea: analysis of a nationally representative population-based cohort.

OBJECTIVES: We examined the associations of socioeconomic factors, health behaviors, and comorbidities with early-onset lung cancer. METHODS: The study included 6,794,287 individuals aged 20-39 years who participated in a Korean national health check-up program from 2009 to 2012. During the follow-up period, 4,684 participants developed lung cancer. Multivariable Cox regression analysis was used to estimate the independent associations of potential risk factors with incident lung cancer. RESULTS: Older age (multivariable hazard ratio [mHR], 1.13; 95% confidence interval [CI], 1.12 to 1.14) and female sex (mHR, 1.62; 95% CI, 1.49 to 1.75) were associated with increased lung cancer risk. Current smoking was also associated with elevated risk (<10 pack-years: mHR, 1.12; 95% CI, 1.01 to 1.24; ≥10 pack-years: mHR, 1.30; 95% CI, 1.18 to 1.45), but past smoking was not. Although mild alcohol consumption (<10 g/day) was associated with lower lung cancer risk (mHR, 0.92; 95% CI, 0.86 to 0.99), heavier alcohol consumption (≥10 g/day) was not. Higher income (highest vs. lowest quartile: mHR, 0.86; 95% CI, 0.78 to 0.94), physical activity for at least 1,500 metabolic equivalent of task-min/wk (vs. non-exercisers: mHR, 0.83; 95% CI, 0.69 to 0.99) and obesity (vs. normal weight: mHR, 0.89; 95% CI, 0.83 to 0.96) were associated with lower lung cancer risk, whereas metabolic syndrome was associated with increased risk (mHR, 1.13; 95% CI, 1.03 to 1.24). CONCLUSIONS: In young adults, age, female sex, smoking, and metabolic syndrome were risk factors for early-onset lung cancer, while high income, physical activity, and obesity displayed protective effects.

Disparities in Cancer Incidence across Income Levels in South Korea.

BACKGROUND: Recent nationwide studies of disparities in cancer incidence by income are scarce in Korea. This study investigated such disparities in cancer incidence and the stage at cancer diagnosis across income groups in Korea. METHODS: This study utilized data from a national cancer database, specifically focusing on cases recorded in the year 2018. Income levels were categorized into quintiles according to the insurance premium paid in addition to the Medicaid benefit. The slope index of inequality (SII) and relative index of inequality (RII) were used to measure absolute and relative differences in cancer incidence by income. A multivariable logistic regression was performed to estimate the risk of a distant stage at cancer diagnosis. RESULTS: The total number of cases of incident cancer was 223,371 (men: 116,320, women: 107,051) with shares of the total of 29.5% (5Q), 20.4% (4Q), 16.0% (3Q), 13.5% (2Q), 15.6% (1Q), and 5% (Medicaid). The most common cancer type was thyroid cancer, followed by gastric and colorectal cancers. The age-standardized incidence rate for all cancers was lowest in the highest income group, but the SII was not statistically significant (SII: -35.7), and the RII was -0.07. Colorectal and cervical cancers had lower incidence rates for higher income groups, while thyroid and prostate cancers had higher incidence rates for higher income groups. The odds ratio for a distant stage at diagnosis for all cancers increased for lower income groups relative to 5Q. CONCLUSIONS: Disparities in cancer incidence in a Korean population differed by cancer type, and lower income was a significant predictor of a distant stage at diagnosis for cancers overall. These results emphasize the need for further study of the underlying causes of disparities in cancer incidence and the stage at diagnosis, as well as the need for interventions to mitigate these disparities.

Association between breakfast frequency and metabolic syndrome among young adults in South Korea.

Skipping breakfast is highly prevalent but it is not clear whether breakfast frequency is associated with metabolic syndrome in young adults. We aimed to assess the association between breakfast frequency and metabolic syndrome in Korean young adults. This cross-sectional study was based on health check-up data of university students aged 18-39 years between 2016 and 2018. Participants were stratified into three groups by breakfast frequency (non-skipper, skipper 1-3 days/week, skipper 4-7 days/week). Multivariable-adjusted logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) of metabolic syndrome. Out of 12,302 participants, 56.8% skipped breakfast at least 4 days/week. Metabolic syndrome prevalence was higher in those skipping breakfast for 4 or more days/week compared to non-skipper. (3.1% vs 1.7%) In the age- and sex-adjusted model, individuals skipping breakfast for 4-7 days per week had a higher OR of metabolic syndrome (OR 1.73, 95% CI 1.21-2.49) compared to non-skipper. Although this association became insignificant (OR 1.49, 95% CI 0.99-2.23) after a fully adjusted multivariable model, trends of positive association between frequency of breakfast skipping and metabolic syndrome was significant (P for trend = 0.038). Frequent breakfast skipping was associated with higher odds of metabolic syndrome in young adults. Further longitudinal studies in the long term are needed to understand the association of meal patterns with metabolic syndrome.

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.

Racial differences in long-term social, physical, and psychological health among adolescent and young adult cancer survivors.

BACKGROUND: The current guidelines for survivorship in adolescents and young adults (AYA) cancer are based on studies conducted in the United States and European AYA survivors. However, previous studies have shown that the health-related quality of life in cancer survivors can vary depending on race, yet the long-term health differences among AYA survivors by race/ethnicity have not been fully explored. Therefore, our aim is to compare the psychosocial and physical health of AYA survivors and their matched controls across different racial and ethnic groups. METHODS: We conducted a cross-sectional study using US National Health and Nutrition Examination Survey (NHANES) and the Korea NHANES from 2007 to 2018. We included AYA cancer survivors who were diagnosed with any type of cancer aged between 15 and 39 years, and who were adult with aged over 18 years old at survey year. We then stratified the study population by race/ethnicity with Non-Hispanic White (NHW, n = 310), African American (AA, n = 42), Hispanic (n = 81) from NHANES, and Asian (n = 389) from the Korea NHANES. We also selected 5 times age-, sex-, race-, and survey year-matched general population among participants who had never been diagnosed with cancer (N = 4110). Variables were defined using questionnaire data, physical exams, and laboratory tests. RESULTS: Compared to NHW, Hispanics (aOR 1.15, 95% CI 1.00-1.32) had poor or fair general health, lower education (aOR 1.23, 95% CI 1.07-1.40), and lower household income (aOR 1.16, 95% CI 1.01-1.33). AA survivors were more likely to be non-coupled (aOR 1.35, 95% 1.15-1.60) and have hypertension (aOR 1.18, 95% CI 1.03-1.36). Asians were more former/current drinkers (aOR 1.21, 95% CI 1.05-1.40). NHW are more likely to experience psychological limitation. Compared to matched general, NHW and Asian survivors had poor general health and psychological health. CONCLUSIONS: This study provides evidence for future studies concerning long-term health after AYA cancer survivorship that may vary according to race.

Smoking behavior change and risk of cardiovascular disease incidence and mortality in patients with type 2 diabetes mellitus.

BACKGROUND: We aimed to examine the association between smoking behavior change and risk of cardiovascular disease (CVD) incidence and mortality in patients with type 2 diabetes mellitus (T2DM). METHODS: This study used nationwide data from the Korean National Health Insurance System and included 349,137 T2DM patients who smoked. Smoking behavior changes were defined with five groups: quitters, reducers I (≥ 50% reduction), reducers II (20-50% reduction), sustainers (± 20%), and increasers (≥ 20% increase) from the number of cigarettes/day at the baseline. RESULTS: During a median follow-up of 5.1 years, 6,514 cases of myocardial infarction (MI) (1.9%), 7,837 cases of ischemic stroke (IS) (2.2%), and 14,932 deaths (4.3%) were identified. Quitters had a significantly decreased risk of MI (adjusted hazard ratio [aHR] 0.80, 95% CI 0.75-0.86) and IS (aHR 0.80, 95% CI 0.75-0.85) compared to sustainers, whereas reducers did not have a significant association with the risk of MI (aHR 1.03, 95% CI 0.94-1.13) and IS (aHR 1.00, 95% CI 0.92-1.08) in reducer I. Quitters also had a lower all-cause and CVD mortality than sustainers. CONCLUSIONS: Smoking cessation was associated with decreased CVD incidence, and all-cause and CVD mortality among T2DM patients. However, smoking reduction was not associated with decreased risks for these.

Current Status and Physicians' Perspectives of Childhood Cancer Survivorship in Korea: A Nationwide Survey of Pediatric Hematologists/Oncologists.

BACKGROUND: Data on the status of long-term follow-up (LTFU) care for childhood cancer survivors (CCSs) in Korea is lacking. This study was conducted to evaluate the current status of LTFU care for CCSs and relevant physicians' perspectives. METHODS: A nationwide online survey of pediatric hematologists/oncologists in the Republic of Korea was undertaken. RESULTS: Overall, 47 of the 74 board-certified Korean pediatric hematologists/oncologists currently providing pediatric hematology/oncology care participated in the survey (response rate = 63.5%). Forty-five of the 47 respondents provided LTFU care for CCSs five years after the completion of primary cancer treatment. However, some of the 45 respondents provided LTFU care only for CCS with late complications or CCSs who requested LTFU care. Twenty of the 45 respondents oversaw LTFU care for adult CCSs, although pediatric hematologists/oncologists experienced more difficulties managing adult CCSs. Many pediatric hematologists/oncologists did not perform the necessary screening test, although CCSs had risk factors for late complications, mostly because of insurance coverage issues and the lack of Korean LTFU guidelines. Regarding a desirable LTFU care system for CCSs in Korea, 27 of the 46 respondents (58.7%) answered that it is desirable to establish a multidisciplinary CCSs care system in which pediatric hematologists/oncologists and adult physicians cooperate. CONCLUSION: The LTFU care system for CCS is underdeveloped in the Republic of Korea. It is urgent to establish an LTFU care system to meet the growing needs of Korean CCSs, which should include Korean CCSs care guidelines, provider education plans, the establishment of multidisciplinary care systems, and a supportive national healthcare policy.

Blood pressure and dementia risk by physical frailty in the elderly: a nationwide cohort study.

BACKGROUND: Midlife hypertension has been recognized as a modifiable risk factor for dementia, but association between blood pressure (BP) in late life and dementia has been inconclusive. In addition, few studies have investigated effects of BP control on dementia incidence in the frail elderly. Thus, this study aimed to investigate the association of BP and dementia incidence with concomitant consideration of physical frailty in the young elderly population. METHODS: Using the Korean National Health Information Database, we identified 804,024 subjects without history of dementia at age 66. Dementia diagnosis was defined with prescription records of anti-dementia drugs and dementia-related diagnostic codes. Physical frailty was measured using the Timed Up and Go test. Association of BP and dementia incidence with concomitant consideration of physical frailty was investigated using Cox hazards analyses. RESULTS: The risks of Alzheimer's and vascular dementia increased from systolic BP ≥ 160 and 130-139 mmHg, respectively; a significant association of dementia incidence with low BP was not observed. In the analyses stratified by the physical frailty status, low BP was not associated with increased risks of dementia within the groups both with and without physical frailty. CONCLUSIONS: High BP was associated with increased risks of dementia, especially for vascular dementia, while low BP was not associated with increased risks of any type of dementia in young elderly people, even in those with physical frailty. This study suggests the need for tight BP control in young elderly people, irrespective of frailty status, to prevent dementia and supports the current clinical guidelines of hypertension treatment.

Different correlation of body mass index with body fatness and obesity-related biomarker according to age, sex and race-ethnicity.

The relationship between body mass index (BMI) and body fatness could differ according to age, sex, and race-ethnicity. We aimed to evaluate in which contexts BMI could be a good measure for body fatness compared to dual-energy X-ray absorptiometry (DXA) derived measures. The study population included 18,061 participants (9141 men and 8920 women) aged 18 and older who tested DXA from the National Health and Nutrition Examination Survey (NHANES) database from 1999 to 2006, and 8107 men and 10,754 women with DXA data from Korea NHANES from 2008 to 2011 to represent the Asian population. We calculated Pearson correlation coefficients between BMI and DXA derived fat mass index (FMI) and percentage body fat (PBF) depending on age, sex, and race-ethnicity. The correlation between BMI, FMI and PBF and obesity-related biomarkers was also estimated among the subgroup with both DXA and information on each biomarker. BMI was strongly correlated with FMI (r = 0.944 in men and 0.976 in women), PBF (r = 0.735 in men and 0.799 in women), and truncal fat mass (r = 0.914 in men and 0.941 in women) with correlations stronger in women than in men except for with waist-height ratio (r = 0.921 in men and 0.911 in women). The correlation between BMI and DXA derived adiposity weakened with age in both sexes. BMI was less correlated with FMI (r = 0.840 in men and 0.912 in women), PBF (r = 0.645 in men and 0.681 in women), and truncal fat mass (r = 0.836 in men and 0.884 in women) in Korean compared to other race-ethnicities. Among obesity-related biomarkers, insulin was the most strongly correlated to body adiposity indices in both sexes and strength of these correlations generally decreased with age. BMI predicted obesity-related biomarkers as well as FMI and truncal fat mass and superior to PBF. BMI could be a good measure for body fatness, particularly among young age groups, women, the US population, but less so in Korean populations. The lower correlation between BMI and body fatness in older compared to younger age groups could be related to increasing PBF and decreasing lean body mass.

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.

Associations of reproductive factors with incidence of myocardial infarction and ischemic stroke in postmenopausal women: a cohort study.

BACKGROUND: To assess the association between the reproductive factors of age at menarche, age at menopause, and reproductive span and the incidence of myocardial infarction (MI) and ischemic stroke (IS). METHODS: We used a population-based retrospective cohort study from the National Health Insurance Service database of Korea including a total of 1,224,547 postmenopausal women. Associations between age at menarche (≤ 12, 13-14 [reference], 15, 16, and ≥ 17 years), age at menopause (< 40, 40-45, 46-50, 51-54 [reference], and ≥ 55 years), and reproductive span (< 30, 30-33, 34-36, 37-40 [reference], and ≥ 41 years) and the incidence of MI and IS were assessed by Cox proportional hazard models with adjustment for traditional cardiovascular risk factors and various reproductive factors. RESULTS: During a median follow-up of 8.4 years, 25,181 MI and 38,996 IS cases were identified. Late menarche (≥ 16 years), early menopause (≤ 50 years), and short reproductive span (≤ 36 years) were linearly associated with a 6%, 12-40%, and 12-32% higher risk of MI, respectively. Meanwhile, a U-shaped association between age at menarche and risk of IS was found, with a 16% higher risk in early menarche (≤ 12 years) and a 7-9% higher risk in late menarche (≥ 16 years). Short reproductive span was linearly associated with an increased risk of MI, whereas both shorter and longer reproductive spans were associated with an increased risk of IS. CONCLUSIONS: This study demonstrated different patterns of association between age at menarche and incidence of MI and IS: a linear association for MI versus a U-shaped association for IS. Female reproductive factors in addition to traditional cardiovascular risk factors should be considered when assessing overall cardiovascular risk in postmenopausal women.

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 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.

Gamma-glutamyl transferase and risk of all-cause and disease-specific mortality: a nationwide cohort study.

Population-based data regarding the prognostic implication of gamma-glutamyl transferase (GGT) have been inconsistent. We examined the association of GGT with all-cause and disease-specific mortality. Using the Korean nationwide database, we included 9,687,066 subjects without viral hepatitis or cirrhosis who underwent a health examination in 2009. Subjects were classified into three groups by sex-specific tertile of serum GGT levels. The underlying causes of death were classified by 10th Revision of the International Classification of Diseases codes. During the median follow-up period of 8.3 years, 460,699 deaths were identified. All-cause mortality increased as serum GGT levels became higher (hazard ratio [HR], 95% confidence interval [CI] 1.05, 1.04-1.05 in the middle tertile, and 1.33, 1.32-1.34 in the high tertile) compared to the low tertile of serum GGT levels. Similar trends were observed for cardiovascular disease (CVD) (HR, 95% CI 1.07, 1.05-1.09 in the middle tertile, 1.29, 1.26-1.31 in the high tertile), cancer (HR, 95% CI 1.08, 1.07-1.10 in the middle tertile, 1.38, 1.36-1.39 in the high tertile), respiratory disease (HR, 95% CI 1.10, 1.08-1.13 in the middle tertile, 1.39, 1.35-1.43 in the high tertile), and liver disease mortality (HR, 95% CI 1.74, 1.66-1.83 in the middle tertile, 6.73, 6.46-7.01 in the high tertile). Regardless of smoking, alcohol consumption and history of previous CVD and cancer, a higher serum GGT levels were associated with a higher risk of mortality. Serum GGT levels may be useful for risk assessment of all-cause and disease-specific mortality in general population.

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.

The association of fatty liver index and BARD score with all-cause and cause-specific mortality in patients with type 2 diabetes mellitus: a nationwide population-based study.

BACKGROUND: Type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) commonly coexist. However, NAFLD's effect on mortality in Asian patients with type 2 diabetes awaits full elucidation. Therefore, we examined NAFLD-related all-cause and cause-specific mortality in a nationwide Asian population with type 2 diabetes. METHODS: We included patients who had undergone general health checkups between 2009 and 2012 using the National Health Insurance Service database linked to death-certificate data. Hepatic steatosis was defined as a fatty liver index (FLI) ≥ 60, and advanced hepatic fibrosis was determined using the BARD score. FINDINGS: During the follow-up period of 8.1 years, 222,242 deaths occurred, with a mortality rate of 14.3/1000 person-years. An FLI ≥ 60 was significantly associated with increased risks of all-cause and cause-specific mortality including cardiovascular disease (CVD)-, cancer-, and liver disease (FLI ≥ 60: hazard ratio [HR] = 1.02, 95% confidence interval [CI] 1.01-1.03 for all-cause; 1.07, 1.04-1.10 for CVD; 1.12, 1.09-1.14 for cancer; and 2.63, 2.50-2.77 for liver disease). Those with an FLI ≥ 60 and fibrosis (BARD ≥ 2) exhibited increased risks of all-cause (HR, 95% CI 1.11, 1.10-1.12), CVD- (HR, 95% CI 1.11, 1.09-1.14), cancer- (HR, 95% CI 1.17, 1.15-1.19), and liver disease-related (HR, 95% CI 2.38, 2.29-2.49) mortality. CONCLUSION: Hepatic steatosis and advanced fibrosis were significantly associated with risks of overall and cause-specific mortality in patients with type 2 diabetes. Our results provide evidence that determining the presence of hepatic steatosis and/or fibrosis potentially plays a role in risk stratification of mortality outcomes in patients with type 2 diabetes mellitus.