Screening mammography performance according to breast density: a comparison between radiologists versus standalone intelligence detection.

BACKGROUND: Artificial intelligence (AI) algorithms for the independent assessment of screening mammograms have not been well established in a large screening cohort of Asian women. We compared the performance of screening digital mammography considering breast density, between radiologists and AI standalone detection among Korean women. METHODS: We retrospectively included 89,855 Korean women who underwent their initial screening digital mammography from 2009 to 2020. Breast cancer within 12 months of the screening mammography was the reference standard, according to the National Cancer Registry. Lunit software was used to determine the probability of malignancy scores, with a cutoff of 10% for breast cancer detection. The AI's performance was compared with that of the final Breast Imaging Reporting and Data System category, as recorded by breast radiologists. Breast density was classified into four categories (A-D) based on the radiologist and AI-based assessments. The performance metrics (cancer detection rate [CDR], sensitivity, specificity, positive predictive value [PPV], recall rate, and area under the receiver operating characteristic curve [AUC]) were compared across breast density categories. RESULTS: Mean participant age was 43.5 ± 8.7 years; 143 breast cancer cases were identified within 12 months. The CDRs (1.1/1000 examination) and sensitivity values showed no significant differences between radiologist and AI-based results (69.9% [95% confidence interval [CI], 61.7-77.3] vs. 67.1% [95% CI, 58.8-74.8]). However, the AI algorithm showed better specificity (93.0% [95% CI, 92.9-93.2] vs. 77.6% [95% CI, 61.7-77.9]), PPV (1.5% [95% CI, 1.2-1.9] vs. 0.5% [95% CI, 0.4-0.6]), recall rate (7.1% [95% CI, 6.9-7.2] vs. 22.5% [95% CI, 22.2-22.7]), and AUC values (0.8 [95% CI, 0.76-0.84] vs. 0.74 [95% CI, 0.7-0.78]) (all P < 0.05). Radiologist and AI-based results showed the best performance in the non-dense category; the CDR and sensitivity were higher for radiologists in the heterogeneously dense category (P = 0.059). However, the specificity, PPV, and recall rate consistently favored AI-based results across all categories, including the extremely dense category. CONCLUSIONS: AI-based software showed slightly lower sensitivity, although the difference was not statistically significant. However, it outperformed radiologists in recall rate, specificity, PPV, and AUC, with disparities most prominent in extremely dense breast tissue.

Association between body composition and subsequent cardiovascular diseases among 5-year breast cancer survivors.

BACKGROUND AND AIMS: Cardiovascular disease (CVD) remain one of the leading causes of mortality in breast cancer survivors. This study aimed to investigate the association between body composition and subsequent CVD in breast cancer survivors. METHODS AND RESULTS: A retrospective cohort study of more than 70 thousand 5-year breast cancer survivors aged 40 years or older was conducted using data from the National Health Insurance Service of South Korea. Based on the percentage of predicted lean body mass (pLBMP), appendicular skeletal muscle mass (pASMP), and body fat mass (pBFMP), which were calculated using prediction equations with anthropometric data and health habits, groups were equally divided into quartiles. The risk of CVD was evaluated using multivariate Cox proportional hazards regression. Compared to those with the lowest pLBMP and pASMP, those with the highest pLBMP and pASMP had a 38% and 42% lower risk of CVD, respectively. In contrast, those with the highest pBFMP had a 57% higher risk of CVD compared to those with the lowest pBFMP. Each 1 % increase in pLBMP and pASMP was associated with a decreased risk of CVD [pLBMP, adjusted hazard ratio (aHR): 0.96, 95% CI 0.94-0.98, p < 0.05; pASMP, aHR: 0.91, 95% CI 0.87-0.95, p < 0.05] while each 1 % increase in pBFMP was associated with the increased risk of CVD (aHR: 1.05, 95% CI 1.03-1.07, p < 0.01). CONCLUSION: In this cohort study, a high pLBMP, a high pASMP, and a low pBFMP were associated with a lower risk of CVD.

Early-onset vasomotor symptoms and development of depressive symptoms among premenopausal women.

BACKGROUND: We investigated the association between vasomotor symptoms (VMSs) and the onset of depressive symptoms among premenopausal women. METHODS: This cross-sectional study included 4376 premenopausal women aged 42-52 years, and the cohort study included 2832 women without clinically relevant depressive symptoms at baseline. VMSs included the symptoms of hot flashes and night sweats. Depressive symptoms were evaluated using the Center for Epidemiological Studies Depression Scale; a score of ≥16 was considered to define clinically relevant depressive symptoms. RESULTS: Premenopausal Women with VMSs at baseline exhibited a higher prevalence of depressive symptoms compared with women without VMSs at baseline (multivariable-adjusted prevalence ratio 1.76, 95 % confidence interval [CI] 1.47-2.11). Among the 2832 women followed up (median, 6.1 years), 406 developed clinically relevant depressive symptoms. Women with versus without VMSs had a significantly higher risk of developing clinically relevant depressive symptoms (multivariable-adjusted hazard ratio, 1.72; 95 % CI 1.39-2.14). VMS severity exhibited a dose-response relationship with depressive symptoms (P for trend <0.05). LIMITATIONS: Self-reported questionnaires were only used to obtain VMSs and depressive symptoms, which could have led to misclassification. We also could not directly measure sex hormone levels. CONCLUSIONS: Even in the premenopausal stage, women who experience hot flashes or night sweats have an increased risk of present and developed clinically relevant depressive symptoms. It is important to conduct mental health screenings and provide appropriate support to middle-aged women who experience early-onset VMSs.

Inverse association with COVID-19 vaccination status of the incidence of pneumonia after SARS-CoV-2 infection: A nationwide retrospective cohort study.

BACKGROUND: Although one of the characteristics of COVID-19 is accompanied by acute pneumonia immediately after infection, large-scale cohort studies focused on this issue are lacking. In addition, there is interest in how COVID-19 vaccinations reduce the incidence of acute pneumonia for people infected with different strains of SARS-CoV-2. Thus, we assess the short-term incidence of pneumonia after COVID-19 with the vaccination and SARS-CoV-2 variants. METHODS: As data for 2136,751 COVID-19 patients between January 01, 2020 and February 28, 2022 was collected, they were observed for one month from the day of infection. Patients in retrospective cohort study were classified according to doses of the received vaccine and the epidemic phase when SARS-CoV-2 variants prevailed. Multivariable logistic regression analysis calculated adjusted odds ratios (aOR) and 95% confidence intervals (CIs) for the pneumonia risk. RESULTS: In B.1.1.7-B.1.351, B.1.617.2, and B.1.617.2 variants, the aORs (95% CIs; p-value) for incidence of pneumonia were 0.93 (0.89-0.98; <0.001), 0.74 (0.70-0.78; <0.001), and 0.04 (0.038-0.043; <0.001), respectively, compared to the original strain. More than 80% of patients have received the second and more doses of the vaccine (average age=44.67 years). The aORs (95% CIs; p-value) for pneumonia were 0.61 (0.58-0.64; <0.001), 0.39 (0.38-0.40; <0.001), and 0.18 (0.166-0.184; <0.001) in patients who received the first (N = 68,216), second (N = 898,838), and ≥ third doses (N = 836,173), respectively, compared to unvaccinated patients. According to the received vaccine (second dose of mRNA or viral vector), those who received BNT162b2 and mRNA-1273 (N = 787,980) had lower risk of pneumonia, compared to that in those who received h ChAdOx1 nCov-19 and AD26. COV2-S (N = 89,024). CONCLUSIONS: Our findings suggest that the second and ≥ third doses (61% and 82% of risk aversion effect increased, respectively) of the COVID-19 vaccine can prevent the COVID-19-related pneumonia, regardless of the variants.

Human papillomavirus infection and cardiovascular mortality: a cohort study.

BACKGROUND AND AIMS: High-risk human papillomavirus (HR-HPV) infection-a well-established risk factor for cervical cancer-has associations with cardiovascular disease (CVD). However, its relationship with CVD mortality remains uncertain. This study examined the associations between HR-HPV infection and CVD mortality. METHODS: As part of a health examination, 163 250 CVD-free Korean women (mean age: 40.2 years) underwent HR-HPV screening and were tracked for up to 17 years (median: 8.6 years). National death records identified the CVD mortality cases. Hazard ratios (HRs) and 95% confidence intervals (CIs) for CVD mortality were estimated using Cox proportional hazard regression analyses. RESULTS: During 1 380 953 person-years of follow-up, 134 CVD deaths occurred, with a mortality rate of 9.1 per 105 person-years for HR-HPV(-) women and 14.9 per 105 person-years for HR-HPV(+) women. After adjustment for traditional CVD risk factors and confounders, the HRs (95% CI) for atherosclerotic CVD (ASCVD), ischaemic heart disease (IHD), and stroke mortality in women with HR-HPV infection compared with those without infection were 3.91 (1.85-8.26), 3.74 (1.53-9.14), and 5.86 (0.86-40.11), respectively. The association between HR-HPV infection and ASCVD mortality was stronger in women with obesity than in those without (P for interaction = .006), with corresponding HRs (95% CI) of 4.81 (1.55-14.93) for obese women and 2.86 (1.04-7.88) for non-obese women. CONCLUSIONS: In this cohort study of young and middle-aged Korean women, at low risks for CVD mortality, those with HR-HPV infection had higher death rates from CVD, specifically ASCVD and IHD, with a more pronounced trend in obese individuals.

Baseline and change in serum uric acid level over time and resolution of nonalcoholic fatty liver disease in young adults: The Kangbuk Samsung Health Study.

AIMS: To determine the association between: (i) baseline serum uric acid (SUA) level and (ii) SUA changes over time, and nonalcoholic fatty liver disease (NAFLD) resolution. MATERIALS AND METHODS: A retrospective cohort study, comprising 38 483 subjects aged <40 years with pre-existing NAFLD, was undertaken. The effects of SUA changes over time were studied in 25 266 subjects. Participants underwent a health examination between 2011 and 2019, and at least one follow-up liver ultrasonography scan up to December 2020. Exposures included baseline SUA level and SUA changes between baseline and subsequent visits, categorized into quintiles. The reference group was the third quintile (Q3) containing zero change. The primary endpoint was resolution of NAFLD. RESULTS: During a median follow-up of 4 years, low baseline SUA level and decreases in SUA levels over time were independently associated with NAFLD resolution (p for trend <0.001). Using SUA as a continuous variable, the likelihood of NAFLD resolution was increased by 10% and 13% in men and women, respectively, per 1-mg/dL decrease in SUA. In a time-dependent model with changes in SUA treated as a time-varying covariate, adjusted hazard ratios (95% confidence intervals) for NAFLD resolution comparing Q1 (highest decrease) and Q2 (slight decrease) to Q3 (reference) were 1.63 (1.49-1.78) and 1.23 (1.11-1.35) in men and 1.78 (1.49-2.12) and 1.18 (0.95-1.46) in women, respectively. CONCLUSIONS: Low baseline SUA levels and a decrease in SUA levels over time were both associated with NAFLD resolution in young adults.

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.

Protective effect of vaccination on the risk of cardiovascular disease after SARS-CoV-2 infection.

OBJECTIVE: This study investigated the incidence of CVDs after COVID-19. METHODS: Data for 2,146,130 infected people were collected, including the vaccination status. COVID-19 patients were classified according to the number of the received vaccine doses: no, first, second, and ≥ third. To evaluate the short-term risk of CVDs after infection, adjusted odds ratios (aOR) and 95% confidence intervals (CIs) were calculated by multivariable logistic regression analysis after adjustments for covariates. RESULTS: Compared to non-infected people, aORs [95% CIs; p value] for CVDs within a month after infection were 2.80 [2.64-2.97; < 0.001] in overall infected people and 4.62 [4.23-5.05; < 0.001], 4.20 [3.45-5.11; < 0.001], 2.79 [2.55-3.05; < 0.001], and 2.07 [1.91-2.24; < 0.001] in those who were infected after receiving no, first, second, and ≥ third vaccine doses, respectively. Among participants who received second doses of vaccine prior to contracting COVID-19, the aOR in those vaccinated with only the mRNA-based vaccine (BNT162b2 and mRNA-1273; Reference) was lower than those vaccinated with the virus-derived vaccine (ChAdOx1 nCov-19 and AD26.COV2-S; aOR 1.25 [1.06-1.48; < 0.01]). CONCLUSION: Although COVID-19 increased the CVD risk, the inverse association in the risk of CVDs according to vaccine doses was significant in a dose-response manner. Our findings suggest that ≥ second doses of the COVID-19 vaccine prevent the risk of CVDs after SARS-CoV-2 infection.

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.

Potential role of Fibrosis-4 score in hepatocellular carcinoma screening: The Kangbuk Samsung Health Study.

AIM: Hepatocellular carcinoma (HCC) is a major cause of cancer-related death, with low survival rates worldwide. Fatty liver disease (FLD) significantly contributes to HCC. We studied the screening performance of different methods for identifying HCC in patients with FLD or with metabolic risk factors for FLD. METHODS: Korean adults (n = 340 825) without a prior HCC diagnosis were categorized into four groups: normal (G1), ≥2 metabolic risk factors (G2), FLD (G3), and viral liver disease or liver cirrhosis (G4). The National Cancer Registry data were used to identify HCC cases within 12 months. We assessed the area under the receiver operating characteristic curve, sensitivity, specificity, and positive and negative predictive values of individual or combined screening methods. RESULTS: In 93 HCC cases, 71 were identified in G4, whereas 20 cases (21.5%) in G2 and G3 combined where ultrasound and Fibrosis-4 performed similarly to alpha-fetoprotein and ultrasound. In G2, Fibrosis-4 and ultrasound had the highest area under the receiver operating characteristic curve (0.93 [0.87-0.99]), whereas in G3, the combined screening methods had the highest area under the receiver operating characteristic curve (0.98 [0.95-1.00]). The positive predictive value was lower in G2 and G3 than in G4, but was >5% when restricted to a high Fibrosis-4 score. CONCLUSIONS: More than 21% of HCC cases were observed in patients with diagnosed FLD or at risk of FLD with metabolic risk factors. Nevertheless, screening for HCC in individuals without cirrhosis or viral hepatitis yielded very low results, despite the potential value of the Fibrosis-4 score in identifying individuals at high risk of HCC.

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

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

Effect of changes in sleeping behavior on skeletal muscle and fat mass: a retrospective cohort study.

BACKGROUND: An association between sleep behaviors and muscle-fat mass is continuously interesting topic. METHODS: Based on the survey on sleep behaviors (quality and duration), the poor quality of sleep was evaluated when the subject did not feel satisfied after sleep, while the good quality was evaluated as they feel refreshed. A total of 19,770 participants were divided into the four groups according to changes in sleep quality: Good-to-Good (those who continuously maintained good quality), Good-to-Poor (those who reported initial good quality but subsequently reported a poor quality), Poor-to-Poor (those who continuously maintained poor quality), and Poor-to-Good (those who reported improved quality of sleep). As changes in skeletal muscle and fat mass index [kg/m2] were estimated by a validated prediction equation, multiple linear regression was used to calculate adjusted mean (adMean) of muscle and fat mass according to changes in sleep behavior. RESULTS: When sleep duration decreased and quality of sleep deteriorated (from good to poor), fat mass index significantly increased (adMean: 0.087 for the Good-to-Good group and 0.210 for the Good-to-Poor group; p-value = 0.006). On the other hand, as the quality of sleep deteriorated, skeletal muscle mass more decreased despite the maintained sleep duration (adMean: -0.024 for the Good-to-Good group and - 0.049 for the Good-to-Poor group; p-value = 0.009). CONCLUSION: Our results showed that changes in sleep quality and duration affect changes in muscle and fat mass. Thus, we suggest maintaining a good quality of sleep, even if sleep duration is reduced, to preserve muscle mass and inhibit the accumulation of fat.

Metabolic-associated fatty liver disease is associated with colorectal adenomas in young and older Korean adults.

BACKGROUND AND AIMS: Given that the majority of colorectal cancers (CRCs) develop from high-risk adenomas, identifying risk factors for high-risk adenomas is important. The relationship between metabolic dysfunction-associated fatty liver disease (MAFLD) and the risk of colorectal adenoma in young adults remains unclear. We aimed to evaluate this relationship in adults <50 (younger) and ≥50 (older) years of age. METHODS: This cross-sectional study included 184 792 Korean adults (80% <50 years of age) who all underwent liver ultrasound and colonoscopy. Participants were grouped into those with and without MAFLD and classified by adenoma presence into no adenoma, low-risk adenoma, or high-risk adenoma (defined as ≥3 adenomas, any ≥10 mm, or adenoma with high-grade dysplasia/villous features). RESULTS: The prevalence of low- and high-risk adenomas among young and older adults was 9.6% and 0.8% and 22.3% and 4.8%, respectively. MAFLD was associated with an increased prevalence of low- and high-risk adenomas in young and older adults. Young adults with MAFLD had a 1.30 (95% CIs 1.26-1.35) and 1.40 (1.23-1.59) times higher prevalence of low- and high-risk adenomas, respectively, compared to those without MAFLD. These associations were consistent even in lean adults (BMI < 23 kg/m2 ) and those without a family history of CRC. CONCLUSIONS: MAFLD is associated with an increased prevalence of low- and high-risk adenomas in Korean adults, regardless of age or obesity status. Whether reducing metabolic risk factors, such as MAFLD, reduces the risk of precancerous lesions and ultimately reduces the risk of early-onset CRC requires further investigation.

Diagnostic performance of screening mammography according to menstrual cycle among Asian women.

PURPOSE: To investigate the performance metrics of screening mammography according to menstrual cycle week in premenopausal Asian women. METHODS: This retrospective study included 69,556 premenopausal Asian women who underwent their first screening mammography between 2011 and 2019. The presence or absence of a breast cancer diagnosis within 12 months after the index screening mammography served as the reference standard, determined by linking the study data to the national cancer registry data. Menstrual cycles were calculated, and participants were assigned to groups according to weeks 1-4. The performance metrics included cancer detection rate (CDR), sensitivity, specificity, and positive predictive value (PPV), with comparisons across menstrual cycles. RESULTS: Among menstrual cycles, the lowest CDR at 4.7 per 1000 women (95% confidence interval [CI], 3.8-5.8 per 1000 women) was observed in week 4 (all P < 0.05). The highest sensitivity of 72.7% (95% CI, 61.4-82.3) was observed in week 1, although the results failed to reach statistical significance. The highest specificity of 80.4% (95% CI, 79.5-81.3%) was observed in week 1 (P = 0.01). The lowest PPV of 2.2% (95% CI, 1.8-2.7) was observed in week 4 (all P < 0.05). CONCLUSION: Screening mammography tended to show a higher performance during week 1 and a lower performance during week 4 of the menstrual cycle among Asian women. These results emphasize the importance of timing recommendations that consider menstrual cycles to optimize the effectiveness of screening mammography for breast cancer detection.

Serum 25-Hydroxyvitamin D Levels and Risk of Colorectal Cancer: An Age-Stratified Analysis.

BACKGROUND & AIMS: The role of circulating 25-hydroxyvitamin D (25(OH)D) in the prevention of early-onset colorectal cancer (CRC) in young adults aged <50 years is uncertain. We evaluated the age-stratified associations (<50 vs ≥50 years) between circulating 25(OH)D levels and the risk of CRC in a large sample of Korean adults. METHODS: Our cohort study included 236,382 participants (mean age, 38.0 [standard deviation, 9.0] years) who underwent a comprehensive health examination, including measurement of serum 25(OH)D levels. Serum 25(OH)D levels were categorized as <10, 10 to 20, and ≥20 ng/mL. CRC, along with the histologic subtype, site, and invasiveness, was ascertained through linkage with the national cancer registry. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident CRC according to the serum 25(OH)D status, with adjustment for potential confounders. RESULTS: During the 1,393,741 person-years of follow-up (median, 6.5 years; interquartile range, 4.5-7.5 years), 341 participants developed CRC (incidence rate, 19.2 per 105 person-years). Among young individuals aged <50 years, serum 25(OH)D levels were inversely associated with the risk of incident CRC with HRs (95% CIs) of 0.61 (0.43-0.86) and 0.41 (0.27-0.63) for 25(OH)D 10 to 19 ng/mL and ≥20 ng/mL, respectively, with respect to the reference (<10 ng/mL) (P for trend <.001, time-dependent model). Significant associations were evident for adenocarcinoma, colon cancer, and invasive cancers. For those aged ≥50 years, associations were similar, although slightly attenuated compared with younger individuals. CONCLUSIONS: Serum 25(OH)D levels may have beneficial associations with the risk of developing CRC for both early-onset and late-onset disease.

Association of Thyroid Hormone Medication Adherence With Risk of Dementia.

CONTEXT: Recent studies suggest that hypothyroidism is a risk factor for dementia. Based on existing literature, it is unclear if treatment or compliance to treatment is associated with decreased dementia risk in hypothyroidism patients. OBJECTIVE: To determine the association between thyroid hormone medication adherence and risk of dementia. METHODS: A population-based cohort study following patients with newly diagnosed hypothyroidism until incidence of dementia, death, or December 31, 2020, whichever came earliest. The study comprised 41 554 older adults age 50 and above with newly diagnosed hypothyroidism between 2004 and 2008 who underwent health screening. Risk of dementia was evaluated using multivariable-adjusted Cox proportional hazards regression. RESULTS: Among 5188 men (12.5%) and 36 366 (87.5%) women, 2120 cases of incident dementia were identified. After stratification of the participants according to the interquartile range of the medication possession ratio (MPR), the fourth quartile (highest adherence) showed a 14% lower risk of overall dementia compared with the first quartile (lowest adherence) (adjusted hazard ratio 0.86; 95% CI 0.76-0.97). No consistent association was observed between thyroid hormone medication adherence and vascular dementia. After a dichotomous stratification of the MPR, higher MPR (≥0.8) showed a lower risk of Alzheimer disease (adjusted hazard ratio 0.91; 95% CI 0.84-0.99) than lower MPR (<0.8). CONCLUSION: Better adherence to thyroid hormone medication may be beneficial in preventing incident dementia, especially Alzheimer disease, in older adults with newly diagnosed hypothyroidism. Along with the resolution of hypothyroid symptoms and the reduction of cardiovascular risk factors, the reduction of dementia risk may be another potential benefit of thyroid hormone medication.

Vasomotor and other menopause symptoms and the prevalence of ideal cardiovascular health metrics among premenopausal stage women.

OBJECTIVE: We examined the association between menopause symptoms and the prevalence of ideal cardiovascular health (CVH) metrics among premenopausal women. METHODS: This cross-sectional study comprised 4,611 premenopausal women aged 42 to 52 years. Data for CVH metrics were collected during health screening examinations. Menopause symptoms were measured using the Korean version of the Menopause-Specific Quality of Life questionnaire. For vasomotor, psychosocial, physical, and sexual symptoms, participants were divided into absent or symptomatic groups, further divided into tertiles (range, 0-7; 7 being the most bothersome). Ideal CVH metrics were defined according to the American Heart Association Life Simple 7 metrics, except dietary component. Cardiovascular health metrics were scored from 0 (unhealthy) to 6 (healthy) and classified as poor (0-2), intermediate (3-4), and ideal (5-6). Multinomial logistic regression models were used to estimate the prevalence ratios for intermediate and poor CVH metrics using ideal CVH as the reference. RESULTS: The overall and 4 menopause-specific quality of life domain scores were significantly associated with poorer CVH metrics scores in a dose-response manner ( P < 0.05). After adjusting for age, parity, education level, anti-Mullerian hormone levels, and alcohol intake, women with the most bothersome degree for vasomotor, psychosocial, physical, and sexual symptoms had significantly higher prevalence of poor CVH metrics, with corresponding prevalence ratios (95% confidence interval) of 2.90 (1.95-4.31), 2.07 (1.36-3.15), 3.01 (1.19-7.65), and 1.66 (1.15-2.39), respectively, compared with those without each vasomotor, psychosocial, physical, and sexual symptom. CONCLUSIONS: Premenopausal stage women with either vasomotor or nonvasomotor menopausal symptoms have significantly higher prevalence of poor CVH metrics, compared with those without any menopausal symptoms.

Nonalcoholic fatty liver disease without overlapping metabolic-associated fatty liver disease and the risk of incident type 2 diabetes.

BACKGROUND AND AIMS: Re-classifying NAFLD as metabolic-associated fatty liver (MAFLD) has been proposed. While some people fulfil criteria for NAFLD, they do not have MAFLD; and whether NAFLD-only subjects have increased the risk of type 2 diabetes remains unknown. We compared risk of incident T2D in individuals with: (a) NAFLD-only; and (b) MAFLD, to individuals without fatty liver, considering effect modification by sex. METHODS: 246 424 Koreans without diabetes or a secondary cause of ultrasound-diagnosed hepatic steatosis were studied. Subjects were stratified into: (a) NAFLD-only status and (b) NAFLD that overlapped with MAFLD (MAFLD). Cox proportional hazards models with incident T2D as the outcome were used to estimate hazard ratios (HRs) for: (a) and (b). Models were adjusted for time-dependent covariates, and effect modification by sex was analysed in subgroups. RESULTS: A total of 5439 participants had NAFLD-only status and 56 839 met MAFLD criteria. During a median follow-up of 5.5 years, 8402 incident cases of T2D occurred. Multivariable-adjusted HRs (95% CI) for incident T2D comparing NAFLD-only and MAFLD to the reference (neither condition) were 2.39 (1.63-3.51) and 5.75 (5.17-6.36) (women), and 1.53 (1.25-1.88) and 2.60 (2.44-2.76) (men), respectively. The increased risk of T2D in the NAFLD-only group was higher in women than in men (p for interaction by sex <0.001) and consistently observed across all subgroups. Risk of T2D was increased in lean participants regardless of metabolic dysregulation (including prediabetes). CONCLUSIONS: NAFLD-only participants without metabolic dysregulation and the criteria for MAFLD are at increased risk of developing T2D. This association was consistently stronger in women than in men.

Nonalcoholic fatty liver disease and risk of incident young-onset hypertension: Effect modification by sex.

BACKGROUND AND AIMS: Although nonalcoholic fatty liver disease (NAFLD) and hypertension are increasingly common among young adults, it is uncertain if NAFLD affects incidence of young-onset hypertension, and if the association is modified by sex. We investigated potential effect modification by sex on the association between NAFLD and incident hypertension in young adults (<40 years). METHOD AND RESULTS: This cohort study comprised 85,789 women and 67,553 men aged <40 years without hypertension at baseline. Hepatic steatosis was assessed by liver ultrasound and classified as mild or moderate/severe. Hypertension was defined as blood pressure (BP) ≥130/80 mmHg; self-reported history of physician-diagnosed hypertension; or current use of BP-lowering medications. Cox proportional hazard models were used to estimate hazard ratios (HRs; 95% confidence intervals [CIs]) for incident hypertension by NAFLD status (median follow-up 4.5 years). A total of 25,891 participants developed incident hypertension (incidence rates per 103 person-years: 15.6 for women and 63.5 for men). Multivariable-adjusted HRs (95% CIs) for incident hypertension comparing no NAFLD (reference) with mild or moderate/severe NAFLD were 1.68 (1.56-1.80) and 1.83 (1.60-2.09) for women and 1.21 (1.17-1.25) and 1.23 (1.17-1.30) for men, respectively. Stronger associations were consistently observed between NAFLD and incident hypertension in women, regardless of obesity/central obesity (all p-values for interaction by sex <0.001). CONCLUSIONS: NAFLD is a potential risk factor for young-onset hypertension with a relatively greater impact in women and in those with more severe hepatic steatosis.

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.