Fatty liver disease and changes in dense breasts in pre- and postmenopausal women: the Kangbuk Samsung Health Study.

PURPOSE: While increased breast density is a risk factor for breast cancer, the effect of fatty liver disease on breast density is unknown. We investigated whether fatty liver is a risk factor for changes in breast density over ~ 4 years of follow-up in pre- and postmenopausal women. METHODS: This study included 74,781 middle-aged Korean women with mammographically determined dense breasts at baseline. Changes in dense breasts were identified by more screening mammograms during follow-up. Hepatic steatosis (HS) was measured using ultrasonography. Flexible parametric proportional hazards models were used to determine the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs), and a Weibull accelerated failure time model (AFT) was used to determine the time ratios (TRs) and 95% CIs. RESULTS: During a median follow-up of 4.1 years, 4022 women experienced resolution of the dense breasts. The association between HS and dense breast resolution differed by the menopause status (P for interaction < 0.001). After adjusting for body mass index and other covariates, the aHRs (95% CI) for dense breast resolution comparing HS to non-HS were 0.81 (0.70-0.93) in postmenopausal women, while the association was converse in premenopausal women with the corresponding HRs of 1.30 (1.18-1.43). As an alternative approach, the multivariable-adjusted TR (95% CI) for dense breast survival comparing HS to non-HS were 0.81 (0.75-0.87) and 1.19 (1.06-1.33) in premenopausal and postmenopausal women, respectively. CONCLUSION: The association between HS and changes in dense breasts differed with the menopause status. HS increased persistent dense breast survival in postmenopausal women but decreased it in premenopausal women.

Discordance Between Apolipoprotein B and Low-Density Lipoprotein Cholesterol and Progression of Coronary Artery Calcification in Middle Age.

BACKGROUND: A high level of apolipoprotein B (apoB) is associated with incident coronary artery disease (CAD) when low-density lipoprotein cholesterol (LDL-C) level is discordantly low or concordantly high. However, data on the relationship of apoB with subclinical measure of CAD are limited.Methods and Results:A total of 14,205 men (mean age 41.0 years) who were free of cardiovascular disease at baseline and who underwent a health checkup exam, including measurement of coronary artery calcium (CAC), were studied. Of the study group, 2,773 participants (19.5%) had CAC at baseline, and CAC progression was observed in 2,550 (18.0%). The multivariate-adjusted CAC score ratios (95% confidence interval) comparing discordantly high apoB/low LDL-C and concordantly high apoB/high LDL-C with concordantly low apoB/low LDL-C were 1.51 (0.98-2.32) and 2.70 (2.19-3.33), respectively. The corresponding relative risks for CAC progression were 1.26 (1.02-1.56) and 1.49 (1.34-1.66), respectively. These associations did not change appreciably after adjustment for insulin resistance and subclinical inflammation. CONCLUSIONS: Discordant analysis showed that a high apoB level was strongly associated with prevalence and progression of CAC independent of LDL-C in a large cohort of healthy adults. The present study results highlighted the importance of an apoB measure as a potential target for primary prevention of coronary atherosclerosis in healthy adults.

Coexistence of Colorectal Adenomas and Coronary Calcification in Asymptomatic Men and Women.

GOALS: Because of shared risk factors between clinically manifest cardiovascular disease and colorectal cancer, we hypothesized the coexistence of subclinical atherosclerosis measured by coronary artery calcium (CAC) and colorectal adenoma (CRA) and that these 2 processes would also share common risk factors. BACKGROUND: No study has directly compared the risk factors associated with subclinical coronary atherosclerosis and CRA. STUDY: This was a cross-sectional study using multinomial logistic regression analysis of 4859 adults who participated in a health screening examination (2010 to 2011; analysis 2014 to 2015). CAC scores were categorized as 0, 1 to 100, or >100. Colonoscopy results were categorized as absent, low-risk, or high-risk CRA. RESULTS: The prevalence of CAC>0, CAC 1 to 100 and >100 was 13.0%, 11.0%, and 2.0%, respectively. The prevalence of any CRA, low-risk CRA, and high-risk CRA was 15.1%, 13.0%, and 2.1%, respectively. The adjusted odds ratios (95% confidence interval) for CAC>0 comparing participants with low-risk and high-risk CRA with those without any CRA were 1.35 (1.06-1.71) and 2.09 (1.29-3.39), respectively. Similarly, the adjusted odds ratios (95% confidence interval) for any CRA comparing participants with CAC 1 to 100 and CAC>100 with those with no CAC were 1.26 (1.00-1.6) and 2.07 (1.31-3.26), respectively. Age, smoking, diabetes, and family history of CRC were significantly associated with both conditions. CONCLUSIONS: We observed a graded association between CAC and CRA in apparently healthy individuals. The coexistence of both conditions further emphasizes the need for more evidence of comprehensive approaches to screening and the need to consider the impact of the high risk of coexisting disease in individuals with CAC or CRA, instead of piecemeal approaches restricted to the detection of each disease independently.

Relationship Between Low Relative Muscle Mass and Coronary Artery Calcification in Healthy Adults.

OBJECTIVE: Sarcopenia or low muscle mass is related to cardiovascular risk factors; however, the association between low muscle mass and subclinical atherosclerosis has been largely unexplored. We investigated whether muscle mass is related to coronary artery calcification (CAC) in a large sample of middle-aged asymptomatic adults. APPROACH AND RESULTS: We performed a cross-sectional study of 31 108 asymptomatic adults without cancer, diabetes mellitus, or known cardiovascular disease who underwent a health checkup examination including cardiac tomography estimation of CAC scores between 2012 and 2013. Skeletal muscle mass index (SMI) [SMI (%)=total skeletal muscle mass (kg)/body weight (kg)×100] was estimated using a bioelectrical impedance analyzer. We assessed the relationship between SMI and CAC scores using both multivariate-adjusted Tobit models and multinomial logistic regression models. Of the 31 108 subjects, 3374 subjects (10.9%) had a CAC score 1 to 100, and 628 subjects (2.0%) had a CAC score >100. SMI was inversely associated with CAC score ratios. Specifically, in a multivariable-adjusted model adjusting for potential confounders, CAC score ratios (95% confidence intervals) of SMI for quartiles 1, 2, and 3 compared with quartile 4 were 2.27 (1.70-3.05), 1.46 (1.15-1.85), and 1.24 (0.98-1.55), respectively (P for trend <0.001). Adjusting for insulin resistance reduced the magnitude of the associations, but they remained statistically significant. CONCLUSIONS: Relative muscle mass was negatively associated with the prevalence of coronary calcification, supporting low muscle mass as an independent risk factor of coronary heart disease.

Sleep Duration, Sleep Quality, and Markers of Subclinical Arterial Disease in Healthy Men and Women.

OBJECTIVE: Short and long sleep duration are associated with increased risk of clinical cardiovascular events, but the association between sleep duration and subclinical cardiovascular disease is not well established. We examined the association between sleep duration and sleep quality with coronary artery calcification (CAC) and with brachial-ankle pulse wave velocity (PWV) in a large sample of young and middle-aged asymptomatic adults. APPROACH AND RESULTS: We conducted a cross-sectional study of adult men and women who underwent a health checkup examination, including assessment of sleep duration and quality and coupled with either CAC (n=29 203) or brachial-ankle PWV (n=18 106). The multivariate-adjusted CAC score ratios (95% confidence interval) comparing sleep durations of ≤5, 6, 8, and ≥9 hours with 7 hours of sleep were 1.50 (1.17-1.93), 1.34 (1.10-1.63), 1.37 (0.99-1.89), and 1.72 (0.90-3.28), respectively (P for quadratic trend=0.002). The corresponding average differences in brachial-ankle PWV were 6.7 (0.75-12.6), 2.9 (-1.7 to 7.4), 10.5 (4.5-16.5), and 9.6 (-0.7 to 19.8) cm/s, respectively (P for quadratic trend=0.019). Poor subjective sleep quality was associated with CAC in women but not in men, whereas the association between poor subjective sleep quality and brachial-ankle PWV was stronger in men than in women. CONCLUSIONS: In this large study of apparently healthy men and women, extreme sleep duration and poor subjective sleep quality were associated with increased prevalence of CAC and higher PWV. Our results underscore the importance of an adequate quantity and quality of sleep to maintain cardiovascular health.

Metabolic syndrome, insulin resistance, and mammographic density in pre- and postmenopausal women.

Little is known about the association of metabolic syndrome (MetS) or insulin resistance (IR) with mammographic density, a strong risk factor for breast cancer. The goal of this study was to evaluate these associations in pre- and postmenopausal women. A cross-sectional study was performed in 73,974 adult women who underwent a comprehensive health screening examination that included a mammogram between 2011 and 2013 (mean age 42.6 years). MetS was defined according to the modified National Cholesterol Education Program Adult Treatment Panel III. IR was assessed with the homeostasis model assessment-insulin resistance (HOMA-IR). Adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for dense breast were estimated using logistic regression models after adjustment for potential confounders. In premenopausal women, MetS and all its components except waist circumference were associated with dense breast. After adjustment for potential confounders, the OR (95% CI) for dense breast in women with MetS compared with those without MetS was 1.22 (1.06-1.39). In postmenopausal women, however, there was positive but non-significant association between MetS and dense breast. In both pre- and postmenopausal women, high blood glucose and IR were positively associated with dense breast. The OR (95% CI) for dense breast between the highest and lowest quartiles of HOMA-IR was 1.29 (1.20-1.39) for premenopausal women and 1.44 (1.05-1.97) for postmenopausal women. In a large sample of Korean women, MetS and IR were associated with mammographic dense breast, demonstrating that IR, a potentially modifiable risk factor, may increase breast cancer risk, possibly through high mammographic density.

Menopausal stages and non-alcoholic fatty liver disease in middle-aged women.

OBJECTIVES: There is no established evidence regarding the influence of the menopausal transition period on non-alcoholic fatty liver disease (NAFLD). The goal of this study was to examine the association between menopausal stages and the prevalence of NAFLD in middle-aged Korean women. METHODS: This study was a cross-sectional analysis of 1559 women aged 44-56 years, who underwent a comprehensive health screening examination in the Kangbuk Samsung Hospital Total Healthcare Centers during 2012 and 2013. Information regarding menopause status was collected using a standardized, self-administered questionnaire. The presence of fatty liver was determined using ultrasonography. Menopausal stages were defined according to the criteria of the Stages of Reproductive Aging Workshop (STRAW+10) as follows: early menopausal transition was defined as a persistent difference in consecutive menstrual cycle length of seven or more days; late menopausal transition was defined as having an interval of amenorrhea of 60 days or more; post-menopause was defined as the absence of menstrual periods for 12 or more months since the last period; pre-menopause was defined as having a regular menstrual cycle and not meeting the above criteria. Odds ratios and 95% confidence intervals for NAFLD were estimated by menopausal stages. RESULTS: Of the 1559 women, 334 had NAFLD. A higher prevalence of NAFLD was observed across menopausal stages (p for trend <0.05). After adjusting for age, center, BMI, smoking status, alcohol intake, physical activity, educational level, parity and age at menarche, the odds ratios (95% CIs) for NAFLD comparing early transition, late transition, and post-menopause to pre-menopause were 1.07 (0.68-1.67), 1.87 (1.23-2.85), and 1.67 (1.01-2.78), respectively. CONCLUSIONS: This study performed in middle-aged Korean women suggests that there is an increased prevalence of NAFLD in the late menopausal transition as well as post-menopausal stages, independent of a variety of potential confounders. The findings of this study suggest that early intervention strategies implemented before women begin to experience the menopausal transition are needed to reduce the risk of NAFLD.

Intraocular pressure and coronary artery calcification in asymptomatic men and women.

OBJECTIVE: We evaluated the relationship between intraocular pressure (IOP) and the risk of coronary artery calcification as a predictable marker of cardiovascular disease (CVD) in a large study of asymptomatic men and women. METHODS: A cross-sectional study was performed in 10 732 asymptomatic men and women without diagnosed CVD or glaucoma. Coronary artery calcium (CAC) was measured by cardiac CT. The IOPs of all participants were measured by experienced nurses with a non-contact tonometer and automatic air puff control. Logistic regression was used to estimate the OR (95% CI) for the presence of CAC (score >0) with IOP quartiles. RESULTS: The prevalence of detectable CAC was 13.7% in men and 4.3% in women. Increasing levels of right IOP were significantly associated with an increased prevalence of CAC. After adjusting for age, sex, smoking, alcohol intake, physical activity, body mass index, educational level, centre, family history of CVD, use of dyslipidaemia medication, diabetes, hypertension, total cholesterol, high density lipoprotein cholesterol and triglycerides, the ORs for CAC score >0, comparing 2-4 quartiles of the right IOP to the lowest quartiles, were 1.32 (95% CI 1.09 to 1.59), 1.20 (95% CI 0.98 to 1.46), and 1.28 (95% CI 1.05 to 1.56), respectively. These associations did not differ by clinically relevant subgroups. CONCLUSIONS: A higher IOP is significantly associated with the presence of CAC regardless of conventional cardiovascular risk factors. The present study provides more insight into understanding the process of subclinical atherosclerosis in CVD and the relationship with a higher IOP as a common pathophysiology.

Impact of body mass index on the risk of colorectal adenoma in a metabolically healthy population.

Metabolically healthy obese (MHO) states exist that seem to be protected from cardiovascular risks. Although obesity is a risk factor for colorectal adenoma (CRA), there has yet to be any study of the risks of CRA in MHO individuals. In this study, we compared CRA prevalence in MHO individuals versus metabolically healthy individuals who were normal in weight. This cross-sectional study involved 18,085 Korean adults (39.1 ± 6.7 years) who had a health checkup including a colonoscopy. High-risk CRA was defined as any adenoma over 1 cm, 3 or more adenomas, adenoma with a villous component, or high-grade dysplasia. Multinomial logistic regression models were used to measure the associations between body mass index (BMI) and the risk of low-risk and high-risk CRA. Low-risk and high-risk CRA were present in 9.3% and 1.4% of the study population, respectively. After adjusting for age, sex, smoking, drinking, exercise, family history of colorectal cancer, education, and use of analgesic and aspirin, compared with normal healthy individuals, the prevalence of low-risk and high-risk CRA was increased in MHO individuals [OR = 1.44; 95% confidence interval (CI), 1.23-1.69 and OR = 1.62; 95% CI, 1.09-2.41, respectively]. In fully adjusted models, the prevalence of low-risk and high-risk CRA was associated with increasing categories of BMI in a dose-response manner (P for trend < 0.001 and 0.01, respectively). Thus, excess body weight, even in the absence of a metabolic unhealthy state, was found to be positively associated with increased presence of CRAs.

Sleep duration and quality in relation to non-alcoholic fatty liver disease in middle-aged workers and their spouses.

BACKGROUND & AIMS: Although accumulated evidence implies that short sleep duration and poor sleep quality may lead to an altered metabolic milieu, potentially triggering the development of non-alcoholic fatty liver disease (NAFLD), no studies have explored this association. This study sought to examine whether short sleep duration or poor sleep quality is associated with NAFLD in the general population. METHODS: We assessed sleep duration and quality using the Pittsburgh Sleep Quality Index in 69,463 middle-aged workers and their spouses and carried out biochemical and anthropometric measurements. The presence of fatty liver was determined using ultrasonographic findings. Logistic regression models were used to evaluate the association of sleep duration and quality with NAFLD, after adjusting for potential confounders. RESULTS: After controlling for the relevant confounding factors (age, alcohol intake, smoking, physical activity, systolic blood pressure, education level, marital status, presence of job, sleep apnea, and loud snoring), the adjusted odds ratio (95% confidence interval) for NAFLD comparing sleep duration ≤5 h to the reference (>7h) was 1.28 (1.13-1.44) in men and 1.71 (1.38-2.13) in women. After further adjustments for BMI, this association was not significant in men (OR: 1.03, 95% CI: 0.90-1.19) but remained significant in women (OR: 1.59, 95% CI: 1.23-2.05). The multivariate-adjusted odds ratio comparing participants with poor sleep quality vs. participants with good sleep quality was 1.10 (95% CI 1.02-1.19) and 1.36 (95% CI 1.17-1.59) in men and women, respectively. CONCLUSIONS: In the middle-aged, general population, short sleep duration, and poor sleep quality were significantly associated with an increased risk of NAFLD. Prospective studies are required to confirm this association.

Serum ferritin levels predict incident non-alcoholic fatty liver disease in healthy Korean men.

Little research has been done to examine the temporal relationship between serum ferritin and the development of nonalcoholic fatty liver disease. The aim of this study was to examine whether serum ferritin levels predict incident fatty liver in non-diabetic men. The study cohort comprised 2410 healthy Korean male who were aged 30 to 59years old with no evidence of ultrasonographically detectable fatty liver (USFL) at baseline. Alcohol intake was assessed with a self-reported questionnaire. At each visit, biochemical and anthropometric measurements and abdominal ultrasonography were done. Cox proportional hazard models were used to calculate the adjusted hazard ratios in separate models for USFL. During 7545.9 person-years of follow-up, 586 participants developed USFL. The hazard ratio (95% confidence interval) for incident USFL comparing the highest quartile of serum ferritin level to the lowest quartile was 1.54 (1.21-1.94) after adjusting for age, body mass index, smoking, alcohol intake, and exercise. That association remained significant after further adjustment for cardiovascular risk factors and in time-dependent models. The association between serum ferritin and incident USFL was still significant in the non-overweight group or the no current smoker group. Serum ferritin level was an independent risk factor of incident fatty liver detected by ultrasonography even in non-obese, healthy Korean men. Increased serum ferritin levels appear to be an early predictor for incident fatty liver.

Changes of body weight and inflammatory markers after 12-week intervention trial: results of a double-blind, placebo-control pilot study.

PURPOSE: Low grade inflammation is a well-known characteristic in obese subjects. We investigated body weight changes and inflammatory markers after 12-week intervention trial. MATERIALS AND METHODS: Twenty-six obese subjects were enrolled and 19 (13 men and 6 women) completed the study. Sibutramine is an FDA-approved drug for body weight control; therefore, we chose this drug as the standard treatment medication in this study. Patients were randomly allocated to receive an anti-inflammatory agent (Diacerein treatment group; n = 12) or placebo (n = 7) for 12 weeks. Anthropometry, body proportion by dual-energy X-ray absorptiometry, and metabolic parameters at the beginning and end of study were measured and compared. RESULTS: The treatment group had a tendency towards more reduction in anthropometry as compared to the placebo group, in body weight reduction (-7.0 kg vs. -4.6 kg), body mass index (-2.51 kg/m² vs. -1.59 kg/m²), and waist circumference (-7.3 cm vs. -4.4 cm). These reductions were not statistically significant. Changes in levels of high-sensitivity C-reactive protein and adiponectin in the treatment group were more favorable than in the placebo group. CONCLUSION: This small pilot study showed no statistical difference for changes in anthropometry, and inflammatory markers between the two groups. Therefore, we could not find any additional effects of Diacerein on weight loss and inflammatory variables in this study.

Ketonuria after fasting may be related to the metabolic superiority.

Obese individuals are less able to oxidize fat than non-obese individuals. Caloric reduction or fasting can detect ketonuria. We investigated the differences of metabolic parameters in the presence of ketonuria after a minimum 8 hr fast in a cross-sectional analysis of 16,523 Koreans (6,512 women and 10,011 men). The relationship between the presence of ketonuria of all subjects and prevalence of obesity, central obesity, metabolic syndrome, and obesity-related metabolic parameters were assessed. The ketonuria group had lower prevalence of obesity, central obesity, and metabolic syndrome than the non-ketonuria group. In addition, all metabolic parameters (including body weight, waist circumference, blood glucose, high-density lipoprotein, triglyceride, blood pressure, and insulin) were favorable in the ketonuria group than in the non-ketonuria group, even after adjustment for age, tobacco use, and alcohol consumption. The odds ratios of having obesity (odds ratio [OR]=1.427 in women, OR=1.582 in men, P<0.05), central obesity (OR=1.675 in women, OR=1.889 in men, P<0.05), and metabolic syndrome (OR=3.505 in women, OR=1.356 in men, P<0.05) were increased in the non-ketonuria group compared to the ketonuria group. The presence of ketonuria after at least an 8 hr fast may be indicative of metabolic superiority.