Bo-Kyoung Kim

Age at menarche and non-alcoholic fatty liver disease

BACKGROUND & AIMS The goal of this study was to examine the association between age at menarche and non-alcoholic fatty liver disease (NAFLD) in Korean women and to explore whether any observed associations were mediated by adult adiposity. METHODS A cross-sectional study was performed for 95,183 Korean women, aged 30 or older, who underwent a regular health screening examination between March 2011 and April 2013. Information regarding age at menarche was collected using standardized, self-administered questionnaires. The presence of fatty liver was determined using ultrasonographic findings. Poisson regression models with robust variance were used to evaluate the association between age at menarche and NAFLD. RESULTS Of the 76,415 women evaluated in this study, 9601 had NAFLD. Age at menarche was inversely associated with the prevalence of NAFLD. In a multivariable-adjusted model, the prevalence ratios (95% CIs) for NAFLD comparing menarche at <12, 12, 14, 15, and 16-18 years to menarche at 13 years were 1.31 (1.18-1.45), 1.05 (0.97-1.13), 0.93 (0.87-0.99), 0.87 (0.82-0.93), and 0.78 (0.73-0.84), respectively (p for trend <0.001). Adjusting for adult BMI or percent fat mass (%) substantially reduced these associations; however, they remained statistically significant. The association between age at menarche and NAFLD was modified by age. CONCLUSIONS We identified an inverse association between age at menarche and NAFLD in a large sample of middle-aged women. This association was partially mediated by adiposity. The findings of this study suggest that obesity prevention strategies are needed in women who undergo early menarche to reduce the risk of NAFLD.

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.

Mammographic density and risk of breast cancer in Korean women.

We carried out this study to evaluate the association between mammographic density adjusted for age and BMI and early-onset breast cancer in Asian women. We recruited 213 Korean patients with breast cancer (45% diagnosed before the age of 50 years) and 630 controls matched for age, menopausal status, and examination date. The percentage and absolute size of dense areas on digital mammograms were measured using a computer-assisted thresholding technique (Cumulus). We carried out an analysis using the conditional logistic regression model with adjustment for covariates. An increase by 1 SD in age and BMI-adjusted absolute dense area and percentage dense area was associated with a 1.15-fold (95% confidence interval: 1.03, 1.29) and 1.20-fold (95% confidence interval: 1.06, 1.37) increased risk of breast cancer, respectively. These associations were stronger for premenopausal disease (P=0.07 and 0.01, respectively) and for disease diagnosed before age 50 (P=0.07 and 0.02, respectively) than for postmenopausal disease (P=0.16 and 0.23, respectively) or later onset disease (P=0.10 and 0.10, respectively). There was no difference in the associations with premenopausal versus postmenopausal and early-onset versus late-onset disease. After adjusting for age and BMI, both a greater absolute dense area and a greater percentage dense area were associated with an increased risk of breast cancer, particularly at a young age.

Factors Associated with Persistent Smoking after the Diagnosis of Cardiovascular Disease

Background Although cigarette smoking is a major modifiable risk factor for the occurrence of primary and secondary cardiovascular disease (CVD), not all survivors from CVD attacks can successfully stop smoking. However, little is known about the factors associated with the change in smoking behavior after CVD attack. Methods Study subjects included 16,807 participants (≥19 years) in the fourth Korean National Health and Nutrition Examination Surveys. From them, we selected 180 persons who had previous CVD diagnosis (angina pectoris, myocardial infarction, or stroke) and were smoking at the time of CVD diagnosis. Then, we categorized the 180 persons into two groups according to change in smoking status after the CVD: quitter and non-quitter. Logistic regression analysis was done to evaluate multivariable-adjusted association. Results Even after CVD diagnosis, 63.60% continued to smoke. Fully-adjusted analysis revealed that regular drinking (odds ratio [OR], 4.44) and presence of smokers among family members (OR, 5.86) were significantly (P < 0.05) associated with greater risk of persistent smoking, whereas lower education level (OR, 0.20), larger amount of smoking (OR, 0.95), longer time since diagnosis (OR, 0.88), and diabetes (OR, 0.36) were significantly (P < 0.05) associated with decreased risk of persistent smoking after CVD. Conclusion A great proportion of CVD patients tended to continue smoking in the Korean population. In order to reduce smoking rates among CVD patients further, more aggressive efforts towards smoking cessation should be continuously made with consideration of individual socioeconomic, behavioral, and clinical characteristics of CVD patients.

Menopausal stages and serum lipid and lipoprotein abnormalities in middle-aged women

OBJECTIVES Whether menopausal stage is associated with abnormalities in serum lipid and lipoprotein profiles remains unclear; studies have been conducted mostly in Western populations. This study aimed to examine the prevalence of lipid and lipoprotein abnormalities by recently updated menopausal stages in middle-aged women. STUDY DESIGN This study was cross-sectional analysis of 1553 women aged 44-56 years, who underwent a comprehensive health screening examination in the Kangbuk Samsung Hospital Total Healthcare Centers, Korea, during 2012-2013. Lipid and lipoprotein profiles including total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), lipoprotein (a) (Lp(a)), apolipoprotein A1 (Apo A1), apolipoprotein B (Apo B) were assessed. Prevalence ratios and 95% confidence intervals for lipid and lipoprotein abnormalities were estimated by menopausal stages as defined by the 2011 Stages of Reproductive Aging Workshop+10 criteria. RESULTS Increased prevalence of lipid and lipoprotein abnormalities were observed across menopausal stages. The increased prevalence of high non-HDL-C was associated with the late menopausal transition and post-menopausal stages and was more pronounced in women with body mass index (BMI) <23 kg/m(2) than in those with BMI ≥23 kg/m(2) (P for interaction=0.006). Similarly, there was an interaction between BMI and menopausal stages in relation to high Apo B (P for interaction=0.05) and high Apo B/Apo A1 ratio (P for interaction=0.06). CONCLUSIONS Our findings extend previous results and suggest that the increased prevalence of lipid and lipoprotein abnormalities was associated not only with the post-menopausal stage but also late menopausal transition period.

Age at Menarche and Gallstone Disease in Middle-Aged Women.

The goal of this study was to explore the association between age at menarche and gallstone disease (GSD) in Korean women and to determine whether any of the observed associations were mediated by adult adiposity. A cross-sectional study was performed on 83 275 Korean women, aged 30 years or older, who underwent a health checkup examination between March 2011 and April 2013. Information regarding age at menarche was collected using standardized, self-administered questionnaires. Gallstone disease was defined as either having gallstones or having had a cholecystectomy based on ultrasound. Logistic regression models were used to evaluate the association between age at menarche and GSD. Of the 83 275 women evaluated in this study, 3341 had GSD. Age at menarche was negatively associated with the prevalence of GSD. In a multivariable-adjusted model adjusting for potential confounders including reproductive factors and body weight at age 20, the odds ratios (95% confidence intervals) for GSD comparing menarche at <12, 12, 14, 15, and 16 to 18 years to menarche at 13 years were 1.46 (1.23-1.75), 1.19 (1.04-1.35), 0.97 (0.87-1.09), 0.92 (0.82-1.03), and 0.89 (0.78-1.02), respectively (P for trend <.001). Adjusting for adult body mass index or percentage fat mass (%) partially reduced these associations; however, they remained statistically significant. Early menarche was associated with increasing prevalence of GSD in a large sample of middle-aged women. The findings of this study extend the range of adverse health outcomes associated with early menarche and suggest that obesity prevention strategies could be useful for reducing the risk of GSD in women who experience early menarche.

[296] DOWN-REGULATION OF SURVIVIN IN GROWTH INHIBITION OF HEPATOMA CELLS INDUCED BY SELECTIVE CYCLOOXYGENASE-2 INHIBITOR

Background/Aims: Cyclooxygenase-2 (COX-2) inhibitors reportedly inhibit the growth of hepatocellular carcinoma (HCC) via caspase-dependent or caspase-independent apoptosis, which is due to COX-2 being associated with hepatocarcinogenesis. Survivin is highly expressed in most human cancers, but the mechanism regulating survivin expression remains unclear. We investigated the regulatory expression of survivin in selective-COX-2-inhibitor-induced growth inhibition of hepatoma cells. Methods: After treatment with NS-398 (a selective COX-2 inhibitor) at various concentrations (10, 50, 100, 150, and 200 µM), the growth inhibition of Hep3B hepatoma cells was assessed by an MTT cell-viability assay, DNA fragmentation gel analysis, and flow cytometry. The expression of survivin transcript was analyzed by reverse-transcription polymerase chain reactions. Results: NS-398 inhibited the growth of hepatoma cells by an amount dependent on the concentration and the time since treatment. Apoptotic DNA ladder and flow-cytometry shifting to the sub-G1 phase were revealed in NS-398-induced growth inhibition of hepatoma cells. NS-398 suppressed the expression of the survivin gene in a concentration- and time-dependent manner. Conclusions: Survivin was down-regulated in the growth inhibition of hepatoma cells induced by a selective COX-2 inhibitor, NS-398, in a concentration- and time-dependent manner. These results suggest the therapeutic inhibition of COX-2 via suppression of survivin in HCC. (Korean J Hepatol 2008;14:351-359)