Sex differences in medicine are still in the midst of development; however, one of the areas that recognizes its importance and continues to lead the advancement of evidence is preventive cardiology. ...Postmenopausal women have a worse prognosis for acute coronary syndrome (ACS) than age-matched men, accounting for the majority of patients after the age of 75. Diabetes mellitus (DM) and smoking have a larger impact on cardiovascular disease (CVD)-related mortality in women than in men, which is widely recognized and utilized in clinical practice. Given that the first women-specific guideline for CVD prevention was published by the American Heart Association in 1999, it has been continuously updated, with the most recent being the 2020 update. It provides evidence on female-specific risk factors, such as preterm birth, hypertensive disorder of pregnancy, gestational DM and other pregnancy-associated conditions, as well as hormonal factors, such as premature menopause.
Metabolomics has developed as a powerful tool for investigating the complex pathophysiology underlying atherosclerosis and cardiovascular disease. Many epidemiological studies have applied this ...technique to accurately and comprehensively assess the effects of environmental factors on health outcomes, which used to be a perpetual challenge. Metabolites are defined as small molecules which are intermediate products of metabolic reactions catalyzed by numerous enzymes occurring within cells. Consequent to both genetic variation and environment, they allow us to explore the gene–environment interactions and to gain a better understanding of multifactorial diseases like cardiovascular disease. This review article highlights the findings of well-known prospective cohort studies around the world that have utilized metabolomics for a wide range of purposes, including biomarker discovery, improving cardiovascular risk prediction and early disease diagnosis, and exploring detailed mechanisms of disease onset and progression. However, technical challenges still exist in applying them clinically. One limitation is due to various analytical platforms that are used based on the judgment of each study; comparative assessments among different platforms need to be conducted in order to correctly interpret and validate each data externally. Secondly, metabolite levels obtained in most high-throughput metabolomics profiling studies are often semiquantitative rather than fully quantitative concentrations, which makes it difficult to compare and combine results among different studies and to determine the levels for practical use. In 2014, the Consortium of Metabolomics Studies was developed, which is expected to take the lead in overcoming these issues.
Background: Although self-reported questionnaires are widely employed in epidemiologic studies, their validity has not been sufficiently assessed. The aim of this study was to evaluate the validity ...of a self-reported questionnaire on medication use by comparison with health insurance claims and to identify individual determinants of discordance in the Tsuruoka Metabolomics Cohort Study.Methods: Participants were 2,472 community-dwellers aged 37 to 78 years from the Tsuruoka Metabolomics Cohort Study. Information on lifestyle and medications was collected through a questionnaire. Sensitivity and specificity were determined using health insurance claims from November 2014 to March 2016, which were used as a standard. Potential determinants of discordance were assessed using multivariable logistic regression.Results: The self-reported questionnaire on medication use showed high validity. Sensitivity and specificity were 0.95 (95% CI, 0.93–0.96) and 0.97 (95% CI, 0.96–0.98) for antihypertensive medications, 0.94 (95% CI, 0.91–0.97) and 0.98 (95% CI, 0.98–0.99) for diabetes medications, and 0.84 (95% CI, 0.82–0.87) and 0.98 (95% CI, 0.97–0.99) for dyslipidemia medications, respectively. Males without high education and those who currently smoke cigarettes were found to be associated with discordant reporting which affected sensitivity, especially those with medication use for dyslipidemia.Conclusions: In this population-based cohort study, we found that the self-reported questionnaire on medication use was a valid measure to capture regular medication users. Sensitivity for dyslipidemia medications was lower than those for the other medications. Type of medication, sex, education years, and smoking status influenced discordance, which affected sensitivity in self-reporting.
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FFLJ, NUK, ODKLJ, UL, UM, UPUK
Endometrial cancer is increasing worldwide and the number of patients with this disease is likely to continue to grow, including younger patients. Many endometrial cancers show estrogen‐dependent ...proliferation, but the carcinogenic mechanisms are unknown or not completely explained beyond mutations of single oncogenes and tumor suppressor genes. Possible carcinogenic mechanisms include imbalance between endometrial proliferation by unopposed estrogen and the mismatch repair (MMR) system; hypermethylation of the MMR gene hMLH1; mutation of PTEN, β‐catenin and K‐ras genes in type I endometrial cancer and of HER‐2/neu and p53 genes in type II endometrial cancer; hypermethylation of SPRY2, RASSF1A, RSK4, CHFR and CDH1; and methylation of tumor suppressor microRNAs, including miR‐124, miR‐126, miR‐137, miR‐491, miR‐129‐2 and miR‐152. Thus, it is likely that the carcinogenic mechanisms of endometrial cancer involve both genetic and epigenetic changes. Mutations and methylation of MMR genes induce various oncogenic changes that cause carcinogenesis, and both MMR mutation in germ cells and methylation patterns may be inherited over generations and cause familial tumorigenesis. Determination of the detailed carcinogenic mechanisms will be useful for prevention and diagnosis of endometrial cancer, risk assessment, and development of new treatment strategies targeting MMR genes.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Background: Progress in reducing the global low birthweight (LBW) has been insufficient. Although the focus has been on preventing preterm birth, evidence regarding LBW in term births is limited. ...Despite its low preterm birth prevalence, Japan has a higher LBW proportion than other developed countries. This study aimed to examine the prevalence of LBW in term singleton births and its associated factors using a national database.Methods: We retrospectively analyzed the data of neonates registered in the Japan Society of Obstetrics and Gynecology Successive Pregnancy Birth Registry System who were born 2013–2017. Exclusion criteria included stillbirths, delivery after 42 gestational weeks, and missing data. Logistic regression analyses were performed to investigate the maternal and perinatal factors associated with LBW in term singletons using the data of 715,414 singleton neonates.Results: The overall prevalence of LBW was 18.3%, and 35.7% of LBWs originated from singleton term pregnancies. Multiple logistic regression analyses indicated that both modifiable and non-modifiable factors were independently associated with LBW in term neonates. The modifiable maternal factors included pre-pregnancy underweight, inadequate gestational weight gain, and smoking during pregnancy, while the non-modifiable factors included younger maternal age, nulliparity, hypertensive disorders of pregnancy, cesarean section delivery, female offspring, and congenital anomalies.Conclusion: Using the Japanese pregnancy birth registry data, more than one-third of LBWs were found to originate from singleton term pregnancies. Both modifiable and non-modifiable factors were independently associated with LBW in term neonates. Prevention strategies on modifiable risk factor control will be effective in reducing LBW worldwide.
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FFLJ, NUK, ODKLJ, UL, UM, UPUK
Menopausal disorders include obscure symptomatology that greatly reduce work productivity among female workers. Quantifying the impact of menopause-related symptoms on work productivity is very ...difficult because no such guidelines exist to date. We aimed to develop a scale of overall health status for working women in the perimenopausal period.
In September, 2021, we conducted an Internet web survey which included 3,645 female workers aged 45-56 years in perimenopausal period. We asked the participants to answer 76 items relevant to menopausal symptomatology, that were created for this study and performed exploratory and confirmatory factor analyses for the scale development. Cronbach's alpha, receiver operating characteristic analysis, and logistic regression analysis were used to verify the developed scale.
Approximately 85% participants did not have menstruation or disrupted cycles. Explanatory factor analysis using the maximum likelihood method and Promax rotation identified 21 items with a four-factor structure: psychological symptoms (8 items, α = 0.96); physiological symptoms (6 items, alpha = 0.87); sleep difficulty (4 items, alpha = 0.92); human relationship (3 items, alpha = 0.92). Confirmatory factor analyses found excellent model fit for the four-factor model (RMSR = 0.079; TLI = 0.929; CFI = 0.938). Criterion and concurrent validity were confirmed with high correlation coefficients between each of the four factors, previously validated menopausal symptom questionnaire, and Copenhagen Burnout Inventory scales, respectively (all ps < 0.0001). The developed scale was able to predict absenteeism with 78% sensitivity, 58% specificity, and an AUC of 0.727 (95%CI: 0.696-0.757). Higher scores of each factor as well as total score of the scale were more likely to be associated with work absence experience due to menopause-related symptoms even after adjusting for Copenhagen Burnout Inventory subscales (all ps < 0.0001).
We found that the developed scale has high validity and reliability and could be a significant indicator of absenteeism for working women in perimenopausal period.
Aim: This study investigated the relationship between birth physique and cardiovascular risk factors in Japanese urban residents aged 40 years and more. Methods: A self-administered questionnaire on ...birth physique was performed among 624 individuals (165 men and 459 women) who participated in the KOBE study. We examined whether self-reported birth physique and available recorded birth weights matched for 72 participants. Then the association between birth physique and risk factors for all participants was examined by gender. Body size at birth in the questionnaire (large, medium, small) was set as an exposure and laboratory values from the baseline survey (2010-2011) were used as outcomes. Results: Mean (standard deviation) recorded birth weight of 72 participants was 3665 (318), 3051 (300), and 2653 (199) g, in the large, medium, and small group, respectively. In the analysis for all participants, odds ratio for having both hypertension and impaired glucose tolerance were significantly higher in the small versus large birth weight group, which was 7.42 (95% CI 1.75–31.50) for men and 4.44 (95% CI 1.14–17.30) for women after adjusting for age, body mass index, smoking/alcohol/exercise habits, and menstrual status in women. Similar results were observed in participants with recorded birth weight. Conclusions: The present study indicates that individuals with small physique at birth might be at higher risk for hypertension and impaired glucose tolerance in middle age compared to those with large birth weight.
Currently, large-scale cohort studies for metabolome analysis have been launched globally. However, only a few studies have evaluated the reliability of urinary metabolome analysis. This study aimed ...to establish the reliability of urinary metabolomic profiling in cohort studies. In the Tsuruoka Metabolomics Cohort Study, 123 charged metabolites were identified and routinely quantified using capillary electrophoresis-mass spectrometry (CE-MS). We evaluated approximately 750 quality control (QC) samples and 6,720 participants' spot urine samples. We calculated inter- and intra-batch coefficients of variation in the QC and participant samples and technical intraclass correlation coefficients (ICC). A correlation of metabolite concentrations between spot and 24-h urine samples obtained from 32 sub-cohort participants was also evaluated. The coefficient of variation (CV) was less than 20% for 87 metabolites (70.7%) and 20-30% for 19 metabolites (15.4%) in the QC samples. There was less than 20% inter-batch CV for 106 metabolites (86.2%). Most urinary metabolites would have reliability for measurement. The 96 metabolites (78.0%) was above 0.75 for the estimated ICC, and those might be useful for epidemiological analysis. Among individuals, the Pearson correlation coefficient of 24-h and spot urine was more than 70% for 59 of the 99 metabolites. These results show that the profiling of charged metabolites using CE-MS in morning spot human urine is suitable for epidemiological metabolomics studies.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK