Explaining the decline in coronary heart disease mortality rates in Japan: Contributions of changes in risk factors and evidence-based treatments between 1980 and 2012

Background We aimed to quantify contributions of changes in risks and uptake of evidence-based treatment to coronary heart disease (CHD) mortality trends in Japan between 1980 and 2012. Methods We conducted a modelling study for the general population of Japan aged 35 to 84 years using the validated IMPACT model incorporating data sources like Vital Statistics. The main outcome was difference in the number of observed and expected CHD deaths in 2012. Results From 1980 to 2012, age-adjusted CHD mortality rates in Japan fell by 61%, resulting in 75,700 fewer CHD deaths in 2012 than if the age and sex-specific mortality rates had remained unchanged. Approximately 56% (95% uncertainty interval [UI]: 54–59%) of the CHD mortality decrease, corresponding to 42,300 (40,900–44,700) fewer CHD deaths, was attributable to medical and surgical treatments. Approximately 35% (28–41%) of the mortality fall corresponding to 26,300 (21,200–31,000) fewer CHD deaths, was attributable to risk factor changes in the population, 24% (20–29%) corresponding to 18,400 (15,100–21,900) fewer and 11% (8–14%) corresponding to 8400 (60,500–10,600) fewer from decreased systolic blood pressure (8.87 mm Hg) and smoking prevalence (14.0%). However, increased levels of cholesterol (0.28 mmol/L), body mass index (BMI) (0.68 kg/m2), and diabetes prevalence (1.6%) attenuated the decrease in mortality by 2% (1–3%), 3% (2–3%), and 4% (1–6%), respectively. Conclusions Japan should continue their control policies for blood pressure and tobacco, and build a strategy to control BMI, diabetes, and cholesterol levels to prevent further CHD deaths

NEUROPSYCHOLOGICAL ASSESSMENT OF COMMUNITY-DWELLING OLDER ADULTS IN ALMATY, KAZAKHSTAN

Cognitive impairment in older adults is a major public concern for Kazakhstan’s aging population. We aimed to (1) administer a neuropsychological test battery (NTB) in domains relevant to aging-associated cognitive impairment in a sample of adults aged 60+ without dementia in Almaty, Kazakhstan; (2) investigate the associations between demographic factors and test performance; and (3) provide information on the distribution of NTB scores as preliminary local normative data relevant for this population. A cross-sectional evaluation of 276 participants aged 60+ in Almaty, Kazakhstan, was conducted using cognitive instruments including tests of memory, attention, language, executive functions, visuospatial abilities, and processing speed. Multiple linear regression analyses were used to examine the association of demographic factors with neuropsychological test performance. The results from the regression analysis showed that those who are younger, have more years of education, are women, and are of Russian ethnicity had significantly better performance. The current study illustrated (1) the feasibility of administering the NTB to older adults in the general population in Kazakhstan; (2) the preliminary local normative neuropsychological measures; and (3) their independent associations with age, education, gender, and ethnicity. The findings are a platform for future research on dementia and cognitive impairment in older adults in Kazakhstan

A cross-sectional association of obesity with coronary calcium among Japanese, Koreans, Japanese-Americans, and US-Whites

[Aims] Conflicting evidence exists regarding whether obesity is independently associated with coronary artery calcium (CAC), a measure of coronary atherosclerosis. We examined an independent association of obesity with prevalent CAC among samples of multi-ethnic groups whose background populations have varying levels of obesity and coronary heart disease (CHD). [Methods and results] We analysed a population-based sample of 1212 men, aged 40–49 years free of clinical cardiovascular disease recruited in 2002–06; 310 Japanese in Japan (JJ), 294 Koreans in South Korea (KN), 300 Japanese Americans (JA), and 308 Whites in the USA (UW). We defined prevalent CAC as an Agatston score of ≥10. Prevalent CAC was calculated by tertile of the body mass index (BMI) in each ethnic group and was plotted against the corresponding median of tertile BMI. Additionally, logistic regression was conducted to examine whether an association of the BMI was independent of conventional risk factors. The median BMI and crude prevalence of CAC for JJ, KN, JA, and UW were 23.4, 24.4, 27.4, and 27.1 (kg/m2); 12, 11, 32, and 26 (%), respectively. Despite the absolute difference in levels of BMI and CAC across groups, higher BMI was generally associated with higher prevalent CAC in each group. After adjusting for age, smoking, alcohol, hypertension, lipids, and diabetes mellitus, the BMI was positively and independently associated with prevalent CAC in JJ, KN, UW, but not in JA. [Conclusion] In this multi-ethnic study, obesity was independently associated with subclinical stage of coronary atherosclerosis among men aged 40–49 years regardless of the BMI level

Long-chain n-3 polyunsaturated fatty acids intake and cardiovascular disease mortality risk in Japanese: a 24-year follow-up of NIPPON DATA80

Background:Dietary intake of long-chain n-3 PUFA (LCn3FA) among Japanese is generally higher than that in Western populations. However, little is known whether an inverse association of LCn3FA with cardiovascular disease (CVD) risk exists in a population with higher LCn3FA intake.Objective:To investigate the association between LCn3FA intake and the long-term risk of CVDs in a Japanese general population.Methods:We followed-up a total of 9190 individuals (56.2% women, mean age 50.0 years) randomly selected from 300 areas across Japan and free from CVDs at baseline. Dietary LCn3FA intake was estimated using household weighed food records. Cox models were used to calculate multivariate-adjusted hazard ratios (HR) and confidence intervals (CI) according to sex specific quartiles of LCn3FA intake.Results:During 24-year follow-up (192,897 person-years), 879 cardiovascular deaths were observed. The median daily intake of LCn3FA was 0.37% kcal (0.86 g/day). Adjusted HR for CVD mortality was lower in the highest quartile of LCn3FA intake (HR 0.80; 95% CI 0.66-0.96) compared with the lowest quartile, and the trend was statistically significant (P = 0.038). The similar but statistically non-significant trends were observed for coronary heart disease death and stroke death. In analyses by age groups, the inverse associations of LCn3FA intake with the risk of total CVD death and stroke death were significant in younger individuals (30-59 years at baseline).Conclusion:LCn3FA intake was inversely and independently associated the long-term risk of total CVD mortality in a representative sample of Japanese with high LCn3FA intake

Immunohistochemical Localization of REG Ia Protein in Salivary Gland Tumors

The regenerating gene( Reg) Ia protein has a trophic effect on gastric epithelial cells, and its overexpressionis reported in gastrointestinal cancers. The salivary gland is a component of the digestive system, andtherefore, REG Ia protein may play some role in the pathophysiology of salivary gland tumors. In the presentstudy, we determined the immunohistochemical localization of REG Ia protein in salivary gland tumorsand moreover investigated its relationship to clinicopathological features. Twenty-eight patients with salivarygland tumor were enrolled. The specimens resected by surgery from those patients were examinedusing immunohistochemistry for REG Ia protein and Ki67. Five of the 16 pleomorphic adenomas (31.3%)were positive for REG Ia protein. Regarding salivary gland carcinomas, four of five mucoepidermoid carcinomas(80%), three of five adenoid cystic carcinomas (60%), one of two polymorphous low-grade adenocarcinomas(50%) were also positive for REG Ia protein. However, no relationships were found betweenREG Ia protein expression and clinicopathological features. Regarding the Ki67 expression, strong signalwas observed in the tumor cells of patients with salivary gland adenoma as well as carcinoma. REG Ia proteinis expressed not only in adenocarcinoma but also precancerous adenoma cells proliferating actively,suggesting that REG Ia protein may play a role at least in part in the development of salivary gland tumors

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target