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Although diabetes and cardiovascular disease account for substantial disease prevalence among adults in the United States, their prevalence among racial and ethnic subgroups is inadequately characterized. To fill this gap, CDC described the prevalence of diagnosed cardiometabolic diseases among U.S. adults, by disaggregated racial and ethnic subgroups, among 3,970,904 respondents to the Behavioral Risk Factor Surveillance System during 2013-2021. Prevalence of each disease (diabetes, myocardial infarction, angina or coronary heart disease, and stroke), stratified by race and ethnicity, was based on self-reported diagnosis by a health care professional, adjusting for age, sex, and survey year. Overall, mean respondent age was 47.5 years, and 51.4% of respondents were women. Prevalence of cardiometabolic diseases among disaggregated race and ethnicity subgroups varied considerably. For example, diabetes prevalence within the aggregated non-Hispanic Asian category (11.5%) ranged from 6.3% in the Vietnamese subgroup to 15.2% in the Filipino subgroup. Prevalence of angina or coronary heart disease for the aggregated Hispanic or Latino category (3.8%) ranged from 3.1% in the Cuban subgroup to 6.3% in the Puerto Rican subgroup. Disaggregation of cardiometabolic disease prevalence data by race and ethnicity identified health disparities among subgroups that can be used to better help guide prevention programs and develop culturally relevant interventions., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Purpose: Whether acute cardiovascular diseases (CVDs), such as acute heart failure (AHF), acute myocardial infarction (AMI), and acute aortic dissection (AAD), have distinct seasonal variations in the number of hospitalizations and in-hospital mortality was investigated using a nationwide database in Japan., Methods: The hospitalized patients with AHF, AMI, and AAD between April 2012 and March 2020 were identified. Multilevel mixed-effects logistic regression was conducted and adjusted odds ratio (aOR) was calculated. Also, the Poisson regression model was conducted to calculate the peak-to-trough ratio (PTTR) with peak month., Results: Patients identified were as follows: 752,434 AHF patients (median age, 82 years; male, 52.2%), 346,110 AMI patients (median age, 71 years; male, 72.2%), and 118,538 AAD patients (median age, 72 years; male, 58.0%). The monthly proportion of hospitalized patients was the highest in winter and the lowest in summer in all three diseases. Based on aOR, 14-day mortality was the lowest in spring for AHF, summer for AMI, and spring for AAD. Furthermore, the PTTRs with peak month were 1.24 for AHF in February, 1.34 for AMI in January, and 1.33 for AAD in February., Conclusions: A clear seasonal pattern was observed in the number of hospitalizations and in-hospital mortality of all acute CVDs, independent of confounders., Competing Interests: Declaration of Competing Interest All authors have no competing interests to declare regarding of the manuscript entitled “Impact of seasonal variation on admission and in-hospital mortality of acute cardiovascular diseases: a contemporary nationwide database study” which we request you to consider for publication as an Original Article in the Annals of Epidemiology., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: We aimed to validate a claims-based diagnostic algorithm to identify hospitalized patients with acute major cardiovascular diseases (CVDs) from health insurance claims in Japan., Methods and results: This retrospective multicenter validation study was conducted at 4 institutes, including Japanese Circulation Society-certified and uncertified hospitals in Japan. Data on patients with CVDs in departmental lists or with International Classification of Diseases, 10th Revision (ICD-10) codes for CVDs hospitalized between April 2018 and March 2019 were extracted. We examined the sensitivity and positive predictive value of a diagnostic algorithm using ICD-10 codes, medical examinations, and treatments for acute coronary syndrome (ACS), acute heart failure (HF), and acute aortic disease (AAD). We identified 409 patients with ACS (mean age 70.6 years; 24.7% female), 615 patients with acute HF (mean age 77.3 years; 46.2% female), and 122 patients with AAD (mean age 73.4 years; 36.1% female). The respective sensitivity and positive predictive value for the algorithm were 0.86 (95% confidence interval [CI] 0.82-0.89) and 0.95 (95% CI 0.92-0.97) for ACS; 0.74 (95% CI 0.70-0.77) and 0.79 (95% CI 0.76-0.83) for acute HF; and 0.86 (95% CI 0.79-0.92) and 0.83 (95% CI 0.76-0.89) for AAD., Conclusions: The validity of the diagnostic algorithm for Japanese claims data was acceptable. Our results serve as a foundation for future studies on CVDs using nationwide administrative data.

The relation between chronic kidney disease (CKD) and cardiovascular disease (CVD) in the general population is well elucidated. In patients with CKD, anemia is associated with adverse outcomes. However, the effects of CKD and anemia on CVD in the general population remains poorly explored, especially in Asian populations. This study aimed to investigate the effect of CKD and/or anemia on CVD mortality in a long-term cohort study involving Japanese community dwellers. We assessed 7,339 participants (aged ≥30 years) with no CVD history. These participants were divided into 4 categories according to their CKD (estimated glomerular filtration rate <60 or urine protein >1+ by dipstick qualitative test) and/or anemia (hemoglobin: <13 g/100 ml [men], <12 g/100 ml [women]) statuses. For each category, we calculated the hazard ratios (HRs) of CVD mortality by using the Cox proportional hazards model after adjusting for age, body mass index, hypertension, diabetes, dyslipidemia, smoking, and alcohol drinking. Within 25 years of follow-up, 637 participants died because of CVD. The HRs of CVD in patients with CKD only, anemia only, and both were 1.27, 1.59, and 2.60 (95% confidence intervals [CI] 1.06 to 1.53, 1.34 to 1.90, and 1.80 to 3.76) in men and 1.42, 1.08, and 2.00 (95% CI 1.19 to 1.69, 0.99 to 1.18, and 1.54 to 2.60) in women, respectively. In conclusion, CKD with anemia is associated with an increased risk for CVD mortality in a general population in Japan., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Body mass index (BMI) distribution and its impact on cardiovascular disease (CVD) vary between Asian and western populations. The study aimed to reveal time-related trends in the prevalence of obesity and underweight and safe ranges of BMI in Japanese patients with CVD. We analyzed 5,020,464 records from the national Japanese Registry of All Cardiac and Vascular Diseases-Diagnosis Procedure Combination dataset over time (2012-2019) and evaluated BMI trends and the impact on in-hospital mortality for six acute CVDs: acute heart failure (AHF), acute myocardial infarction (AMI), acute aortic dissection (AAD), ischemic stroke (IS), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH). Patients were categorized into five groups using the WHO Asian-BMI criteria: underweight (< 18.5 kg/m 2 ), normal (18.5-22.9 kg/m 2 ), overweight at risk (23.0-24.9 kg/m 2 ), obese I (25.0-29.9 kg/m 2 ), and obese II (≥ 30.0 kg/m 2 ). Age was significantly and inversely related to high BMI for all diseases (P < 0.001). The proportion of BMI categories significantly altered over time; annual BMI trends showed a significant and gradual increase, except AAD. In adjusted mixed models, underweight was significantly associated with a high risk of in-hospital mortality in all CVD patients (AHF, OR 1.41, 95% CI 1.35-1.48, P < 0.001; AMI, OR 1.27, 95% CI 1.20-1.35, P < 0.001; AAD, OR 1.23, 95% CI 1.16-1.32, P < 0.001; IS, OR 1.45, 95% CI 1.41-1.50, P < 0.001; ICH, OR 1.18, 95% CI 1.13-1.22, P < 0.001; SAH, OR 1.17, 95% CI 1.10-1.26, P < 0.001). Moreover, obese I and II groups were significantly associated with a higher incidence of in-hospital mortality, except AHF and IS. Age was associated with in-hospital mortality for all BMI categories in six CVD patients. BMI increased annually in patients with six types of CVDs. Although underweight BMI was associated with high mortality rates, the impact of obesity on in-hospital mortality differs among CVD types., (© 2022. The Author(s).)

Background: Although many quality indicator (QI) sets have been developed for acute cardiovascular diseases, a comprehensive summary is lacking. In this scoping review we aimed to summarize the available evidence on the QI sets for acute cardiovascular diseases, and assess the QI set development process. We followed the Joanna Briggs Institute framework and the PRISMA extension for scoping reviews., Methods: We conducted a systematic search of MEDLINE, EMBASE, and major international guidelines on QIs for acute major cardiovascular diseases. The study included articles published after 2000., Results: Among the 3112 articles screened, 18 were included in this scoping review. Among the 18 articles included, 12 were on acute coronary syndrome (ACS), five on acute heart failure (AHF), and two on acute aortic dissection (AAD); one article included QIs for both ACS and AHF. Only four of these studies conducted a systematic search with a search strategy. From the 18 articles, 268 QIs containing duplication between articles were identified (191 QIs were for ACS, 57 were for AHF, and 20 were for AAD) and QI measurements varied across articles., Conclusions: This scoping review provides a comprehensive list of QIs for acute cardiovascular diseases. Our results may be helpful to clinicians and organizations seeking to develop QIs for acute cardiovascular care in the future., (© 2022. The Author(s).)

Introduction: Primary dyslipidemias are inherited disorders in plasma lipoprotein metabolism that lead to serious cardiovascular and other complications. The Japanese Ministry of Health, Labor and Welfare (MHLW) covers medical expenses, under the Research Program on Rare and Intractable Diseases, for homozygous familial hypercholesterolemia (FH), familial chylomicronemia, sitosterolemia, cerebrotendinous xanthomatosis, lecithin:cholesterol acyltransferase deficiency, Tangier disease, and abetalipoproteinemia. Apolipoprotein A1 deficiency, heterozygous FH, and type III hyperlipoproteinemia are covered by the MHLW Pediatric Chronic Disease Program. Heterozygous FH and type III hyperlipoproteinemia are also important for their relatively common prevalence and, accordingly, high impact on Japanese public health by significant contribution to the overall prevalence of cardiovascular diseases. Therefore, a systemic survey of these diseases is mandatory to estimate their actual situation, such as prevalence, clinical manifestations, and prognoses among the Japanese population. The impact of these rare and intractable diseases on cardiovascular and other complications will likely be higher among Japanese people than other ethnicities because the general Japanese population has many cardioprotective aspects. The current study intends to conduct a multicenter registry of these diseases to assess their demographics and clinical features comprehensively., Methods and Analysis: The Prospective Registry Study of Primary Dyslipidemia is a registry-based prospective, observational, multicenter cohort study in Japan, enrolling patients who fulfill the Japanese clinical criteria of the primary dyslipidemias listed above, from 26 participating institutes from August 2015 to March 2023. A total of 1,000 patients will be enrolled in the study and followed for 10 years. Clinical parameters are collected, including physical and laboratory findings, genetic analysis, drugs, lifestyle management, and clinical events, especially cardiovascular events. The primary endpoint of this study is the new onset of cardiovascular disease and acute pancreatitis, and the secondary endpoint is death from any causes., Ethics and Dissemination: This study complies with the Declaration of Helsinki, the Ethical Guidelines for Medical and Health Research Involving Human Subjects, and all other applicable laws and guidelines in Japan. The institutional review boards have approved this study protocol at all participating institutes. The final results are to be published at appropriate international conferences and in peer-reviewed journals.

Cardiovascular and cerebrovascular diseases are frequently interconnected due to underlying pathology involving atherosclerosis and thromboembolism. The aim of this study was to investigate the impact of clinical interactions among cardiovascular and cerebrovascular diseases on patient outcomes using a large-scale nationwide claims-based dataset. Cardiovascular diseases were defined as myocardial infarction, heart failure, atrial fibrillation, and aortic dissection. Cerebrovascular diseases were defined as cerebral infarction, intracerebral hemorrhage, and subarachnoid hemorrhage. This retrospective study included 2,736,986 inpatient records (1,800,255 patients) at 911 hospitals from 2015 to 2016 from Japanese registry of all cardiac and vascular disease-diagnostic procedure combination dataset. Interactions among comorbidities and complications, rehospitalization, and clinical outcomes including in-hospital mortality were investigated. Among hospitalization records that involved cardiovascular disease, 5.9% (32,686 records) had cerebrovascular disease as a comorbidity and 2.1% (11,362 records) included an incident cerebrovascular complication after hospitalization. Cerebrovascular disease as a comorbidity or complication was associated with higher in-hospital mortality than no cerebrovascular disease (adjusted odds ratio (OR) [95% confidence interval]: 1.10 [1.06-1.14], 2.02 [1.91-2.13], respectively). Among 367,904 hospitalization records that involved cerebrovascular disease, 17.7% (63,647 records) had cardiovascular disease listed as comorbidity and 3.3% (11,834 records) as a complication. Only cardiovascular disease as a complication was associated with higher in-hospital mortality (adjusted OR [95% confidence interval]: 1.29 [1.22-1.37]). In addition, in-hospital mortality during rehospitalization due to the other disease was significantly higher than mortality during the hospitalization due to the first disease. In conclusion, substantial associations were observed between cardiovascular and cerebrovascular disease in a large-scale nationwide claims-based dataset; these associations had a significant impact on clinical outcomes. More intensive prevention and management of cardiovascular and cerebrovascular disease might be crucial., Competing Interests: Dr. Iihara reports personal fees and other funding from Megwell, personal fees from Daiichi Sankyo. Co. Ltd., personal fees from Otsuka Pharmaceutical, and grants from Idorsia Pharmaceuticals Japan outside of the submitted work. Dr. Komuro reports grants and personal fees from Daiichi Sankyo Company, Ltd., grants from Sumitomo Dainippon Pharma Co., Ltd., grants and personal fees from Takeda Pharmaceutical Company Ltd., grants from Mitsubishi Tanabe Pharma Corporation, grants from Teijin Pharma Ltd., grants from Idorsia Pharmaceuticals Ltd., grants from Otsuka Pharmaceutical Co., Ltd., grants and personal fees from Bayer Yakuhin, Ltd., grants and personal fees from Ono Pharmaceutical Co., Ltd., grants from Toa Eiyo Ltd., and personal fees from AstraZeneca, and personal fees from Pfizer Japan Inc. outside of the submitted work. Dr. Matoba reports grants and personal fees from Bayer Yakuhin, Ltd., grants from Amgen, personal fees from Merck & Co., Inc., and personal fees from Abbott Vascular outside of the submitted work. Dr. Nishimura reports personal fees from Philips Japan, Ltd., personal fees from Tokyo Electric Power Company, personal fees from Terumo Company, and personal fees from H.U. group holdings outside of the submitted work. Dr. Nakayama reports personal fees from Pfizer Japan Inc, AstraZeneca K.K., Astellas Pharma Inc., Toppan Forms Co., InterSystems Corporation, Fujitsu Research Institute, Nikkei Business Publications, Inc., NIHON KOHDEN Co., FUKUDA DENSHI, Deloitte Tohmatsu Consulting LLC, and PwC Consulting LLC, outside of the submitted work. Dr. Toyoda reports personal fees from Daiichi-Sankyo, personal fees from Bayer Yakuhin, personal fees from Bristol-Myers-Squibb, personal fees from Outsuka Pharmaceutical Company Ltd., personal fees from Novartis Pharma Japan., and personal fees from Abbott Medical Japan Co., Ltd.,outside of the submitted work. Dr. Tsujita reports personal fees from Amgen K.K., grants and personal fees from Bayer Yakuhin, Ltd., grants and personal fees from Daiichi Sankyo Co., Ltd., personal fees from Kowa Pharmaceutical Co. Ltd., personal fees from Novartis Pharma K.K., grants and personal fees from Otsuka Pharmaceutical Co., Ltd., personal fees from Pfizer Japan Inc., grants from AMI Co., Ltd., grants from Bristol-Myers K.K., grants from EA Pharma Co. Ltd., grants from Mochida Pharmaceutical Co., Ltd., grants from Nippon Boehringer Ingelheim, grants from Chugai Pharmaceutical Co., Ltd., grants from Edwards Lifesciences Corporation., grants from Johnson & Johnson K.K., grants from Ono Pharmaceutical Co., Ltd., grants from Takeda Pharmaceutical Co., Ltd., other funding from Abbott Japan Co., Ltd., other funding from Boston Scientific Japan K.K., other funding from Fides-one, Inc., other funding from ITI Co., Ltd., other funding from Kaneka Medix Co., Ltd., other funding from Nipro Corporation, other funding from Terumo Co., Ltd., other funding from Abbott Medical Co., Ltd., other funding from Cardinal Health Japan, other funding from Fides-one, Inc., other funding from Fukuda Denshi Co., Ltd., other funding from Japan Lifeline Co., Ltd., other funding from Medical Appliance Co., Ltd., and other funding from Medtronic Japan Co., Ltd. outside of the submitted work. Dr. Yasuda reports personal fees from Bristol-Meyers, grants and personal fees from Bayer, personal fees from Daiichi-Sankyo, grants and other funding from Takeda Pharmaceutical Company Ltd., grants from NEC, grants from Daiichi-Sankyo, grants and other funding from Abbott, other funding from Terumo Co., Ltd., other funding from Nihon Kohden, other funding from Medtronic, other funding from Japan Lifeline, other funding from Otsuka, other funding from Ono, other funding from Nippon Boehringer Ingelheim, other funding from Kowa, other funding from Zeon, other funding from Shionogi, other funding from Nippon-Shinyaku, other funding from Mochida, and other funding from Tesco outside of the submitted work. Dr. Miyamoto reports personal fees from Tokyo Marine, personal fees from Nichido Fire Insurance Co., Ltd., personal fees from Fujitsu Co., Ltd., personal fees from Softbank Co., Ltd., personal fees from Meiji Yasuda Life Insurance Company., and personal fees from Saraya Co., Ltd. outside of the submitted work. Dr. Ogawa reports personal fees from Towa Pharmaceutical Co., Ltd., personal fees from Bristol-Meyers Squibb Co., Ltd., personal fees from Pfizer Co., Ltd., personal fees from Toa Eiyo Co., Ltd., personal fees from Bayer Yakuhin Co., Ltd., and personal fees from Novartis Pharma Co., Ltd., personal fees from Takeda Pharmaceutical Co., LTD, personal fees from Daiichisankyo Co., Ltd., personal fees from Eisai Co., Ltd., personal fees from Teijin Co., Ltd. personal fees from Behringer Ingelheim Co., Ltd., Abbott Medical Japan Co., Ltd. outside of the submitted work. No other potential conflict of interest relevant to this article was reported. There are no patents, products in development or marketed products associated with this research to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

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.

Background Lifetime risk is an informative estimate for driving lifestyle and behavioral changes especially for young adults. The impact of composite risk factors for cardiovascular disease on lifetime risk stratified by sex has not been investigated in the Japanese population, which has a much lower mortality of coronary heart disease compared with the Western population. We aimed to estimate lifetime risk of death from cardiovascular disease attributable to traditional risk factors. Methods and Results We analyzed pooled individual data from the Evidence for Cardiovascular Prevention from Observational Cohorts in a Japanese cohort study. A modified Kaplan-Meier approach was used to estimate the remaining lifetime risk of cardiovascular death. In total, 41 002 Japanese men and women with 537 126 person-years of follow-up were included. The lifetime risk at the index-age of 45 years for those with optimal risk factors (total cholesterol <4.65 mmol/L, systolic blood pressure <120 mm Hg, diastolic blood pressure <80 mm Hg, absence of diabetes, and absence of smoking habit) was lower compared with the highest risk profile of ≥2 risk factors (6.8% [95% CI, 0%-11.9%] versus 19.4% [16.7%-21.4%] for men and 6.9% [1.2%-11.5%] versus 15.4% [12.6%-18.1%] for women). Conclusions The magnitude and the number of risk factors were progressively associated with increased lifetime risk even in individuals in early adulthood who tend to have low short-term risk. The degree of established cardiovascular risk factors can be converted into lifetime risk. Our findings may be useful for risk communication in the early detection of future cardiovascular disease risk.

Background It is uncertain whether risk classification under the nationwide program on screening and lifestyle modification for metabolic syndrome captures well high-risk individuals who could benefit from lifestyle interventions. We examined the validity of risk classification by linking the incidence of cardiovascular disease (CVD). Methods and Results Individual-level data of 29 288 Japanese individuals aged 40 to 74 years without a history of CVD from 10 prospective cohort studies were used. Metabolic syndrome was defined as the presence of high abdominal obesity and/or overweight plus risk factors such as high blood pressure, high triglyceride or low high-density lipoprotein cholesterol levels, and high blood glucose levels. The risk categories for lifestyle intervention were information supply only, motivation-support intervention, and intensive support intervention. Sex- and age-specific hazard ratios and population attributable fractions of CVD, which were also further adjusted to consider non-high density lipoprotein cholesterol levels, were estimated with reference to nonobese/overweight individuals, using Cox proportional hazard regression. Since the reference category included those with risk factors, we set a supernormal group (nonobese/overweight with no risk factor) as another reference. We documented 1023 incident CVD cases (565 men and 458 women). The adjusted CVD risk was 60% to 70% higher in men and women aged 40 to 64 years receiving an intensive support intervention, and 30% higher in women aged 65 to 74 years receiving a motivation-support intervention, compared with nonobese/overweight individuals. The population attributable fractions in men and women aged 40 to 64 years receiving an intensive support intervention were 17.7% and 6.6%, respectively, while that in women aged 65 to 74 years receiving a motivation-support intervention was 9.4%. Compared with the supernormal group, nonobese/overweight individuals with risk factors had similar hazard ratios and population attributable fractions as individuals with metabolic syndrome. Conclusions Similar CVD excess and attributable risks among individuals with metabolic syndrome components in the absence and presence of obesity/overweight imply the need for lifestyle modification in both high-risk groups.

Aims: We aimed to develop and validate risk prediction models to estimate the absolute 10-year risk of death from coronary heart disease (CHD), stroke, and cardiovascular disease (CVD)., Methods: We evaluated a total of 44,869 individuals aged 40-79 years from eight Japanese prospective cohorts to derive coefficients of risk equations using cohort-stratified Cox proportional hazard regression models. Discrimination (C-index) of the equation was examined in each cohort and summarised using random-effect meta-analyses. Calibration of the equation was assessed using Hosmer-Lemeshow chi-squared statistic., Results: Within a median follow-up of 12.7 years, we observed 765 deaths due to CVD (276 CHDs and 489 strokes). After backward selection, age, sex, current smoking, systolic blood pressure (SBP), proteinuria, prevalent diabetes mellitus, the ratio of total cholesterol to high-density lipoprotein cholesterol (TC/HDLC), interaction terms of age by SBP, and age by current smoking were retained as predictors for CHD. Sex was excluded in the stroke equation. We did not consider TC/HDLC as a risk factor for the stroke and CVD equations. The pooled C-indices for CHD, stroke, and CVD were 0.83, 0.80, and 0.81, respectively, and the corresponding p-values of the Hosmer-Lemeshow tests were 0.18, 0.003, and 0.25, respectively., Conclusions: Risk equations in the present study can adequately estimate the absolute 10-year risk of death from CHD, stroke, and CVD. Future work will evaluate the system as an education and risk communication tool for primary prevention of CHD and stroke.

Weather temperatures affect the incidence of cardiovascular diseases (CVD), but there is limited information on whether CVD hospitalizations are affected by changes in weather temperatures in a super-aging society. We aimed to examine the association of diurnal weather temperature changes with CVD hospitalizations. We included 1,067,171 consecutive patients who were admitted to acute-care hospitals in Japan between April 1, 2012 and March 31, 2015. The primary outcome was the number of CVD hospitalizations per day. The diurnal weather temperature range (DTR) was defined as the minimum weather temperature subtracted from the maximum weather temperature on the day before hospitalization. Multilevel mixed-effects linear regression models were used to estimate the association of DTR with cardiovascular hospitalizations after adjusting for weather, hospital, and patient demographics. An increased DTR was associated with a higher number of CVD hospitalizations (coefficient, 4.540 [4.310-4.765]/°C change, p < 0.001), with greater effects in those aged 75-89 (p < 0.001) and ≥ 90 years (p = 0.006) than among those aged ≤ 64 years; however, there were no sex-related differences (p = 0.166). Greater intraday weather temperature changes are associated with an increased number of CVD hospitalizations in the super-aging society of Japan, with a greater effect in older individuals.

Although exposure to particulate matter with aerodynamic diameters ≤ 2.5 µm (PM 2.5 ) influences cardiovascular disease (CVD), its association with CVD-related hospitalizations of super-aged patients in Japan remains uncertain. We investigated the relationship between short-term PM 2.5 exposure and CVD-related hospitalizations, lengths of hospital stays, and medical expenses. We analyzed the Japanese national database of patients with CVD (835,405) admitted to acute-care hospitals between 2012 and 2014. Patients with planned hospitalizations and those with missing PM 2.5 exposure data were excluded. We classified the included patients into five quintiles based on their PM 2.5 exposure: PM-5, -4, -3, -2, and -1 groups, in descending order of concentration. Compared with the PM-1 group, the other groups had higher hospitalization rates. The PM-3, -4, and -5 groups exhibited increased hospitalization durations and medical expenses, compared with the PM-1 group. Interestingly, the hospitalization period was longer for the ≥ 90-year-old group than for the ≤ 64-year-old group, yet the medical expenses were lower for the former group. Short-term PM 2.5 exposure is associated with increased CVD-related hospitalizations, hospitalization durations, and medical expenses. The effects of incident CVDs were more marked in elderly than in younger patients. National PM 2.5 concentrations should be reduced and the public should be aware of the risks.

Decreases in masticatory function are believed to be related to the development of cardiovascular disease (CVD) through inappropriate nutritional intake. This study focused on maximum bite force (MBF), which is an objective, quantitative index of masticatory function, and its association with the development of CVD (stroke and coronary heart disease) was investigated. The subjects were 1547 participants of the Suita study with no history of CVD who underwent medical and dental health examinations between June 2008 and June 2013. In addition to undergoing a basic physical examination at baseline, their MBF was measured. They subsequently underwent follow-up surveys for the development of CVD (mean follow-up, 3.5 years). The association between baseline MBF and the development of CVD was investigated by multivariate adjustment using a Cox proportional hazards model. CVD developed in 32 subjects during follow-up. The trend test showed a significant association between baseline MBF and CVD in a model that combined men and women. When analysed by sex, the trend test found a significant association between baseline MBF and CVD in women. Low MBF, which is an objective and quantitative index of masticatory function, may be a risk factor for the development of CVD.

Background Patients with familial hypercholesterolemia who harbored both low-density lipoprotein receptor ( LDLR ) and PCSK9 (proprotein convertase subtilisin/kexin type 9) gene variants exhibit severe phenotype associated with substantially high levels of low-density lipoprotein cholesterol. In this study, we investigated the cardiovascular outcomes in patients with both LDLR and PCSK9 gene variants. Methods and Results A total of 232 unrelated patients with LDLR and/or PCSK9 gene variants were stratified as follows: patients with LDLR and PCSK9 ( LDLR/PCSK9 ) gene variants, patients with LDLR gene variant, and patients with PCSK9 gene variant. Clinical demographics and the occurrence of primary outcome (nonfatal myocardial infarction) were compared. The observation period of primary outcome started at the time of birth and ended at the time of the first cardiac event or the last visit. Patients with LDLR/PCSK9 gene variants were identified in 6% of study patients. They had higher levels of low-density lipoprotein cholesterol ( P =0.04) than those with LDLR gene variants. On multivariate Cox regression model, they experienced a higher incidence of nonfatal myocardial infarction (hazard ratio, 4.62; 95% CI, 1.66-11.0; P =0.003 versus patients with LDLR gene variant). Of note, risk for nonfatal myocardial infarction was greatest in male patients with LDLR/PCSK9 gene variants compared with those with LDLR gene variant (86% versus 24%; P <0.001). Conclusions Patients with LDLR/PCSK9 gene variants were high-risk genotype associated with atherogenic lipid profiles and worse cardiovascular outcomes. These findings underscore the importance of genetic testing to identify patients with LDLR/PCSK9 gene variants, who require more stringent antiatherosclerotic management.

Aim: To construct a risk prediction model for cardiovascular disease (CVD) based on the Suita study, an urban Japanese cohort study, and compare its accuracy against the Framingham CVD risk score (FRS) model., Methods: After excluding participants with missing data or those who lost to follow-up, this study consisted of 3,080 men and 3,470 women participants aged 30-79 years without CVD at baseline in 1989-1999. The main outcome of this study was incidence of CVD, defined as the incidence of stroke or coronary heart disease. Multivariable Cox proportional hazards models with stepwise selection were used to develop the prediction model. To assess model performance, concordance statistics (C-statistics) and their 95% confidence intervals (CIs) were calculated using a bootstrap procedure. A calibration test was also conducted., Results: During a median follow-up period of 16.9 years, 351 men and 241 women developed CVD. We formulated risk models with and without electrocardiogram (ECG) data that included age, sex, systolic blood pressure, diastolic blood pressure, high-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, diabetes mellitus, smoking, and urinary protein as risk factors. The C-statistics of the Suita CVD risk models with ECG data (0.782; 95% CI, 0.766-0.799) and without ECG data (0.781; 95% CI, 0.765-0.797) were significantly higher than that of the FRS model (0.768; 95% CI, 0.750-0.785)., Conclusions: The Suita CVD risk model is feasible to use and improves predictability of the incidence of CVD relative to the FRS model in Japan.

Aim: To investigate the relationship between perinatal condition around birth and cardiovascular risk in later life., Methods: Retrospective data were examined from 1241 city dwellers (521 men, 720 women; age 41-69 years) who had undergone medical examination at a single institution including blood tests and physical measurements from 2007 to 2008. The questionnaire was conducted to determine how perinatal factors affect their lives later. We also selected and studied a total of 28 individuals (12 men and 16 women) specifically about the conformity rate of the breastfeeding method between participants' memories and what was written in the maternal and child health handbooks., Results: The conformity rate of the breastfeeding method between a self-questionnaire and his/her maternal and child health handbook was well correlated (r=0.73; p＜0.025). Among the data in women who were born at home, HbA1C levels (5.36±0.03 vs. 5.25±0.05 mg/dL, p=0.03) and low-density lipoprotein cholesterol (136.0±1.4 vs. 129.3±2.5 mg/dL, p=0.04) were higher than women who were born at the hospital. Women raised by formula showed higher low-density lipoprotein cholesterol levels than women fed breast milk or a mixture of breast milk and formula (150.2±4.8 vs. 138.7±3.7, 142.5±2.6 mg/dL, p=0.04). Fasting blood glucose levels at an adult time in men and women born through breech presentation were higher than those by the cephalic presentation (123.2±7.8 vs. 106.8±1.2 mg/dL, p=0.03)., Conclusion: The study proposed that some perinatal conditions around birth such as delivery place, presenting part, and lactation affected especially Japanese women's cardiovascular risks between ages 41 and 69 years.

Objectives: Although there are 14 097 board-certified cardiologists in Japan, it is unknown whether the number of institutional board-certified cardiologists is related to the prognosis of cardiovascular disease patients., Design: Cross-sectional analysis., Setting: Data were collected from the nationwide database of acute care hospitals in Japan (2371 hospitals) between 2012 and 2013., Participants: A total of 1 422 703 consecutive patients were initially included in this study, but 518 610 patients were excluded due to age <18 years, missing data or prior hospitalisations; therefore, 896 171 patients comprised the final sample population., Main Outcome Measures: The primary outcome was in-hospital mortality due to any cause. For the per-hospital analysis, Poisson regression models were used to estimate the association of board-certified cardiologists with in-hospital mortality, adjusted for hospital facilitation. For the per-patient analysis, hierarchical logistic regression models were used to estimate the ORs of the number of institutional board-certified cardiologists, adjusted for patient demographics, diagnoses, therapies and hospital facilities., Results: The regression model of the per-hospital analysis indicated that the number of board-certified cardiologists was associated with a lower rate ratio of in-hospital mortality (rate ratio, 0.988; 95% CI 0.983 to 0.993; p<0.01). The per-patient analysis indicated that the median age was 73 years and the in-hospital mortality rate was 11.7%. The regression model indicated that the presence of more board-certified cardiologists was associated with a lower risk of in-hospital mortality (OR, 0.980; 95% CI 0.975 to 0.986; p<0.01) after adjustments for hospital facilities, patient characteristics and treatments., Conclusions: Among cardiovascular disease patients admitted to acute care hospitals in Japan, the presence of more board-certified cardiologists was associated with a lower risk of in-hospital mortality. These results have implications for national and institutional strategies for determining the required number of board-certified cardiologists., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background Few previous studies used information on changes in fasting plasma glucose ( FPG ) assessed at multiple points in time in relationship to cardiovascular disease ( CVD ) incidence. The present study aimed to identify subgroups of FPG trajectories with assessing CVD incidence. Methods and Results The present study was based on the Suita study, a population-based cohort study in Japan. The primary outcome was incidence of the first CVD events consisting of stroke and coronary heart diseases between 1989 and 2013. The main exposure was FPG assessed every 2 years. We used joint latent class mixed models to derive FPG trajectories over time while evaluating cumulative incidence of CVD , and categorized participants into several subgroups based on those trajectories and cumulative incidence. We observed 356 and 243 CVD events during the median follow-up of 17.2 and 20.2 years among 3120 men and 3482 women, respectively. The joint latent mixed models found 3 subgroups in men and 2 subgroups in women. Of the 3 subgroups in men, 1 subgroup had FPG levels that increased sharply (96.5-205.0 mg/dL from aged 40 to 80 years) and higher CVD cumulative incidence. Of the 2 subgroups in women, 1 subgroup had FPG levels that increased sharply (97.7-190.5 mg/dL from aged 40 to 80 years) and tended to have slightly higher CVD incidence compared with the other subgroup. Conclusion It can be important to manage CVD risk factors especially for people whose FPG trajectories sharply increased to prevent CVD .

Background: No prospective study of the relationship between intima-media thickness (IMT) progression and incident cardiovascular disease (CVD) has been performed., Methods and Results: We studied 4724 participants (mean age: 59.7±11.9 years; without CVD at the baseline) who had carotid ultrasonographic measurement of IMT on both sides of the entire carotid artery area (ie, the entire scanned common carotid artery [CCA], carotid artery bulb, internal carotid artery, and external carotid artery areas for both sides) between April 1994 and August 2001. Carotid ultrasonographic follow-up was performed every 2 years between April 1994 and March 2005 in 2722 of these participants, newly revealing 193 CCA plaques (maximum IMT in the CCA >1.1 mm). We followed up for incident CVD until December 2013. Statistical analyses were performed using a Cox proportional hazards regression model, evaluated using C statistics, and net reclassification improvement. During the 59 909 person-years of follow-up, we observed 221 strokes and 154 coronary heart disease events. CCA plaque and maximum IMT in the whole carotid artery area >1.7 mm were risk factors for CVD. CCA plaque presented an increased risk of CVD based on C statistics and the reclassification improvement of the current risk prediction model. After adding the new incident CCA plaques, during the 23 702 person-years of follow-up, 69 strokes and 43 coronary heart disease events occurred. The adjusted hazard ratios for incident CCA plaque were 1.95 (95% confidence interval, 1.14-3.30) in CVD and 2.01 (95% confidence interval, 1.01-3.99) in stroke., Conclusions: Maximum IMT in the CCA contributed significantly but modestly to the predictive power of incident CVD used in calculating traditional risk factors. This study provides the first demonstration that new progression of incident CCA plaque is a CVD risk., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Higher levels of positive affect have been associated with better physical health. While positive affect is seen as highly desirable among Westerners, East Asians tend to deemphasize positive affect. Using large probability samples of Japanese and U.S. adult populations, the present study examined the relations of positive affect with serum lipid profiles, known to be strongly predictive of risk for cardiovascular disease, and tested whether their associations depend on cultural contexts. As predicted, positive affect was associated with healthier lipid profiles for Americans but not for Japanese. Further analyses showed that this cultural moderation was mediated by body mass index. This study highlights the role of culture in the link between positive emotions and key biological risk factors of cardiovascular disease.

Low levels of serum high-density lipoprotein cholesterol (HDL-C) have been shown to be associated with increased risk of coronary heart disease (CHD). However, because this is usually observed in the context of other lipid abnormalities, it is not known whether isolated low serum HDL-C levels are an independent risk factor for CHD. We performed a large pooled analysis in Japan using data from nine cohorts with 41,206 participants aged 40-89 years who were free of cardiovascular disease at baseline. We divided participants into three groups: isolated low HDL-C, non-isolated low HDL-C, and normal HDL-C. Cohort-stratified Cox proportional hazards models were used to estimate multivariate-adjusted hazard ratios (HRs) for death due to CHD, ischemic stroke, and intracranial cerebral hemorrhage; during a 12.9-year follow-up, we observed 355, 286, and 138 deaths, respectively, in these groups. Non-isolated low HDL-C was significantly associated with increased risk of CHD compared with normal HDL-C (HR 1.37, 95 % confidence interval (CI) 1.04-1.80); however, isolated low HDL-C was not. Although isolated low HDL-C was significantly associated with decreased risk of CHD (HR 0.51, 95 % CI 0.29-0.89) in women, it was significantly associated with increased risk of intracranial cerebral hemorrhage in all participants (HR 1.62, 95 % CI 1.04-2.53) and in men (HR 2.00, 95 % CI 1.04-3.83). In conclusion, isolated low HDL-C levels are not associated with increased risk of CHD in Japan. CHD risk may, therefore, be more strongly affected by serum total cholesterol levels in this population.

Aim: This study was conducted to examine whether babies born small develop cardiovascular problems in later life., Methods: Data were examined retrospectively for 1241 city dwellers (men 521, women 720) aged 40-69 years who received a medical examination at a single institution. Blood tests, physical measurements, and a questionnaire survey regarding birth weight (small, medium, large), medication history and lifestyle (alcohol consumption, smoking, exercise) was administered. We selected 28 persons (12 men and 16 women) from and studied the rate of conformity between the participants' memory (small, medium, large) and the actual birth weight recorded in their maternal and child health handbook (< 2500, 2500-3500, > 3500 g)., Results: Participants' recall of their birth weight correlated well with the weight recorded in the maternal notebook (r = 0.73; P < 0.025). Low-density lipoprotein (P < 0.05), and total cholesterol (P < 0.01) levels in men, and systolic (P < 0.05) and diastolic (P < 0.05) blood pressure in women were significantly inversely related to birth weight when controlling for age, body mass index, medication, and lifestyle. The percentage of women born small, medium, and large taking antidiabetic agents was 17.8%, 2.9% and 0% (P < 0.05), respectively., Conclusion: A low birth weight was associated with high low-density lipoprotein and total cholesterol levels in men, and hypertension and diabetes mellitus in women aged 40-69., (© 2017 Japan Society of Obstetrics and Gynecology.)

Aim: In Japan Atherosclerosis Society guidelines for the prevention of atherosclerotic cardiovascular diseases 2012 (JAS2012), NIPPON DATA80 risk assessment chart (ND80RAC) was adopted to estimate the 10-year probability of coronary artery disease (CAD) mortality. However, there was no comparison between the estimated mortality calculated by ND80RAC and actual mortality in external populations. Accordingly, we used the large pooled database of cohorts in Japan, EPOCH-JAPAN, as an external population., Methods: The participants of EPOCH-JAPAN without a history of cardiovascular disease (15,091 men and 18,589 women aged 40-74 years) were analyzed based on sex. The probability of a 10-year risk of CAD/stroke mortality was estimated by ND80RAC. The participants were divided into both decile of their estimated mortality and three categories according to JAS2012. The calibration between the mean estimated mortality and the actual mortality was performed by the Hosmer and Lemeshow (H-L) test., Results: In both sexes, the estimated CAD mortality was higher than the actual mortality, particularly in higher deciles of estimated mortality, and the estimated stroke mortality was almost concordant with the actual mortality in low/moderate deciles of estimated mortality. As for the categories according to JAS2012, the estimated CAD mortality was higher than the actual mortality in both sexes; actual mortality in Category III was lower than that in Category II in women. However, it increased in the ascending order of category when we excluded the presence of diabetes from Category III., Conclusions: The estimated CAD mortality by ND80RAC tended to be higher than the actual mortality in the population in which the baseline survey was more recently performed.

Expression of anger is associated with biological health risk (BHR) in Western cultures. However, recent evidence documenting culturally divergent functions of the expression of anger suggests that its link with BHR may be moderated by culture. To test this prediction, we examined large probability samples of both Japanese and Americans using multiple measures of BHR, including pro-inflammatory markers (interleukin-6 and C-reactive protein) and indices of cardiovascular malfunction (systolic blood pressure and ratio of total to HDL cholesterol). We found that the link between greater expression of anger and increased BHR was robust for Americans. As predicted, however, this association was diametrically reversed for Japanese, among whom greater expression of anger predicted reduced BHR. These patterns were unique to the expressive facet of anger and remained after we controlled for age, gender, health status, health behaviors, social status, and reported experience of negative emotions. Implications for sociocultural modulation of bio-physiological responses are discussed., (© The Author(s) 2015.)

Because few studies have developed food frequency questionnaires (FFQ) and examined their reliability for Japanese urban populations, FFQ developed for urban Japanese populations may show reasonable reliability for estimating intakes of nutrients and food groups. Therefore, the objective of this study was to examine the reliability of an FFQ developed for a prospective cohort study in a Japanese urban area. A total of 29 men and 29 women aged 47 to 78 years were selected from participants in the Suita study from February 1997 to February 1998. Seven-consecutive-day dietary records (DR) was collected in each season (28-day DR). The FFQ were administered 3 times in total in each season, except in autumn. We calculated Spearman correlation coefficients to assess the validation of the first and third FFQ compared with 28-day DR and to assess the repeatability for 3-, 6-, and 9-month intervals. Reasonable validity of each FFQ compared with 28-day DR were observed for energy intake and for 27 nutrients, and 11 food groups were selected. Median (range) Spearman rank correlation coefficients for energy-adjusted nutrient and food group intakes of the first FFQ were 0.52 (0.14-0.88) and 0.53 (0.24-0.74), and those of the third FFQ were 0.51 (0.07-0.84) and 0.57 (0.16-0.75), respectively. The repeatability of each interval was relatively good; median (range) Spearman correlation coefficients of nutrients for 3-, 6-, and 9-month intervals were 0.67 (0.40-0.85), 0.63 (0.25-0.93), and 0.62 (0.31-0.87), respectively; those for food groups were 0.58 (0.42-0.76), 0.56 (0.24-0.80), and 0.65 (0.30-0.76), respectively. In conclusion, this FFQ is useful for evaluating the associations of nutrient and food intakes with cardiovascular diseases and their risk factors in Japanese urban populations., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Aims: The population-attributable fraction (PAF) is an indicator of the disease burden. In Western countries, the PAF of hypercholesterolemia in cardiovascular disease (CVD) is the highest among that for traditional risk factors; however, data for Asian populations are limited., Methods: A 24-year cohort study was conducted among 9,209 randomly selected participants who were not taking statins. We estimated the hazard ratio (HR) after adjusting for covariates and PAF associated with the serum total cholesterol (TC) levels in relation to CVD mortality., Results: The TC level was found to be positively associated with an increased risk of CVD, coronary heart disease (CHD) and cardiac death (CHD plus heart failure), with an HR of 1.08 (95% confidence interval [CI]: 1.00-1.16), 1.33 (95% CI: 1.14-1.55) and 1.21 (95% CI: 1.08-1.35) for a 1-SD increment in the serum TC level, respectively. Similar positive associations between the TC level and both CHD and cardiac death were observed after classifying the patients by age and sex. Furthermore, the highest serum TC level (≥ 6.72 mmol/L) was positively associated with CVD death, with an HR of 1.76 (95% CI: 1.25-2.47), as well as both CHD death and cardiac death. In contrast, no significant relationships were observed between the serum TC level and stroke. Meanwhile, the PAF for CVD, CHD, and cardiac deaths due to hypercholesterolemia (serum TC level ≥ 5.69 mmol/L, defined by the Japan Atherosclerosis Society) was 1.7%, 10.6% and 5.6%, respectively., Conclusions: The estimated PAF of CVD death due to hypercholesterolemia is moderately high, but lower than that for other risk factors, such as hypertension.

Background: Waist-to-height ratio (WHtR) has been shown to be a useful screening tool for metabolic syndrome and cardiovascular disease (CVD). We investigated the association of WHtR with CVD incidence by age group., Methods: We conducted a 13.0-year cohort study of Japanese adults (2600 men and 2888 women) with no history of CVD. WHtR was calculated as waist circumference (cm) (WC) divided by height (cm). We stratified participants by sex and age group (30-49, 50-69, ≥70 years). Using the Cox proportional hazards model, we calculated hazard ratios (HRs) and 95% CIs for CVD in relation to WHtR quartile for participants aged 50 to 69 years and 70 years or older., Results: Men aged 50 to 69 years in the highest quartile had significantly increased risks of CVD and coronary heart disease as compared with the lowest quartile; the HRs (95% CI) were 1.82 (1.13-2.92) and 2.42 (1.15-5.12), respectively. Women aged 50 to 69 years in the highest quartile had a significantly increased risk of stroke (HR, 2.43; 95% CI, 1.01-5.85). No significant results were observed in men or women aged 70 years or older. The likelihood ratio test showed that the predictive value of WHtR was greater than that of WC among men aged 50 to 69 years., Conclusions: The association between WHtR and CVD risk differed among age groups. WHtR was useful in identifying middle-aged Japanese at higher risk of CVD and was a better predictor than WC of CVD, especially in men.

Background: The aim of the present study was to clarify the association between waist circumference and all-cause and cardiovascular disease (CVD) mortality risk in relatively lean Japanese subjects., Methods and Results: A total of 3,554 men and 4,472 women who had no history of CVD were examined and their waist circumference measured at baseline. The subjects were aged ≥40 years and were obtained from 3 prospective cohort studies during 1988-1996. Hazard ratios for all-cause and CVD mortality were analyzed over a follow-up period of 14.7 years using a Cox proportional hazards model and penalized spline method, after adjustment for study cohort, age, smoking, alcohol drinking, hypertension, dyslipidemia, and diabetes. Compared with the lowest quintile, the highest quintile of waist circumference in men was associated with a linear reduction in all-cause mortality risk (multivariate-adjusted hazard ratio, 0.73; 95% confidence interval: 0.60-0.89; P for trend=0.001). CVD mortality risk was increased in men aged ≤65 years with a higher waist circumference. This relationship was U-shaped. Waist circumference was not associated with all-cause or CVD mortality risk in women., Conclusions: Waist circumference was associated inversely with increased risk of all-cause death in men, but not in women. Middle-aged men with a greater waist circumference potentially have an increased risk of CVD mortality.

Objective: Serum 1,5-anhydro-D-glucitol (1,5-AG) is well-known to be a useful clinical marker of both short-term glycemic status and postprandial hyperglycemia. In addition, previous epidemiological studies have shown that an increased postload glucose level in an oral glucose tolerance test is a risk factor for cardiovascular diseases (CVD). However, no previous prospective study has reported the association between serum 1,5-AG levels and the risk of CVD. In this study, we examined whether serum 1,5-AG levels can predict the incidence of first-ever CVD., Methods: Our study was a population-based cohort study in an urban area of Japan. Study subjects comprised 2095 initially healthy Japanese (991 men and 1104 women, mean age: 58.5 years) with no history of coronary heart disease (CHD) or stroke. They were followed up for an average of 11.1 years, and 147 CVD events (64 CHD and 83 strokes) were observed., Results: The adjusted hazard ratios (HRs) of all CVD in men increased linearly (p=0.004). The HR in the category with serum 1,5-AG levels of 14.0 μg/mL or less was 2.22 (95% confidence interval; 1.24-3.98) compared to the reference category (24.5 μg/mL or greater). Similar results were also shown with a sensitivity analysis in non-diabetic men. Conversely, no significant relationship between serum 1,5-AG levels and CVD risks was observed in women., Conclusions: Our results suggest that measurement of serum 1,5-AG levels is useful to detect individuals, especially men, at higher risk for CVD, regardless of the presence or absence of diabetes., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Indoxyl sulfate, an extensively investigated uremic toxin, is involved in the progression of chronic kidney disease (CKD). Recent clinical data indicate that serum levels of indoxyl sulfate are a powerful predictor of overall and cardiovascular mortality. Under CKD conditions, indoxyl sulfate induces oxidative stress, which involves the production of excessive levels of reactive oxygen species in renal tubular cells, mesangial cells, vascular endothelial cells, and osteoblast cells. In contrast, our recent findings explain, at least in part, the role that indoxyl sulfate plays in protecting against oxidative stress under normal-physiological conditions. Namely, under CKD conditions, the pro-oxidant properties of indoxyl sulfate exceed its anti-oxidant properties. These findings provide new insights into the dual role of indoxyl sulfate, which appears to be concentration-dependent, with respect to its pro- or anti-oxidative properties., (© 2011 The Authors. Therapeutic Apheresis and Dialysis © 2011 International Society for Apheresis.)

Few prospective studies have examined the combined impact of blood pressure (BP) categories and glucose abnormalities on the incidence of cardiovascular disease (CVD) in the general Asian population. This study aimed to examine the effect of the combined risks of these factors on the incidence of CVD in a general Japanese population. We studied 5321 Japanese individuals (aged 30-79 years), without CVD at baseline, who received follow-up for an average of 11.7 years. Serum fasting glucose categories were defined according to the 2003 American Diabetes Association recommendations. BP categories were defined by the 2009 Japanese Society of Hypertension Guidelines for the Management of Hypertension. The Cox proportional hazard ratios (HRs) for CVD according to the serum glucose and BP categories were calculated. In 62,036 person-years of follow-up, we documented 364 CVD events (198 stroke and 166 coronary heart disease (CHD)). Compared with normoglycemic subjects, the multivariable HRs (95% confidence intervals (CIs)) for CVD, CHD and stroke were 1.25 (1.00-1.58), 1.46 (1.04-2.04) and 1.11 (0.81-1.52), respectively, in individuals with impaired fasting glucose (IFG), whereas these values were 2.13 (1.50-3.03), 2.28 (1.34-3.88) and 2.08 (1.29-3.35), respectively, in individuals with diabetes mellitus (DM). Compared with normoglycemic and optimal blood pressure (BP) subjects, increased risks of CVD were observed in the normoglycemic subjects with high-normal BP or hypertension, the IFG subjects with normal or higher BP, and the DM subjects regardless of BP category (P-value for interaction=0.046). In conclusion, the high-normal BP subjects in all glucose categories and the normal BP subjects with IFG showed increased risk of CVD in this Japanese population. Further investigation of larger cohorts of DM subjects should be conducted to better understand this phenomenon.

Aim: The effects of exercise intervention and to assess its long-term efficacy in preventing subsequent cardiovascular events in patients with type 2 diabetes were little known on randomized controlled trial., Methods: Thirty-eight type 2 diabetic patients (21 men and 17 women) were assigned to either the exercise group (n=21) or the control group without exercise training (n=17) by simple randomization. The exercise training group was scheduled for aerobic and resistance exercise programs for 3 months. After the 3-month, we investigated endothelial function, insulin resistance, adipocytokines and inflammatory markers. The endothelial function was evaluated by examining a flow-mediated endothelium-dependent vasodilatation (FMD). Furthermore, we followed the incidence of cardiovascular events for 24 months., Results: After 3-month, HbA1C was decreased significantly in both groups. FMD was increased from 7.3+/-4.7% to 10.9+/-6.2% only in the exercise group (p<0.05). Long-term follow-up data showed that the control group developed cardiovascular events more frequently than did the exercise group (p<0.05)., Conclusions: Exercise improves endothelial dysfunction independently of glycemic control and insulin sensitivity in patients with type 2 diabetes. The beneficial effects of 3-month exercise to reduce cardiovascular events persist for 24 months.

Objective: Only a small number of population-based cohort studies have directly compared the predictive value of low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDLC) for coronary artery disease in Asian populations, such as Japan., Methods: We performed an 11.9-year cohort study of 4694 men and women, aged 30-74 years, selected randomly from an urban general population in Japan. Baseline LDL-C levels were estimated using the Friedewald formula. The predictive values of LDL-C and non-HDLC for myocardial infarction (MI) and stroke were compared., Results and Conclusion: During the follow-up period, there were 80 incident cases of MI and 139 of stoke, comprised of 23 intracerebral hemorrhages, 85 cerebral infarctions and 31 other types of stroke. The Hazard ratio (HR) for MI was highest in the top quintile of LDL-C (HR: 3.03, 95% CI, 1.32-6.96) when male and female data were combined. The HR for MI was also highest in the top quintile of non-HDLC (HR: 2.97, 95% CI, 1.26-6.97). Analysis of trends showed a significant positive relationship between MI incidence and serum LDL-C and non-HDLC levels (both P=0.02). However, there was no relationship between the incidence of any subtype of stroke and either LDL-C or non-HDLC. The predictive value of LDL-C and non-HDLC for MI, assessed by calculating the differences in the -2 logarithm likelihood (-2ln [L]) and area under the curve (AUC), were almost similar.

Epidemiologic studies have shown that in utero malnutrition is a risk factor for adult cardiovascular disease (CVD). Recently, we reported a mouse animal model of 30% maternal caloric reduction, in which offspring showed a significant increase in systolic blood pressure (SBP) as well as in cardiac remodeling-associated morphological parameters such as cardiac enlargement and coronary perivascular fibrosis in adulthood. Using a similar animal model, we here demonstrated that an increased level of protein consumption during an undernourished pregnancy (high-protein diet; HPD) corrected for the development of CVD risk factors found in fetal undernourishment with less protein consumption (standard-protein diet; SPD). In contrast, maternal ad libitum feeding with HPD resulted in significantly elevated SBP and cardiac enlargement in offspring at 16 wks. Appropriate maternal protein ingestion might partly protect against the development of CVD risk factors in offspring.

Abdominal obesity is a prerequisite for some definitions of metabolic syndrome (MetS). We investigated the impact of MetS defined by two different criteria, which either did or did not require abdominal obesity as a prerequisite, on cardiovascular disease (CVD) incidence in an urban Japanese cohort study. We studied 5,332 Japanese (aged 30-79 years, without CVD at baseline), who completed a baseline survey (September 1989 to March 1994) and were followed up through December 2005. MetS was defined by the NCEP-ATPIII (modified by Asian obesity criteria) and the Japanese criteria. After 61,846 person-years of follow-up, we documented 317 CVD incidences. The MetS frequencies of the Japanese and of the modified NCEP-ATPIII criteria were 17.7% and 25.1% for men and 5.0% and 14.3% for women, respectively. The multivariate hazard ratios (HRs; 95% confidence intervals [CI]) of CVD incidence for MetS by the modified NCEP-ATPIII criteria were 1.75 (1.27-2.41) in men and 1.90 (1.31-2.77) in women, and those for MetS by the Japanese criteria were 1.34 (0.96-1.87) in men and 2.20 (1.31-3.68) in women. The multivariate HRs of CVD incidence for MetS for the Japanese and for the modified NCEP-ATPIII criteria were 2.92 (1.54-5.55) and 1.94 (0.98-3.82) in men under 60 years old, respectively. The CVD incidence risks increased according to the number of MetS components. The risks were similar among participants with the same number of MetS components, regardless of abdominal obesity. In conclusion, the number of MetS components (modified NCEP-ATPIII criteria) may be more strongly associated with CVD incidence than the abdominal obesity essential criteria (the Japanese criteria) in a general urban Japanese population. (Hypertens Res 2008; 31: 2027-2035).

Evidence has emerged that undernutrition in utero is a risk factor for cardiovascular disorders in adulthood, along with genetic and environmental factors. Recently, the local expression of angiotensinogen and related bioactive substances has been demonstrated to play a pivotal role in cardiac remodeling, i.e. fibrosis and hypertrophy. The aim of the present study was to clarify the possible involvement of the local cardiac angiotensin system in fetal undernutrition-induced cardiovascular disorders. We developed a mouse model of undernutrition in utero by maternal food restriction, in which offspring (UN offspring) showed an increase in systolic blood pressure (8 wk of age, P < 0.05; and 16 wk, P < 0.01), perivascular fibrosis of the coronary artery (16 wk, P < 0.05) and cardiac cardiomegaly (16 wk, P < 0.01), and cardiomyocyte enlargement, concomitant with a significant augmentation of angiotensinogen (P < 0.05) and endothelin-1 (P < 0.01) mRNA expression and a tendency to increase in immunostaining for both angiotensin II and endothelin-1 in the left ventricles (16 wk). These findings suggest that fetal undernutrition activated the local cardiac angiotensin system-associated bioactive substances, which contributed, at least partly, to the development of cardiac remodeling in later life, in concert with the effects of increase in blood pressure.

Aim To compare the effects of the basal insulin analogues glargine and detemir on endothelial function and adipocytokine levels in people with Type 2 diabetes. Methods We studied 32 people with Type 2 diabetes whose blood glucose control was unsatisfactory while receiving only oral hypoglycaemic drugs. Participants were randomized to either insulin glargine or detemir for 24 weeks and then crossed over to the other treatment without a washout period. Flow-mediated vasodilatation, adipocytokine levels (plasminogen activator inhibitor-1 and leptin/adiponectin ratio), and fasting ghrelin levels were monitored. Results HbA1c levels were significantly decreased by both basal insulin therapies. Body weight was significantly increased by glargine but not by detemir. The proportion of flow-mediated vasodilatation was significantly increased by detemir but not glargine (glargine: from 5.17 ± 0.69 to 5.94 ± 0.83%; detemir: from 4.89 ± 0.78 to 7.92 ± 0.69%). Plasminogen activator inhibitor-1 level was significantly decreased by only detemir (glargine: from 16.4 ± 1.8 to 17.3 ± 2.1; detemir: from 19.2 ± 2.8 to 16.0 ± 1.6 ng/ml). The leptin/adiponectin ratio was significantly increased only by glargine. Acyl ghrelin level was significantly decreased by glargine but not detemir. Conclusions These results suggest that the effect on endothelial function and adipocytokine profiles may differ between glargine and detemir in people with diabetes (Trial registration ID: UMIN000004973). [ABSTRACT FROM AUTHOR]

Aims Circulating progenitor cells such as CD34+ cells play a key role in maintenance of vascular endothelial function and neovascularization, and a decrease in the number of CD34+ cells is associated with cardiovascular disease. However, the contribution of circulating progenitor cells to microvascular disease, such as diabetic nephropathy, is unclear. This study was therefore designed to clarify the association between diabetic nephropathy and circulating CD34+ cells. Methods We measured circulating CD34+ cell numbers in 85 Type 2 diabetic patients aged 40–70 years with normo- and microalbuminuria and determined the association with urinary albumin excretion rate (UAER). Results The number of circulating CD34+ cells significantly correlated with log UAER ( r = –0.289, P = 0.008). Furthermore, in patients with low numbers of CD34+ cells (0.68 > cells/µl, lowest quartile of CD34+ cell number) UAER increased significantly after 12 months compared with baseline [from 34.3 ± 7.0 to 53.6 ± 10.8 mg/g creatinine (gCr), P < 0.05], whereas in patients with a high number of CD34+ cells (1.0 < cells/µl, highest quartile of CD34+ cell number) UAER did not change (from 16.7 ± 4.8 to 20.1 ± 3.0 mg/gCr). Conclusions These results suggest that a decreased number of circulating CD34+ cells is involved in the progression of diabetic nephropathy and may be a predictor of the disease. [ABSTRACT FROM AUTHOR]