Aims: We assessed 27-year trends in obesity and blood lipid levels of 10-year-old children to estimate the risk of metabolic syndrome in adulthood.

Methods: Based on a screening program for lifestyle-related diseases in school children in Oita City, Japan, we evaluated secular trends in height, weight, percentage of overweight (POW), total cholesterol (TC), triglyceride (TG), HDL cholesterol (HDL-C), and non-HDL cholesterol (non-HDL-C) of fifth graders (median age: 10.8 years) in Oita City from 1991 to 2017. We focused on the secular trend in the percentage of children with inappropriate serum levels of each lipid. We also evaluated the long-term trends in the 95^th, 50^th, and 5^th percentiles for each parameter, as dependent variables, with the calendar year as an independent variable. Percentages of children with mild obesity (POW-20), moderate obesity (POW-30), and severe obesity (POW-50) were set as dependent variables.

Results: A total of 58,699 boys and 56,864 girls were evaluated during the study period. The percentage of children with severe obesity (POW-50) consistently increased during these years, and the 95^th percentile of degree of obesity significantly increased in both boys and girls. The plot of percentages of children with inappropriate levels of TC, TG, and non-HDL-C showed a mild inverted U shape during the study period. The HDL-C level typically decreased in the study period, and the TC, TG, and non-HDL-C levels were markedly higher while the HDL level was lower in obese children than in non-obese children.

Conclusion: The number of children with severe obesity increased, and obese children had higher percentages of inappropriate lipid levels than non-obese children. The rate of dyslipidemia with low HDL levels gradually increased in all children in Oita City, Japan, over the past 27 years.

Aim: In addition to the quantity and quality, the carriers, such as lipoproteins and albumin, can affect the physiological properties and clinical significance of lipids. This study aimed to elucidate the modulation of the levels of ceramides and sphingosine, which are considered as proatherosclerotic lipids, in lipoproteins and lipoprotein-depleted fractions in subjects with type 2 diabetes.

Methods: We separated the serum samples collected from healthy subjects (n=22) and subjects with type 2 diabetes (n=39) into Triglyceride (TG)-rich lipoproteins (TRL), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and lipoprotein-depleted fractions via ultracentrifugation. Then, we measured the levels of six species of ceramides, sphingosine, and dihydrosphingosine via LC-MS/MS and statistically analyzed them to identify the sphingolipids in each fraction, which are associated with diabetes as well as cardiovascular and renal complications.

Results: In subjects with diabetes, the levels of sphingosine and dihydrosphingosine in the TRL, LDL, and lipoprotein-depleted fractions were higher, whereas those in the HDL were lower. In addition, the ceramide levels in HDL were lower, whereas those in lipoprotein-depleted fractions were higher. Furthermore, The levels of ceramides in lipoproteins, especially LDL, were negatively associated with the presence of cardiovascular diseases and stage 4 diabetic nephropathy.

Conclusions: The contents of ceramides and sphingosine in lipoproteins and lipoprotein-depleted fractions were differently modulated in diabetes and associated with cardiovascular diseases and diabetic nephropathy. The carrier might be an important factor for the biological properties and clinical significance of these sphingolipids.

Aim: Secular trends in the risk of recurrent stroke have been reported in several epidemiological studies worldwide, but this issue has not been investigated in general Japanese populations. We examined the trends in the 5-year risk of recurrent stroke over a half century using community-based prospective data in Japan.

Methods: We established 4 cohort studies in 1961, 1974, 1988, and 2002. To examine the risk of recurrent stroke, participants who developed stroke during a 10-year follow-up period in each cohort were followed-up for 5 years from the date of first onset. A total of 154 (first sub-cohort: 1961-1971), 144 (second sub-cohort: 1974-1984), 172 (third sub-cohort: 1988-1998), and 146 (fourth sub-cohort: 2002-2012) participants from each cohort were enrolled in the present study. The 5-year cumulative risk of recurrent stroke was compared among the sub-cohorts using the Kaplan-Meier method and the age- and sex-adjusted Cox proportional hazards model.

Results: The risks of recurrent stroke after any stroke and ischemic stroke decreased significantly from the first to the third sub-cohort, but they did not clearly change from the third to the fourth sub-cohort. The risk of recurrent stroke after hemorrhagic stroke decreased mainly from the first to the second sub-cohort and there was no apparent decrease from the second to the fourth sub-cohort. These trends were substantially unchanged after adjusting for age and sex.

Conclusions: In the Japanese community, the risk of recurrent stroke decreased mainly from the 1960s to 1990s, but there was no apparent decrease in recent years.

Aim: We investigated the effects of metabolic syndrome (MetS) and its components, including a body shape index (ABSI), on increased arterial stiffness measured using the cardio-ankle vascular index (CAVI) according to sex and age strata.

Methods: A total of 7127 asymptomatic Korean participants aged 21–90 years (men, 69.4%) were included. Age–sex-specific increased CAVI was defined as having the highest quartile of CAVI in each age group.

Results: The CAVI increased with age and was higher in men. MetS was associated with an increased risk of high CAVI by 1.30 times in men and 1.45 times in women. The risk of high CAVI with an increasing MetS risk score was greater in women. MetS was significantly associated with increased CAVI in men only aged 51–70 years and in women aged ≥ 51 years, and the size of association increased with age (odds ratio (OR) of 1.41 in 51–70 years vs. OR of 2.96 in ≥ 71 years of women). Among MetS components, triglyceride (men, all ages), hypertension (men, 51–70 years; women, ≤ 70 years), glucose intolerance (men, 51–70 years; women, ≥ 51 years), and HDL-cholesterol (women, ≥ 71 years) were associated with increased CAVI.

Unlike increased waist circumference (WC), increased ABSI revealed an association with high CAVI. MetS diagnosed with ABSI instead of WC was more significantly associated with increased CAVI in all age–sex groups.

Conclusion: The association of MetS and its components with increased CAVI differed with age and sex, which might provide a new insight for the management of MetS risk factors to promote vascular health.

Aim: Issuance of the WHO Housing and health guidelines has paralleled growing interest in the housing environment. Despite accumulating evidence of an association between outdoor temperature and serum cholesterol, indoor temperature has not been well investigated. This study examined the association between indoor temperature and serum cholesterol.

Methods: We collected valid health checkup data of 2004 participants (1333 households), measured the indoor temperature for 2 weeks in winter, and divided participants according to whether they lived in a warm (average bedroom temperature ≥ 18℃), slightly cold (12–18℃) or cold house (＜12˚C). The relationship between bedroom temperature and serum cholesterol was analyzed using multivariate logistic regression models, adjusting for demographics, lifestyle habits and the season in which the health checkup was conducted, with a random effect of climate areas in Japan.

Results: The sample sizes for warm, slightly cold, and cold houses were 206, 940, and 858, respectively. Compared to those in warm houses, the odds ratio of total cholesterol exceeding 220 mg/dL was 1.83 (95%CI: 1.23–2.71, p=0.003) for participants in slightly cold houses and 1.87 (95%CI: 1.25–2.80, p=0.002) in cold houses. Similarly, the odds ratio of LDL/non-HDL cholesterol exceeding the standard range was 1.49 (p=0.056)/1.67 (p=0.035) for those in slightly cold houses and 1.64 (p=0.020)/1.77 (p=0.021) in cold houses. HDL cholesterol and triglycerides were not significantly associated with bedroom temperature.

Conclusion: Besides lifestyle modification, improving indoor thermal environment through strategies such as installing high thermal insulation and appropriate use of heating devices may contribute to better serum cholesterol condition.

Aims: This study aimed to investigate the association of elevated RC levels with adverse cardiovascular outcomes in acute coronary syndrome (ACS) patients with and without diabetes.

Methods: We analyzed data from 1716 patients with ACS undergoing percutaneous coronary intervention. RC was calculated as total cholesterol minus high-density lipoprotein cholesterol minus low-density lipoprotein cholesterol. RC ＞75th percentile of the cohort (＞0.79 mmol/L) was defined as abnormally elevated RC. Cox-regression models and Kaplan-Meier analyses were used to assess the relationship between RC ＞0.79 mmol/L and major adverse cardiovascular events (MACE).

Results: During a median follow-up of 927 days, a total of 354 patients had at least one event. In the overall population, compared with those with RC ≤ 0.79 mmol/L, patients with RC ＞0.79 mmol/L had a significantly higher risk of MACE after adjustment for potential confounders (hazard ratio: 1.572, 95% confidence interval: 1.251-1.975, P＜0.001). In addition, RC ＞0.79 mmol/L was associated with an increased risk of MACE of 66.7% (P=0.001) and 50.1% (P=0.022) in the diabetic and non-diabetic subgroups (P for interaction=0.073), respectively. The addition of RC significantly improved the predictive ability of baseline models for MACE in diabetic patients (all P＜0.05), but not in non-diabetic patients (all P＞0.05).

Conclusion: Abnormally elevated RC was significantly associated with worse prognosis in both diabetic and non-diabetic patients with ACS; however, the prognostic value of RC might be superior among diabetic patients.

Aims: T-cadherin (T-cad) is a specific binding partner of adiponectin (APN), adipocyte-specific secretory protein. APN exhibits organ protection via the T-cad-dependent accumulation onto several tissues such as the aorta, heart, and muscle. Recently, for the first time, we showed that three forms (130, 100, and 30 kDa) of soluble T-cad existed in human serum and correlated with several clinical parameters in patients with type 2 diabetes. Nevertheless, the significance of soluble T-cad has not been elucidated in the acute stage of cardiovascular diseases. We herein examined soluble T-cad concentrations and investigated their clinical significance in patients with emergency hospital admission due to ST-segment elevation myocardial infarction (STEMI).

Methods: This observational study enrolled 47 patients with STEMI who were treated via primary percutaneous coronary intervention (PCI). Soluble T-cad and APN concentrations were measured by using an enzyme-linked immunosorbent assay. This study is registered with the University Hospital Medical Information Network (Number: UMIN 000014418).

Results: Serum concentrations of soluble 130 and 100 kDa T-cad rapidly and significantly decreased after hospitalization and reached the bottom at 72 h after admission (p＜0.001 and p＜0.001, respectively). The patients with high soluble T-cad and low APN concentrations on admission showed a significantly higher area under the curve of serum creatine kinase-MB (p＜0.01).

Conclusion: Serum soluble T-cad concentration changed dramatically in patients with STEMI, and the high T-cad and low APN concentrations on admission were associated with the myocardial infarction size. Further study is needed to investigate the usefulness of categorizing patients with STEMI by serum T-cad and APN for the prediction of severe prognoses.

Aim: Serum levels of cholesterol absorption and synthesis markers are known to be associated with cardiovascular risk. Individuals with reduced kidney function or chronic kidney disease (CKD) are at an increased risk for cardiovascular disease. Hence, we examined the relationship between estimated glomerular filtration rate (eGFR) and serum markers of cholesterol absorption and synthesis.

Methods: The CACHE (Cholesterol Absorption and Cholesterol synthesis in High-risk patiEnts) Consortium, comprised of 13 research groups in Japan possessing data of lathosterol (Latho, synthesis marker) and campesterol (Campe, absorption marker) measured via gas chromatography, compiled the clinical data using the REDCap system. Among the 3597 records, data from 2944 individuals were utilized for five analyses including this CKD analysis.

Results: This study analyzed data from 2200 individuals including 522 hemodialysis patients; 42.3% were female, the median age was 58 years, and the median eGFR was 68.9 mL/min/1.73 m². Latho, Campe, and Campe/Latho ratio were significantly different when compared across CKD stages. When the associations of eGFR with these markers were assessed with multivariable nonlinear regression models, Latho, Campe, and Campe/Latho ratio showed positive, inverse, and inverse associations with eGFR. These associations were significantly modified by sex, the presence/absence of diabetes mellitus, and the presence/absence of statin use.

Conclusion: We showed that individuals with lower eGFR have lower cholesterol synthesis marker levels and higher cholesterol absorption marker levels in this large sample.

Aims: Vascular smooth muscle cells are key participants in atherosclerosis. Circular RNA hsa_circ_0000345 (circ_0000345) and miR-647 are related to oxygenized low-density lipoprotein (ox-LDL)-induced arterial smooth muscle cell (ASMC) dysregulation. However, the relationship between circ_0000345 and miR-647 in ox-LDL-induced ASMC dysregulation is unclear.

Methods: Relative levels of circ_0000345, miR-647, and PAP-associated domain containing 5 (PAPD5) mRNA in AS patient’s serum and ox-LDL-induced ASMCs were detected via RT-qPCR. Gain-of-function experiments were utilized to analyze the effects of circ_0000345 upregulation on ox-LDL-induced cell proliferation, migration, invasion, and inflammatory response in ASMCs. The relationship between circ_0000345 or PAPD5 and miR-647 was validated by dual-luciferase reporter and RNA immunoprecipitation assays.

Results: Circ_0000345 and PAPD5 were lowly expressed in AS patient’s serum and ox-LDL-induced ASMCs, while miR-647 expression had an opposing trend. Mechanistically, circ_0000345 was verified as a miR-647 sponge, and miR-647 overexpression impaired the inhibitory effects of circ_0000345 upregulation on ox-LDL-induced ASMC proliferation, migration, invasion, and inflammatory response. Further experiments demonstrated that PAPD5 was a miR-647 target, and circ_0000345 adsorbed miR-647 to mediate PAPD5 expression. Also, PAPD5 inhibition relieved miR-647 silencing-mediated suppression on ox-LDL-induced ASMC proliferation, migration, invasion, and inflammatory response.

Conclusions: Circ_0000345 elevated PAPD5 expression via acting as a miR-647 sponge, resulting in alleviating ox-LDL-induced ASMC dysregulation. The study highlighted the critical role of circ_0000345 in AS.

Aim: This study aims to investigate the association of the Cardio-Ankle Vascular Index (CAVI) with self-reported sleep duration and sleep quality in community-dwelling older adults aged ≥ 65 years.

Methods: The Tarumizu Study was a cohort of community-based health checkups conducted in the Tarumizu City, Japan, in 2018 and 2019. In total, 997 participants aged ≥ 65 years (median age, 74 years) were examined. We obtained the average sleep duration and sleep quality using self-reported questionnaires and classified them into three separate groups according to sleep duration (＜6 h, 6–8 h, and ≥ 8 h) and sleep quality (good, medium, and poor). The arterial stiffness was measured using the CAVI.

Results: As per our findings, the CAVI was significantly higher in the ≥ 8 h sleep group (CAVI=9.6±1.3) than in the ＜6 h (CAVI=9.1±1.1) or 6–8 h (CAVI=9.1±1.2) groups (p＜0.001). After adjustment for age, sex, systolic blood pressure, current smoking status, body mass index, frequency of exercise, educational background, frailty, sleep medication, sleep quality, and nap duration, multivariable regression analysis demonstrated that the CAVI was significantly higher in the ≥ 8 h group than in the 6–8 h group (p=0.016). In contrast, multivariable regression analysis showed that there was no significant association between sleep quality and CAVI.

Conclusions: A significant association was noted between long sleep duration (≥ 8 h) and elevated CAVI in community-dwelling older adults aged ≥ 65 years. We, therefore, suggest that long sleep duration, not sleep quality, is correlated with arterial stiffness in older adults.