Aim: We aimed to clarify post-prandial accumulation of remnant-like particles (RLP) in patients with sitosterolemia.

Methods: Oral fat tolerance test cream (Jomo Shokuhin, Takasaki, Japan) 50 g was given per body surface area (m²); blood sampling was performed at 2 h intervals up to 6 h. Plasma lipoprotein fractions and RLP fractions were determined in four sitosterolemic subjects with double mutations in ATP-binding cassette (ABC) sub-family G member 5 or member 8 (ABCG5 or ABCG8) gene (mean age=18 yr, median low-density lipoprotein cholesterol [LDL-C]=154 mg/dL), six heterozygous carriers (mean age=31 yr, median LDL-C=105 mg/dL), and five subjects with heterozygous familial hypercholesterolemia (FH, mean age=32 yr, median LDL-C=221 mg/dL). The incremental area under curve (iAUC) of lipids, including LDL-C, apolipoprotein B-48 (apoB48), RLP cholesterol (RLP-C), and RLP triglyceride (RLP-TG) were evaluated.

Results: After oral fat load, there was no significant difference of the iAUC of LDL-C between sitosterolemia and heterozygous FH, whereas the iAUC of apoB48 was significantly larger in the sitosterolemic subjects compared with that of heterozygous FH (2.9 µg/mL×h vs. 1.3 µg/mL×h, p＜0.05). Under these conditions, the iAUCs of RLP-C and RLP-TG levels were significantly larger in the sitosterolemic subject compared with those of heterozygous FH (9.5 mg/dL×h vs. 5.7 mg/dL×h, p＜0.05; 149 mg/dL×h vs. 40 mg/dL×h, p＜0.05, respectively), whereas those of heterozygous carriers were comparable with those with heterozygous FH.

Conclusions: Post-prandial lipoprotein metabolism in sitosterolemia appeared to be impaired, leading to their elevation in serum sterol levels. (UMIN Clinical Trials Registry number, UMIN000020330)

Aim: Recent studies have suggested that non-high-density lipoprotein cholesterol (non-HDL-C) may be a good marker of coronary heart disease and cardiovascular disease risk. Therefore, we investigated the relationship between cardiorespiratory fitness (CRF) and non-HDL-C.

Methods: We evaluated CRF and the incidence of high level of non-HDL-C in 4,067 Japanese men without dyslipidemia. The participants were given a submaximal exercise test, a medical examination, and questionnaires on their health habits in 1986. A cycle ergometer was used to measure the CRF and maximal oxygen uptake was estimated. The incidence of a high level of non-HDL -C (≥170 mg/dL) from 1986 to 2006 was ascertained based on the fasting blood levels. A high level of non-HDL-C was found in 1,482 participants during the follow-up. Cox proportional hazard models were used to obtain the hazard ratios (HRs) and 95% confidence intervals (CIs) for the incidence of a high level of non-HDL-C.

Results: Following age adjustment, and using the lowest CRF group (quartile Ⅰ) as reference, the HRs and 95% CIs for quartiles II through IV were: 1.00 (95% CI: 0.87–1.15), 0.87 (95% CI: 0.76–1.00), and 0.70 (95% CI: 0.60–0.81), respectively (P for trend ＜0.001). After additional adjustment for body mass index, systolic blood pressure, smoking, alcohol intake, and family history of dyslipidemia, the HRs and 95% CIs were: 1.05 (95% CI: 0.92–1.21), 0.94 (95% CI: 0.81–1.08), and 0.79 (95% CI: 0.67–0.92), respectively (P for trend=0.001).

Conclusions: These results suggest that there is an inverse relationship between CRF levels and the incidence of a high level of non-HDL-C in Japanese men.

Aim: Shift workers have a high risk of cardiovascular disease (CVD). Systemic inflammation measured has been associated with the risk of CVD onset, in addition to classical risk factors. However, the association between work schedule and inflammatory cytokine levels remains unclear. The purpose of this study was to examine the association between work schedule and interleukin-6 (IL-6)/high-sensitivity C-reactive protein (hs-CRP) levels among Japanese workers.

Methods: The present cross-sectional study was a part of the Japanese Study of Health, Occupation and Psychosocial Factors Related Equity (J-HOPE). A total of 5259 persons who measured inflammatory cytokine were analyzed in this study. One-way analysis of variance was used to test log-transformed IL-6/hs-CRP differences by work schedule. Multiple regression analysis was used to examine the difference adjusted for other possible CVD risk factors.

Results: There were 3660 participants who had a regular work schedule; the remaining schedules were shift work without night work for 181 participants, shift work with night work for 1276 participants, and only night work for 142 participants. The unadjusted model showed that only night workers were significantly related to high levels of IL-6 compared with regular workers. Even in the multiple regression analysis, the higher level of IL-6 among only night workers remained significant (β=0.058, P=0.01). On the contrary, hs-CRP was not.

Conclusion: The present study revealed that only night shift work is significantly associated with high levels of IL-6 in Japanese workers. These observations help us understand the mechanism for the association between work schedule and CVD onset.

Aims: Sweet preference has been reported to be associated with various health problems. This study examined the influence of sweet taste preference on the risk of dyslipidemia in Korean middle-aged women.

Methods: The study selected 3,609 middle-aged women from the Korean Genome and Epidemiology Study (KoGES) and classified them into two groups on the basis of whether or not they preferred sweet taste. Dietary intake was analyzed using a semiquantitative food frequency questionnaire. Serum lipid profiles and anthropometric variables were measured.

Results: Subjects who preferred the sweet taste had significantly higher intakes of sugar products and sweet drink than those who did not prefer the sweet taste. Subjects who preferred the sweet taste showed higher carbohydrate and fat intake and less fiber intake than those who did not prefer the sweet taste. The serum concentrations of total cholesterol and low-density lipoprotein (LDL) cholesterol were significantly higher in subjects who preferred the sweet taste than those who did not prefer. Furthermore, subjects who preferred the sweet taste showed a significantly higher odds ratio (OR) for hypercholesterolemia (OR 1.22; 95% CI (1.01–1.45)) and hyper-LDL cholesterolemia (OR 1.33; 95% CI (1.11–1.60)) than those who did not prefer the sweet taste.

Conclusion: Our results suggested that preference for sweet taste may increase the consumption of sugar products and sweet drinks, which is partially linked to the risk of hypercholesterolemia and hyper-LDL cholesterolemia in Korean middle-aged women.

Aim: To investigate the association between the volumes of different aging intraplaque hemorrhage (IPH) and minor fibrous cap disruption (MFCD) in carotid arteries.

Methods: Patients with cerebrovascular symptoms and carotid atherosclerotic plaques determined by ultrasound were recruited and underwent multi-contrast magnetic resonance (MR) vessel wall imaging for carotid arteries. Carotid plaques with IPH on MR imaging were included in the analysis. The age (fresh or recent) and the volume of IPH for each plaque were evaluated.

Results: In total, 41 carotid plaques in 37 patients (mean age 70.2±11.0 years old; 32 males) were eligible for statistical analysis. The absolute volume of fresh IPH in plaques with MFCD was significantly larger than that in plaques without MFCD (109.83±75.49 mm³ vs. 30.54±20.62 mm³, P=0.002). Logistic regression showed that the absolute volume of fresh IPH was significantly associated with MFCD before (odds ratio [OR], 1.735; 95% confidence interval [CI], 1.127-2.670; P=0.012) and after adjusting for confounding factors (OR, 1.823; 95% CI, 1.076-3.090; P=0.026). There was no significant association between recent IPH volume and MFCD (P＞0.05).

Conclusion: The volume of fresh IPH is independently associated with MFCD in carotid plaques, suggesting that integrity of fibrous cap may change with different age and size of IPH.

Aim: Aberrant global DNA methylation is involved in the development of several diseases, including cardiovascular disease (CVD). We investigated whether the methylation of long interspersed nuclear element-1 (LINE-1) in leukocytes is associated with dyslipidemia, a major risk factor for CVD, in the Japanese general population.

Methods: We conducted a cross-sectional study consisting of 420 Japanese subjects (187 men and 233 women) without a clinical history of cancer, stroke, or ischemic heart disease. LINE-1 DNA methylation levels in leukocytes were measured using a pyrosequencing method.

Results: Significantly higher odds ratios (ORs) for hypermethylation were observed in the high LDL cholesterol and high LDL/HDL ratio groups than the corresponding normal group (high LDLC group: OR, 1.88; 95% confidence interval [CI], 1.20–2.96, high LDL/HDL ratio group: OR, 1.90; 95% CI, 1.20–3.01). Subjects with 2 or more lipid abnormalities had significantly higher ORs for hypermethylation than those with no lipid abnormality (OR, 2.31; 95% CI, 1.11–4.82).

Conclusion: LINE-1 DNA hypermethylation in leukocytes was associated with CVD risk profiles: high LDLC, high LDL/HDL ratio, and the degree of abnormal lipid metabolism.

Aim: CCL22, mainly synthesized by monocyte-derived alternative (M2) macrophages, belongs to the CC family of chemokines and is involved in monocyte migration and recruitment. We have previously investigated CCL22 and histamine in atherosclerosis. Here, we investigated the hypothesis that CCL22 is involved in atherosclerosis, which is influenced by the differentiation of macrophage phenotypes via histamine.

Methods: CCL22 expression was investigated in human carotid arteries and coronary arteries with bare metal stents. Ligated carotid arteries of wild-type (C57BL/6J) and apolipoprotein E-deficient mice were also used as atherosclerotic models. The localization and expression of CCL22 and classical (M1)-like and M2-like macrophages in various human and mouse atherosclerotic lesions were investigated by immunohistochemical examination and quantitative real-time polymerase chain reaction. Histamine is expressed in atherosclerosis, and it induces inflammation and immunity. Human- and mice-derived monocytes and macrophages were used to examine the role of histamine in macrophage differentiation and CCL22-expression. Macrophages derived from histamine receptor 1 (H1R)- and 2 (H2R)-knockout (KO) mice were also examined.

Results: Atherosclerotic lesions showed a distribution of heterogeneous macrophage phenotypes with M1-like and M2-like macrophage dominant sites. CCL22 was distributed in sparse areas of vascular smooth muscle cells (VSMCs) and associated with M2-like macrophages. Moreover, H2R stimulation was associated with CCL22 expression via M2-like macrophage dominant differentiation.

Conclusion: The expression of M1- or M2-like macrophages in atherosclerosis were observed to be dependent on the distribution of VSMCs owing to differences in causal stimuli and the switching of histamine receptors via Th1 or Th2 cytokines. These results suggest that CCL22 may control atherosclerosis.

Aim: The recommended low-density lipoprotein cholesterol (LDL-C) levels of the guideline may be appropriate for Caucasian patients but not for other ethnic groups.

Methods: A cohort study was conducted in Hong Kong, and acute coronary syndrome (ACS) patients who received percutaneous coronary intervention (PCI) between 2005 and 2015 were enrolled. The primary outcomes of interest were the total cost of care and cardiovascular-related cost during one-year follow-up. The cost difference by lipid goal attainments was analyzed by Poisson regression with multivariate treatment effects. The clinical outcomes achieved by lipid goal attainments in terms of major adverse cardiovascular events were analyzed by multivariate Cox regression.

Results: Among the 4638 patients, 79.50%, 48.64%, and 36.14% attained the LDL-C goals of ＜2.6, ＜2.0, and ＜1.8 mmol/L for one year, respectively. Only about 16% patients achieved the ≥50% reduction from baseline. None of these lipid goals was associated with a significant reduction in the total cost of care. We only identified the clinical benefits associated with the lipid goal of ＜2.6 mmol/L. Other more stringent lipid goals seemed to bring a significant economic burden on cardiovascular-related cost, but their clinical benefits were uncertain.

Conclusions: Lowering LDL-C to achieve the guideline-recommended target levels for post-PCI ACS patients may lead to fewer cardiovascular events, but it may not necessarily lead to economic benefits within one year of follow-up.

Aim: The level of accumulated advanced glycation end-products (AGEs) in the skin has been shown to predict the risk of complications in patients with diabetes mellitus (DM). Recently, the level of accumulated fluorescent AGEs in the skin has become measurable as skin autofluorescence (skin AF) using a non-invasive apparatus, autofluorescence reader. The purpose of this study was to evaluate the association between skin AF and the subclinical atherosclerosis markers, especially endothelial dysfunction, in patients with DM.

Methods: We enrolled 140 Japanese subjects with DM who attended Osaka University Hospital, and measured the skin level of AGEs by skin AF and three subclinical atherosclerosis markers: endothelial function by flow-mediated vasodilation, FMD; carotid intima–media thickness, IMT; and brachial-ankle pulse wave velocity, baPWV.

Results: FMD was significantly associated with skin AF (r=－0.259, p=0.002). Furthermore, a stepwise multivariate regression analysis revealed that skin AF was an independent determinant of FMD (β=－0.180, p=0.038). Although there were significant associations between skin AF and maximum carotid intima-media thickness (max-IMT)(r=0.298, p＜0.001) as well as baPWV (r=0.284, p= 0.001) in univariate analysis, skin AF was not an independent determinant of either carotid max-IMT or baPWV after adjustment for conventional cardiovascular risk factors. Receiver-operating characteristic curve analysis revealed that skin AF can identify the subjects whose FMD, max-IMT, and baPWV were completely within the normal range (C-statistics, 0.73; 95% confidence interval, 0.61–0.84; p＜0.001).

Conclusions: Skin AF was independently associated with FMD as an indicator of endothelial dysfunction, and can be utilized as a screening marker of atherosclerosis in Japanese patients with DM.