Lipoprotein apheresis has been developed as the treatment for refractory familial hypercholesterolemia (FH) to remove low-density lipoprotein (LDL), which is the main pathogenic factor. Currently, three procedures are available in Japan, including the plasma exchange, double-membrane filtration, and selective LDL adsorption. Selective LDL adsorption, which was developed in Japan, has been one of the most common treatment methods in the world. Lipoprotein apheresis enabled the prevention of atherosclerosis progression even in homozygous FH (HoFH) patients. However, in our observational study, HoFH patients who started lipoprotein apheresis in adulthood had a poorer prognosis than those who started in childhood. Therefore, HoFH patients need to start lipoprotein apheresis as early as possible. Although the indication for lipoprotein apheresis in heterozygous FH (HeFH) patients has been decreasing with the advent of strong statins, our observational study showed that HeFH patients who discontinued lipoprotein apheresis had a poorer prognosis than patients who continued apheresis therapy. These results suggest that it is beneficial for very-high-risk HeFH patients to be treated by lipoprotein apheresis even if their LDL cholesterol is controlled well by lipid-lowering agents. Since launching a new class of lipid-lowering agents, proprotein convertase subtilisin/kexin type 9 (PCSK9) antibody and microsome triglyceride transfer protein inhibitors, the indication for lipoprotein apheresis in FH has been changing. However, despite the development of these drugs, lipoprotein apheresis is still an option with a high therapeutic effect for FH patients with severe atherosclerotic cardiovascular disease.

Bilirubin is a fundamental metabolic end product of heme degradation. Despite acting as a cytotoxic metabolite at high concentrations, bilirubin at physiological concentrations has antioxidant effects, such as scavenging reactive oxygen species, leading to a decrease in oxidative stress. Endothelial dysfunction is an early feature of and plays an important role in the development and progression of atherosclerosis, leading to cardiovascular complications. One mechanism of endothelial dysfunction is an increase in oxidative stress, by which the bioavailability of nitric oxide is decreased. Therefore, bilirubin is expected to improve endothelial function, to inhibit the progression of atherosclerosis, and to reduce cardiovascular complications by inactivating oxidative stress through its antioxidant effects. In this review, we will focus on the clinical associations of the antioxidant bilirubin with endothelial function and cardiovascular complications.

Aim: Coronary computed tomography angiography (CCTA)-derived fractional flow reserve (FFR_CT) accurately diagnoses ischemic lesions of intermediate stenosis severity. However, significant determinants of FFR_CT have not been fully evaluated.

Methods: This was a sub-analysis of the Treatment of Alogliptin on Coronary Atherosclerosis Evaluated by Computed Tomography-Based Fractional Flow Reserve trial. Thirty-nine diabetic patients (117 vessels) with intermediate coronary artery stenosis [percent diameter stenosis (%DS) ＜70%] in whom FFR_CT was measured were included in this study. CCTA-defined, vessel-based volumetric and morphological characteristics of plaques were examined to determine their ability to predict FFR_CT.

Results: Patient-based, multivariate linear regression analysis showed that hemoglobinA1c, triglycerides, and the estimated glomerular filtration rate were significant independent factors associated with FFR_CT. Vessel-based, univariate linear regression analysis showed that the total atheroma volume (r=－0.233, p=0.01) and the percentage atheroma volume (PAV) (r=－0.284, p=0.002) as well as %DS (r=－0.316, p=0.006) were significant determinants of FFR_CT. Among the plaque components, significant negative correlations were observed between FFR_CT and low- (r=－0.248, p=0.007) or intermediate-attenuation plaque volume (r=－0.186, p=0.045), whereas calcified plaque volume was not associated with FFR_CT. In the left anterior descending coronary artery (LAD), the plaque volume of each component was associated with FFR_CT.

Conclusions: Plaque volume, PAV, and %DS were significant determinants of FFR_CT. Plaque morphology, particularly in LAD, was associated with FFR_CT in diabetic patients with intermediate coronary artery stenosis.

Aim: Bacteroides vulgatus and B. dorei have a protective effect against atherosclerosis, suggesting that expansion of these species in the gut microbiota could help patients with coronary artery disease (CAD). This study aimed to investigate the effect of resistant starch (RS) on the gut microbiota and its metabolites in fecal sample cultures from patients with CAD and individuals without CAD, using a single-batch fermentation system.

Methods: Fecal samples from 11 patients with CAD and 10 individuals without CAD were fermented for 30 h with or without RS in the Kobe University Human Intestinal Microbiota Model (KUHIMM). Gut microbiota and the abundance of B. vulgatus and B. dorei were analyzed using 16S ribosomal ribonucleic acid (rRNA) gene sequencing and the quantitative polymerase chain reaction. Short-chain fatty acids were analyzed using high-performance liquid chromatography.

Results: Gut microbial analysis showed significantly lower levels of B. vulgatus and B. dorei in the original fecal samples from patients with CAD, which was simulated after 30 h of fermentation in the KUHIMM. Although RS significantly increased the absolute numbers of B. vulgatus and B. dorei, and butyrate levels in CAD fecal sample cultures, the numbers varied among each patient.

Conclusions: The effect of RS on gut microbiota and its metabolites in the KUHIMM varied between CAD and non-CAD fecal sample cultures. The KUHIMM may be useful for preclinical evaluations of the effects of RS on the gut microbiota and its metabolites.

Aim: The present study aimed to investigate the association between shape and location of atherosclerotic plaques and intraplaque hemorrhage (IPH) in carotid arteries using magnetic resonance (MR) imaging.

Methods: Overall, 114 symptomatic patients (mean age: 64.9±10.9 years; 81 males) who underwent MR imaging and had advanced carotid plaques were included in analysis. IPH presence and carotid plaque shape and location (below and above bifurcation) were evaluated. The plaque shape was defined as follows: type-I: the arc-length of plaque is greater in the upstream; type-II: the arc-length of plaque in downstream and upstream is equal; and type-III: the arc-length of plaque is greater in downstream. The plaque shape and location were compared between plaques with and without IPH and their associations with IPH were determined.

Results: Of 181detectedplaques, 57 (31.5%) had IPH. Compared with plaques without IPH, those with IPH had higher incidence of the plaque shape of type-I (66.7% vs. 32.2%, P＜0.001), lower incidence of plaque shape of type-III (24.6% vs. 50.0%, P=0.001), and were more likely located above carotid bifurcation (71.9% vs. 48.4%, P=0.003). The plaque shape of type-I (OR, 4.01; 95%CI, 1.36–11.83; P=0.012) and location above bifurcation (OR, 3.21; 95%CI, 1.07–9.61; P=0.037) of carotid plaques were significantly associated with IPH after adjusting for confounder factors.

Conclusions: Carotid plaque shape and location are significantly associated with the occurrence of IPH. Our findings could provide new insights for the pathogenesis of IPH and vulnerably plaques.

Aim: Patients undergoing percutaneous coronary intervention (PCI) who require both oral anticoagulant (OAC) and antiplatelet therapy (APT) are exposed to a serious risk of bleeding. The aim of this study was to clarify the relationship among nutritional and inflammation status and long-term bleeding in patients requiring both OACs and APT after PCI.

Methods: We performed PCI in 3,718 consecutive patients between April 2011 and March 2017, 302 of whom were treated with both OACs and APT. Patients were followed for up to 3 years for bleeding events, defined as the Bleeding Academic Research Consortium (BARC) class ≥3 bleeding. We retrospectively evaluated the ability of the Geriatric Nutritional Risk Index (GNRI) and high-sensitivity C-reactive protein (hs-CRP) to detect bleeding events.

Results: During a median follow-up of 1,080 days, bleeding events were observed in 53 (17.5%) patients. Bleeding events were associated with a low GNRI (≤98) (hazard ratio [HR], 3.16; 95% confidence interval [CI], 1.84-5.45; p＜0.0001) and hs-CRP level ≥2.5 mg/L (HR, 2.75; 95% CI, 1.61-4.78; p=0.0003). A low GNRI＋high hs-CRP showed a 5.12-fold increase in the incidence of BARC class ≥3 bleeding (95% CI, 2.68-9.91; p＜0.0001) compared with a normal GNRI＋low hs-CRP. The addition of the GNRI and hs-CRP to the PRECISE-DAPT score improved C-statistics from 0.67 to 0.71 and enhanced the net reclassification improvement (NRI) and integrated discrimination improvement (IDI) (NRI, 0.36, p＜0.0001; IDI, 0.066, p＜0.0001).

Conclusions: The GNRI and hs-CRP were novel predictors of the long-term bleeding risk in patients requiring both OACs and APT after PCI.

Aim: To elucidate the role of pentraxin-3 (PTX3) in atherosclerosis, we evaluated lipid and cardiovascular risk profiles according to the plasma PTX3 levels in subjects from the general population.

Methods: A sub-cohort of 2,000 subjects was randomly sampled from a Korean community-based cohort study. After excluding those with a medication history for dyslipidemia, 1,747 subjects (902 men and 845 women) were included in the final analyses. Linear and logistic regressions with adjustment for appropriate variables were performed.

Results: The PTX3 level was positively associated with the high-density lipoprotein cholesterol (HDL-C) level and negatively associated with the log-transformed triglyceride (TG) level, total cholesterol/HDL-C ratio, and low-density lipoprotein cholesterol (LDL-C)/HDL-C ratio (p＜0.05). Subjects with the highest PTX3 levels (≥ 1.17 ng/dl) exhibited a lower risk of metabolic syndrome (odds ratio [OR] 0.73, 95% confidence interval [CI] 0.57-0.94), overweight/obesity (OR 0.65, 95% CI 0.50-0.83), increased TG level (OR 0.66, 95% CI 0.51-0.86), and increased HDL-C level (OR 0.67, 95% CI 0.51-0.88) compared to those with the lowest PTX3 level (＜0.7 ng/dl).

Conclusion: The circulating PTX3 level was inversely associated with metabolic syndrome, overweight/obesity, and parameters of dyslipidemia, suggesting a cardioprotective role of PTX3 in atherosclerosis.