Abetalipoproteinemia (ABL) is a rare autosomal recessive disorder caused by biallelic pathogenic mutations in the MTTP gene. Deficiency of microsomal triglyceride transfer protein (MTTP) abrogates the assembly of apolipoprotein (apo) B-containing lipoprotein in the intestine and liver, resulting in malabsorption of fat and fat-soluble vitamins and severe hypolipidemia. Patients with ABL typically manifest steatorrhea, vomiting, and failure to thrive in infancy. The deficiency of fat-soluble vitamins progressively develops into a variety of symptoms later in life, including hematological (acanthocytosis, anemia, bleeding tendency, etc.), neuromuscular (spinocerebellar ataxia, peripheral neuropathy, myopathy, etc.), and ophthalmological symptoms (e.g., retinitis pigmentosa). If left untreated, the disease can be debilitating and even lethal by the third decade of life due to the development of severe complications, such as blindness, neuromyopathy, and respiratory failure. High dose vitamin supplementation is the mainstay for treatment and may prevent, delay, or alleviate the complications and improve the prognosis, enabling some patients to live to the eighth decade of life. However, it cannot fully prevent or restore impaired function. Novel therapeutic modalities that improve quality of life and prognosis are awaited. The aim of this review is to 1) summarize the pathogenesis, clinical signs and symptoms, diagnosis, and management of ABL, and 2) propose diagnostic criteria that define eligibility to receive financial support from the Japanese government for patients with ABL as a rare and intractable disease. In addition, our diagnostic criteria and the entry criterion of low-density lipoprotein cholesterol (LDL-C) ＜15 mg/dL and apoB ＜15 mg/dL can be useful in universal or opportunistic screening for the disease. Registry research on ABL is currently ongoing to better understand the disease burden and unmet needs of this life-threatening disease with few therapeutic options.

Aims: Cardiovascular diseases (CVD) are a global leading cause of mortality. However, few biomarkers are available to predict future coronary plaque rupture. We have recently demonstrated that low levels of anti-apolipoprotein B-100 autoantibody (anti-apo B-100 Ab) correlated with an increased CVD risk in Japanese patients with diabetes. In the present study, we examined the relationship between serum anti-apo B-100 Ab levels and coronary plaque characteristics in patients undergoing elective percutaneous coronary intervention (PCI).

Methods: We conducted iMAP^®-intravascular ultrasound (IVUS) in 88 Japanese male patients undergoing elective PCI, and the five consecutive slices of IVUS images at the center of the most stenotic culprit lesion were used for identifying the plaque characteristics. The serum levels of anti-apo B-100 Ab against synthetic peptides (p45 or p210) were measured using a homemade enzyme-linked immunosorbent assay.

Results: Serum IgG levels of anti-apo B-100 Ab against both native p45 and p210 (IgG _N-p45 and IgG_N-p210) and malondialdehyde (MDA)-modified p45 and p210 (IgG_MDA-p45 or IgG_MDA-p210) showed a negative correlation with plaque burden in total male patients undergoing elective PCI. Additionally, both IgG_N-p45 and IgG_N-p210, but neither IgG_MDA-p45 nor IgG_MDA-p210, correlated negatively with necrotic and positively with fibrotic components of iMAP^®-IVUS plaque characteristics in the patients with ＜1 month statin treatment before elective PCI (“statin-untreated” group). There was no significant correlation between anti-apo B-100 Ab and any plaque characteristics in the patients with statin treatment for 1 month or more before elective PCI (“statin-treated” group).

Conclusion: Measuring serum levels of anti-apo B-100 Ab might be helpful in the evaluation of unstable coronary plaque in male CVD patients without statin treatment.

Aim: The Japan Diet (JD) recommended by the Japan Atherosclerosis Society based on the traditional Japanese diet is presumably favorable for preventing atherosclerotic cardiovascular diseases, but few high-quality controlled clinical trials have examined its benefits as compared with other diets. We studied effects of nutrition education for JD intake as compared with partial JD (PJD) intake on serum lipids and inflammatory parameters in subjects with dyslipidemia.

Methods: A randomized parallel controlled clinical trial was conducted on outpatients with dyslipidemia. Participants were randomly divided into the JD or the PJD group. Face-to-face nutrition education based on each diet at baseline and at 3 months, as well as monthly counseling by mail during the intervening 3-month period, were provided and participants practiced up to 6 months. Both groups were advised to reduce consumptions of animal fat/ fatty meat/poultry, confections, and alcoholic drinks. Additionally, the JD group participants were recommended to consume more fish, soybean products especially natto, vegetables, and seaweed/mushrooms/konjak, and to switch from refined to unrefined cereals or barley.

Results: Mean LDL-cholesterol was 125 +/- 29 mg/dL at baseline, and the JD group ( n=49) showed a greater mean LDL-cholesterol decrease than the PJD group (n=49) [- 8 mg/dL in JD vs 1 mg/dL in PJD, difference, -9 mg/dL (95%CI, -17 to 0) p=0.043)], and triglyceride (p=0.023) and insulin (p=0.033) reductions were larger in the JD group than in the PJD group at 6 months.

Conclusion: Nutrition education for JD intake was suggested to improve serum lipid and metabolic parameters in patients with dyslipidemia.

Aims: Type 2 diabetes mellitus (T2DM) is no longer regarded as a coronary risk equivalent, and heterogeneity of cardiovascular risk exists, suggesting that further risk stratification should be mandatory. This study aimed to determine the prevalence and clinical predictors of coronary artery calcium (CAC) score, and evaluate the CAC score as a predictor of cardiovascular outcome in a large asymptomatic T2DM cohort.

Methods: A total of 2,162 T2DM patients were recruited from a Diabetes Shared Care Network and the CAC score was measured. Cardiovascular outcomes were obtained for 1,928 patients after a follow-up of 8.4 years. Multiple regression analysis and Cox proportional hazard regression were applied to identify clinical predictors of CAC and calculate the incidence and hazard ratios (HRs) for all-cause mortality and cardiovascular events by CAC category.

Results: Of the recruited patients, 96.8% had one or more risk factors. The distribution of CAC scores was as follows: CAC=0 in 24.2% of the patients, 0 ＜CAC ≤ 100 in 41.5%, 100 ＜CAC ≤ 400 in 20.3%, CAC ＞400 in 14.7%. The multivariable predictor of increased CAC included age (years) (odds ratio, 1.07; 95% confidence interval, 1.06–1.08), male sex (1.82; 1.54–2.17), duration (years) of T2DM (1.07; 1.05–1.09), and multiple risk factors (1.94; 1.28–2.95). Increasing severity of CAC was associated with higher all-cause or cardiac mortality and higher incident cardiovascular events. The HRs for cardiac death or major cardiac events in CAC ＞400 vs CAC=0 were 8.67 and 10.52, respectively ( p＜0.001)

Conclusion: CAC scoring provides better prognostication of cardiovascular outcome than traditional risk factors in asymptomatic T2DM patients, and may allow identifying a high-risk subset for enhancing primary prevention.

Aim: Arterial narrowing associated with the progression of atherosclerosis leads to serious conditions such as stroke, coronary artery disease, or even death. High-resolution magnetic resonance imaging (HR-MRI) is better for detecting arterial wall status and discriminating tissue characteristics than conventional imaging. We used HR-MRI to investigate the frequency of patients with basilar artery (BA) stenosis observed distinctively on routine angiography and identify the clinical features associated with this imaging. We analyzed the nature of the vessel wall causing the basal artery stenosis by HR-MRI, and related clinical factors.

Methods: Patients with BA stenosis underwent HR-MRI. The association between atherosclerosis (with or without intraplaque hemorrhage [IPH]) and dissection was analyzed. High signal intensity within a BA plaque on magnetization-prepared rapid acquisition with gradient echo was defined as an area with a signal intensity ＞200% that of the adjacent muscle.

Results: Fifteen patients were diagnosed with BA dissection on HR-MRI. IPH was identified in 14 patients. Patients with BA plaque with IPH were older and had higher prevalence of hypertension and hyperlipidemia than the other patients. The frequencies of alcohol drinking and number of current smokers were higher in the dissection group than in the other groups. Hyperlipidemia was identified as an influencing factor for IPH development in atherosclerotic plaque. Young age was identified as the influencing factor for the occurrence of BA dissection.

Conclusions:The etiology of stenosis or occlusion was unclear until the development of HR-MRI. With HR-MRI, stroke etiology is better understood, and factors affecting each etiology can be identified. Further studies that clarify the etiology of posterior circulation stroke are required.

Aim: Low T3 syndrome is characterized by low serum triiodothyronine (T3) levels without elevation of thyroid-stimulating hormone (TSH) in patients without apparent thyroid disease, which is known to be associated with worse clinical outcomes in various populations including those with kidney failure. In this study, we examined whether low free T3 (FT3) levels are independent predictor of cardiovascular disease (CVD) events in patients undergoing hemodialysis.

Methods: This was a prospective cohort study of patients with chronic kidney disease undergoing hemodialysis. From the total of 518 patients, we excluded patients with treated or untreated hyperthyroidism or hypothyroidism and those treated with corticosteroids.

Results: We analyzed data from 438 eligible patients. During the 5-year follow-up, 154 new CVD events and 86 all-cause deaths were recorded. Kaplan-Meier analysis showed that lower FT3 levels were associated with higher risks for new cardiovascular events and all-cause death. This inverse association of FT3 and new CVD events remained significant after adjustment for age, sex, duration of hemodialysis, diabetic kidney disease, hypertension, dyslipidemia, and smoking; however, it was no longer significant after further adjustment for prior CVD or N-terminal fragment of probrain natriuretic peptide (NT-proBNP). FT3 did not show an independent association with all-cause mortality.

Conclusions: Our results indicate that low FT3 status is not an independent predictor of new CVD events and that the following factors are closely associated: prior CVD, low FT3 and high NT-proBNP levels at present, and future risk of new CVD events in hemodialysis patients.

Aim: In the TOHO Lipid Intervention Trial Using Pitavastatin (TOHO-LIP), a multicenter randomized controlled trial, pitavastatin significantly reduced cardiovascular (CV) events compared to atorvastatin in patients with hypercholesterolemia. To investigate the mechanism by which pitavastatin preferentially prevents CV events, we investigated the relationship between CV events and cardio-ankle vascular index (CAVI) using the TOHO-LIP database.

Methods: For the subgroup analysis, we selected patients from a single center, Toho University Sakura Medical Center. After excluding those who had CV events at baseline or during the first year, 254 patients were enrolled. The primary end point was the same as that of TOHO-LIP, and three-point major cardiac adverse events (3P-MACE) was added as secondary end point.

Results: The cumulative 5-year incidence of 3P-MACE (pitavastatin 1.6%, atorvastatin 6.1%, P=0.038) was significantly lower in pitavastatin group (2 mg/day) than in atorvastatin group (10 mg/day). CAVI significantly decreased only in pitavastatin group during the first year (9.50–9.34, P=0.042), while the change in low-density lipoprotein cholesterol (LDL-C) did not differ between the two groups. The change in CAVI during the first year positively correlated with 3P-MACE and tended to be an independent predictor of 3P-MACE in Cox proportional hazards model (hazard ratio, 1.736; P=0.079). The annual change in CAVI throughout the observation period was significantly higher in subjects with CV events compared to those without.

Conclusions: In this subgroup analysis, the reduction in CV events tended to be associated with the CAVI-lowering effect of pitavastatin, which was independent of the LDL-C-lowering effect.

Aim: Familial hypercholesterolaemia (FH) is the most common autosomal dominant lipid disorder, leading to severe hypercholesterolaemia. Early detection and treatment with lipid-lowering medications may reduce the risk of premature coronary artery disease in FH patients. However, there is scarcity of data on FH prevalence, detection rate, treatment and control with lipid-lowering therapy in the Malaysian community.

Methods: Community participants (n=5130) were recruited from all states in Malaysia. Blood samples were collected for lipid profiles and glucose analyses. Personal and family medical histories were collected by means of assisted questionnaire. Physical examination for tendon xanthomata and premature corneal arcus were conducted on-site. FH were clinically screened using Dutch Lipid Clinic Network Criteria.

Results: Out of 5130 recruited community participants, 55 patients were clinically categorised as potential (Definite and Probable) FH, making the prevalence FH among the community as 1:100. Based on current total population of Malaysia (32 million), the estimated number of FH patients in Malaysia is 320,000, while the detection rates are estimated as 0.5%. Lipid-lowering medications were prescribed to 54.5% and 30.5% of potential and possible FH patients, respectively, but none of them achieved the therapeutic LDL-c target.

Conclusion: Clinically diagnosed FH prevalence in Malaysian population is much higher than most of the populations in the world. At community level, FH patients are clinically under-detected, with majority of them not achieving target LDL-c level for high-risk patients. Therefore, public health measures are warranted for early detection and treatment, to enhance opportunities for premature CAD prevention.