Atherosclerotic cardiovascular disease (ASCVD) is a leading global cause of mortality, and recent research has underscored the critical role of lipoproteins in modulating cardiovascular (CV) risk. Elevated low-density lipoprotein cholesterol (LDL-C) levels have been linked to increased CV events, and while numerous trials have confirmed the efficacy of lipid-lowering therapies (LLT), significant gaps remain between recommended LDL-C targets and real-world clinical practice. This review addresses care gaps in LLT, emphasizing the necessity for innovative approaches that extend beyond LDL-C management. It explores combination therapy approaches such as statins combined with ezetimibe or PCSK9 inhibitors, which have shown promise in enhancing LDL-C reduction and improving outcomes in high-risk patients. Additionally, this review discusses new approaches in lipid modification strategies, including bempedoic acid, inclisiran, and drugs that lower Lp(a), highlighting their potential for CV risk reduction. Furthermore, it emphasizes the potential of polygenic risk scores to guide LLT and lifestyle changes despite challenges in implementation and genetic testing ethics. This article discusses the current guidelines and proposes innovative approaches for optimizing lipoprotein management, ultimately contributing to improved patient outcomes in ASCVD prevention.

Apolipoprotein E (apoE) is a key apoprotein in lipid transport and is susceptible to genetic mutations. ApoE variants have been studied for four decades and more than a hundred of them have been reported. This paper presents an up-to-date review of the function and structure of apoE in lipid metabolism, the E2, E3, and E4 isoforms, the APOE gene, and various pathologies, such as familial type III hyperlipidemia and lipoprotein glomerulopathy, caused by apoE variants. Alzheimer’s disease was barely mentioned in this paper. But this review should help researchers obtain a comprehensive overview of human apoE in lipid metabolism.

Aim: Severity, functional outcomes, and their secular changes in acute atrial fibrillation (AF)-associated stroke patients were determined.

Methods: Acute ischemic stroke patients with AF in a hospital-based, multicenter, prospective registry from January-2000 through December-2020, were compared with those without AF. The co-primary outcomes were the initial severity assessed by the NIH Stroke Scale (NIHSS) score and favorable outcome assessed by the modified Rankin Scale scores 0-2 at hospital discharge.

Results: Of the 142,351 patients studied, 33,870 had AF. AF patients had higher NIHSS scores (median 9 vs. 3, adjusted coefficient 5.468, 95% CI 5.354-5.582) than non-AF patients. Favorable outcome was less common in AF patients than in non-AF patients in the unadjusted analysis (48.4% vs. 70.4%), but it was more common with adjustment for the NIHSS score and other factors (adjusted OR 1.110, 95% CI 1.061-1.161). In AF patients, the NIHSS score decreased throughout the 21-year period (adjusted coefficient -0.088, 95% CI -0.115 – -0.061 per year), and the reduction was steeper than in non-AF patients (P＜0.001). In AF patients, favorable outcome became more common over the period (adjusted OR 1.018, 95% CI 1.010-1.026), and the increase was steeper than in non-AF patients (P＜0.001); the increase was no longer significant after further adjustment by reperfusion therapy.

Conclusions: Initial stroke severity became milder and functional outcomes improved in AF patients over the 21-year period. These secular changes were steeper than in non-AF patients, suggesting that AF-associated stroke seemed to reap more benefit of recent development of stroke care than stroke without AF.

Aim: The present study assessed low-density lipoprotein cholesterol (LDL-C) levels in school-aged children from the Ogasa District of Shizuoka Prefecture and evaluated the utility of non-invasive vascular tests, namely flow-mediated dilation (FMD) and intima-media thickness (IMT), in pediatric patients with familial hypercholesterolemia (FH).

Method: We analyzed the lipid test results of 8,568 students screened for prevention of lifestyle-related diseases and 78 children under 15 years old with cholesterol levels exceeding 220 mg/dL who visited Chutoen General Medical Center. We examined the LDL-C distribution from school-age screenings and conducted FMD and IMT assessments on those meeting the 2022 Pediatric FH Guidelines criteria.

Results: Among the screened students, 186 (2.2%) exhibited LDL-C levels above 140 mg/dL, including 123 fourth-graders (2.8%) and 63 first-year junior high students (1.5%). The mean LDL-C level across all students was 90.0 mg/dL (standard deviation: 21.3 mg/dL), with the 95th percentile at approximately 125.0 mg/dL. Of the 78 children who visited the hospital, 65 met the FH diagnostic criteria. In children ≥ 10 years old, no significant IMT differences were observed between the Definitive and Probable FH groups and the Possible FH group; however, a significant difference in the FMD percentage was noted between these groups (9.9% [8.1%-11.9%] vs. 14.2% [11.6%-16.3%], P=0.003).

Conclusions: Our findings highlight the LDL-C distribution in FH screening and suggest a potential reduction in FMD in pediatric FH patients ≥ 10 years old. These results emphasize the importance of initiating pharmacological interventions in school-aged children to maintain optimal LDL-C levels for lifelong cardiovascular health.

Aims: This study aimed to develop a cardiovascular disease (CVD) risk model using data from a large occupational cohort.

Methods: A risk prediction model was developed using the routine health checkup data of 96,117 Japanese employees (84.0% men) who were 30–64 years of age and had no CVD at baseline. Cox proportional hazards regression models were employed to develop a risk model for assessing the 10-year CVD risk. Measures of discrimination and calibration were used to assess the predictive performance of the model and internal validation was used to examine potential overfitting.

Results: During a mean follow-up period of 6.7 years (range, 0.1–11.0 years), 422 cases of incident CVD were confirmed. The final model, which included predictor variables of age, smoking, diabetes, systolic blood pressure, and low- and high-density lipoprotein cholesterol levels, demonstrated a good predictive ability (Harrell’s C-statistic, 0.796; 95% confidence interval, 0.775–0.817) with excellent calibration between observed and predicted values. Internal validation revealed minimal overfitting.

Conclusions: The developed model can accurately predict the 10-year CVD risk. Because it is based on routine health checkup data, the prediction model can be easily implemented in the workplace. Further studies are required to assess the external validity and transferability of the proposed CVD risk model.

Aim: The Fukushima Daiichi Nuclear Power Plant accident caused lifestyle changes and psychological distress in residents living near the plant. This study clarified the associations between changes in residents’ lifestyles and psychological factors with the onset of metabolic syndrome (METs) after the accident.

Methods: This longitudinal study included 10,373 residents who underwent the Comprehensive Health Check and Mental Health and Lifestyle Survey in Fiscal Year (FY) 2013. Follow-up surveys were conducted between FY 2014 and FY 2017. Lifestyle changes and the METs incidence were evaluated using a logistic regression model.

Results: METs developed in 14.0% of subjects. In addition to metabolic factors, such as the body mass index, hypertension, dyslipidemia, and diabetes mellitus, there were differences in physical activity, fast walking, eating fast, eating habits before bedtime, skipping breakfast, current smoking, and alcohol intake between subjects with and without new-onset METs. Eating fast, current smoking, and drinking alcohol were positively associated with new-onset METs, whereas starting physical activity and fast walking were inversely associated with new-onset METs.

Conclusions: Disaster-related lifestyle changes, such as eating fast, starting to smoke, and continued alcohol intake, were risk factors for new-onset METs after the Fukushima Daiichi Nuclear Power Plant accident.

Aim: We aimed to elucidate the effect of a healthy diet containing adequate amounts of protein and vegetables on metabolic indices.

Methods: In this randomized crossover study, twenty-two healthy Japanese participants ingested two different test meals: fish diet (F) or fish diet with adequate vegetable content (FV). Each 5-day diet load test was separated by a washout period of at least seven days. Metabolic indices were measured in fasting blood and 24-h urine samples.

Results: The delta (Δ) plasma glucose and Δserum low-density lipoprotein (LDL) cholesterol concentrations were significantly larger in the participants in group FV than in group F (p=0.042, p=0.013, respectively). The urinary pH in participants in group F on day 6 was significantly lower than on day 1 (p=0.008), and the Δurinary pH and Δnet gastrointestinal absorption of alkali of participants in group FV tended to be smaller than in group F (p=0.070, p=0.075, respectively).

Conclusions: This study showed that a healthy diet containing adequate protein and vegetables reduced the dietary acid load and improved plasma glucose and serum LDL concentrations in healthy Japanese participants.

Aims: Efficacy, safety, and pharmacokinetics of the selective PPARα modulator pemafibrate as once-daily extended-release (XR) tablets were compared with those of twice-daily immediate-release (IR) tablets in patients with hypertriglyceridemia.

Methods: A multicenter, randomized, single-blind, active-controlled crossover, phase 2 clinical pharmacology study was performed in patients with hypertriglyceridemia. Patients were randomly assigned to IR 0.2 mg/day, XR 0.4 mg/day, or XR 0.8 mg/day before/after meals (fasted/fed) and treated for a total of eight weeks. The primary endpoint was percentage change in fasting serum triglycerides (TG).

Results: Of 63 randomized patients, 60 received the study drug. Patients were 78.3% male, mean age (±SD) 57.5±9.8 years, BMI 25.5±3.7 kg/m², and fasting TG 221.3±68.1 mg/dL. Fasting serum TG decreased significantly from baseline in all groups (LS mean [95% CI];−43.6 [−47.7, −39.5] % for IR 0.2 mg/day, −41.1 [−45.1, −37.0] % for XR 0.4mg/day, −39.7 [−43.8, −35.6] % for XR 0.8 mg/day), indicating that XR 0.4 and XR 0.8 mg/day were not inferior to IR 0.2 mg/day. TG-lowering effects tended to be stronger for fed than fasted administration. MRT_ss, t_max, and t_1/2 were longer for XR than for IR. Adverse events showed no major inter-group differences: 12.5% (5/40 patients) for IR 0.2, 17.5% (7/40) for XR 0.4, and 20.0% (8/40) for XR 0.8 mg/day.

Conclusions: In patients with hypertriglyceridemia, XR substantially lowered TG at all doses, with maximum effectiveness at 0.4 mg/day, the dose approved in Japan, to a level comparable to IR 0.2 mg/day. There were no safety concerns up to 0.8 mg/day.

Aims: It is uncertain if there is a connection between subclavian steal phenomenon (SSP) and atherosclerotic stenosis in the opposite vertebral artery (VA). We aimed to explore the association between SSP and the incidence of contralateral vertebral artery stenosis (VAS) in vivo.

Methods: In this prospective registry study, we included patients diagnosed with ＞50% stenosis of proximal subclavian artery (SA) or innominate artery (INA) by digital subtraction angiography (DSA) from our comprehensive stroke center between 2011 and 2022. VAS and SSP was diagnosed by DSA in the resting state. Propensity score matching (PSM) was conducted among all participants and subgroups with a 1:1 ratio according to the presence of SSP. We further conducted sensitivity analysis by dividing all participants into subgroups according to the degree of stenosis and type of SSP. Binomial logistic regression analysis was applied to investigate the association of SSP with contralateral VAS.

Results: A total of 774 patients were included in this study and 309 (39.9%) were found with SSP. After PSM, presence of SSP was associated with lower prevalence of contralateral VAS among all participants (OR 0.45; 95% CI 0.31−0.65; p＜0.001). In subgroup analysis, the association was respectively found within left subclavian (LSA) stenosis group (OR 0.43; 95% CI 0.29−0.65; P＜0.001) and right subclavian artery (RSA) / INA stenosis group (OR 0.36; 95% CI 0.19−0.69; P=0.002).

Conclusions: SSP is associated with lower prevalence of contralateral VAS.