Intraplaque hemorrhage (IPH) is a key feature of plaque vulnerability that contributes to atherothrombotic events. Non-invasive coronary plaque imaging has been challenging because of the small size of the coronary arteries and motion caused by cardiac contraction and respiration. Recent advances in magnetic resonance imaging (MRI) have enabled the non-invasive detection of coronary IPH. Compared with coronary computed tomography angiography and intravascular imaging modalities, MRI offers unique noninvasive tissue characterization based on intrinsic signal properties. Histopathological and intravascular imaging investigations have indicated that erythrocyte-derived materials, rather than lipid components, constitute the predominant substrate of coronary high-intensity plaques, reflecting recent IPH. This review summarizes the pathophysiological basis, imaging characteristics, and clinical implications of MRI-detected coronary IPH, in the context of other imaging modalities.

Aims: Homozygous Familial hypercholesterolemia (HoFH) is a rare genetic disease characterized by very high levels of low-density lipoprotein cholesterol (LDL-C). Owing to LDL receptor activity being completely or nearly all lost in HoFH, LDL-C levels greatly exceed normal levels, and are even higher than in heterozygous (HeFH), which can cause fatal cardiovascular disease even in infancy. The current study updates differences in clinical characterization, therapeutic strategies and cardiovascular outcomes between HoFH and HeFH.

Methods: A total of 157 patients who were genetically or clinically diagnosed with FH (HoFH: 15, HeFH: 142) were retrospectively analyzed. Clinical characteristics, lipid profiles and atherosclerotic prognosis were evaluated between HoFH and HeFH patients.

Results: Age and sex were similar between the two groups. Untreated LDL-C in HoFH was about double that in HeFH (498.4±164.3 vs. 232.0±60.5 mg/dL, p＜0.001), while on-treatment LDL-C with lipid lowering therapies did not differ significantly (83.8±59.1 vs. 127.1±59.6 mg/dL, p = 0.15). There was wide diversity in lipid lowering therapies between the two groups and a significantly higher prevalence of coronary artery and valvular disease in HoFH. Consequently, HoFH patients were more likely to receive percutaneous and surgical interventions at a younger age compared to HeFH patients.

Conclusions: The findings of this observational study show the clinical relevance of FH. Although both HeFH and HoFH are inherited disorders of lipoprotein metabolism, HoFH should be treated with a different, stricter therapeutic strategy to prevent premature ASCVD.

Aims: Small dense low-density lipoprotein cholesterol (sdLDLC) has been suggested to be more harmful for cardiovascular outcomes than total LDLC. This study aimed to clarify the prognostic significance of the estimated sdLDLC for the incidence of coronary artery diseases (CAD).

Methods: We analyzed the clinical information obtained at an annual health checkup of 365,083 adults aged 40–74 years enrolled in the National Health Insurance system in Japan. The incidence of CAD was determined using the health insurance claims data. Additionally, we calculated Japanese-specific coefficients of the sdLDLC estimation equation using general population data, where the measured sdLDLC value was available (n = 9,558).

Results: The estimated sdLDLC level calculated from the total LDLC and triglyceride levels was correlated with the measured sdLDLC level (coefficient of determination = 0.768) and it was significantly associated with the CAD incidence (hazard ratio per 10 mg/dL = 1.21, p＜0.001). Although the total LDLC showed a similar association, the estimated sdLDLC ≥ 30 mg/dL (hazard ratio = 1.97, p = 0.016) and ≥ 40 mg/dL (hazard ratio = 2.57, p = 0.001) were significantly associated with CAD, even in participants with normal LDLC levels (＜120 mg/dL). The cross-sectional association of the measured sdLDLC with the pulse wave velocity of the large artery (β = 0.034, p＜0.001) was significant, while that of the estimated sdLDLC (β = 0.014, p = 0.057) was not.

Conclusion: The estimated sdLDLC may be a straightforward and cost-effective marker for identifying individuals with normal LDLC levels at risk of CAD. However, the measured sdLDLC may be a more favorable marker than the estimated sdLDLC.

Aim: This study explored the association between retinol-binding protein 4 (RBP4) and cardiovascular events in patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI).

Methods: A total of 736 AMI patients who underwent successful PCI were prospectively enrolled between January 2020 and January 2022. The baseline RBP4 levels were measured by ELISA and categorized into quartiles. The incidence of major adverse cardiovascular events (MACEs), including all-cause mortality, recurrent myocardial infarction, revascularization, heart failure, and stroke, was assessed at the 1- and 3-year follow-up. Multivariate Cox proportional hazards models were used to evaluate the association between RBP4 and MACEs. A receiver operating characteristic (ROC) curve analysis was performed to determine the predictive efficiency of RBP4 for predicting the 1-year and 3-year MACEs.

Results: During follow-up, 110 (14.95%) and 165 (22.42%) patients developed MACEs at one and three years, respectively. Elevated RBP4 (the fourth quartile vs. the first quartile) was associated with an increased risk of MACEs (HR = 2.18, 95%CI = 1.42~4.37, P = 0.007) and heart failure (HR = 3.89, 95%CI = 1.68~5.75, P＜0.001) at the 1-year follow-up. Additionally, the elevated RBP4 were associated with an increased risk of MACEs (HR = 4.41, 95%CI = 2.57~7.31, P＜0.001), revascularization (HR = 3.43, 95%CI = 1.82~4.87, P＜0.001) and heart failure (HR = 7.12, 95%CI = 3.78~11.92, P＜0.001) at 3-year follow-ups. An ROC curve analysis revealed that the serum RBP4 cutoff for predicting the 1-year MACEs was 46.3 ng/mL (AUC = 0.74, 95%CI = 0.69~0.78, P＜0.001), and for predicting the 3-year MACEs, it was 43.9 ng/mL (AUC = 0.81, 95%CI = 0.77~0.85, P＜0.001). A Stratified Cox regression analysis suggested that the renal function did not significantly modify the association between RBP4 and MACEs.

Conclusion: Elevated RBP4 levels are independently associated with an increased risk of MACEs in patients with AMI post-PCI, thus highlighting its potential as a prognostic biomarker for risk stratification.

Aim: The clinical effect of high-intensity statin therapy after percutaneous coronary intervention (PCI) in Japanese patients with chronic coronary syndrome (CCS) remains unclear. We investigated the association between high-intensity statin therapy and the cardiovascular outcomes following PCI in patients with CCS.

Methods: We retrospectively evaluated 716 patients with CCS who underwent PCI and categorized them into high- or non-high-intensity statin groups, according to the Japan Atherosclerosis Society guidelines. The primary outcome was a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and revascularization, while the secondary outcome was all-cause death. The outcomes were further assessed according to the low-density lipoprotein cholesterol (LDL-C) levels (＜55 mg/dL, 55–69 mg/dL, and ≥ 70 mg/dL). The hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using the Cox model.

Results: Over a median follow-up of 2 years, high-intensity statin therapy reduced the incidence of the primary outcome (HR, 0.32; 95% CI, 0.17–0.61; P＜0.01) and all-cause death (HR, 0.18; 95% CI, 0.06–0.57; P＜0.01). This association with the primary composite outcome was consistently observed across the achieved LDL-C categories.

Conclusions: High-intensity statin therapy was associated with a reduced risk of cardiovascular events after PCI in Japanese patients with CCS, independent of the achieved LDL-C levels.

Aims: Preclinical studies have shown that remote ischemic conditioning (RIC) has a neuroprotective effect; however, the findings of clinical studies are inconsistent. This study aimed to show the effect of RIC on acute ischemic stroke while considering its severity at baseline.

Methods: We enrolled 79 patients with ischemic stroke who had National Institute of Health Stroke Scale (NIHSS) scores of 5–20 within 48 h after stroke onset and randomized them into the RIC [n = 43] and control groups [n = 36]. The intervention was performed using an inflatable cuff on one lower extremity. In the RIC group, each treatment consisted of four cycles of 5 min cuff inflation and deflation. The treatment was repeated once daily for at least three days. Based on the NIHSS score, the patients were divided into three groups: mild (NIHSS 5–9), moderate (NIHSS 10–14), and severe (NIHSS 15–20). The primary outcome was a good functional outcome at 90 days, defined as a modified Rankin Scale score of 0–1 in the mild group, 0–2 in the moderate group, and 0–3 in the severe group.

Results: Among the 79 patients (mean age, 65.0 years, 40 women), 7 (16.3%) in the RIC group and 8 (22.2%) in the control group had good functional outcomes (odds ratio, 0.73 [95% confidence interval, 0.29-1.82]; P = 0.502). The incidences of major adverse cardiovascular events, aspiration pneumonia, and serious adverse events were similar in both the groups.

Conclusion: Although this study may have been underpowered, RIC initiated within 48 h of stroke onset did not seem to improve the functional outcomes in acute ischemic stroke.

Aims: Data on recurrence and its patterns after paclitaxel-coated balloon (PCB) angioplasty for femoropopliteal artery disease are limited. We evaluated the incidence and predictors of re-recurrence according to the retreatment strategy (PCB or scaffold) and recurrence pattern (restenosis or reocclusion) in patients with recurrence after primary PCB therapy.

Methods: This multicenter retrospective study included 276 limbs of 246 patients who underwent repeat endovascular therapy (EVT) using either PCB (PCB group, n = 217) or a scaffold (scaffold group, n = 59) for primary PCB recurrence. The primary endpoint was 1-year freedom from re-recurrence, and secondary analyses identified the predictors of re-recurrence.

Results: In the PCB group, 174 restenotic and 43 reoccluded lesions were treated with PCBs. In the scaffold group, 32 restenotic and 27 reoccluded lesions were treated with scaffolds. In both groups, reoccluded lesions had significantly lower freedom from re-recurrence rates than restenotic lesions (PCB: 43.0% vs. 68.6%, p＜0.001; scaffold: 52.6% vs. 81.5%, p = 0.033). Freedom from re-reocclusion was also significantly lower in reoccluded lesions than in restenotic lesions (PCB: 48.5% vs. 88.6%, p＜0.001; scaffold: 65.8% vs. 93.2%, p = 0.033). The independent predictors of re-recurrence after PCB treatment were male sex (hazard ratio [HR] 2.01, p = 0.010), reoccluded lesions (HR 2.71, p = 0.001), poor BK run-off (HR 1.97, p = 0.020), use of first-generation low-dose PCB (HR 2.32, p = 0.017), and residual stenosis ＞30% (HR 2.60, p = 0.009). After scaffold treatment, reoccluded lesions were also identified as a significant predictor of re-recurrence (HR 2.99, p = 0.043).

Conclusion: Reocclusion after PCB therapy was strongly associated with subsequent re-recurrence, including re-reocclusion, regardless of the retreatment strategy.

Aim: The association between serum fatty acids and atherosclerotic disease remains unclear. In this cross-sectional study, we examined the association of serum fatty acids and the EPA/AA ratio with hypertriglyceridemia (HTG), a key metabolic factor underlying atherosclerosis.

Methods: A total of 2,413 adults aged 40–74 years were randomly selected after excluding those with clinically validated myocardial infarction or stroke. We analyzed the serum fatty-acid composition and categorized saturated fatty acids (SFA), monounsaturated fatty acids (MUFA), n-6 polyunsaturated fatty acids (PUFA), n-3 PUFA, and the EPA/AA ratio into quartiles, defined HTG at triglyceride levels ≥ 150 or ≥ 175 mg/dL in fasting or non-fasting samples, respectively, and calculated the adjusted odds ratios (AORs) and 95 % confidence intervals (CIs) using multivariable logistic regression.

Results: After adjusting for age, sex, body mass index, social status, lifestyle, and the self-reported medical history of hypertension, diabetes, dyslipidemia, other cardiovascular diseases, and cerebrovascular conditions (excluding validated myocardial infarction or stroke), the odds of HTG were significantly higher in the highest quartile of SFA (AOR, 8.13; 95 % CI, 5.62–11.77) and MUFA (AOR, 64.7; 95 % CI, 31.4–133.2). In contrast, higher n-6 PUFA (AOR, 0.02; 95 % CI, 0.01–0.04) and n-3 PUFA (AOR, 0.36; 95 % CI, 0.26–0.50) levels, and a higher EPA/AA ratio (AOR, 0.64; 95 % CI, 0.46–0.88) were associated with lower odds of HTG.

Conclusions: Higher serum SFA and MUFA were associated with increased odds, while higher n-6 PUFA, n-3 PUFA, and the EPA/AA ratio were associated with decreased odds of HTG.

Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent worldwide. Conventional fibrates effectively lower triglycerides but may elevate liver enzymes and creatinine, limiting long-term use. Pemafibrate, a selective PPARα modulator (SPPARMα), offers potent triglyceride reduction with favorable hepatic and renal safety. This study evaluated the effects of switching from conventional fibrates to pemafibrate on lipid profiles, liver enzyme, fibrosis indices(Fibrosis-4 index) with particular emphasis on renal safety in clinical practice.

Methods: We retrospectively analyzed 144 patients with dyslipidemia, including those with MASLD or chronic kidney disease, who were switched from bezafibrate 200mg (N = 24) or 400mg (N = 30), or fenofibrate 80mg (N = 51) or 160mg (N = 39), to pemafibrate (0.2mg/day). Laboratory parameters were assessed at baseline and 6 months post-switch.

Results: Triglycerides decreased significantly, particularly in the bezafibrate 200 mg and fenofibrate 80 mg groups, while other lipid profiles remained stable. Serum alanine aminotransferase decreased significantly with bezafibrate 200mg (29±27 to 17±13U/L, p＜0.05) and fenofibrate 80mg (26±18 to 20±10 U/L, p＜0.05), whereas treatment with bezafibrate (400mg) and fenofibrate (160mg) showed a trend toward reduction. The glutamyl transferase showed a similar trend. The Fibrosis-4 index showed reductions across all groups, reaching statistical significance in bezafibrate200mg (1.51±0.63→1.36±0.47, p = 0.02) and fenofibrate 80mg (1.17±0.37→1.07±0.33, p = 0.001). Renal function remained stable across all groups, with no clinically significant deterioration in estimated glomerular filtration rate, supporting the renal safety of pemafibrate.

Conclusion: Switching from conventional fibrates to pemafibrate improved triglyceride levels, liver enzymes, and fibrosis indices in patients with MASLD, while maintaining a favorable renal safety profile.

Aims: Lowering low-density lipoprotein cholesterol (LDL-C) is essential for reducing the risk of atherosclerotic cardiovascular disease (ASCVD). This study assessed the clinical efficacy of evolocumab, a human monoclonal antibody targeting PCSK9, in Japanese patients using data from the PROFICIO program.

Methods: Data were pooled from Japanese participants enrolled in five clinical trials: YUKAWA-1, YUKAWA-2, OSLER-1, OSLER-2, and FOURIER. The primary endpoint was percent change in LDL-C from baseline to Week 12. Secondary endpoints included changes in other lipid parameters, achievement of LDL-C targets, incidence of major adverse cardiovascular events (MACE), and subgroup analyses.

Results: A total of 1,040 patients with high cardiovascular risk or established ASCVD were included. At Week 12, the mean percent reduction in LDL-C was 75.7% with evolocumab compared with 1.3% with placebo (least-square mean treatment difference: ‑75.0%; 95% confidence interval [CI]: -76.7 to -73.4; p＜0.001), which was consistent across subgroups. Other lipid parameters showed directionally consistent percent changes, with variable magnitudes across markers. Overall, 92.9% of patients treated with evolocumab achieved an LDL-C ＜55 mg/dL at Week 12 compared with 0.8% of patients in the placebo group. In FOURIER, over a median follow-up of 2.1 years, incidence of MACE was lower with evolocumab than placebo (5.9% vs. 12.4%; hazard ratio: 0.47; 95% CI: 0.24–0.92). Treatment effects on MACE were consistent in both primary and secondary prevention groups (pooled odds ratio: 0.42; 95% CI: 0.23–0.79).

Conclusion: Evolocumab significantly and consistently lowered LDL-C and reduced the risk of MACE in Japanese patients.