Cardiovascular diseases (CVD) have imposed a substantial burden on population health and society. In Japan, the National Plan for the Promotion of Measures Against Cerebrovascular and Cardiovascular Disease, grounded in national legislation, seeks to improve the quality of care and standardize treatment for cerebrovascular disease and CVD. The plan emphasizes the need to develop standardized systems for collecting and disseminating medical information, as well as promoting data-driven research. The Japanese Registry Of All cardiac and vascular Diseases (JROAD) was launched by the Japanese Circulation Society to assess the clinical activities of institutions nationwide that have a dedicated cardiovascular inpatient service. Information from participating facilities is accumulated, and a database is constructed by linking Diagnosis Procedure Combination data, which includes patient characteristics and clinical data. Using this real-world data is expected to generate high-quality evidence, leading to a better understanding of CVD, improvements in the quality of care and clinical outcomes, and the implementation of effective health policies, including the appropriate allocation of medical resources and the reduction of medical costs. Ultimately, these efforts aim to extend the life span and healthy life expectancy. This design paper outlines the overall concept of the JROAD investigation in cardiovascular care. In addition, it summarizes representative CVD data, reviews the literature on the quality of care, and describes the prospects of the investigation.

Background: Intracoronary acetylcholine (ACh) provocation testing is a guideline-recommended invasive standard for diagnosing vasospastic angina (VSA)/coronary spastic angina. A positive ACh test is usually defined as significant epicardial vasospasm accompanied by signs of ischemia, namely chest symptoms and/or electrocardiographic (ECG) changes. However, the differential impact of diagnostic ACh test criteria on clinical characteristics and outcomes is unclear.

Methods and Results: From 2012 to 2024, 973 patients underwent ACh provocation testing for VSA diagnosis. Patients were divided into 3 groups: negative ACh test; and positive ACh test (2 groups), defined as significant epicardial vasospasm with either narrow (both chest symptoms and ECG changes) or broad (chest symptoms or ECG changes) definitions of signs of ischemia. Clinical characteristics and adverse outcomes during ACh testing and follow-up were compared among the 3 groups. In all, 356 (36.6%), 166 (17.1%), and 451 (46.4%) had positive ACh tests with narrow and broad definitions of ischemia and negative ACh tests, respectively. Among patients with positive ACh tests, there were no significant differences in baseline characteristics and adverse outcomes between those with narrow and broad definitions of ischemia.

Conclusions: In patients undergoing ACh provocation testing, there were no significant differences in clinical characteristics and outcomes between those diagnosed as having VSA using narrow and broad definitions of signs of ischemia, suggesting that either sign can be used as a criterion of ischemia.

Background: Comprehensive management of acute coronary syndrome (ACS) requires seamless treatment across institutions, including intensive care centers and local clinics. However, maintaining guideline-directed medical therapy remains challenging. One promising option to improve the situation may be the implementation of regional collaborative clinical pathways. This study evaluated the prevalence and functionality of such pathways for ACS in Japan.

Methods and Results: A nationwide survey was conducted through questionnaires and web searches, targeting all 47 prefectural managers of Japanese Circulation Association (JCA) branches. The study focused on pathways managed at the prefectural or regional levels, excluding inactive or institutional pathways. In all, 18 pathways were identified: 11 (23%) prefecture wide and 4 (9%) region wide. Most pathways included risk factor targets such as low-density lipoprotein cholesterol (LDL-C), HbA1c, and blood pressure, but only 8 pathways set an LDL-C target of <70 mg/dL. Pathways updated between 2022 and 2024 and incorporating LDL-C management protocols were considered functional. In all, 45 JCA branches viewed future ACS pathways established by the government or academic societies as potentially useful resources.

Conclusions: Regional collaborative clinical pathways for ACS patients in Japan show variable implementation across prefectures, with approximately one-third of prefectures having established pathways. Future efforts should prioritize the establishment of comprehensive, sustainable, and standardized pathways to optimize ACS management and improve patient outcomes nationwide.

Background: Patients with atrial fibrillation (AF) often present with symptoms similar to acute coronary syndrome (ACS), including chest pain and elevated levels of high-sensitivity cardiac troponin (hs-cTn). The 0/1-hour algorithm using hs-cTn is a rapid diagnostic tool endorsed by the European Society of Cardiology to rule out myocardial infarction (MI). However, because its effectiveness in patients with AF remains unclear, in this study we assessed the diagnostic accuracy of the 0/1-hour algorithm in patients with and without AF presenting with chest pain in the emergency department.

Methods and Results: We conducted a secondary analysis of the DROP-ACS cohort, including 1,333 patients from Japan and Taiwan, with AF in 10.3% of cases. We examined the algorithm’s negative predictive value (NPV), sensitivity, positive predictive value (PPV), and specificity for ruling MI in or out. Patients with AF were more frequently placed in the observe group (54% vs. 34.9%, P<0.05) and less often in the rule-out group (24.1% vs. 44.6%, P<0.05). The NPV and sensitivity for ruling out MI were 100%, while the PPV and specificity were lower in patients with AF (60% and 89.7%, respectively).

Conclusions: The 0/1-hour algorithm effectively ruled out MI in patients with AF, with high safety and accuracy. However, patients with AF are more likely to be stratified into the observe group, requiring further examination for final diagnosis.

Background: Hemodialysis (HD) is associated with adverse cardiovascular events after percutaneous coronary intervention (PCI). Although the ultrathin strut biodegradable polymer sirolimus-eluting stent (ultrathin strut BP-SES) has had better results in patients undergoing PCI compared with other drug-eluting stents (DES), its usefulness in HD patients is unknown.

Methods and Results: This study involved 286 lesions in 162 HD patients who underwent PCI with a DES between January 2018 and June 2022. The incidence of clinically driven target lesion revascularization (TLR), target vessel failure (TVF: cardiac death, target vessel MI and clinically driven target vessel revascularization [TVR]) was assessed. During a median 636 days, clinically driven TLR occurred in 32 lesions. Clinically driven TLR at 2 years was significantly lower in the ultrathin strut BP-SES group than in the other DES group (2.9% vs. 17.3%, log-rank P=0.028). TVF occurred in 43 patients. The cumulative incidence of TVF was not different between two groups; however, clinically driven TVR was significantly lower in patients treated with the ultrathin strut BP-SES than with other DES (4.5% vs. 25.7%, log-rank P=0.027). In the quantitative coronary angiography analysis, late lumen loss at follow-up was significantly smaller in the ultrathin strut BP-SES group (0.13±0.40 vs. 0.67±1.02 mm, P<0.001).

Conclusions: In patients on HD undergoing PCI, the incidence of clinically driven TLR was significantly lower in ultrathin strut BP-SES compared to other DES.

Background: There are few studies regarding the predictors of stent underexpansion (SUE) in post-debulking calcified lesions. We investigated predictors of SUE in severely calcified lesions after debulking using optical coherence tomography-guided rotational atherectomy (RA) or orbital atherectomy (OA).

Methods and Results: As a post hoc analysis of the DIRO trial, we compared various parameters, including calcium and lipid parameters (lipid-rich plaque, thin cap fibroatheroma [TCFA], maximum lipid arc, mean lipid arc, lipid length, and lipid volume index), between groups with adequate stent expansion (ASE) and SUE. To find predictors of SUE, multivariable analysis was performed using significant factors from the univariable analysis. We also evaluated adverse events 8 months after the procedure. The SUE group consisted of 57 (65.5%) patients. After suitable debulking of severely calcified lesions using RA or OA, there was no correlation between calcium parameters and SUE; however, the lipid parameters of maximum lipid arc ≥224° and TCFA were significantly and independently correlated with SUE Approximately 45% of severely calcified lesions contained lipid-rich plaques. Adverse events occurred more frequently in the SUE than ASE group.

Conclusions: The role of calcium parameters in predicting SUE in severely calcified lesions after suitable debulking using RA or OA is weak; however, maximum lipid arc and TCFA are important predictors of SUE.

Background: The effect of the location of calcification in the left main coronary artery (LMCA) bifurcation on cardiovascular events remains unclear.

Methods and Results: This retrospective study included 498 patients who underwent LMCA stenting at a single center between 2014 and 2018. Moderate or severe calcification was visually assessed by coronary angiography. The primary endpoint was 3-year target lesion failure (TLF), defined as cardiac death, target vessel myocardial infarction, or clinically driven target lesion revascularization. Most patients (n=314; 63.1%) had no calcification in the LMCA bifurcation. One-segment calcification was observed in 45 (9.0%) patients, primarily in the left anterior descending artery (LAD; n=43 [8.6%]). Two-segment calcification was observed in 81 (16.3%) patients, most commonly involving the LMCA and LAD (n=70; 14.1%). Three-segment calcification was observed in 58 (11.6%) patients. Overall, 58 (11.6%) patients developed TLF within 3 years. Multivariable Cox regression analysis revealed a significant association between calcification in the left circumflex artery (LCX) and 3-year TLF (adjusted hazard ratio [aHR] 4.46; 95% confidence interval [CI] 1.81–10.99; P=0.001). In contrast, there was no significant association between calcification at the LMCA (aHR 1.29; 95% CI 0.47–3.55; P=0.623) or LAD (aHR 0.49; 95% CI 0.17–1.45; P=0.199) and the primary endpoint.

Conclusions: Moderate or severe calcification in the LCX is significantly associated with 3-year TLF in patients who have undergone LMCA stenting.

Background: Percutaneous coronary intervention (PCI) is a good option for patients with ischemic cardiomyopathy (ICM) at high operative risk. However, evidence shows little benefit of PCI, potentially due to heterogeneity in ICM. Here, we applied latent class analysis (LCA) to clinical data to characterize ICM phenotypes based on clinical features and to assess differences in clinical outcomes.

Methods and Results: LCA was performed on data from 492 patients with a left ventricular (LV) ejection fraction <50% who underwent PCI. Primary outcomes included all-cause mortality and heart failure (HF) hospitalization. The optimal number of clinical phenotypes was 3. Phenotype 1 (n=101) was characterized by severe chronic kidney disease and a high frequency of hemodialysis. Phenotype 2 (n=192) included men with early-onset ICM, a high frequency of lifestyle-related diseases, and a high body mass index. Phenotype 3 (n=199) included older adults with a high prevalence of atrial fibrillation, moderate/severe mitral regurgitation, and high B-type natriuretic peptide levels. The risk of combined all-cause mortality and HF hospitalization was significantly lower for Phenotype 2 than the other phenotypes. LV reverse remodeling (LVRR) was associated with a lower incidence of the primary outcome in Phenotype 3, but not in the other phenotypes.

Conclusions: We identified differences in clinical outcomes and LVRR across clinical ICM phenotypes after PCI, suggesting distinct underlying mechanisms across ICM phenotypes that may benefit from targeted treatments.

Background: This study compared postoperative outcomes in patients with a preoperative left ventricular ejection fraction (LVEF) of ≤35% who underwent multiple (MAG) or single (SAG) arterial grafting during off-pump isolated coronary artery bypass grafting.

Methods and Results: Of 1,627 patients who underwent isolated coronary artery bypass grafting at Shiga University of Medical Science between 2002 and 2023, 176 with a preoperative LVEF ≤35% underwent MAG (n=115) or SAG (n=61). Baseline patient characteristics were comparable in the MAG and SAG groups after adjustment using inverse probability of treatment weighting. The study’s mean (±SD) follow-up duration was 4.8±4.7 years. In the MAG and SAG groups, the adjusted estimated 5-year rates of freedom from all-cause death were 71.5% and 69.1%, respectively, while those of cardiac death were 94.1% and 89.5%, respectively. Kaplan-Meier curves showed significant differences in all-cause death (P=0.013) and cardiac death (P=0.001) favoring the MAG group. In a multivariable Cox hazards model, MAG was a predictor of all-cause death (hazard ratio 0.568; P=0.034) and cardiac death (hazard ratio 0.276; P=0.008).

Conclusions: Compared with SAG, MAG was associated with significantly lower rates of all-cause death and cardiac death.

Background: This study evaluated the efficacy of dual antiplatelet therapy (DAPT) on the long-term prognosis of coronary artery bypass grafting (CABG) patients with high inflammatory risk.

Methods and Results: We analyzed 2,409 patients who underwent isolated CABG between January 2001 and December 2017 and had baseline high-sensitivity C-reactive protein (hs-CRP) levels >2.0 mg/L. Patients were divided into 2 groups: those on DAPT for ≥12 months (n=545) and those on single antiplatelet therapy (SAPT; n=1,864). The primary outcome was all-cause death or myocardial infarction (MI) after CABG. Propensity score (PS) matching was used to minimize confounding factors and selection bias. During follow-up, the ≥12-month DAPT group had a significantly lower risk of the primary outcome than the SAPT group (7.5% vs. 13.3%; hazard ratio [HR] 0.42; 95% confidence interval [CI] 0.24–0.72; P=0.002). After PS matching, the incidence of the primary outcome remained lower in the DAPT group (HR 0.36; 95% CI 0.19–0.71; P=0.003). The benefit of prolonged DAPT was consistent across subgroups.

Conclusions: In CABG patients with high inflammatory risk, prolonged DAPT (≥12 months) was associated with significantly lower rates of all-cause death or MI compared with SAPT.

Background: The efficacy of exercise-based cardiac rehabilitation (CR) in patients with angina and non-obstructive coronary artery disease (ANOCA) remains unclear. This study investigated whether a multidisciplinary CR program improves myocardial flow reserve (MFR), symptom status, and exercise capacity in patients with ANOCA.

Methods and Results: Myocardial blood flow at rest and during ATP-induced hyperemia was quantified using ¹³N-ammonia positron emission tomography (PET) in 29 patients diagnosed with ANOCA and impaired MFR (<2.5). Overall, 16 patients completed the 5-month CR program (complete CR group) and 13 did not (non-complete CR group). At baseline and the 5-month follow-up PET, symptom status and exercise capacity were assessed using the Seattle Angina Questionnaire (SAQ)-7 and cardiopulmonary exercise testing, respectively. The MFR in the complete CR group increased significantly (P=0.001) from a median of 1.60 (interquartile range [IQR] 1.43–1.98) to 2.09 (IQR 1.83–2.48). Significant improvements were also seen in the median SAQ-7 total score (from 16 [IQR 11–20] to 11 [IQR 8–14]; P=0.008) and peak oxygen consumption (V̇O₂; from 14.2 [IQR 12.4–15.8] to 15.3 [13.0–17.9] mL/kg/min; P=0.02). In contrast, there were no improvements in MFR (P=0.83) or peak V̇O₂(P=0.27) in the non-complete CR group.

Conclusions: The 5-month exercise-based CR significantly improved MFR, symptom status, and exercise capacity in patients with ANOCA and impaired MFR.

Background: Nodular calcification (NC) detected via intracoronary imaging is associated with adverse cardiovascular events after percutaneous coronary intervention (PCI). However, the impact of NC detected on pre-PCI non-contrast computed tomography (CT) on clinical outcomes has not been fully investigated.

Methods and Results: We retrospectively included 267 consecutive patients with chronic coronary syndrome who underwent electrocardiography-gated non-contrast CT before PCI for severely calcified lesions. The primary outcome was major adverse cardiac and cerebrovascular events (MACCE), a composite of all-cause death, stroke, non-fatal myocardial infarction, and target lesion revascularization (TLR). Fifty-eight patients had NC detected on non-contrast CT in target lesions. The MACCE-free survival rate was significantly lower in patients with than without NC (P<0.001). All-cause death, cardiac death, and TLR-free survival rates were significantly lower among patients with than without NC. Multivariate Cox regression analysis revealed that hemodialysis (hazard ratio [HR] 3.00; P=0.003), peripheral artery disease (HR 2.65; P=0.01), and the presence of NC (HR 5.25; P<0.001) were independently associated with MACCE. Adding NC to traditional cardiovascular risk factors, peripheral artery disease, and hemodialysis can provide discriminatory and reclassification abilities in predicting MACCE.

Conclusions: NC detected on non-contrast CT was independently associated with MACCE. Therefore, evaluating NC using preprocedural non-contrast CT may be useful in predicting future clinical outcomes after PCI.

Background: We previously reported that a high level of small dense low-density lipoprotein cholesterol (sdLDL-C) calculated by the Sampson equation was independently associated with the development of ischemic heart disease (IHD), but it remains unclear whether the effect depends on the level of low-density lipoprotein cholesterol (LDL-C).

Methods and Results: We investigated the associations of new onset of IHD with categorized groups of high (H-) and low (L-) levels of estimated sdLDL-C and LDL-C using 25^thpercentile levels of sdLDL-C level (25.2 mg/dL) and LDL-C (100 mg/dL) as cutoff values in 17,963 Japanese individuals (men/women: 11,508/6,455, mean age: 48 years) who underwent annual health checkups. During a 10-year follow-up period, 570 subjects (men/women: 449/121) had new development of IHD. Multivariable Cox proportional hazard analyses after adjustment of age, sex, smoking habit, hypertension and diabetes mellitus at baseline showed that the hazard ratio (HR) [95% confidence interval (CI)] for new onset of IHD was significantly higher in subjects with H-sdLDL-C/H-LDL-C (1.49 [1.06–2.08]) and subjects with H-sdLDL-C/L-LDL-C (1.49 [1.00–2.22]) than in subjects with L-sdLDL-C/L-LDL-C as the reference.

Conclusions: A high level of sdLDL-C estimated by the Sampson equation was a predominant predictor for the development of IHD, regardless of the level of LDL-C, in a general Japanese population.

Background: The Friedewald equation, commonly used to calculate low-density lipoprotein cholesterol (LDL-C), occasionally yields inaccurate estimations for very-low-density lipoprotein cholesterol, suggesting the need for an alternative method such as the Martin equation. In this study, we aimed to evaluate the discrepancies between the Friedewald and Martin equations, particularly in the context of pathogenic variants associated with familial hypercholesterolemia (FH).

Methods and Results: We evaluated the discrepancies between LDL-C levels calculated using the Friedewald and Martin equations, and for the presence of pathogenic variants of FH in 53 children with hypercholesterolemia detected through universal lipid screening. Genetic testing revealed pathogenic variants of FH in 24 of the 53 children. Chi-squared tests indicated a significant difference in the presence of pathogenic variants of FH between the “Friedewald ≥ Martin” and “Friedewald < Martin” groups (χ²=11.348, P<0.001). Even in 37 children with LDL-C <180 mg/dL, discrepancies between the equations were still associated with the presence of pathogenic FH variants (Fisher’s exact test, P=0.028).

Conclusions: Discrepancies in LDL-C levels measured by the Friedewald and Martin equations might serve as a useful predictive marker for identifying pathogenic variants of FH, especially in cases of LDL-C <180 mg/dL, which are often challenging to diagnose.

Background: The prognosis for survivors of acute coronary syndrome (ACS) remains substantially worse compared with the general population. In Japan, regional clinical alliance paths (RCAPs) have been promoted to support the secondary prevention of ACS within community settings. However, the implementation of RCAPs is currently low, and their clinical efficacy has not been established. This study evaluated the impact of RCAP implementation on secondary prevention outcomes in ACS patients.

Methods and Results: Of 405 patients admitted to Tottori University Hospital for ACS between May 2020 and April 2023, 136 who underwent primary percutaneous coronary intervention (PCI) and received follow-up care at primary care clinics were included in the study. Sixty-five (47.8%) patients received care under an RCAP, whereas 71 received standard care. RCAP implementation was associated with a higher proportion of patients achieving low-density lipoprotein cholesterol (LDL-C) levels below 70 mg/dL and with greater reductions in LDL-C levels overall. Propensity score-weighted analysis confirmed that the RCAP group achieved significantly better LDL-C control after adjustment for baseline characteristics using inverse probability weighting.

Conclusions: RCAP implementation improved the rate of LDL-C target achievement and the degree of LDL-C reduction in post-ACS patients receiving follow-up care from family physicians. RCAP implementation is an effective strategy for the secondary prevention of ACS, particularly by enhancing adherence to established pharmacological therapies.

Background: Lipid-lowering therapy with high-intensity statins has not been widely implemented in Japan for patients with coronary artery disease who undergo percutaneous coronary intervention (PCI). We examined the efficacy and safety of high-intensity statin therapy in a real-world setting.

Methods and Results: We used the Clinical Deep Data Accumulation System (CLIDAS) to accumulate multimodal data from the electronic medical records of 7 cardiovascular centers. We analyzed 9,690 patients who underwent PCI between 2013 and 2019 and completed a median 2.5-year follow-up (CLIDAS-PCI database). The risk of developing major adverse cardiac and cerebrovascular events (MACCE) was significantly greater in patients with acute (ACS) than chronic (CCS) coronary syndrome. High-intensity statins were prescribed to 49% of ACS patients and 33% of CCS patients within the first 30 days after the index PCI. After propensity score matching, MACCE event rates were similar between the high- and moderate-intensity statin groups. Importantly, among ACS patients, Cox proportional hazard analysis revealed that the rate of myocardial infarction was lower (adjusted hazard ratio [aHR] 0.65; 95% confidence interval [CI] 0.44–0.97) and the rate of stroke was greater (aHR 1.71; 95% CI 1.12–2.62) in the high-intensity statin group, driven mostly by intracranial hemorrhage.

Conclusions: The CLIDAS-PCI database provides real-world evidence for the efficacy and safety of high-intensity statins in Japanese ACS patients who have undergone PCI.

Background: Coronary artery disease (CAD) is a major cause of mortality worldwide. Serum carboxyl-terminal telopeptide of type I collagen (CITP), a marker of collagen degradation in the heart and blood vessels, is associated with plaque vulnerability and cardiac remodeling in patients with acute myocardial infarction. However, the effect of CITP on the clinical outcomes of patients with CAD has not yet been elucidated.

Methods and Results: Serum CITP concentrations were measured in 621 consecutive patients with CAD. All patients were prospectively followed up for a median period of 1,554 days. The primary endpoint was a composite of hospitalization for heart failure or cardiovascular death; the secondary endpoints were all-cause death and heart failure rehospitalization. B-Type natriuretic peptide and the left ventricular mass index were higher in the highest CITP tertile group. Kaplan-Meier analysis demonstrated that the CAD patients in the highest CITP tertile group had the greatest risk of both primary and secondary endpoints, independent of acute or chronic coronary syndrome. Multivariate Cox proportional hazard regression analysis demonstrated that CITP was an independent predictor of both primary and secondary endpoints after adjusting for confounding risk factors, regardless of acute or chronic coronary syndrome.

Conclusions: The serum CITP concentration could be a feasible marker for clinical outcomes in patients with CAD.

Background: Relative hyperglycemia, as defined by the stress hyperglycemia ratio (SHR), is linked to death and ischemic events in patients with acute coronary syndrome (ACS). As a modifiable factor, the association between SHR and bleeding risk after percutaneous coronary intervention (PCI) across different glycemic status remains unexplored.

Methods and Results: In this study, ACS patients treated with PCI were extracted from the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome (CCC-ACS) registry and the Tianjin Health and Medical Data Platform (THMDP). SHR was derived from admission fasting blood glucose and hemoglobin A1c. Patients were classified as having diabetes mellitus, pre-diabetes mellitus (Pre-DM), or normal glucose regulation. The primary outcome was in-hospital major bleeding. Among the 33,265 patients in the CCC-ACS cohort, major bleeding was recorded for 437. A high SHR (>1.0) independently predicted major bleeding in the total cohort (adjusted odds ratio [aOR] 1.51; 95% confidence interval [CI] 1.24–1.83), with the highest risk in the Pre-DM group (aOR 1.98; 95% CI 1.34–2.92). These findings were externally validated among 23,423 patients with myocardial infarction in the THMDP cohort. Early guideline-directed medical therapy mitigated the bleeding risk associated with a high SHR.

Conclusions: In this study, a high SHR was an independent risk factor for in-hospital major bleeding after PCI, particularly in patients with Pre-DM. Further clinical trials are needed to explore SHR-targeted therapies in Pre-DM.

Background: This study examined the association between Life’s Essential 8 (LE8) and the Korean population’s risk of all-cause and cardiovascular disease (CVD) mortality.

Methods and Results: This study included 21,482 adults aged ≥19 years who were enrolled in the Korea National Health and Nutrition Examination Survey. Cardiovascular health (CVH) was assessed using the LE8 score, which comprises the following 8 components: diet, physical activity, nicotine exposure, sleep health, body mass index, blood lipids, blood glucose, and blood pressure. The LE8 score ranges from 0 to 100 and was categorized as low (0–49), middle (50–79), high (≥80), with higher scores indicating better CVH. A Cox proportional hazards model was used to estimate hazard ratios, and the population attributable fraction (PAF) was used to determine individual risks associated with each CVH metric. During a median follow-up of 6.3 years, there were 709 all-cause and 122 CVD-related deaths. In the fully adjusted model, compared with low scores, middle and high LE8 scores were associated with 34% and 42% lower risks of all-cause mortality, respectively. A similar reduction in CVD mortality was observed with higher LE8 scores. Physical activity showed the highest PAF, contributing 37% for all-cause mortality and 51% for CVD mortality.

Conclusions: Higher LE8 scores were significantly associated with lower all-cause and CVD mortality. Physical activity had the greatest impact on PAF for mortality.

Background: HMGB2 is reported to be strongly associated with cardiovascular diseases, but its relationship with coronary collateralization is unclear.

Methods and Results: We determined the serum HMGB2 levels in 322 patients with type 2 diabetes and coronary chronic total occlusion (CTO), and evaluated the degree of coronary collaterals by Rentrop classification (poor collaterals: Rentrop score 0 or 1; good collaterals: Rentrop score 2 or 3). Anti-HMGB2 neutralizing antibody was administered in a diabetic ischemic hindlimb mouse model, followed by laser Doppler perfusion imaging and histological examinations. Human umbilical vein endothelial cells (HUVECs) were treated with HMGB2 to assess the potential mechanisms. Serum HMGB2 decreased stepwise across Rentrop score 0 to 3 (P<0.001), with significantly higher levels in patients with poor collaterals than in those with good collaterals (P<0.001). After adjustment for various confounders, HMGB2 remained an independent factor for poor coronary collateralization (adjusted odds ratio, 1.234; 95% confidence interval, 1.136–1.340; P<0.001). In diabetic mice with hindlimb ischemia, administration of anti-HMGB2 neutralizing antibody increased blood flow restoration. HMGB2 inhibited migration and tube formation of HUVECs in a dose-dependent manner under high-glucose and hypoxic conditions, and promoted NLRP3-mediated pyroptosis.

Conclusions: Elevated circulating HMGB2 was associated with poor coronary collateralization in CTO patients with diabetes. HMGB2 impaired angiogenesis and collateral vessel growth in diabetic mice. Such effects are mediated by NLRP3.

Background: Statins can effectively reduce low-density lipoprotein cholesterol (LDL-C), but additional options are needed for inadequate responses to statins or statin intolerance. Bempedoic acid is a small-molecule oral LDL-C-lowering drug that inhibits ATP citrate lyase, an enzyme 2 steps upstream of 3-hydroxy-3-methylglutaryl coenzyme A reductase in the metabolic pathway for cholesterol synthesis.

Methods and Results: The CLEAR-J trial evaluated bempedoic acid 180 mg/day for 12 weeks in Japanese patients with inadequately controlled LDL-C. Percentage changes in LDL-C between baseline and Week 12 (primary endpoint) were −25.25% and −3.46% in the bempedoic acid and placebo groups, respectively, with a significant between-group difference (−21.78%; 95% confidence interval [CI] –26.71%, –16.85%; P<0.001). Changes in secondary endpoints in the bempedoic acid and placebo groups were as follows: non-high-density lipoprotein cholesterol, −20.33% and −2.76%, respectively (between-group difference −17.57%; 95% CI −22.03%, −13.12%); total cholesterol −16.36% and −2.23%, respectively (between-group difference –14.13%; 95% CI −17.79%, −10.47%); and apolipoprotein B −18.10% and −0.67%, respectively (between-group difference −17.43%; 95% CI –21.97%, −12.89%). At 12 weeks, 62.5% of the bempedoic acid group had achieved target LDL-C values. Treatment-emergent adverse events appeared in 3 patients taking bempedoic acid and 2 patients taking placebo.

Conclusions: This study confirmed the safety and efficacy of bempedoic acid after 12 weeks treatment in Japanese patients with high LDL-C who had inadequate response to statins or statin intolerance.

Background: With aging of the population, atherosclerotic diseases have increased in Japan, with acute coronary syndrome (ACS) a significant cause of morbidity and mortality. In Kagoshima Prefecture, ACS mortality rates exceed the national average, reflecting challenges in lipid management and access to care.

Methods and Results: The Optimal Therapy for All Kagoshima Acute Coronary Syndrome (OK-ACS) Registry, initiated in April 2022, enrolled 2,328 ACS patients across Kagoshima. This study evaluated the impact of a standardized lipid management pathway, the “Kagoshima Style,” on low-density lipoprotein cholesterol (LDL-C) control and guideline adherence, as well as the regional profile of ACS in Kagoshima. The pathway was implemented at all percutaneous coronary intervention facilities to optimize lipid management and secondary prevention. LDL-C levels decreased significantly (P<0.0001) from admission to discharge and at 3 months (113.3±39.9, 74.6±28.0, and 69.2±25.9 mg/dL, respectively), with no difference according to place of residence. The proportion of patients with LDL-C <70 mg/dL increased from 12% at admission to 59% at 3 months. Maximum tolerated doses of high-intensity statin use increased from 7% at baseline to 9.3% after pathway implementation. Geographic disparities were evident, with patients from isolated islands experiencing delayed treatment access.

Conclusions: The Kagoshima Style pathway improved lipid management, reducing LDL-C and enhancing guideline adherence. This interim analysis provides insights into lipid management and regional disparities in patients with ACS across Kagoshima prefecture.