In Japan, cerebrovascular diseases and cardiovascular diseases (CVDs) are major causes of death and long-term care. Against this, the Cerebrovascular and Cardiovascular Disease Control Act was passed by a legislative body and promulgated in December 2018, and enacted on December 1, 2019. Based on the Japanese National Plan for Promotion of Measures Against Cerebrovascular and Cardiovascular Disease (Japanese National Plan), prefectural plans have been formulated and published from March 2021 to January 2023. Although the majority of individual measures were comprehensively articulated in accordance with the Japanese National Plan, some prefectures did not describe individual measures such as research, collection of medical information, consultation support for patients with CVD, palliative care, assistance for patients with sequelae, support for maintaining a balance between treatment and work, and measures from childhood and adolescence. Furthermore, a few specific indicators were set for these measures and those related to chronic care. This review identifies the current status of prefectural plans and discusses future challenges and directions.

Background: Elevated lipoprotein(a) [Lp(a)] levels are a causal risk factor for peripheral artery disease. However, data on their effect on delayed wound healing in patients with chronic limb-threatening ischemia (CLTI) are limited. The present study assessed the association between elevated Lp(a) levels and delayed wound healing in patients with CLTI.

Methods and Results: This study included 280 patients who successfully received endovascular therapy for CLTI between September 2016 and August 2021. High Lp(a) levels were defined as those >30 mg/dL. The primary outcome was wound healing. During a median follow-up of 20.4 months (interquartile range 6.8–38.6 months), 146 patients achieved wound healing. The wound healing rate at 24 months was significantly lower in the high Lp(a) than low Lp(a) group (41.1% vs. 86.3%, respectively; P<0.001). The adjusted risk ratio was 0.19 (95% confidence interval 0.13–0.29, P<0.001). Lp(a) levels of 31–50 and >50 mg/dL, but not 16–30 mg/dL, were significantly associated with delayed wound healing relative to Lp(a) levels of ≤15 mg/dL.

Conclusions: Elevated Lp(a) levels were independently associated with delayed wound healing in patients with CLTI treated with endovascular therapy.

Background: Although revascularization is first-line therapy for chronic limb-threatening ischemia (CLTI), there are no established treatments for patients in whom revascularization is not (or is a poor) option, including CLTI that has responded poorly to revascularization. This study verified the efficacy of the Rheocarna^®, a novel apheresis device, for no-option CLTI or poor-response CLTI after revascularization.

Methods and Results: This multicenter retrospective observational study analyzed 221 patients (221 limbs) with no- or poor-option CLTI (mean [±SD] age 71±10 years; males, 70.1%; diabetes, 76.5%; dialysis, 87.8%; Rutherford category 6, 26.4%) undergoing apheresis with the Rheocarna between March 2021 and March 2022. The primary endpoint was the 1-year wound-healing rate. After apheresis with the Rheocarna, C-reactive protein, fibrinogen, and low-density lipoprotein cholesterol (LDL-C) levels decreased significantly, and the ankle-brachial index (ABI) and skin perfusion pressure (SPP) increased significantly (all P<0.05). At 1 year, the wound-healing rate was 60.7%, and rates of limb salvage, freedom from reintervention, overall survival, and amputation-free survival were 83.4%, 69.2%, 70.2% and 61.3%, respectively. At baseline, non-ambulatory status, lower ejection fraction, and lower blood albumin levels were independently associated with a lower wound-healing rate.

Conclusions: Apheresis with the Rheocarna in patients with no- or poor-option CLTI reduced LDL-C and fibrinogen levels and improved ABI and SPP, achieving a 1-year wound healing rate of 60.7%. This novel approach could provide additional treatment options for conventional CLTI.

Background: Endovascular therapy (EVT) with a drug-coated balloon (DCB) is an established treatment for patients with atherosclerotic lesions in the femoropopliteal (FP) artery, including complex lesions. Currently, 3 types of DCBs are available, but the most effective DCB for FP chronic total occlusive (CTO) lesions is unknown.

Methods and Results: In this retrospective, single-center study, we enrolled 539 consecutive patients (562 FP lesions) treated with EVT between January 2018 and December 2022. Of these patients, 161 with FP CTO lesions who underwent EVT with DCBs were included. Propensity-score matching was performed to compare the clinical outcomes of the high-dose (HD) and low-dose (LD) DCB groups, resulting in the analysis of 56 matched pairs. Primary patency and freedom from target lesion revascularization were significantly higher with HD-DCB than with LD-DCB (89.9% vs. 70.8%, respectively P=0.03; and 93.6% vs. 79.7%, respectively, P=0.046). Multivariate analysis showed that a larger minimum lumen area and the use of HD-DCB (vs. LD-DCB) were favorable predictors of primary patency at 1 year, while a small vessel diameter (≤4.5 mm) was an unfavorable predictor.

Conclusions: For FP CTO lesions, EVT performed with HD-DCB is superior to that with LD-DCB.

Background: Fluoropolymer-coated drug-eluting stents (FP-DESs) are widely used to treat femoropopliteal artery (FPA) disease. However, data on the pattern and timing of recurrence after FP-DES implantation are limited. This study aimed to address this knowledge gap.

Methods and Results: This multicenter retrospective study analyzed 439 limbs of 398 patients treated with FP-DESs for de novo FPA lesions. The outcome measures were clinical outcomes in cases of recurrence, defined as a composite of restenosis and reocclusion. The timing of recurrence was categorized into early (within 1 year of treatment) and late (after 1 year). The factors associated with recurrence were analyzed by comparing cases of early and late recurrence. The early recurrence group showed a significantly higher frequency of reocclusion, particularly stent thrombosis. In addition, in this group, patients with reocclusion tended to exhibit significantly more severe clinical symptoms than those with restenosis. Deployment of FP-DES beyond the P1 segment was independently associated with early recurrence. Chronic total occlusion was independently associated with early reocclusion. Female sex, diabetes, not using statins, and long lesions were independently associated with late recurrence. Not using statins, warfarin use, and long lesions were independent predictive factors for late reocclusion.

Conclusions: The patterns and clinical symptoms of recurrence after FP-DES implantation for FPA differed according to the timing of recurrence, as did the factors associated with recurrence.

Background: This study analyzed the risk factors for type 1a endoleak after hybrid thoracic endovascular repair (TEVAR) for aortic arch diseases based on preoperative patient characteristics and multidetector computed tomography measurements.

Methods and Results: In all, 213 patients who underwent proximal landing zone 1 and 2 hybrid TEVAR for aortic arch pathologies (zone 1, n=82 [38.5%]; zone 2, n=131 [61.5%]; median age 72 years) between May 2008 and February 2020 were enrolled in this study; the median follow-up period was 6.0 years. The rates of type 1a endoleak at 1, 3, 5, and 10 years were 1.4%, 1.4%, 4.1%, and 4.1%, respectively. Multivariate Cox proportional hazard regression analysis revealed that the angle of the aortic arch was a significant risk factor for type 1a endoleak (hazard ratio 1.08; 95% confidence interval 0.85–0.99; P=0.045). The estimated area under the curve in receiver operating characteristic curve analysis was 0.76, and the cut-off value of the aortic arch angle was 95°.

Conclusions: It is essential to prevent type 1a endoleak, the most severe complication of hybrid TEVAR. The risk factor for type 1a endoleak in this study was a sharper angle of the aortic arch (≤95°). For patients at high risk of type 1a endoleak, it is necessary to consider alternative procedures depending on a patient’s surgical risk.

Background: White blood cell (WBC) counts were reported to be a risk factor for acute adverse events in patients with venous thromboembolism (VTE). However, there are limited data on VTE patients without active cancer.

Methods and Results: The COMMAND VTE Registry-2 was a multicenter study enrolling 5,197 consecutive patients with acute symptomatic VTE. We divided 3,668 patients without active cancer into 4 groups based on WBC count quartiles (Q1–Q4) at diagnosis: Q1, ≤5,899 cells/μL; Q2, 5,900–7,599 cells/μL, Q3, 7,600–9,829 cells/μL; and Q4, ≥9,830 cells/μL. Patients in Q4 more often presented with pulmonary embolism (PE) than patients in Q1, Q2, and Q3 (68% vs. 37%, 53%, and 61%, respectively; P<0.001). The proportion of massive PEs among all PEs was higher in Q4 than in Q1, Q2, and Q3 (21% vs. 3.4%, 5.8%, and 11%, respectively; P<0.001). Compared with Q1, Q2, and Q3, patients in Q4 had a higher cumulative 5-year incidence of all-cause death (17.0%, 15.2%, 16.1%, and 22.8%, respectively; P<0.001) and major bleeding (10.9%, 11.0%, 10.3%, and 14.4%, respectively; P=0.002). The higher mortality risk of Q4 relative to Q2 was consistent regardless of the presentations of VTEs.

Conclusions: An elevated WBC count on VTE diagnosis was associated with a higher risk of mortality and major bleeding regardless of VTE presentation, suggesting the potential usefulness of WBC counts for further risk stratification.

Background: Accurate prediction of short-term mortality in patients with acute pulmonary embolism (PE) is critical for optimizing treatment strategies and improving patient outcomes. The Pulmonary Embolism Severity Index (PESI) is the current reference score used for this purpose, but it has limitations regarding predictive accuracy. Our aim was to develop a new short-term mortality prediction model for PE patients based on deep learning (DL) with multimodal data, including imaging and clinical/demographic data.

Methods and Results: We developed a novel multimodal deep learning (mmDL) model using contrast-enhanced multidetector computed tomography scans combined with clinical and demographic data to predict short-term mortality in patients with acute PE. We benchmarked various machine learning architectures, including XGBoost, convolutional neural networks (CNNs), and Transformers. Our cohort included 207 acute PE patients, of whom 53 died during their hospital stay. The mmDL model achieved an area under the receiver operating characteristic curve (AUC) of 0.98 (P<0.001), significantly outperforming the PESI score, which had an AUC of 0.86 (P<0.001). Statistical analysis confirmed that the mmDL model was superior to PESI in predicting short-term mortality (P<0.001).

Conclusions: Our proposed mmDL model predicts short-term mortality in patients with acute PE with high accuracy and significantly outperforms the current standard PESI score.

Background: This study aimed to clarify recent clinical features and treatment outcomes in Japanese patients with newly diagnosed Takayasu arteritis (TAK) during the first 2 years of treatment.

Methods and Results: A nationwide multicenter retrospective cohort study for TAK was implemented to collect data between 2007 and 2014. The primary outcome of the study was clinical remission at Week 24. Of the 184 participants registered, 129 patients with newly diagnosed TAK were analyzed: 84% were female and the mean age at onset was 35 years. Clinical symptoms at diagnosis were mostly associated with large-vessel lesions. Frequent sites of vascular involvement included the carotid artery, subclavian artery, aortic arch, and descending aorta. The mean initial dose of prednisolone administered was 0.68 mg/kg/day, and 59% and 17% of patients received immunosuppressive drugs and biologics, respectively, by Week 104. Clinical remission at Week 24 and sustained clinical remission with daily prednisolone at ≤10 mg at Week 52 were achieved in 107 (82.9%) and 51 (39.5%) patients, respectively. The presence of signs and symptoms linked to large-vessel lesions was associated with failure to achieve sustained clinical remission at Week 52.

Conclusions: We elucidated the clinical characteristics, treatment outcomes, and factors associated with failure to achieve sustained clinical remission in patients with newly diagnosed TAK in Japan during the first 2 years of treatment.

Background: Biological age serves as a common starting point for various age-related diseases and can be associated with a wide range of cardiovascular outcomes. However, associations between cardiovascular biological age (CBA) and various types of cardiovascular disease (CVD) remain unclear.

Methods and Results: Analyzing 262,343 UK Biobank participants, we constructed CBA based on composite biomarkers using the Klemera-Doubal method (denoted as KDM-CBA). We measured KDM-CBA acceleration as the difference between KDM-CBA and chronological age. We then examined the associations between KDM-CBA and 17 CVD types using Cox proportional hazard models. We used restricted cubic spline models to assess potential nonlinear associations of KDM-CBA and KDM-CBA acceleration with different types of CVDs. We observed that KDM-CBA (per 1SD increase) was associated with various CVD types, but with different extent (hypertension: hazard ratio (HR)=2.115, 95% confidence interval (CI): 2.083–2.148; coronary atherosclerosis: HR=1.711, 95% CI: 1.545–1.896). We observed similar results for KDM-CBA acceleration and KDM-CBA. KDM-CBA and KDM-CBA acceleration showed J-type nonlinear associations with nearly all CVD types (cutoff values of ≈55 and −1.7 years for KDM-CBA and KDM-CBA acceleration, respectively).

Conclusions: Our study showed that CBA is associated with increased incidence of CVD, which further validates aging as a common starting point for different CVD types as well as highlighting CBA’s role as an early CVD indicator, providing valuable insights for CVD interventions.

Background: The relationship between cumulative non-high-density lipoprotein-cholesterol (cum-non-HDL-C) and the risk of new-onset arterial stiffness has not been characterized.

Methods and Results: A total of 6,852 participants with 3 consecutive measurements of total cholesterol and HDL-C and a baseline brachial-ankle pulse wave velocity (baPWV) <1,400 cm/s during 2010–2011, 2012–2013, and 2014–2015 were included. The cum-non-HDL-C concentrations were determined using time weighting, and the participants were grouped: G1 <130 mg/dL, G2 130–159 mg/dL, G3 160–189 mg/dL, and G4 ≥190 mg/dL. Cox models were used to characterize the relationships between cum-non-HDL-C and arterial stiffness by calculating hazard ratios (HRs) and 95% confidence intervals (CIs). Arterial stiffness (baPWV ≥1,800 cm/s) was present in 327 (4.77%) participants over a median follow-up period of 7.7 (interquartile range 7.2–8.2) years. After adjustment for multiple confounders, G2–4 had adjusted HRs (95% CIs) of 1.12 (0.85, 1.48), 1.45 (1.05, 1.99), and 2.52 (1.69, 3.74), respectively (P=0.0004), vs. G1. The adjusted HRs (95% CIs) for exposures of 2, 4, and 6 years were 1.17 (0.87, 1.58), 1.46 (1.96, 2.01), and 1.67 (1.14, 2.44), respectively (P=0.0029), vs. 0 years. Restricted cubic spline analysis revealed a linear dose–response relationship between cum-non-HDL-C and arterial stiffness risk.

Conclusions: A high cum-non-HDL-C concentration and prolonged exposure to this increase the risk of arterial stiffness. The monitoring and maintenance of appropriate cum-non-HDL-C may reduce the risk of arterial stiffness.

Background: The effect of guideline-directed medical therapy (GDMT) on mid-term mortality in Asian patients, including Japanese patients, who have undergone endovascular therapy (EVT) for lower extremity artery disease remains still unclear. This study evaluated the effects of GDMT, defined as the combined prescription of antiplatelet agents, statins, and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, on 2-year mortality in Japanese patients undergoing EVT for femoropopliteal (FP) lesions.

Methods and Results: In this multicenter retrospective study, 1,756 registered patients were divided into 2 groups: those who received all 3 medications that comprised GDMT (full GDMT group) and those who received ≤2 medications (non-GDMT group). After propensity score matching, the baseline characteristics did not differ significantly between the 413 pairs of participants in the full GDMT and non-GDMT groups. All-cause mortality within 2 years was significantly lower in the full GDMT than non-GDMT group (14.3% vs. 20.8%; log-rank P=0.030). Mortalities from cardiovascular and cardiocerebrovascular diseases within 2 years were also significantly lower in the GDMT group (4.2% vs. 9.5% [log-rank P=0.021] and 4.2% vs. 10.5% [log-rank P=0.007], respectively).

Conclusions: In Japanese patients undergoing EVT for FP lesions, GDMT may improve all-cause, cardiovascular, and cardiocerebrovascular mortality within 2 years.

Background: In large clinical trials, sodium-glucose cotransporter 2 (SGLT2) inhibitors have improved prognosis in heart failure with preserved ejection fraction (HFpEF). Although several beneficial pharmacological effects of SGLT2 inhibitors for HFpEF have been suggested, their presumed metabolic pathways remain insufficiently proven.

Methods and Results: We compared the metabolomic profile, determined using liquid chromatography–mass spectrometry, of 16 patients with HFpEF before and after empagliflozin therapy. Only citrulline levels (expressed as a ratio to methionine sulfone levels) were significantly elevated after therapy (3.57±1.88 vs. 6.47±3.78; P=0.006).

Conclusions: Empagliflozin significantly increased citrulline levels in HFpEF patients. Although further studies are needed, it would be intriguing if this metabolite change were related to the cardiovascular protective effects of empagliflozin.