Hyperuricemia, the biochemical precursor to gout, is usually defined as the theoretical limit of solubility of serum uric acid (UA) of ＞7.0 mg/dL. Hyperuricemia is closely associated with hypertension, diabetes mellitus, and dyslipidemia, which are well known to be related to risk factors for coronary artery disease (CAD). Furthermore, hyperuricemia has been associated with increased mortality in both the general population and individuals with cardiovascular diseases. Elevated UA in patients with CAD is accompanied by surrogate markers of atherosclerosis, including C-reactive protein, platelet activation, and endothelial dysfunction, which can contribute to possible pathogenic links between hyperuricemia and subsequent adverse cardiovascular events. Similarly, patients with gout have higher rates of cardiovascular diseases than those without it, independent of traditional cardiovascular risk factors. Gout is a disease with variable levels of inflammation, driven by deposition of monosodium urate (MSU) crystals. Recent imaging technology has revealed that deposition of MSU crystals can occur in the coronary arteries as well as the joints. However, current evidence does not support the efficacy of urate-lowering therapy on reducing cardiovascular events in patients with hyperuricemia; therefore, identifying individuals who may benefit from a sustained decrease in UA is crucial. We herein review the current understanding and future perspectives for management of hyperuricemia as a residual risk in patients with CAD.

Aim: Per- and polyfluoroalkyl substances (PFASs) are widespread environmental pollutants that were previously associated with dyslipidemia and type 2 diabetes mellitus (T2DM). We therefore investigated the association between PFAS exposure and clinical outcomes after percutaneous coronary intervention (PCI) in patients with T2DM and assessed the extent to which lipidomic alterations mediate this association.

Methods: This case-control study was nested within a prospective cohort of patients with type 2 diabetes who underwent primary PCI for obstructive coronary artery disease between September 2017 and September 2019. During the 2-year follow-up after PCI, 150 matched pairs of patients with T2DM who did not experience major adverse cardiovascular and cerebrovascular events (MACCEs) were included. Serum PFASs and lipidomes were measured at baseline using liquid chromatography–mass spectrometry and analyzed using multipollutant models and integrative approaches.

Results: Overall, a higher exposure to a mixture of nine PFASs was associated with an increased odds of two-year MACCEs after PCI, with perfluoroundecanoic acid and perfluorodecanoic acid contributing the most to the association. Integration with the serum lipidome generated a network of 110 PFAS-associated lipids with differential contributions to discriminating MACCEs, half of which were identified as significant mediators explaining 9.6%–56.4% of the PFAS-MACCE association. Furthermore, we estimated a cluster of patients with high probabilities of developing MACCEs after PCI, characterized by high PFAS levels; increased abundance of phosphatidylcholine, triacylglycerol, diacylglycerol, and acylcarnitine lipids; and decreased abundance of phosphatidylethanolamine and phosphatidylethanol lipids.

Conclusion: With mediation by serum lipidomic perturbations, PFAS exposure contributes to poor outcomes after PCI in patients with T2DM.

Aim: Women with familial hypercholesterolemia (FH) face specific challenges during pregnancy and childbirth, such as treatment restrictions and the absence of guidelines. This study therefore assessed the status of perinatal management and the needs of women with FH.

Methods: We contacted 240 board-certified FH specialists, and these physicians screened eligible patients for the survey. Two internet-based surveys were conducted between August 2023 and March 2024: one for physicians and one for women with FH.

Results: A total of 72 physicians completed the questionnaires. Fifty-seven percent had managed pregnant women with FH, and 64% reported difficulties, including “selecting and adjusting treatment options” and “the absence of guidelines on pregnancy and childbirth for women with FH.” Few physicians referred their patients to obstetricians prior to pregnancy. Eighty-three women with FH completed a questionnaire. Among those who had given birth after being diagnosed with FH, the most common problems reported were “could not be treated,” “obstetricians’ insufficient knowledge of FH,” and “insufficient information about pregnancy and delivery for women with FH.” Half of these women discontinued treatment for over one year. In addition, 78% of women indicated a need for counseling on pregnancy-related matters.

Conclusion: Many physicians have reported challenges in managing pregnant women with FH, and some women have lost years of treatment during pregnancy-related periods. Women with FH should receive advice on planned pregnancy and breastfeeding to balance FH treatment with childbearing and parenting, and obstetricians should actively collaborate with physicians.

Aims: Healed plaque (HP) is associated with rapid plaque growth and luminal narrowing. Thin-cap fibroatheroma (TCFA) is recognized as a precursor lesion to plaque rupture. The aim of the present study was to compare the lipid size among optical coherence tomography (OCT)-derived HP, TCFA, and thick-cap fibroatheroma (ThCFA) using near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS).

Methods: The present study included 173 patients with acute myocardial infarction (AMI) who underwent percutaneous coronary intervention. Non-culprit lesions with angiographically intermediate stenosis were assessed by both OCT and NIRS-IVUS.

Results: The frequency of TCFA, HP, and ThCFA was 35 (20%), 53 (30%), and 85 (49%), respectively. Minimum lumen area was not significantly different between TCFA and HP, but was smaller in TCFA and HP than in ThCFA (4.6 [interquartile range {IQR}: 3.5-6.4] mm² vs. 4.3 [3.4-5.3] mm² vs. 6.5 [4.8-8.6] mm², P＜0.001). Plaque burden was not significantly different between TCFA and HP, but was larger in TCFA and HP than in ThCFA (72 [IQR: 66-80] % vs. 75 [67-80] % vs. 62 [54-69] %, P＜0.001). Maximum lipid core burden index in 4mm (maxLCBI_4mm) was largest in TCFA, followed by HP and ThCFA (493 [IQR: 443-606] vs. 446 [347-520] vs. 231 [161-302], P＜0.001). The frequency of lipid rich plaque with maxLCBI_4mm ＞400 was highest in TCFA, followed by HP and ThCFA (89% vs. 60% vs. 7%, P＜0.001).

Conclusions: Based on NIRS-IVUS findings, non-culprit coronary HP in AMI was associated with vulnerable plaque characteristics, but not as much as TCFA.

Aims: To present an update on undiagnosed coronary artery disease (CAD) in patients starting hemodialysis at a Japanese hospital, with a focus on CAD prevalence, risk factors, and coronary lesions’ distribution in this population.

Methods: A cross-sectional, retrospective study of patients who began hemodialysis due to end-stage renal disease (ESRD) in a Japanese hospital between January 2009 and December 2023 and underwent coronary computed tomography (CCT) was carried out. Coronary artery disease was screened using CCT immediately after the initiation of hemodialysis and then confirmed by CCT/coronary angiography (CAG). Based on these evaluations, patients were divided into CAD and non-CAD groups, and their demographic and clinical characteristics were compared. Logistic regression analysis was performed to detect factors associated with CAD. Additionally, variations in CAD prevalence and coronary artery calcification scores (CACS) over time were assessed considering 3-year intervals.

Results: Data from 272 patients were included. CAD was observed in nearly half (47%) of them. Lesions were mainly observed in the left anterior descending artery (73%). The prevalence of a coronary artery calcification score of ＞65 notoriously increased from 2012–2014 to 2015–2017 and thereafter stabilized, while the proportion of patients diagnosed with CAD tended to decrease overall. Multiple regression analysis indicated that only a history of smoking, statin use, low albumin levels, and low HDL-C levels were independently and significantly associated with CAD occurrence in these ESRD patients.

Conclusions: Many well-known CAD risk factors in the general population were not predictors of undiagnosed CAD in our target population.

Aim: Serum syndecan-1 (SDC-1) concentration is a biomarker for endothelial glycocalyx (EG) degradation, which is elevated in type 2 diabetes (T2D). EG degradation is an early step in vascular endothelial dysfunction. This study investigated the association between serum SDC-1 concentration and visceral fat accumulation, which is closely related to vascular endothelial dysfunction, in people with and without T2D.

Methods: This was a cross-sectional study with two independent groups, one including 219 individuals without diabetes (ND) and the other including 203 individuals with T2D. Visceral fat accumulation was assessed as the visceral fat area (VFA) using computed tomography (CT) in ND or dual bioelectrical impedance analysis (BIA) in T2D. Multivariate analyses were performed for ND and T2D to assess the association between VFA and serum SDC-1 concentrations.

Results: The medians of serum SDC-1 concentration were 16.0 ng/mL and 26.5 ng/mL in ND and T2D, respectively. In the univariate analysis, both CT-VFA in the ND group and BIA-VFA in the T2D group were positively correlated with serum SDC-1 concentration. Moreover, the association between VFAs and serum SDC-1 concentration was independent of other covariates in multivariate analysis for each group. However, neither the body mass index nor subcutaneous fat area were associated with serum SDC-1 concentrations in either group.

Conclusions: CT-VFA and BIA-VFA were independently associated with serum SDC-1 concentrations. Our findings suggest that visceral fat accumulation is involved in the degradation of EG irrespective of the presence of T2D.

Aim: This study investigated regional disparities in the incidence, management, and in-hospital outcomes of critical limb ischemia (CLI) in Japan to inform standardized care practices.

Methods: We conducted a retrospective cohort study using the nationwide Diagnosis Procedure Combination database, including patients ≥ 18 years old who were discharged from acute-care hospitals between April 2018 and March 2020. Patients with CLI were identified using ICD-10 codes and restricted to those undergoing invasive treatments including endovascular therapy (EVT), bypass surgery, or amputation. Regional differences in patient demographics, in-hospital management, and outcomes were analyzed across seven regions in Japan.

Results: In total, 19,699 records were identified. CLI admissions per million population were highest in the Kyushu region (112.1) and lowest in the Kanto region (59.9). The proportion of patients with a body mass index (BMI) ＜18.5 kg/m² ranged from 17.8% (Kanto) to 23.9% (Kansai), while the proportion with a BMI ≥ 30.0 kg/m² ranged from 3.3% (Kyushu) to 8.2% (Okinawa). The proportion of patients requiring dialysis ranged from 33.8% in the Chugoku-Shikoku region to 38.2% in the Okinawa region (P = 0.005). Anti-platelet agents were prescribed to 82.1% of patients with CLI, whereas statins were prescribed to 36.1% of patients. The EVT rates varied from 67.6% (Hokkaido-Tohoku) to 84.8% (Kansai) (P＜0.001), while the amputation rates varied from 22.2% (Kansai) to 33.4% (Chugoku-Shikoku) (P＜0.001). The in-hospital mortality rates varied from 5.7% (Chugoku-Shikoku) to 10.9% (Okinawa) (P = 0.001).

Conclusions: This study revealed significant regional disparities in CLI incidence, management, and outcomes across Japan. These findings highlight the need for standardized, evidence-based care strategies that address regional disparities to improve outcomes for patients with CLI.

Aims: Stroke severity may affect the benefits and safety of antiplatelet therapies. We aimed to investigate whether the efficacy and safety of indobufen versus aspirin were affected by stroke severity.

Methods: We compared the efficacy and safety of indobufen versus aspirin in patients with NIHSS scores of 4–6, 7–9, and 10–18. The primary efficacy outcome was new stroke (ischemic or hemorrhagic) within 90 days, and the primary safety outcome was moderate or severe bleeding within 90 days. The non-inferiority criteria were set at 1.25 for the upper bounds of the 95% CI of the HR for indobufen versus aspirin based on the statistical analysis of the primary clinical trial.

Results: In total, 3921 patients presented with NIHSS scores of 4–6, 998 patients presented with NIHSS scores of 7–9, and 515 patients presented with NIHSS scores of 10–18. The risk of the primary outcome among patients with NIHSS scores of 4–6 was higher in indobufen group than that in aspirin group (HR, 1.62; 95% CI, 1.26 to 2.08). However, indobufen was non-inferior to aspirin in patients with NIHSS scores of 7–9 (HR, 0.66; 95% CI, 0.38 to 1.15; non-inferiority P = 0.01) and NIHSS scores of 10–18 (HR, 0.49; 95% CI, 0.23 to 1.05; non-inferiority P = 0.008), with a significant statistical interaction (P = 0.001). Moderate or severe bleeding risk differences between treatments did not vary with stroke severity.

Conclusions: This exploratory analysis indicates that the benefit of indobufen in reducing new strokes within 3 months may vary across stroke severity. The potential non-inferiority of indobufen relative to aspirin in patients with NIHSS scores of ≥ 7, with no significant difference in safety, requires further study.

Aim: To investigate the association between a prolonged heart rate-corrected QT (QTc) interval on a 12-lead electrocardiogram and the risk of developing dementia and its subtypes using long-term prospective longitudinal data from a Japanese community.

Methods: A total of 1,082 residents ≥ 60 years old without dementia were followed up for 24 years. The QT interval was corrected for the heart rate using Bazett’s equation. QTc prolongation was defined as QTc ≥ 440 ms, and participants with QTc ＜440 ms were divided into tertiles. Therefore, QTc interval levels at baseline were divided into 4 ranges: ≤ 401, 402–417, 418–439, and ≥ 440 ms. The Cox proportional hazards model was used to estimate the hazard ratios (HRs) of QTc interval levels on the risk of dementia.

Results: During the follow-up period, 475 participants developed all-cause dementia, 146 had vascular dementia (VaD), and 295 had Alzheimer’s disease (AD). Compared with the lowest QTc level (≤ 401 ms), the multivariable-adjusted HRs for VaD increased significantly with longer QTc intervals (HR [95% confidence interval] 1.80 [1.05 to 3.08] for 402–417 ms, 1.93 [1.12 to 3.34] for 418–439 ms, and 2.64 [1.49 to 4.68] for ≥ 440 ms; p for trend = 0.01). No significant association was found between QTc interval and the risk of both all-cause dementia and AD.

Conclusion: The present findings suggest that QTc prolongation serves as a potential indicator for identifying individuals at a high risk of developing VaD. QTc measurement may assist in the primary prevention of VaD.

Familial lecithin–cholesterol acyltransferase (LCAT) deficiency with a primary LCAT gene mutation results in various conditions, including corneal opacity, anemia, kidney disease, and low high-density lipoprotein (HDL) levels. In recent years, secondary LCAT deficiency with nearly identical symptoms has been identified as a rare case of immune-mediated acquired LCAT deficiency caused by LCAT autoantibodies. In limited cases, prednisolone treatment is required for severe conditions and has been shown to favorably modulate LCAT autoantibodies and restore LCAT activity, resulting in improved HDL-cholesterol (HDL-C) levels, renal dysfunction, and other complications. However, there is little detailed information regarding LCAT activity, lipid changes, and renal dysfunction after the initiation of prednisorone treatment. In the present study, in addition to the effects on LCAT activity, lipids, and proteinuria, we for the first time monitored the HDL cholesterol efflux capacity (CEC), an important anti-atherosclerotic HDL function, during the first month of treatment in a patient with this disease. We found that the LCAT activity, HDL-C concentration, and HDL CEC increased from undetectable or low values to normal ranges during this period, as did proteinuria. Specifically, the HDL CEC and LCAT activity recovered faster than the HDL-C levels. Based on these findings, the effects of prednisolone treatment on LCAT and HDL CEC activities prior to HDL-C levels suggest that normal HDL-C levels may not be essential as a treatment target in immune-mediated acquired LCAT deficiency patients who require treatment.