Journal of atherosclerosis and thrombosis最新文献

Aims: To investigate the distribution of lipoprotein(a) (Lp(a)) and its association with atherosclerotic cardiovascular disease (ASCVD) in Japanese patients at high risk for ASCVD using a health insurance database.

Methods: Between July 2013 and June 2021, patients eligible for ASCVD prevention according to the 2017 Japan Atherosclerosis Society (JAS) guidelines with documented Lp(a) test results were extracted from the Medical Data Vision claims database and divided into three groups: primary prevention high-risk (Group I), secondary prevention (Group II) and secondary prevention high-risk (Group III). Data on lipid levels, cardiovascular morbidity risk factors and lipid-lowering treatments were extracted.

Results: Of 700,580 patients with documented low-density lipoprotein cholesterol (LDL-C), 2,967 (0.42%) were tested for Lp(a). In 2,170 eligible patients, the median [interquartile range] serum concentration of Lp(a) was 13.9 [7.5-24.6] mg/dL, with 151 patients (7.0%) above the recommended risk threshold of ≥ 50 mg/dL. Lp(a) levels increased with risk across all prevention groups. Being in the highest Lp(a) quintile (Q5) was associated with an increased frequency of ASCVD (28.9% versus 18.9% in the lowest quintile (Q1) for unstable angina; 18.7% versus 10.1% for myocardial infarction; 27.9% versus 17.0% for ischemic stroke). In the secondary prevention groups, the proportion of patients meeting an LDL-C target of ＜70 mg/dL decreased from 30.2% in Q1 to 19.0% in Q5 for Group II and from 32.9% to 16.3% for Group III.

Conclusions: Despite a high prevalence of Lp(a) ≥ 50mg/dL in Japanese patients at high risk for ASCVD, it found that the Lp(a) testing rate was very low.

Aims: The effect of uric acid (UA)-lowering therapy with xanthine oxidoreductase (XOR) inhibitors on the development of cardiovascular disease requires further investigation. This study aimed to evaluate the long-term effects of febuxostat on arterial stiffness, focusing on liver function.

Methods: The PRIZE study involved random assignment of patients with asymptomatic hyperuricemia to receive either add-on febuxostat treatment (febuxostat group) or non-pharmacological treatment (control group). Of the 514 participants, 23 and 14 patients in the febuxostat and control groups, respectively, underwent assessment of arterial stiffness using the cardio-ankle vascular index (CAVI). The participants in each group were further grouped on the basis of their baseline alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels (above or below the media value or 30 U/L). The primary endpoint was the change in the CAVI from baseline to 12 and 24 months.

Results: Overall, no significant differences were found between the control and febuxostat groups in the least-squares mean estimates of changes in CAVI at 24 months (mean between-group difference, -0.41 [95% CI, -1.05 to 0.23]; p=0.204). However, there were significant differences in participants with higher baseline ALT or AST levels above 30 U/L at 24 months (mean between-group difference, -1.12 [95% CI, -2.23 to -0.01]; p=0.048 for ALT ≥ 30 U/L and -1.08 [95% CI, -2.13 to -0.03]; p=0.044 for AST ≥ 30 U/L).

Conclusions: Two-year treatment with febuxostat demonstrated a beneficial effect on CAVI in patients with hyperuricemia and liver dysfunction.

Aims: Several diet quality indicators have been developed primarily for cardiovascular disease (CVD) prevention in Western countries. However, those previous indicators are complicated and less feasible in clinical and health-promoting settings. Therefore, we aimed to develop a concise dietary risk score for CVD prevention in Japanese.

Methods: Using the self-administered food frequency questionnaire with 35 food items, we developed a concise healthy diet score (cHDS) ranging from 0 to 5 points. We examined the association of cHDS with risks of all-cause and cause-specific mortality among 23,115 men and 35,557 women who were free of CVD and cancer.

Results: During 19.2 years of median follow-up, 6,291 men and 5,365 women died. In men, the multivariable hazard ratios (95% confidence intervals) for the highest cHDS (5 points) compared to the lowest (0-1 points) were 0.74 (0.60-0.91, P-trend=0.008) for CVD and 0.86 (0.77-0.95, P-trend=0.05) for all causes. No significant associations were found for stroke, coronary heart disease, and other causes in men. The corresponding hazard ratio in women was 0.65 (0.52-0.81, P-trend＜0.001) for CVD, 0.63 (0.45-0.88, P-trend＜0.001) for stroke, 0.48 (0.30-0.78, P-trend=0.008) for coronary heart disease, 0.67 (0.54-0.84, P-trend＜0.001) for other causes, and 0.75 (0.66-0.85, P-trend＜0.001) for all causes.

Conclusion: We developed a concise diet quality score named cHDS in the Japanese population and found the inverse association of cHDS with mortality from CVD and all causes for both men and women.

Aims: Although administrative claims databases have recently been used for clinical research in Japan, no detailed description of their utilization in stroke research is available. We reviewed stroke studies using the Diagnosis Procedure Combination (DPC), the National Database of Health Insurance Claims and Specific Health Checkups (NDB), and several commercial databases sourced from social health insurance associations, focusing on their applications and limitations.

Methods: Original articles on stroke published by April 2024 using the DPC, NDB, and commercial databases were identified in Ovid MEDLINE. The characteristics of each database were compared in terms of comprehensiveness, traceability, baseline information, and outcome assessment in stroke research.

Results: A total of 114 studies were included (83 for DPC, 6 for NDB, and 25 for commercial databases). The number of stroke studies using administrative databases in Japan is still approximately 10 per year, although there is a slowly increasing trend. The DPC database was utilized for short-term outcome studies because of its detailed baseline and outcome information, although the inability to track patients once they changed facilities limits their use in long-term studies. The NDB database is potentially useful for long-term studies because of its comprehensiveness and traceability, but difficulties in data access restrict its usage. The most commonly used commercial database utilizes baseline information on lifestyle and blood test data, although the lack of coverage for those over 75 years old may limit its generalizability.

Conclusions: Administrative claims databases are beginning to be used in stroke research in Japan but are not yet fully utilized. Researchers need to understand their applications and limitations.

Aim: JNK pathway-associated phosphatase (JKAP) regulates T cell-mediated immunity and inflammation, which are involved in atherosclerosis pathogenesis. This study investigated the effects of JKAP on T-helper (Th) cell polarization, inflammation, and atherosclerotic progression.

Methods: Serum JKAP levels were measured in 30 patients with coronary heart disease (CHD) and 30 controls. CHD blood naïve CD4^＋ T cells were acquired, followed by JKAP overexpression and knockdown with or without treatment with PD98059 (ERK inhibitor) or BAY-11-7082 (NF-κB inhibitor) in vitro. CD4^＋ T-cell conditional JKAP ablation mice were established in vivo, followed by the construction of an atherosclerosis model.

Results: JKAP was reduced and negatively correlated with the Gensini score, CRP, Th1 cells, Th17 cells, and proinflammatory cytokines in patients with CHD. In vitro, JKAP overexpression suppressed Th1 and Th17 cell differentiation and proinflammatory cytokines, whereas JKAP knockdown exerted the opposite effect; however, JKAP modification did not affect Th2 cell differentiation. Interestingly, JKAP negatively regulated the ERK and NF-κB pathways; meanwhile, the PD98059 and BAY-11-7082 treatments repressed Th1 and Th17 cell differentiation, and attenuated the effect of JKAP knockdown on these indices. In vivo, conditional CD4^＋ T-cell JKAP ablation increased Th1 and Th17 cell polarization in the spleen, lymph node, blood, and/or aortic root. Furthermore, CD4^＋ T-cell conditional JKAP ablation exaggerated atherosclerotic lesions in the aorta, elevated CD4⁺ cell infiltration and proinflammatory cytokines in the aortic root, and activated the ERK and NF-κB pathways in the aortic root.

Conclusion: JKAP ablation facilitates atherosclerosis progression by promoting Th1 and 17 polarization and inflammation through regulation of the ERK and NF-κB pathways.

Intervention for severe aortic stenosis (AS) has dramatically progressed since the introduction of transcatheter aortic valve replacement (TAVR). Decades ago, controversies existed regarding comparing clinical outcomes between TAVR and surgical aortic valve replacement (SAVR) in various risk profiles. Recently, we discussed the durability of transcatheter heart valves and their lifetime management after aortic valve replacement (AVR). Regarding the management of AS, we discuss the appropriate timing of intervention for severe aortic stenosis, especially in asymptomatic patients. In spite of dramatic progression of intervention for AS, there are no established medications available to prevent or slow the progression of AS at present. Basic research and genome studies have suggested several targets associated with the progression of aortic valve calcification. Randomized controlled trials evaluating the efficacy of medications to prevent AS progression are ongoing, which might lead to new strategies for AS management. In this review, we summarize the current management of AS and the drugs expected to prevent the progression of AS.

Aim: In this subanalysis of the EXPAND study, we evaluated the risks and benefits of rivaroxaban plus antiplatelet therapy (APT) for patients with non-valvular atrial fibrillation (NVAF) complicated by stable coronary artery disease (CAD), ischemic stroke, or peripheral artery disease (PAD).

Methods: From the EXPAND study population (n=7,141), patients with NVAF complicated by stable CAD (n=886), ischemic stroke (n=1,231), or PAD (n=160) were included. Patients complicated by any of them were set as ALL (n=2,030). Patients were all treated with rivaroxaban (10 or 15 mg/day) with (+) or without (-) APT. Efficacy outcomes were symptomatic stroke＋systemic embolism (SE), symptomatic stroke＋SE＋myocardial infarction＋cardiovascular death, and all-cause death. Safety outcomes included major and any bleeding. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for differences between the APT(+) and APT(-) groups.

Results: There were no significant differences in the efficacy outcomes between the APT(+) and APT(-) groups in the ALL cohort or in the CAD and STROKE sub-cohorts. In the PAD subcohort, the HR [95% CI] for all-cause death in the APT(+) group increased (4.43 [1.05-18.71]; p=0.043). In the APT(+) group, the HR [95% CI] for any bleeding increased in the ALL cohort (1.28 [1.01-1.62]; p=0.044) and STROKE subcohort (1.42 [1.01-2.01]; p=0.047), and for major bleeding in the CAD subcohort (2.00 [1.01-3.93]; p=0.046).

Conclusions: Rivaroxaban with APT did not reduce ischemic outcomes in patients with stable CAD or ischemic stroke; however, it did increase the risk of bleeding in patients with stable CAD or ischemic stroke.

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.