Journal of atherosclerosis and thrombosis最新文献

Japan's health checkup system has developed over the last four decades as a principal national strategy for preventing cerebrovascular and cardiovascular diseases (CVD). Early community-based health checkups, implemented under the Health Services for the Elderly Act of 1982, contributed to reductions in CVD mortality and the demand for inpatient care through the improved detection and management of hypertension. As lifestyle-related diseases became increasingly prominent, the government introduced Health Japan 21 and subsequently launched the Specific Health Checkups and Specific Health Guidance (SHC/SHG) program in 2008 to strengthen evidence-based population-wide prevention targeting of visceral obesity and the associated cardiometabolic risks. The SHC program provides standardized assessments, including anthropometric measurements, laboratory testing, medical history, and lifestyle questionnaires. Risk stratification is primarily based on abdominal obesity and the accumulation of metabolic risk factors, which determine individualized health guidance through motivational or intensive support. The SHG program offers structured behavioral interventions delivered by trained health professionals to promote sustainable lifestyle modifications. Growing evidence supports the effectiveness of the SHC/SHG program. Health checkup participation has been associated with lower mortality, and health guidance has demonstrated favorable improvements in obesity indicators, metabolic parameters, and pharmacotherapy initiation. Economic evaluations further suggest that the program is cost effective. However, some limitations remain, including modest long-term effects and insufficient risk identification among non-obese individuals with elevated cardiometabolic risk. Improving the participation rates and refining risk stratification beyond obesity-based criteria are ongoing priorities. Continued research and periodic revision of checkup items are essential for enhancing the program's impact as a nationwide strategy for ASCVD prevention.

Familial hypercholesterolemia (FH) is a highly prevalent genetic disorder that occurs in approximately one in 300 people in the general population. In cases of heterozygous FH, which are encountered frequently, cardiovascular disease, the main complication, typically manifests after adulthood. However, if the diagnosis and treatment begin in childhood, the onset of such complications can be prevented. Therefore, it can be said that the diagnosis and treatment of this disease from childhood is extremely important; even more so in the case of homozygous FH. However, specific indicators for diagnosing FH physical findings such as Achilles tendon thickening and tendon xanthomas rarely manifest in childhood. It is also difficult to obtain detailed medical histories from relatives. Therefore, it is not always easy to make a clinical diagnosis. In this context, since 2022, genetic testing for FH has been covered by national health insurance in Japan, and it can be considered for children as needed. This paper presents the previous research concerning genetic testing for children, its importance and application, as well as the latest findings on universal screening that includes genetic testing. It is expected that the development of pediatric FH management in our country, which has not been particularly proactive until now, will contribute to the suppression of cardiovascular complications in this condition.

Aims: The global distribution of lipoprotein(a) [Lp(a)] levels varies due to racial and ethnic differences. However, the clinical relevance of Lp(a) levels in Japanese patients has not been fully explored.

Methods: We investigated the association of Lp(a) levels, the Suita score, and the presence of high-risk plaque (HRP) as well as that of ≥ 50% stenosis, quantitative plaque volume, and the value of coronary artery calcium score in coronary computed tomographic angiography (CCTA), among 272 Japanese patients (mean age: 65 years) in whom serum Lp(a) levels were measured due to suspected coronary artery disease. HRP was defined as positive remodeling and/or low attenuation. Plaque volume was quantified as the percent plaque volume.

Results: HRP was identified in 33 (12.1%) patients. The prevalence of HRP, ≥ 50% stenosis, and percent plaque volume progressively increased with higher Lp (a) levels and Suita scores. In multivariate analyses, Lp(a) and the Suita score independently predicted HRP when assessed as continuous (p = 0.02, p＜0.001, respectively) or categorical variables (p = 0.005, p = 0.007, respectively). Patients in the highest tertile of Lp(a) and classified as high- or intermediate-risk by the Suita score had the highest HRP risk, whereas those in the lower 2 tertiles and low-risk group had the lowest. Incorporating Lp(a) into the Suita score improved the prediction of HRP beyond the Suita score alone (p = 0.005).

Conclusions: The combinatorial value of assessing Lp(a) levels and Suita score may provide useful insight regarding Japanese patients undergoing CCTA for the prediction of HRP.

Aim: Small dense low-density lipoprotein cholesterol (sdLDL-C) is recognized as an atherogenic risk factor. This study investigated the prognostic significance of sdLDL-C levels in patients with premature acute coronary syndrome (PACS) and multivessel disease (MVD).

Methods: This retrospective study enrolled 847 hospitalized patients diagnosed with PACS and MVD between May 2022 and November 2023. Patients were stratified based on clinical outcomes and tertiles of sdLDL-C levels. Multivariate Cox proportional hazard models were applied to determine whether or not sdLDL-C was a prognostic risk factor for major adverse cardiovascular events (MACEs). Cumulative event curves were estimated using the Kaplan-Meier method. The predictive efficacy of sdLDL-C for MACEs was assessed through a time-dependent receiver operating characteristic (ROC) analysis. In addition, a restricted cubic spline (RCS) analysis was conducted to explore the relationship between sdLDL-C levels and the risk of MACEs.

Results: During a median follow-up of 12 months (interquartile range: 9-15 months), 124 MACEs (14.64%) were observed. The sdLDL-C levels in the MACEs group were significantly higher compared to the non-MACEs group (P＜0.001). A multivariate Cox hazards regression analysis revealed that the risk of MACEs in the highest sdLDL-C tertile group was 2.38 times greater than in the lowest tertile group (hazard ratio [HR]: 2.38, 95% confidence interval [CI]: 1.42-4.00; P = 0.001). Furthermore, each 1-mg/dL increase in sdLDL-C levels corresponded to a 12.2% increase in the risk of MACEs (HR: 1.12, 95% CI: 1.08-1.16; P＜0.001). A Kaplan-Meier survival analysis identified significant differences in event-free survival among sdLDL-C tertiles (log-rank test, P＜0.001). The time-dependent ROC analysis demonstrated a progressive increase in the area under the curve during the follow-up period, particularly within the first 12 months. The RCS analysis revealed a nonlinear dose-response relationship between higher sdLDL-C levels and increased cumulative risk of MACEs (P_nonlinear = 0.001).

Conclusion: sdLDL-C is a predominant predictor of a poor prognosis in patients with PACS and MVD, underscoring its clinical relevance for risk stratification and the early identification of high-risk individuals who may benefit from targeted intervention.

Aim: Cilostazol, a phosphodiesterase III inhibitor, reduces the risk of stroke recurrence among patients with noncardioembolic ischemic stroke through inhibition of the platelet function and its pleiotropic effects. Its potential mechanisms include inhibiting angiotensin II-induced endothelial cell apoptosis and promoting vasodilation, which may lower systolic blood pressure (SBP). We hypothesized that the decreased risk of stroke recurrence could be attributed to a reduction in SBP.

Methods: In a post hoc analysis of CSPS.com, we defined change in SBP as its change at the last visit compared with baseline and treated it as a time-dependent mediator. We performed causal mediation analyses to separate the overall effects of cilostazol on the first recurrence of ischemic stroke into indirect effects (mediated by change in SBP on cilostazol) and direct effects (mediated through pathways other than a change in SBP on cilostazol). The effects were summarized by cumulative hazard rate difference.

Results: Ischemic stroke recurred in 27 (3%) of 889 patients on dual therapy with cilostazol and aspirin or clopidogrel and 62 (6.8%) of 906 patients on monotherapy with aspirin or clopidogrel alone during a median follow-up period of 1.4 years. The mediation analysis showed that the positive effect of dual therapy was not mediated by the association between SBP change and stroke recurrence. The estimated direct and indirect effects of cilostazol on stroke recurrence during the same follow-up period were cumulative hazard rate differences of -0.043 (95% CI, -0.070 to -0.015) and -0.0008 (-0.0024 to 0.00035), respectively.

Conclusions: Our results indicate that cilostazol reduced stroke recurrence without lowering SBP, likely through other pleiotropic pathways.

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: 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.

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.