Journal of atherosclerosis and thrombosis最新文献

Aim: Few studies have evaluated the midterm prognosis of patients with intermittent claudication who underwent endovascular therapy (EVT) for femoropopliteal lesions. Therefore, we aimed to assess 2-year mortality and prognostic factors in these patients.

Methods: We retrospectively analyzed 947 patients who underwent EVT for intermittent claudication between January 2018 and December 2021 at eight Japanese cardiovascular centers. Kaplan-Meier survival analysis was performed for mortality, and prognostic factors were analyzed using the Cox proportional hazards regression model. Patient backgrounds and medications were included in the investigation of prognostic factors.

Results: Notably, 79 deaths occurred during the mean follow-up period of 20.9±6.2 months. The 2-year mortality rate was 9.1%. In multivariate analysis, body mass index (BMI) ＜18.5 kg/m² (p＜0.001), coronary artery disease (CAD) (p＜0.001), dialysis (p＜0.001), and ankle-brachial pressure index (ABI) ＜0.6 (p=0.012) were risk factors. Statins and cilostazol were protective factors (p=0.014 and p=0.036, respectively). When the study population was stratified based on the number of these risk factors, the mortality rate was highest (32.5% at 2 years) in patients with at least three risk factors. However, when stratified according to protective factors, the mortality rate was lowest in patients with two protective factors (2.1% at 2 years).

Conclusions: Dialysis, low BMI, CAD, and low ABI were risk factors for a worse 2-year prognosis in patients with intermittent claudication who underwent EVT for femoropopliteal lesions. Statins and cilostazol may improve the 2-year prognosis of patients with lower extremity artery disease.

Aim: In the PEMA-FL study in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), pemafibrate was shown to significantly decrease low-density lipoprotein cholesterol (LDL-C) levels. We aimed to investigate the mechanisms of pemafibrate-induced LDL-C reduction in patients with MASLD by conducting an additional sub-analysis of the PEMA-FL study.

Methods: The PEMA-FL study randomized 118 patients with MASLD to receive pemafibrate or placebo for 72 weeks. This sub-analysis examined the percentage change in LDL-C and related lipid markers by tertile of baseline LDL-C levels and the correlation between these changes in the pemafibrate group.

Results: Pemafibrate significantly decreased LDL-C levels approximately 25% (p＜0.001 at all timepoints) from baseline in the highest tertile of baseline LDL-C levels (≥ 137.5 mg/dL), with similar trends for non-high-density lipoprotein cholesterol (non-HDL-C) and apolipoprotein B (ApoB) levels. Lipoprotein (a) [Lp(a)] levels decreased only in patients with the highest baseline LDL-C levels. Regardless of the baseline LDL-C levels, pemafibrate altered the LDL particle profile (increased LDL particle size and decreased the number); reduced lathosterol, β-sitosterol, and campesterol; and increased angiopoietin-like protein 3 (ANGPTL3). The percentage change in LDL-C positively correlated with that in ApoB, non-HDL-C, Lp(a), lathosterol, β-sitosterol, and campesterol but not HDL-C and ANGPTL3.

Conclusion: Pemafibrate reduced LDL-C, ApoB, and non-HDL-C levels in patients with MASLD, and the effect was greater in those with higher baseline LDL-C levels. Pemafibrate may clinically benefit patients with MASLD by improving LDL-C levels and the LDL particle profile.

Aims: To investigate the association between triglyceride levels and major adverse cardiovascular events (MACE) in primary and secondary prevention cohorts.

Methods: This retrospective study was conducted with a nationwide health insurance claims database, which included approximately 3.8 million participants with medical checkups between January 2005 and August 2020 in Japan. The participants were classified into primary prevention (n=3,415,522) and secondary prevention (n=29,806) cohorts based on cardiovascular or cerebrovascular disease history. Each participant was categorized as having very low (triglyceride ＜50 mg/dL), low normal (50-99), high normal (100-149), or hypertriglyceridemia (≥ 150). The primary prevention cohort was further stratified into low-, intermediate-, and high-risk groups according to atherosclerotic cardiovascular diseases risk. Outcome was MACE, including acute myocardial infarction (AMI), unstable angina, ischemic stroke, and cardiac death.

Results: Over a mean follow-up of 3.25 years, 0.3% and 2.6% MACE occurred in primary and secondary prevention, respectively. Hypertriglyceridemia was associated with high risk of MACE in the primary prevention, but not in the secondary prevention. A significant interaction was observed between prevention categories and the association of TG levels with MACE in those with TG ＜150 mg/dL and ischemic stroke in those with TG ≥ 150 mg/dL. The population-attributable fraction for hypertriglyceridemia in primary prevention was 4.1% for MACE. In primary prevention, lower risks of AMI were observed in the lower TG category compared to the current threshold.

Conclusions: This study suggests distinct triglyceride thresholds for MACE risk in primary and secondary prevention cohorts, requiring further prospective validation for clinical implementation.

A 59-year-old Japanese woman was referred for an extremely low level of circulating high-density lipoprotein cholesterol (HDL-C). The serum HDL-C level had long been within the normal range but suddenly decreased asymptomatically to 7 mg/dL. She had no typical symptoms associated with familial lecithin, cholesterol acyltransferase deficiency (FLD), including proteinuria, anemia, and corneal opacity. The circulating level of ApoA-1 was also markedly decreased at 48 mg/dL, and the proportion of esterified cholesterol to free cholesterol was irregularly low at 26%. Whole-genome sequencing revealed no apparent pathological mutations in the LCAT gene. Notably, anti-LCAT antibodies were detected in the serum at 146±1.7 ng/mL, resulting in her being diagnosed with acquired LCAT insufficiency (ALCATI) caused by anti-LCAT antibodies. Five years after her HDL-C levels spontaneously decreased, they increased without any identifiable cause. To our knowledge, only six cases of ALCATI caused by anti-LCAT antibodies have been reported to date. In contrast to the present case, previously reported cases of ALCATI manifested proteinuria that improved with steroid therapy. The unique clinical course in the present case highlights the heterogeneity of ALCATI, warranting further research to clarify the molecular pathophysiology of FLD and ALCATI.

Aims: Plasma S-adenosylhomocysteine (SAH) level is positively associated with cardiovascular risk. However, the relationship between plasma SAH levels and the risk of all-cause and cardiovascular mortality remains unknown. This study aimed to explore the relationship between plasma SAH levels and the risk of all-cause and cardiovascular mortality in patients with coronary artery disease (CAD).

Methods: Plasma SAH levels were measured in 1553 patients with CAD. The association between plasma SAH level and the risk of all-cause and cardiovascular mortality was estimated using Cox Proportional hazards regression models.

Results: Relative to participants in the lowest quartile of plasma SAH levels, those in the highest quartile of plasma SAH levels had a higher risk of all-cause death (adjusted Hazard Ratio [HR], 2.15; 95% CI, 1.54-3.01; P＜0.001) and cardiovascular death (adjusted HR, 2.20; 95% CI, 1.49-3.25; P=0.001) in the age- and sex-adjusted model. The results of the multivariable adjusted analysis were similar (all-cause death [adjusted HR, 1.81; 95% CI, 1.27-2.58; P=0.002] and cardiovascular death [adjusted HR, 1.84; 95% CI, 1.21-2.79; P=0.031]). The age- and sex-adjusted HRs for each 1 SD increase in plasma SAH level were 1.30 (95% CI, 1.22-1.38) for all-cause mortality, and 1.34 (95% CI, 1.25-1.43) for cardiovascular mortality, respectively. A 1 SD increase in the SAH level was associated with a 25% higher risk of total death (adjusted HR, 1.25; 95% CI, 1.17-1.34) and a 29% greater risk of cardiovascular death (adjusted HR, 1.29; 95% CI, 1.20-1.39) in multivariable adjusted analysis.

Conclusions: We found that the plasma SAH level is positively correlated with the risk of all-cause and cardiovascular mortality in patients with CAD in both age- and sex-adjusted and multivariable-adjusted models.

Aims: There is a lack of evidence regarding the sex-specific impact of arterial stiffness on the incidence of chronic kidney disease (CKD). This study assessed the relationship between arterial stiffness based on brachial-ankle pulse wave velocity (baPWV) and incident CKD in men and women.

Methods: Individuals who participated in health checkups and underwent concomitant baPWV measurement between 2006 and 2019 were included. They were free of CKD at baseline. The participants were categorized into 4 groups based on their baPWV values (cm/s) as follows: ＜1,200 cm/s for normal, ≥ 1,200 and ＜1,400 for high normal, ≥ 1,400 and ＜1,800 for borderline, and ≥ 1,800 cm/s. The primary outcome was CKD development (estimated glomerular filtration rate ＜60 mL/min/1.73 m²).

Results: A total of 130,100 participants were enrolled, with a mean age of 40.5±8.2 years old. During the mean of 5.6 years of follow-up, 906 (0.7%) participants developed incident CKD. The cumulative incidence of CKD was 0.3%, 0.5%, 1.4%, and 6.2% in the normal, high normal, borderline, and abnormal groups, respectively. In the multivariable-adjusted model including systolic blood pressure, compared with the normal baPWV group, abnormal baPWV group demonstrated a significantly increased risk of incident CKD in women. However, among men, any other baPWV groups were not associated with a significantly elevated risk of incident CKD.

Conclusions: Increased arterial stiffness, as measured by baPWV, was associated with an increased risk of incident CKD, with notable sex-specific differences. These findings underscore the utility of baPWV for identifying CKD risk in women and offer valuable insights into sex-specific differences in arterial stiffness and CKD development.

Aims: Direct oral anticoagulants (DOACs) are used to treat venous thromboembolism (VTE). However, their impact on thrombus regression and the clinical outcomes after 2-week post-therapy computed tomography (CT) monitoring remains unexplored. This study aimed to elucidate the characteristics of patients with VTE treated with individual DOACs, assess the incidence of clinical events, and evaluate their impact on pulmonary artery thrombus regression.

Methods: This prospective, multicenter study in Japan included 175 patients with VTE treated with rivaroxaban, apixaban, and edoxaban. We employed 2-week post-therapy CT monitoring to compare thrombus regression rates, patient backgrounds, and clinical outcomes.

Results: Rivaroxaban users had higher body weight, hemoglobin levels, pulmonary embolism prevalence, and larger thrombus volume, but a lower prevalence of active cancer than apixaban and edoxaban users. The median thrombus regression rate after approximately 2 weeks of treatment was 89.9%, with no significant differences between the DOACs. During the 13.5-month follow-up, the recurrence or aggravation of symptomatic VTE did not differ significantly among the groups; however, the apixaban group exhibited a slightly higher major bleeding rate. Among the 95 patients receiving rivaroxaban intensive therapy, 34 (35.8%) experienced early termination due to sufficient thrombus resolution within 2 weeks compared to the standard duration group. This did not increase VTE recurrence, aggravation, or mortality.

Conclusions: Substantial thrombus regression and a low incidence of VTE and bleeding support the effectiveness of DOACs. Terminating intensive therapy in one-third of the rivaroxaban group after 2-week CT monitoring did not increase the occurrence of VTE events, thereby suggesting suitability for patients at a high risk of bleeding.

Aim: Early and intensive low-density lipoprotein (LDL-C)-lowering therapy plays important roles in secondary prevention of acute coronary syndrome (ACS), but the treatment period for further clinical benefit remains undefined. This single-center, retrospective study explored LDL-C trajectory after ACS and its associations with subsequent cardiovascular events (CVE).

Methods: In 831 patients with ACS, we evaluated LDL-C reduction during the first 2 months post-ACS as an index of early intervention and the area over the curve for LDL-C using 70 mg/dl as the threshold in the next 6 months (AOC-70) as a persistent intensity index. Patients were followed for a median of 3.0 (1.1-5.2) years for CVE, defined as the composite of cardiovascular death, non-fatal myocardial infarction, angina pectoris requiring revascularization, cerebral infarction, and coronary bypass grafting.

Results: LDL-C decreased from baseline to 2 months post-ACS (107±38 mg/dl to 78±25 mg/dl, p＜0.001) through high-intensity statin prescription (91.8%), while achieving rates of LDL-C ＜70 mg/dl at 2 months remained only 40.2% with no significant changes thereafter. During the follow-up period, CVE occurred in 200 patients. LDL-C reduction during the first 2 months and AOC-70 in the next 6 months were both associated with subsequent CVE risk (sub-HR [hazard ratio] [95% confidence interval]: 1.48 [1.16-1.89] and 1.22 [1.05-1.44]). Furthermore, early intervention followed by persistently intensive LDL-C-lowering therapy resulted in further CVE risk reduction.

Conclusions: The present study observed that achieving early and intensive LDL-C reduction within the first two months after ACS and maintaining it for the next six months suppressed subsequent CVE risk, suggesting the importance of early, intensive, and persistent LDL-C-lowering therapy in the secondary prevention of ACS.

Aims: Skin perfusion pressure (SPP) and ankle-brachial index (ABI) are useful in screening for peripheral arterial disease in patients undergoing hemodialysis (HD). We compared the prognostic abilities of the SPP and ABI in predicting the composite outcomes of mortality and atherosclerotic vascular events.

Methods: This single-center prospective cohort study enrolled 258 patients undergoing HD. The patients with SPP and ABI measurements were divided into tertiles. Log-rank tests, Cox regression analyses, and discrimination parameters were used for comparisons.

Results: Over a median follow-up period of 3.7 (1.4-5.0) years, 119 composite events were recorded. The incidence rates of composite events were 27.5, 13.3, and 9.1 per 100 person years, respectively, across the SPP tertiles (log-rank: p＜0.001), and 23.2, 13.2, and 11.6 per 100 person years across the ABI tertiles (p=0.003). With the 3rd tertiles as references, the 1st tertiles of the SPP and ABI were significantly associated with the composite outcome (adjusted hazard ratio [aHR]: 2.58, 95% confidence interval [CI]: 1.57-4.23 and aHR: 1.70, 95% CI: 1.06-2.73, respectively). Adding the tertiles of the SPP to a predictive model with established risk factors significantly improved the model performance. This improvement was larger than that of the ABI in terms of net reclassification (0.330 vs. 0.275) and integrated discrimination (0.045 vs. 0.012). Furthermore, in patients with a normal ABI, the 1st SPP tertile (＜71 mmHg) was significantly associated with the outcome (aHR, 1.97; 95% CI, 1.13-3.41) when compared to the 3rd tertile.

Conclusions: Even patients with a normal ABI have a poor prognosis if their SPP levels are low. SPP outperformed ABI in predicting mortality and cardiovascular outcomes in HD patients.

Aims: Bathing-related ischemic stroke (BIS) is sometimes fatal. However, its mechanisms and risk factors remain unclear. We aimed to identify the incidence of stroke subtypes in BIS, and clarify the impact of cerebral small vessel disease (CSVD) on BIS.

Methods: Consecutive patients with ischemic stroke between October 2012 and February 2022 were retrospectively screened. The inclusion criteria were: 1) onset-to-door time within 7 days; and 2) availability of the results of MRI evaluation of CSVD markers during hospitalization. BIS was defined as an ischemic stroke that occurred while or shortly after bathing. We investigated the incidence of the stroke subtype and the correlation between CSVD markers and BIS.

Results: 1,753 ischemic stroke patients (1,241 [71%] male, median age 69 years) were included. 57 patients (3%) were included in the BIS group. A higher frequency of large artery atherosclerosis (LAA) (prevalence ratio [PR] 2.069, 95% confidence interval [CI] 1.089 to 3.931, p=0.026) and lower frequency of cardio-embolism (CES) (PR 0.362, 95% CI 0.132 to 0.991, p=0.048) in BIS cases were identified. Moreover, lower periventricular hyperintensity (PVH) Fazekas grade (PR 0.671, 95% CI 0.472 to 0.956, p=0.027) and fewer cerebral microbleeds (CMBs) in deep brain region (PR 0.810, 95%CI 0.657 to 0.999, p=0.049) were associated with BIS cases.

Conclusions: The BIS group was more likely to develop LAA and less likely to develop CES. Lower PVH grade and fewer CMBs in deep brain region were associated with the development of BIS.