Journal of atherosclerosis and thrombosis最新文献

Aim: The association between serum fatty acids and atherosclerotic disease remains unclear. In this cross-sectional study, we examined the association of serum fatty acids and the EPA/AA ratio with hypertriglyceridemia (HTG), a key metabolic factor underlying atherosclerosis.

Methods: A total of 2,413 adults aged 40-74 years were randomly selected after excluding those with clinically validated myocardial infarction or stroke. We analyzed the serum fatty-acid composition and categorized saturated fatty acids (SFA), monounsaturated fatty acids (MUFA), n-6 polyunsaturated fatty acids (PUFA), n-3 PUFA, and the EPA/AA ratio into quartiles, defined HTG at triglyceride levels ≥ 150 or ≥ 175 mg/dL in fasting or non-fasting samples, respectively, and calculated the adjusted odds ratios (AORs) and 95 % confidence intervals (CIs) using multivariable logistic regression.

Results: After adjusting for age, sex, body mass index, social status, lifestyle, and the self-reported medical history of hypertension, diabetes, dyslipidemia, other cardiovascular diseases, and cerebrovascular conditions (excluding validated myocardial infarction or stroke), the odds of HTG were significantly higher in the highest quartile of SFA (AOR, 8.13; 95 % CI, 5.62-11.77) and MUFA (AOR, 64.7; 95 % CI, 31.4-133.2). In contrast, higher n-6 PUFA (AOR, 0.02; 95 % CI, 0.01-0.04) and n-3 PUFA (AOR, 0.36; 95 % CI, 0.26-0.50) levels, and a higher EPA/AA ratio (AOR, 0.64; 95 % CI, 0.46-0.88) were associated with lower odds of HTG.

Conclusions: Higher serum SFA and MUFA were associated with increased odds, while higher n-6 PUFA, n-3 PUFA, and the EPA/AA ratio were associated with decreased odds of HTG.

Aims: Preclinical studies have shown that remote ischemic conditioning (RIC) has a neuroprotective effect; however, the findings of clinical studies are inconsistent. This study aimed to show the effect of RIC on acute ischemic stroke while considering its severity at baseline.

Methods: We enrolled 79 patients with ischemic stroke who had National Institute of Health Stroke Scale (NIHSS) scores of 5-20 within 48 h after stroke onset and randomized them into the RIC [n = 43] and control groups [n = 36]. The intervention was performed using an inflatable cuff on one lower extremity. In the RIC group, each treatment consisted of four cycles of 5 min cuff inflation and deflation. The treatment was repeated once daily for at least three days. Based on the NIHSS score, the patients were divided into three groups: mild (NIHSS 5-9), moderate (NIHSS 10-14), and severe (NIHSS 15-20). The primary outcome was a good functional outcome at 90 days, defined as a modified Rankin Scale score of 0-1 in the mild group, 0-2 in the moderate group, and 0-3 in the severe group.

Results: Among the 79 patients (mean age, 65.0 years, 40 women), 7 (16.3%) in the RIC group and 8 (22.2%) in the control group had good functional outcomes (odds ratio, 0.73 [95% confidence interval, 0.29-1.82]; P = 0.502). The incidences of major adverse cardiovascular events, aspiration pneumonia, and serious adverse events were similar in both the groups.

Conclusion: Although this study may have been underpowered, RIC initiated within 48 h of stroke onset did not seem to improve the functional outcomes in acute ischemic stroke.

Aim: This study explored the association between retinol-binding protein 4 (RBP4) and cardiovascular events in patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI).

Methods: A total of 736 AMI patients who underwent successful PCI were prospectively enrolled between January 2020 and January 2022. The baseline RBP4 levels were measured by ELISA and categorized into quartiles. The incidence of major adverse cardiovascular events (MACEs), including all-cause mortality, recurrent myocardial infarction, revascularization, heart failure, and stroke, was assessed at the 1- and 3-year follow-up. Multivariate Cox proportional hazards models were used to evaluate the association between RBP4 and MACEs. A receiver operating characteristic (ROC) curve analysis was performed to determine the predictive efficiency of RBP4 for predicting the 1-year and 3-year MACEs.

Results: During follow-up, 110 (14.95%) and 165 (22.42%) patients developed MACEs at one and three years, respectively. Elevated RBP4 (the fourth quartile vs. the first quartile) was associated with an increased risk of MACEs (HR = 2.18, 95%CI = 1.42~4.37, P = 0.007) and heart failure (HR = 3.89, 95%CI = 1.68~5.75, P＜0.001) at the 1-year follow-up. Additionally, the elevated RBP4 were associated with an increased risk of MACEs (HR = 4.41, 95%CI = 2.57~7.31, P＜0.001), revascularization (HR = 3.43, 95%CI = 1.82~4.87, P＜0.001) and heart failure (HR = 7.12, 95%CI = 3.78~11.92, P＜0.001) at 3-year follow-ups. An ROC curve analysis revealed that the serum RBP4 cutoff for predicting the 1-year MACEs was 46.3 ng/mL (AUC = 0.74, 95%CI = 0.69~0.78, P＜0.001), and for predicting the 3-year MACEs, it was 43.9 ng/mL (AUC = 0.81, 95%CI = 0.77~0.85, P＜0.001). A Stratified Cox regression analysis suggested that the renal function did not significantly modify the association between RBP4 and MACEs.

Conclusion: Elevated RBP4 levels are independently associated with an increased risk of MACEs in patients with AMI post-PCI, thus highlighting its potential as a prognostic biomarker for risk stratification.

Aim: Acute coronary syndrome (ACS) and ischemic stroke are major life-threatening conditions caused by atherosclerosis. Although the mechanisms of atherosclerosis appear to be broadly similar across different vascular beds, growing evidence suggests that there are morphological and histological differences between coronary and carotid atherosclerosis. To identify disease-specific therapeutic strategies, we aimed to compare ACS and chronic coronary syndrome (CCS) in coronary artery disease, and symptomatic and asymptomatic carotid artery disease.

Methods: We analyzed our own single-cell RNA sequencing dataset for coronary artery disease (GSE184073) and a publicly available dataset for carotid artery disease (GSE253903). Myeloid cells were extracted from these datasets and comparative analyses were performed using metabolic profiling and an RNA velocity analysis.

Results: By integrating multiple velocity-inference approaches, including the original and dynamic RNA velocity models, TFvelo using transcription factor regulatory information, and CellRank, we consistently identified a differentiation trajectory toward interleukin-1B (IL1B)^＋ inflammatory macrophages marked by high expression of matrix metalloproteinase 19 (MMP19). This trajectory was accompanied by the activation of the glycolytic and glycosaminoglycan degradation pathways. A similar directional flow toward IL1B^＋ inflammatory macrophages was also observed in symptomatic carotid artery plaques. However, unlike coronary lesions, carotid lesions activated the glycolytic pathway in SPP1^＋ foamy macrophages expressing MMP19.

Conclusions: Our findings revealed a shared differentiation trajectory into IL1B^＋ inflammatory macrophages in carotid and coronary artery diseases, which is associated with plaque vulnerability. Notably, the distinct activation of the glycolytic pathway in a separate macrophage subset suggests that tailored therapeutic strategies may be necessary to effectively address plaque vulnerability in each vascular bed.

Aims: Hyperglycemia and glycemic variability (GV) are predictors of adverse outcomes in critically ill patients; however, their roles in pulmonary embolism (PE) remain unclear. This study investigated the association between the mean blood glucose (MBG), GV, and mortality in patients with PE.

Methods: A retrospective cohort study of patients with PE was conducted using the MIMIC-IV 3.0. GV was quantified using the coefficient of variation (CV). Patients were stratified according to tertiles of MBG and CV. Multivariable logistic regression, restricted cubic splines (RCS), and ROC curves were used to evaluate the associations with ICU and in-hospital mortality, supplemented by the threshold effect, sensitivity, and subgroup analyses.

Results: Among the 1,493 PE patients, the ICU and in-hospital mortality rates were 12.99% and 20.90%, respectively. A higher MBG or CV was significantly associated with an increased risk of ICU mortality and in-hospital mortality. RCS revealed a linear association between MBG and mortality, whereas CV exhibited an inverted U-shaped relationship with inflection points at 38.523% (ICU) and 37.038% (in-hospital). For every 1% increase in CV to the left of the inflection point, the relative risks of ICU and in-hospital mortality increased by 0.035. The combined model (MBG + CV + ERS (European Respiratory Society)) achieved AUCs of 0.735 (ICU) and 0.693 (in-hospital) for mortality prediction.

Conclusions: MBG and CV are independent predictors of mortality in critically ill patients with PE, suggesting that optimal glycemic control may benefit this population.

Aims: Data on recurrence and its patterns after paclitaxel-coated balloon (PCB) angioplasty for femoropopliteal artery disease are limited. We evaluated the incidence and predictors of re-recurrence according to the retreatment strategy (PCB or scaffold) and recurrence pattern (restenosis or reocclusion) in patients with recurrence after primary PCB therapy.

Methods: This multicenter retrospective study included 276 limbs of 246 patients who underwent repeat endovascular therapy (EVT) using either PCB (PCB group, n = 217) or a scaffold (scaffold group, n = 59) for primary PCB recurrence. The primary endpoint was 1-year freedom from re-recurrence, and secondary analyses identified the predictors of re-recurrence.

Results: In the PCB group, 174 restenotic and 43 reoccluded lesions were treated with PCBs. In the scaffold group, 32 restenotic and 27 reoccluded lesions were treated with scaffolds. In both groups, reoccluded lesions had significantly lower freedom from re-recurrence rates than restenotic lesions (PCB: 43.0% vs. 68.6%, p＜0.001; scaffold: 52.6% vs. 81.5%, p = 0.033). Freedom from re-reocclusion was also significantly lower in reoccluded lesions than in restenotic lesions (PCB: 48.5% vs. 88.6%, p＜0.001; scaffold: 65.8% vs. 93.2%, p = 0.033). The independent predictors of re-recurrence after PCB treatment were male sex (hazard ratio [HR] 2.01, p = 0.010), reoccluded lesions (HR 2.71, p = 0.001), poor BK run-off (HR 1.97, p = 0.020), use of first-generation low-dose PCB (HR 2.32, p = 0.017), and residual stenosis ＞30% (HR 2.60, p = 0.009). After scaffold treatment, reoccluded lesions were also identified as a significant predictor of re-recurrence (HR 2.99, p = 0.043).

Conclusion: Reocclusion after PCB therapy was strongly associated with subsequent re-recurrence, including re-reocclusion, regardless of the retreatment strategy.

Aim: A reduction in low-density lipoprotein cholesterol (LDL-C) is beneficial for vascular diseases; however, lower LDL-C levels may be associated with an increased risk of spontaneous intracerebral hemorrhage (sICH). The present study investigated the relationship between the LDL-C levels and in-hospital mortality after sICH using data from the Juntendo Registry of Spontaneous Intra-Cerebral Hemorrhage (J-ICH registry).

Methods: Patients aged ≥ 20 years with non-traumatic sICH admitted to five Juntendo-affiliated hospitals between September 2016 and December 2019 were enrolled in this study. The relationships between the LDL-C levels and in-hospital mortality, statin therapy, and antithrombotic therapy were analyzed.

Results: Among the 1,017 patients with sICH, lower LDL-C levels were associated with older age, a lower BMI, a larger hematoma volume, more severe neurological deficits, and a higher in-hospital mortality. A logistic regression analysis confirmed that LDL-C ＜100 mg/dL independently increased the risk of in-hospital death, along with age, the NIHSS score, hematoma volume, and intraventricular hemorrhage. Subgroup analyses showed that the association between low LDL-C levels and mortality was particularly evident in patients with deep/infratentorial intracerebral hemorrhage, those managed without surgery, and those without prior statin use. Prior statin use was associated with a potential protective effect against in-hospital mortality and hematoma volume.

Conclusion: This study demonstrated that lower LDL-C levels were associated with a higher in-hospital mortality after sICH, whereas prior statin use was not associated with poorer outcomes and may instead offer a protective effect.

Aims: Small dense low-density lipoprotein cholesterol (sdLDLC) has been suggested to be more harmful for cardiovascular outcomes than total LDLC. This study aimed to clarify the prognostic significance of the estimated sdLDLC for the incidence of coronary artery diseases (CAD).

Methods: We analyzed the clinical information obtained at an annual health checkup of 365,083 adults aged 40-74 years enrolled in the National Health Insurance system in Japan. The incidence of CAD was determined using the health insurance claims data. Additionally, we calculated Japanese-specific coefficients of the sdLDLC estimation equation using general population data, where the measured sdLDLC value was available (n = 9,558).

Results: The estimated sdLDLC level calculated from the total LDLC and triglyceride levels was correlated with the measured sdLDLC level (coefficient of determination = 0.768) and it was significantly associated with the CAD incidence (hazard ratio per 10 mg/dL = 1.21, p＜0.001). Although the total LDLC showed a similar association, the estimated sdLDLC ≥ 30 mg/dL (hazard ratio = 1.97, p = 0.016) and ≥ 40 mg/dL (hazard ratio = 2.57, p = 0.001) were significantly associated with CAD, even in participants with normal LDLC levels (＜120 mg/dL). The cross-sectional association of the measured sdLDLC with the pulse wave velocity of the large artery (β = 0.034, p＜0.001) was significant, while that of the estimated sdLDLC (β = 0.014, p = 0.057) was not.

Conclusion: The estimated sdLDLC may be a straightforward and cost-effective marker for identifying individuals with normal LDLC levels at risk of CAD. However, the measured sdLDLC may be a more favorable marker than the estimated sdLDLC.

Aims: The association between alcohol consumption and the risk of cardiovascular disease (CVD) varies according to the presence of underlying cardiovascular risk factors. Incorporating such risk factors may be important to effectively reduce harmful alcohol use through health guidance. However, whether the risk of alcohol consumption is affected due to renal impairment remains unclear.

Methods: A total of 10,583 community-dwelling Japanese adults (mean age 59.4 (SD 10.1) years; 46% men) were followed for 10 years. Alcohol consumption was categorized into five groups for men: never drinkers, former drinkers, light drinkers (＜20 g/day), moderate drinkers (20-39 g/day), and heavy drinkers (≥ 40 g/day), and four groups for women with moderate and heavy combined. Cox proportional hazards models estimated hazard ratios for incident CVD stratified by the presence or absence of reduced estimated glomerular filtration rate (eGFR) (＜60 mL/min/1.73m²) and proteinuria, with adjustment for confounders.

Results: Among men with proteinuria, alcohol consumption was associated with a higher risk of atherosclerotic CVD, whereas an inverse association was observed in men without proteinuria [hazard ratio (95% confidence interval): moderate drinkers without proteinuria, 0.58 (0.34-0.97); moderate drinkers with proteinuria, 3.49 (1.15-10.56)]. Moderate to heavy drinking increased the risk of intracerebral hemorrhage irrespective of the renal status. In women, moderate to heavy drinking was associated with an increased CVD risk only when proteinuria was present. In contrast, a reduced eGFR did not clearly affect the association in either sex.

Conclusions: The CVD risk associated with alcohol consumption may differ according to the renal status, particularly depending on the presence or absence of proteinuria.