Journal of atherosclerosis and thrombosis最新文献

High-density lipoprotein (HDL) levels have long been inversely associated with cardiovascular disease (CVD) and are traditionally evaluated by serum HDL-cholesterol (HDL-C) levels. However, recent studies have raised doubts regarding the causal role of HDL quantity (HDL-C), drawing attention to HDL functionality. Reverse cholesterol transport (RCT) is a major anti-atherosclerotic mechanism involving ATP-binding cassette A1 (ABCA1), ATP-binding cassette G1 (ABCG1), scavenger receptor class B type I (SRB1), and regulatory factors, such as liver X receptor (LXR) and peroxisome proliferator-activated receptor gamma (PPARγ). Notably, HDL-C levels do not necessarily reflect RCT efficiency, and novel regulatory factors, such as microRNAs, endothelial lipase, and ANGPTL3, have been implicated. HDL also exhibits vasoprotective functions by enhancing nitric oxide (NO) production and modulating sphingosine-1-phosphate (S1P) signaling. Furthermore, it exerts anti-inflammatory effects by suppressing adhesion molecules, proinflammatory cytokines, and innate immune activation while modulating adaptive immune responses and attenuating tissue fibrosis. In addition, HDL influences megakaryopoiesis and platelet activation, thereby contributing to its antithrombotic properties. Despite these broad functional spectra, clinical assessments remain largely limited to cholesterol efflux capacity, and other key functional aspects have not been adequately explored. A more comprehensive understanding of HDL's pleiotropic roles, spanning lipid metabolism, vascular biology, inflammation, and hemostasis, is necessary from both the basic and clinical perspectives. Recent studies have further suggested potential roles of HDL in the central nervous system, expanding its relevance beyond cardiovascular prevention and toward broader therapeutic applications.

Aims: The blood inflammatory marker interleukin 6 (IL-6) has been shown to predict future stroke, major adverse cardiovascular events (MACEs), and dementia. However, no study has yet examined this relationship in the same population. The present study compared the predictive utility of IL-6 levels in stroke, MACEs, and Alzheimer's disease (AD) dementia.

Methods: In this post-hoc analysis, we derived data from a Japanese observational registry in which 1011 patients with evidence of cerebral vessel disease were enrolled. After excluding patients who required assistance with daily tasks, were suspected of having dementia, and lacked IL-6 measurement, 471 patients were included. The patients were followed up until March 2023. The outcomes were incident stroke, MACEs, and AD dementia.

Results: During a median follow-up period of 4.6 years, stroke, MACEs, and AD dementia occurred in 24, 36, and 21 patients, respectively. Serum IL-6 levels are associated with age, sex, and vascular factors. A Cox proportional hazard analysis revealed that the highest IL-6 tertile (≥ 2.5 pg/mL) was associated with a significantly higher risk of stroke and MACEs than the lowest IL-6 tertile after adjusting for confounding factors (stroke, adjusted hazard ratio 4.84 [95% confidence interval, 1.02-23.05], P = 0.048; MACEs, adjusted hazard ratio 3.68 [95% confidence interval, 1.01-13.51], P = 0.049). However, no association was found between IL-6 tertile groups and AD dementia.

Conclusion: Serum IL-6 levels predicted stroke and cardiovascular events but not AD dementia in patients with vascular risk factors. The involvement of low-grade systemic inflammation appears to be significantly greater in atherothrombotic events than that in AD dementia.

Aims: To investigate the predictors associated with inadequate adherence in patients receiving proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies (mAbs) in China and to assess the mean LDL-C levels and the percentage reduction of LDL-C.

Methods: Patients with at least one PCSK9-mAbs prescription filled between January 2021 and December 2022 were included in this study. The LDL-C levels before and after treatment initiation were assessed using medical records. Adherence to PCSK9-mAbs was assessed for up to 12 months after treatment initiation using the proportion of days covered.

Results: A total of 415 patients were enrolled. The medication adherence to PCSK9-mAbs after 12 months was 31.8%. A multivariate analysis revealed that better education (junior or high school adjusted OR 2.7 and college or higher adjusted OR 5.2) and LDL-C ＜1.4 mmol/L at 3 months after starting PCSK9-mAbs (adjusted OR 3.0) were consistent predictors of adherence. At 12 months, LDL-C was 1.5mmol/L in the adherence group (mean [SD] decrease, 44.5% [26.5%]) and 1.9 mmol/L in the poor adherence group (mean [SD] decrease, 31.0% [32.7%]), with a group difference of 0.42 mmol/L (group difference in decrease, 13.48%).

Conclusions: A better education and LDL-C ＜1.4 mmol/L at 3 months after starting treatment with PCSK9-mAbs were consistent predictors of adherence. In addition, the treatment effect declined more significantly in the poor adherence group over time.

Aims: Visceral fat accumulation is the central feature of metabolic syndrome and subsequent atherosclerotic cardiovascular disease. Soluble T-cadherin (sT-cad) has been identified in circulation, but its clinical significance in the general population remains unclear. We investigated the associations of circulating sT-cad levels with metabolic syndrome and its components in a population undergoing health checkups.

Methods: A total of 1321 Japanese participants (825 males and 496 females) undergoing health checkups were enrolled. Serum levels of sT-cad (130-kDa, 100-kDa, and 30-kDa), adiponectin (APN), and other clinical parameters were measured. Associations between sT-cad and metabolic risk factors were analyzed.

Results: Among the three sT-cad isoforms, serum 130-kDa sT-cad levels were significantly negatively correlated with waist circumference, blood pressure, Homeostatic Model Assessment for Insulin Resistance (HOMA-R), triglycerides, Alanine aminotransferase (ALT), uric acid, and high-sensitivity C-reactive protein (hsCRP), and positively correlated with high-density lipoprotein (HDL) cholesterol and APN. In multivariate analysis, high TG levels and/or HDL-C levels and hsCRP were independent negative determinants of 130-kDa sT-cad levels in both sexes. Furthermore, 130-kDa sT-cad levels decreased progressively with an increasing number of metabolic risk factors (P for trend ＜0.001).

Conclusion: Low serum 130-kDa sT-cad levels are associated with the presence and accumulation of metabolic syndrome-related abnormalities in a Japanese population undergoing health checkups. Inflammation and lipid abnormalities of metabolic syndrome (high TG and/or low HDL-C) may influence the serum 130-kDa sT-cad levels.

Aim: Tendon xanthomas are part of the clinical triad of diagnostic criteria for familial hypercholesterolemia (FH) in Japan. The Achilles tendon generally has a twisted structure, and we investigated the impact of torsion on Achilles tendon thickness (ATT) assessment.

Methods: In this single-center retrospective study, 61 acute coronary syndrome (ACS) patients who underwent ATT assessment using radiography (ATT-Xp) and ultrasonography (ATT-US) were analyzed. Ultrasonographic ATT assessment used two axes - antero-posterior axis (ATT-US (AP)) and corrected axis according to Achilles tendon torsion (ATT-US (correct)) - and the torsion angle was measured. The association of torsion with each ATT assessment was investigated.

Results: The torsion angle of the Achilles tendon varied widely. Both ATT-US (AP) and ATT-US (correct) were significantly correlated with ATT-Xp, although the correlation between ATT-Xp and ATT-US (correct) was modest compared to the correlation with ATT-US (AP) (ATT-US (AP)-Right: r= 0.91, p＜0.001, Left: r= 0.91, p＜0.001; ATT-US (correct)-Right: r = 0.82, p＜0.001, Left: r = 0.76, p＜0.001, respectively). Torsion angle was well correlated with the differences in ATT between ATT-Xp and ATT-US (correct) (Right: r= 0.62, p＜0.001, Left: r= 0.66, p＜0.001). There were no independent factors associated with Achilles tendon torsion.

Conclusion: This is the first study to quantitatively evaluate the three-dimensional twisted structure of the Achilles tendon and demonstrate that Achilles tendon torsion is associated with the difference between ATT-Xp and ATT-US (correct). Torsion of the Achilles tendon should be considered in Achilles tendon assessment, particularly radiographical assessment.

Aims: Persistent Chlamydia pneumoniae (C. pneumoniae) infection has been suggested to be a risk factor for cardiovascular events; however, only findings from studies on small populations are available so far. This study investigated this hypothesis in a large general population through a longitudinal analysis.

Methods: We included 9,064 community residents who participated in the Nagahama study (mean age: 52.8 years). C. pneumoniae infection (seropositivity) was determined by serum levels of immunoglobulin A and immunoglobulin G assessed by enzyme-linked immunoassay. The incidence rates of cardiovascular diseases (CVDs), including stroke and coronary artery diseases, were determined by reviewing participants' hospital records and death certificates. Basic clinical parameters were obtained using the baseline survey of the Nagahama study.

Results: During a mean follow-up duration of 4,390 days, we observed 323 cases of CVDs. The incidence rates of CVDs were 45.0 and 24.5 per 10,000 person-years in the seropositive and seronegative groups, respectively (log-rank test: p＜0.001). The results of the Cox proportional hazard model analysis indicated that C. pneumoniae seropositivity was remarkably associated with CVDs (1.30, 95% confidence interval: 1.04-1.64) after adjusting for established risk factors, including arterial stiffness (p = 0.023). The hazard ratio was higher in the subpopulation aged ≤ 55 years (2.62, 95% confidence interval: 1.45-4.75, p = 0.001) and reached 3.66 (95% confidence interval: 1.39-9.65, p = 0.009) in the subpopulation aged ≤ 45 years.

Conclusion: C. pneumoniae seropositivity was significantly associated with CVDs incidence, especially in adolescents and middle-aged individuals.

Aim: To compare the effectiveness and safety of moderate-intensity pravastatin 40 mg/day and atorvastatin 10 mg/day in patients with dyslipidemia.

Methods: We conducted a retrospective cohort study using electronic health records of 19 million patients across 14 secondary/tertiary hospitals, standardized to a Common Data Model. New users of pravastatin (40 mg/day) and atorvastatin (10 mg/day) were identified. Six distinct cohorts were used to assess the comparative effectiveness in preventing major adverse cardiovascular events (MACE) and the risks of new-onset diabetes mellitus (NODM), myalgia or rhabdomyolysis, and hepatotoxicity (measured by aspartate aminotransferase [AST]/alanine aminotransferase [ALT]). Propensity score matching (PSM) was applied to each cohort for effectiveness and safety analyses, followed by a meta-analysis of hospital-specific results.

Results: After PSM, patients were equally assigned to the pravastatin and atorvastatin groups for primary (n = 2,688/group) and secondary MACE prevention (n = 1,258/group) and to assess the risk of NODM (n = 2,391/group), new-onset myalgia or rhabdomyolysis (n = 11,799/group), and hepatotoxicity (AST, n = 4,034/group; ALT, n = 3,655/group). No significant differences were observed in the hazard ratios (HRs) for primary (HR = 0.84; 95% CI, 0.59-1.20) and secondary MACE prevention (HR = 0.89; 95% CI, 0.68-1.16). Similarly, no significant difference was observed in the risk of NODM (HR, 0.99; 95% CI, 0.79-1.23). The risk of new-onset myalgia/rhabdomyolysis (HR = 0.82, 95% CI, 0.69-0.96) and the incidence of abnormal elevations in AST levels (2.35% vs. 3.37%, p＜0.05) were significantly lower in the pravastatin group.

Conclusion: Moderate-intensity pravastatin (40 mg/day) showed comparable effectiveness to moderate-intensity atorvastatin (10 mg/day) in preventing MACE with a more favorable safety profile.

Aim: We investigated the association of obesity and metabolic health status with cerebral small-vessel disease (SVD), a predictor of stroke, in stroke-free participants during brain health checkups.

Methods: An observational cross-sectional study was conducted on 6,088 stroke-free participants who underwent brain magnetic resonance imaging (MRI). Abdominal obesity was defined as a waist circumference ≥ 90 cm for men and ≥ 80 cm for women. A metabolically healthy status was defined as having none of the three components of metabolic syndrome, except abdominal obesity. The total SVD scores were derived from four MRI markers: silent lacunar infarcts, cerebral microbleeds, moderate-to-severe white-matter hyperintensity, and enlarged perivascular spaces.

Results: The mean age of participants was 55±12 years old. Obesity was prevalent in 50% of the patients. The prevalence of a total SVD score ≥ 2 (moderate-to-severe SVD) was 348 (6%), which was elevated in metabolically unhealthy individuals regardless of obesity status. Compared with the metabolically healthy non-obese group, the metabolically unhealthy non-obese (odds ratio [OR] 2.08, [95% confidence interval {CI}, 1.33-3.27]) and metabolically unhealthy obese (OR 2.62, [95% CI, 1.70-4.04]) groups had a higher multivariable-adjusted risk for a total SVD score ≥ 2. Similar results were obtained for obesity defined as a body mass index ≥ 25 kg/m² instead of abdominal obesity.

Conclusions: Abdominal and general obesity alone were not associated with high total SVD scores in stroke-free individuals. Metabolically unhealthy status, especially high blood pressure and hyperglycemia, are significant risk factors for moderate-to-severe SVD.

Aims: Sex differences in the risk of venous thromboembolism (VTE) among patients with an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) have so far only been sparsely described. This study aimed to investigate the differences in the risk of VTE events between male and female AECOPD patients and to determine whether any specific risk factors for VTE vary between the sexes.

Methods: We prospectively enrolled patients hospitalized for AECOPD from ten medical centers in China. The primary outcome was the occurrence of VTE. Univariate and multivariate logistic regression analyses were conducted to determine whether sex was an independent risk factor for VTE and also to identify any sex-specific risk factors.

Results: In total, 13,664 patients were included. VTE occurred in 5.5% of females and 3.3% of males (P＜0.001). A multivariate logistic regression analysis identified female sex as an independent risk factor for VTE in patients with AECOPD (odds ratio [OR] = 1.439, 95% confidence interval [CI] = 1.177-1.759, P＜0.001) after adjusting for confounding factors. Common risk factors for both sexes included age, chronic heart failure, severe lung disease, stroke, a recent surgical history, a history of VTE, and respiratory failure. Additional risk factors unique to males were sepsis (OR = 9.514, 95% CI = 4.513-20.056, P＜0.001), varicose veins (OR = 6.170, 95% CI = 3.237-11.763, P＜0.001), and rheumatological disorders (OR = 2.677, 95% CI = 1.184-6.052, P = 0.018). No sex-specific risk factors were identified for females.

Conclusion: Female sex was found to be an independent risk factor for VTE and some sex-specific risk factors exist among inpatients with AECOPD. These findings highlight the importance of considering sex and sex-related factors when assessing the VTE risk in AECOPD patients.

Aim: To explore the prognostic value of the first 24-h urine output (UO) after admission in patients with acute pulmonary embolism (APE) in the intensive-care unit (ICU) for short- and long-term all-cause mortality risk.

Methods: This retrospective cohort study used the MIMIC-IV database. Patients with APE were divided into 4 teams (T1-T4) by their first 24-h UO after admission: T1 (UO ≤ 400 ml), T2 (400＜UO ≤ 800 ml ), T3 (800＜UO ≤ 2500 ml), and T4 (UO＞2500 ml). The primary endpoints were the three-month and one-year all-cause mortality rates. The relationship between UO and mortality was assessed using Kaplan-Meier survival curves and Cox proportional hazards models.

Results: This study included 2012 patients with APE, of whom 50.75% were female. Compared to the T3 group, patients in the T1 and T2 groups had higher all-cause mortality rates. Kaplan-Meier survival curves showed that patients in the T1 and T2 groups had a higher risk of death, while those in the T4 group seemed to have a lower risk of death (P＜0.001). The results remained stable in all three adjusted models and subgroup analyses. A restricted cubic spline analysis (RCS) revealed that the risk of all-cause mortality gradually decreased with an increase in UO, showing an "L"-shaped relationship. A UO of ＜1283 ml increased the risk of death in patients. Subgroup analysis indicated that the first 24-h UO was associated with 3-month and 1-year all-cause mortality rates in most subgroups of patients.

Conclusions: The first 24-h UO after admission is an important indicator for the prognosis of APE patients. A lower 24-h UO is strongly related to a higher risk of short-term and long-term all-cause mortality in ICU patients with APE.