Journal of atherosclerosis and thrombosis最新文献

Aims: Angiopoietin-like proteins (ANGPTLs) are key regulators of lipid metabolism; however, their response to lipid-lowering therapies remains incompletely understood. The PRESTIGE study compared the effects of pemafibrate add-on versus statin dose doubling on small dense low-density lipoprotein-cholesterol (sdLDL-C) in patients with type 2 diabetes and hypertriglyceridemia receiving statins. This post-hoc analysis investigated changes in circulating ANGPTL levels.

Methods: Participants were randomized to receive either pemafibrate (0.2 mg/day; n = 48) or double-dose statin therapy (n = 49). Plasma ANGPTL levels and lipid parameters were assessed at baseline and after 12 weeks. ANGPTLs were quantified using specific human ELISA kits. sdLDL-C, LDL-triglycerides (TG), and HDL3-C were measured using the homogeneous assays.

Results: Pemafibrate treatment significantly increased circulating ANGPTL3 (+71%) and ANGPTL4 (+143%) levels, with no change in ANGPTL8, whereas statin dose doubling had no effect on ANGPTL levels. Pemafibrate markedly reduced TGs and sdLDL-C, while increasing large buoyant LDL-C, LDL-TG, HDL2,3-C, apolipoprotein AI, and apolipoprotein AII. The increase in ANGPTL3 was not correlated with changes in LDL subspecies but was positively associated with changes in HDL2,3-C. When participants were stratified by baseline ANGPTL3 levels, those in the low ANGPTL3 group showed an increase in LDL-C and LDL-TG in response to pemafibrate. The substantial elevation in ANGPTL4 induced by pemafibrate did not show associations with lipid changes.

Conclusions: Pemafibrate markedly elevated circulating ANGPTL3 and ANGPTL4 levels, but these increases were not associated with pro-atherogenic changes in lipoprotein profiles. Notably, baseline ANGPTL3 concentrations may influence the effect of fibrates on LDL-C levels.

Aims: The HELT-E₂S₂ score is a newly developed risk stratification tool for stroke in patients with atrial fibrillation. We investigated the prognostic value of the HELT-E₂S₂ score in patients with lower extremity artery disease (LEAD) and compared it with other risk scores for atrial fibrillation (AF) and LEAD.

Methods: Patients undergoing endovascular therapy (EVT) for symptomatic LEAD between August 2015 and August 2016 were enrolled in the I-PAD NAGANO registry, a prospective, multicenter, observational registry. The primary endpoint was major adverse cardiovascular events (MACEs), defined as a composite of all-cause death, nonfatal myocardial infarction, and stroke at 5 years.

Results: A total of 366 patients were divided into low-risk (HELT-E₂S₂ score ＜2, n = 146) and high-risk (HELT-E₂S₂ score ≥ 2, n = 218) groups. The major criteria of the HELT-E₂S₂ score were hypertension (81.9%) and elderly age (75-84 years old) (34.1%). The incidence of MACEs at 5 years was significantly higher in the high-risk group than in the low-risk group (43.7% vs. 22.8%, P＜0.001). In the COX multivariate analysis, the high-risk group emerged as a significant predictor of MACEs at 5 years (hazard ratio 1.87, 95% confidence interval 1.22-2.89, P = 0.004). The C-statistics for MACEs were comparable among the HELT-E₂S₂ and other AF and LEAD risk scores.

Conclusions: The HELT-E₂S₂ score was associated with an increased risk of cardiovascular events in patients with LEAD undergoing EVT.

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.