Journal of atherosclerosis and thrombosis最新文献

Familial hypercholesterolemia (FH) is an inherited disorder characterized by elevated LDL cholesterol levels and an increased risk of early-onset atherosclerotic cardiovascular disease. In pregnant female with FH, apheresis is the preferred treatment because standard therapeutic agents such as statins are contraindicated during pregnancy. LDL adsorption therapy is commonly used; however, after 27 weeks of gestation, it is often switched to dual filtration plasma exchange (DFPP) due to the significant drop in blood pressure caused by bradykinin production. However, DFPP has limited ability to adapt to the increase in circulating plasma volume associated with pregnancy. Here we discuss the case of a 32-year-old female with homozygous FH who underwent different apheresis strategies during her pregnancies. In her first pregnancy, she continued LDL adsorption therapy using DFPP but ultimately delivered a small-for-gestational-age infant via cesarean section. For her second pregnancy, double-filtration plasmapheresis thermo mode, DF-thermo, was introduced to mitigate the limitations of DFPP and LDL adsorption therapies, such as hypotension during apheresis and albumin loss. By minimizing these complications, DF-thermo allowed for a successful delivery without compromising fetal growth.

Aims: We aimed to evaluate the effect of serum lipoprotein(a) (Lp(a)) levels on carotid artery ulceration using digital subtraction angiography (DSA), which is the gold standard for assessing atherosclerotic plaque surface morphology.

Methods: Of the consecutive cerebrovascular patients prospectively collected serum Lp(a) levels from June 2021 to October 2024 admitted to our institution, patients with carotid artery stenosis were enrolled in this study. Blood samples were collected within three months of admission. Based on common carotid angiography and 3D rotational angiography to confirm the morphology of stenotic lesions, patients were dichotomized according to the presence or absence of carotid artery ulceration.

Results: Of the 439 cerebrovascular patients, 94 with carotid artery stenosis were analyzed (18 females, median 75 [interquartile range, 71-81] years) and carotid artery ulceration was confirmed in 38 (40.0 %) patients. Patients with carotid artery ulceration showed a higher proportion of dyslipidemia (94.7% versus 75.0%; p = 0.013), and higher L(a) levels (28 [11-56] vs 10 [5-25] mg/dL, p = 0.007) than those without. Multivariable logistic analysis adjusted for other atherosclerotic risk factors showed a significant association between higher Lp(a) levels and carotid artery ulceration (odds ratio per 10 mg/dL increase, 1.21; 95%CI, 1.02-1.43; p = 0.026). Receiver operating characteristic curve analysis showed that Lp(a) ≥ 26 mg/dL was the threshold to predict the presence of carotid artery ulceration (area under the curve = 0.67; sensitivity, 52.6%; specificity, 78.6%).

Conclusions: In patients with carotid artery stenosis who may be considered candidates for surgical treatment, elevated Lp(a) levels were associated with carotid artery ulceration.

Inflammation plays a crucial role in the initiation, progression, and destabilization of atherosclerotic plaques and it contributes to recurrent cardiovascular events in patients with coronary artery disease (CAD). High-sensitivity C-reactive protein (hsCRP) is a well-established biomarker of systemic inflammation and it is a predictor of adverse outcomes, independent of low-density lipoprotein cholesterol (LDL-C) levels. Elevated hsCRP levels are consistently associated with higher event rates in both chronic and acute coronary syndromes, thus reflecting the residual inflammatory risk not addressed by lipid-lowering therapy or revascularization. Imaging studies have revealed that higher hsCRP levels correlate with a greater plaque burden and vulnerability. Recent trials have shown that anti-inflammatory therapies, including low-dose colchicine and interleukin-6 inhibition, can reduce this residual risk, while agents such as glucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter 2 inhibitors, and bempedoic acid offer additional anti-inflammatory effects. The integration of anti-inflammatory strategies with intensive lipid management may thus provide additional cardiovascular benefits.

Aims: The phase angle (PhA) derived from a bioelectrical impedance analysis (BIA) is a risk factor for cardiovascular disease (CVD). The present study explored the relationship between PhA and the progression of subclinical atherosclerosis in asymptomatic adults.

Methods: Two cross-sectional studies were performed on 15579 participants who underwent carotid ultrasound testing and a BIA as well as 8228 participants who underwent brachial ankle pulse wave velocity (baPWV) testing and a BIA. We also conducted a longitudinal study in participants without CVD and carotid atherosclerosis (CAS) at baseline who underwent carotid ultrasound ≥ 2 times (n = 2680) or baPWV testing [≥ 2 times] (n = 1775). CAS and the brachial ankle pulse wave velocity (baPWV) were selected as the subclinical atherosclerosis markers.

Results: In the cross-sectional studies, participants with CAS (5.43±0.60° vs. 5.73±0.61°, P＜0.001) or elevated baPWV (5.38±0.62° vs. 5.74±0.59°, P＜0.001) had lower PhA values than controls. Furthermore, the PhA value was independently and inversely correlated with CAS (adjusted odds ratio [OR] = 0.41, 95% confidence interval [CI] 0.37-0.46, P＜0.001) and elevated baPWV (adjusted OR = 0.45, 95% CI 0.39-0.52, P＜0.001). Restricted cubic spline curve analyses indicated dose-response associations of PhA values with subclinical atherosclerosis. In the longitudinal study, high PhA values at baseline decreased the risk of incident CAS (adjusted hazard ratio = 0.44, 95% CI 0.36-0.54, P＜0.001). Multivariate linear regression analyses showed that the PhA was negatively associated with absolute or relative annual changes in baPWV.

Conclusion: The PhA value is significantly associated with the progression of subclinical atherosclerosis, indicating that PhA may serve as a noninvasive marker for monitoring subclinical atherosclerosis in a primary prevention setting.

Aim: The long-term clinical outcomes of endovascular therapy (EVT) for aortoiliac (AI) artery lesions remain unclear. This study aimed to investigate 10-year patency and mortality after AI stent implantation.

Methods: This multicenter retrospective study included 1919 patients (2375 limbs) who underwent AI stent implantation to treat symptomatic peripheral artery disease (PAD) between January 2005 and December 2010. The study outcome was primary patency, which was defined as a treated vessel without restenosis, mortality, and associated factors.

Results: The mean age of the study cohort was 71±9 years. Chronic limb-threatening ischemia (CLTI) accounted for 17.2% of cases, and chronic total occlusion (CTO) was found in 24.6% of cases. During a median follow-up period of 2.9 years (interquartile range: 1.0-6.0 years), 412 patients lost patency, whereas 467 patients died without experiencing loss of patency. At 1, 6, and 10 years post-EVT, respectively, the primary patency rates were estimated to be 92.8%, 79.3%, and 77.2%, and the survival rates were 94.9%, 77.0%, and 63.1%. Female sex, CTO, and the presence of outflow lesions were significantly associated with an increased risk of patency loss after stent implantation (all P＜0.05), whereas age, dialysis-dependent renal failure, heart failure, and CLTI were significantly associated with an increased risk of mortality.

Conclusion: Stent implantation for AI lesions achieved favorable 10-year patency, with patency loss plateauing after six years. No AI lesion characteristic was associated with mortality. These results support the long-term efficacy of EVT in the clinical practice.

Aim: Mounting evidence suggests apolipoprotein E-containing high-density lipoprotein cholesterol (APOE-HDLC) as an indicator of the anti-atherogenic function of HDLC, but data are lacking on whether or not APOE-HDLC is involved in the development of atherosclerosis in humans. This study was performed to explore whether or not APOE-HDLC is associated with atherosclerotic plaque progression in humans.

Methods: Among 823 participants 45 to 74 years old who were free of cardiovascular disease, we assessed nuclear magnetic resonance spectroscopy-measured HDL particle concentrations, APOE-HDLC levels and HDLC levels at baseline, and performed carotid ultrasound measurements in surveys conducted in 2002 and again in 2007 after a 5-year interval. The ratio of APOE-HDLC to total HDLC (APOE-HDLC/HDLC ratio) was calculated to assess the relative proportion of APOE-HDLC in total HDLC, given the strong correlation between them.

Results: The baseline APOE-HDLC/HDLC ratio was significantly associated with the risk of 5-year plaque progression (relative risk [RR] = 0.71; 95% confidence interval [CI] = 0.53-0.95), which is independent of the ratio of HDLC to the HDL particle number (HDLC/P ratio). In particular, participants with an HDLC/P ratio ≥ 44.8 (denoted very high level of cholesterol content per HDLP, a marker of dysfunctional HDL) had a 36% reduced 5-year plaque progression risk (RR = 0.64; 95% CI = 0.43-0.97) if combined with the highest APOE-HDLC/HDLC ratio, as compared with the lowest APOE-HDLC/HDLC ratio.

Conclusions: These results highlight the potential utility of APOE-containing HDL as a candidate emerging biomarker for the anti-atherosclerotic function of HDL particles.

Aims: While glomerular hyperfiltration (GHF) emerged as a risk factor for cardiovascular disease (CVD), little is known about the association between GHF and blood lipid profile. We aimed to examine the association between GHF and blood lipid parameters in adults with few comorbidities.

Methods: A cross-sectional study was performed on adults undergoing health screening in Osaka, Japan. Adults with a history of heart disease or stroke, those with diabetes mellitus, chronic kidney disease (estimated glomerular filtration rate (eGFR) ＜60 mL/min/1.73m²), or those using lipid-lowering medication were excluded. The outcome was GHF, defined as ＞95^th percentile of eGFR after stratification by age and sex. The exposure was blood lipid parameters, including total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), non-HDL-C, TG/HDL-C ratio, small dense LDL-C (sdLDL-C), and sdLDL-C/LDL-C ratio. Associations between blood lipid parameters and GHF were examined by multiple logistic regression under a Bayesian framework, adjusted for established risk factors of GHF, including body mass index, blood pressure, and lifestyle factors.

Results: Of 17,288 eligible individuals (mean age 50.1±9.9 years; 45.5% women), 853 individuals (4.9%) had GHF. Multiple logistic regression analyses demonstrated an association between a higher sdLDL-C/LDL-C ratio and GHF (odds ratio (OR) = 1.51, 95% credible interval (CrI) 1.21-1.88). LDL-C showed an inverse association with GHF (OR = 0.94, 95% CrI 0.92-0.97).

Conclusion: Our findings demonstrated an independent association between a higher sdLDL-C/LDL-C ratio and GHF. The role of an sdLDL-C/LDL-C ratio in GHF development and CVD risk merits further investigation.

Aim: Achilles tendon xanthomas are a characteristic feature of familial hypercholesterolemia (FH). Achilles tendon thickness (ATT) has been associated with the severity of coronary artery disease (CAD) in FH. However, its relevance in non-FH remains unclear. Therefore, we assessed the relationship between ATT and CAD severity in patients with acute coronary syndrome (ACS) without FH.

Methods: A total of 194 patients (mean age: 69.1±11.9 years) with ACS without FH were retrospectively investigated and divided into two groups: single-vessel disease (SVD) or multivessel disease (MVD). ATT was measured using ultrasonography (US-ATT) and radiography (Xp-ATT). The association between ATT and CAD severity was evaluated.

Results: Of the total, 107 patients (55.2%) had SVD, and 87 (44.8%) had MVD. Mean US-ATT and Xp-ATT values were 5.0±0.6 mm and 6.4±1.2 mm, respectively. ATT was significantly greater in the MVD group than in the SVD group (US-ATT: 5.2 mm vs. 4.8 mm, p＜0.01; Xp-ATT: 6.6 mm vs. 6.1 mm, p = 0.01) and correlated with the SYNTAX score (US-ATT: r = 0.30, p＜0.01; Xp-ATT: r = 0.19, p = 0.02). Multivariable analysis identified US-ATT as an independent predictor of MVD (odds ratio: 2.71; 95% confidence interval: 1.46-5.01; p＜0.01).

Conclusion: In patients with ACS without FH, ATT was significantly associated with CAD severity. This suggests that ATT, particularly US-ATT, may serve as a practical, non-invasive marker for cardiovascular risk stratification.