Aims: A functional abnormality in high-density lipoprotein (HDL) particles rather than a quantitative abnormality in HDL cholesterol levels has been suggested to promote atherosclerosis. The modification of HDL may underlie functional changes to HDL such as gaining the ability to bind and activate the lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (LOX-1). We aimed to develop a novel method for measuring modified HDL on the basis of its binding to LOX-1.
Methods: We designed a LOX-1 binding–based enzyme-linked immunosorbent assay (ELISA) with recombinant LOX-1 and anti-apoAI antibody. A lipid-free standard was devised by making a chimeric fusion protein containing anti-LOX-1 antibody and human apoAI fragment. We used this system to detect modified HDL, designated as LOX-1 ligand containing apoAI (LAA).
Results: With our ELISA system, we detected HDL modified by copper oxidation, hypochlorous acid, 4-hydroxynonenal, and potassium cyanate, but not native HDL. Upon oxidation, HDL showed increased LOX-1 binding activity and decreased cholesterol efflux and paraoxonase-1 activities. In the ELISA, the chimeric fusion protein standard showed minimal variation in reference binding curves in contrast to copper-oxidized HDL preparations, suggesting better quality control of the chimeric fusion protein as the standard for measuring modified HDL activity. LAA was detectable in the plasma of healthy individuals and of mice fed a high-fat diet.
Conclusion: We have developed a novel ELISA by using recombinant LOX-1 and anti-apoAI antibody to measure the activity of modified HDL in plasma.
Aim: To evaluate the prognostic value of plasma big endothelin-1 level in the context of three-vessel disease (TVD) with heavy atherosclerotic burden.
Methods: A total of 6,150 patients with TVD and available big endothelin-1 data were included in the study. Participants were divided into two groups according to the optimal cutoff value of big endothelin-1 for mortality prediction. The primary endpoint was all-cause death. C-index, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were calculated to evaluate the added prognostic value of plasma big endothelin-1 level beyond the SYNTAX score Ⅱ.
Results: On the basis of the optimal cutoff value of 0.79 pmol/L, 1,984 patients were assigned to the high big endothelin-1 group. During a median follow-up of 6.8 years, 818 patients experienced all-cause death. Plasma big endothelin-1 level was significantly higher in patients who died than in patients who survived. Multivariable analysis found that high big endothelin-1 level was independently associated with an increased risk of mortality (hazard ratio: 1.36, 95% confidence interval: 1.18–1.57, P＜0.001). The association of big endothelin-1 with all-cause death was relatively consistent across subgroups with no significant interactions. The predictive ability of the SYNTAX score Ⅱ was significantly enhanced by addition of plasma big endothelin-1 level (C-index: 0.723 vs.0.715, P =0.029; NRI: 0.304, P＜0.001; IDI: 0.009, P＜0.001).
Conclusions: Plasma big endothelin-1 level is an independent predictor of long-term mortality in patients with TVD. It can improve the discrimination and reclassification of the SYNTAX score Ⅱ for mortality prediction.
Aim: The primary percutaneous procedure resulted in a significant improvement in the prognosis of myocardial infarction. However, no-reflow phenomenon restrains this benefit of the process. There are studies suggesting that soluble suppression of tumorigenicity (sST2) can be valuable in the diagnosis and progression of heart failure and myocardial infarction. In this study, we aimed to investigate the effect of sST2 on no-reflow phenomenon in ST-elevated myocardial infarction (STEMI).
Method: This study included 379 patients (258 men; mean age, 60±11 years) who underwent primary percutaneous treatment for STEMI. sST2 levels were measured from blood samples taken at admission. Patients were divided into two groups according to Thrombolysis in Myocardial Infarction(TIMI) flow grade: group 1 consists of TIMI 0,1,2, accepted as no-reflow, and group 2 consists of TIMI 3, accepted as reflow.
Results: No-reflow phenomenon occurred in 60 patients (15.8%). The sST2 level was higher in the no-reflow group (14.2±4.6 vs. 11.3±5.0, p=0.003). Moreover, regression analysis indicated that diabetes mellitus, lower systolic blood pressure, multivessel vascular disease, high plaque burden, and grade 0 initial TIMI flow rate were other independent predictors of the no-reflow phenomenon in our study. Besides, when the patients were divided into high and low sST2 groups according to the cut-off value from the Receiver operating characteristics analysis, being in the high sST2 group was associated with 2.7 times increased odds for no-reflow than being in the low sST2 group.
Conclusion: sST2 is one of the independent predictors of the no-reflow phenomenon in STEMI patients undergoing primary percutaneous coronary intervention.
Aim: The purpose of this study was to compare two homogeneous assays of low-density lipoprotein-cholesterol (LDL-C) with a modified beta quantification reference measurement for LDL-C (BQ-LDL), fractions of chylomicron (CM), very low-density lipoprotein (VLDL) and intermediate-density lipoprotein (IDL) by quantitative ultracentrifugation in patients with hypertriglyceridemia.
Methods: Two homogeneous LDL-C assays (LDL-C(K), Kyowa Medex and LDL-C(S), Sekisui Medical) were used to measure 198 samples of fresh anonymized leftover sera with hypertriglyceridemia (≥ 150 mg/dL). Of these, 32 samples with discrepant LDL-C levels or hypertriglyceridemia (≥ 400 mg/dL) were used for further analysis. Quantitative ultracentrifugation was used to separate samples.
Results: The two homogeneous LDL-C assays had a strong correlation with each other for the samples from 198 patients with hypertriglyceridemia. LDL-C(K) and LDL-C(S) in 32 selected samples were strongly correlated with BQ-LDL. In both homogeneous assays, cholesterol in the CM and VLDL fractions was measured as part of the LDL-C. A weak correlation was found between cholesterol in the VLDL fraction and LDL-C using the two homogeneous assays, but no correlation was found with cholesterol in the CM fraction. Cholesterol in the IDL fraction was also measured as part of the LDL-C in both assays.
Conclusion: Both homogeneous assays partially detected cholesterol in the chylomicron and VLDL fractions, but LDL-C measured by both homogeneous assays correlated with BQ-LDL.
Aim: Although current guidelines recommend surgical revascularization as the first-line therapy for chronic total occlusion of the abdominal aorta (Leriche syndrome), endovascular therapy (EVT) has been increasingly utilized because of the development of new technologies and techniques. EVT has demonstrated durable midterm outcomes for aortoiliac occlusive disease (AIOD). Nonetheless, little is known regarding their long-term outcomes and predictors of restenosis.
Methods: We retrospectively analyzed a multicenter database of 64 consecutive patients (age, 73±10 years; 64% male; 22% critical limb ischemia) undergoing EVT for aortoiliac occlusive disease between September 2005 and March 2016. The outcome measures were primary and secondary patency, following EVT, calculated using the Kaplan–Meier method. Independent predictors associated with restenosis were assessed using Cox proportional hazard regression model.
Results: Technical success was achieved in 61 patients (95%). In total, 214 stents (192 self-expandable stents, 22 balloon-expandable stents) were implanted. During the follow-up of 33±28 months, 11 patients experienced loss of patency. The primary patency rates were 88%, 70%, and 70% at 1, 3, and 5 years, respectively. The secondary patency rates were 98%, 87%, and 77% at 1, 3, and 5 years, respectively. In Cox regression analysis, E-Luminexx stent use (in 29 patients, 48%) was associated with restenosis [hazard ratio, 4.41, P=0.038].
Conclusion: In this retrospective study, EVT for AIOD demonstrated favorable 5-year patency. E-Luminexx stent implantation was associated with restenosis in this population.
Aim: Knowledge of subclinical plaque morphology and plaque distribution in the aorta in vivo remains unclear. This study aimed to increase the body of knowledge in this area.
Methods: We enrolled 37 consecutive patients with stable angina pectoris patients who underwent non-obstructive angioscopy for both the coronary artery and aorta immediately after percutaneous coronary intervention. We evaluated the presence of aortic plaques and the distribution of plaque instability. Patients were allocated into two groups according to the number of vulnerable plaques in whole aorta (a low [0–11] and high [≥ 12] group). We evaluated the relationships between the two groups in terms of cardiovascular risk factors.
Results: Aortic plaques were identified using non-obstructive angioscopy in all patients, and the greatest number of plaques was found at the infrarenal abdominal aorta (IAA) (the aortic arch, the descending thoracic aorta, the suprarenal abdominal aorta, the IAA, and common iliac artery; 65%, 76%, 65%, 95%, and 49%, respectively; p＜0.001). The maximum yellow grade, and the number of intense yellow plaques, ruptured plaques, and thrombi were highest at the IAA (p＜0.001). The prevalence of diabetes mellitus and peripheral arterial disease was higher in the high vulnerable plaque group (83.3% vs. 40.0%, p=0.010, 50.0% vs. 8.0%, p=0.005, respectively).
Conclusions: Aortic atherosclerosis was the most severe at the IAA, and aortic plaque vulnerability and distribution were associated with the prevalence of diabetes mellitus and peripheral artery disease in patients with stable angina pectoris. Non-obstructive angioscopy may identify patients at high risk of future aortic events.
Aim: Development of atherosclerotic plaques is affected by vascular geometry and hemodynamics. Hemodynamics in the basilar artery (BA) is unique as the flow converges from vertebral arteries (VAs). Here, we investigated the characteristics of BA plaque based on VA and BA geometry.
Methods: Consecutive patients evaluated using high-resolution magnetic resonance imaging (MRI) at a general health center were screened. Geometric characteristics of VA (VA dominancy and VA-BA angles) and BA (BA convexity and BA angles) were assessed. The burden of BA plaques was investigated in each wall (anterior, posterior, left, and right lateral). The characteristics of BA plaques were compared according to VA dominancy (right vs. left), BA angle of lateral view (lateral mid-BA angle; dichotomized), and total plaque burden (divided by tertiles).
Results: Of the 1029 subjects, BA plaques were observed in 98 (9.5%) patients, and were more frequently located at the anterior wall (32.4%) and posterior wall (35.0%) than the right wall (15.3%) and left lateral wall (17.6%). Right and left lateral plaques were more frequent in the left and right convex BA, respectively (p=0.009 and p=0.024, respectively). Anterior plaques were more frequently observed in low lateral mid-BA angle (p= 0.043). BA plaques were predominant in anterior and posterior walls in patients with lower plaque burden, whereas they were predominant in right and left lateral walls in patients with higher plaque burden (p=0.001 and p=0.025, respectively).
Conclusions: Asymptomatic BA plaque location was associated with BA convexity and lateral mid-BA angle. The anteriorly and posteriorly located BA plaques may extend to the lateral walls as the plaque burden increases.
Aim: Motivated by the paradoxical and differing results of the early atherosclerosis related indices – Cardio-Ankle Vascular Index (CAVI) reflecting arterial stiffness and Reactive Hyperemia Index (RHI) evaluating endothelium dependent flow-induced vasodilation – in obesity, we aimed to assess CAVI and RHI in obese adolescents and young adults in the context of differences in systemic vascular resistance (SVR).
Methods: We examined 29 obese (14f, 15.4 [12.3–18.5] y; BMI: 33.2±4.4 kg.m−2) and 29 non-obese gender and age matched adolescents and young adults (BMI: 21.02±2.3 kg.m−2). CAVI and RHI were measured using VaSera VS-1500 (Fukuda Denshi, Japan) and Endo-PAT 2000 (Itamar Medical, Israel), respectively. Hemodynamic measures were recorded using volume-clamp plethysmography (Finometer Pro, FMS, Netherlands) and impedance cardiography (CardioScreen 2000, Medis GmbH, Germany). SVR and sympathetic activity related indices – Velocity Index (VI) and Heather Index (HI), and LFSAP (spectral power in low frequency band of systolic blood pressure oscillations) were determined.
Results: In obese group, CAVI (4.59±0.88 vs. 5.18±0.63, p=0.002) and its refined version CAVI0 (6.46±1.39 vs.7.33±0.99, p=0.002) were significantly lower. No significant difference in RHI was found. SVR and sympathetic activity indices were all significantly lower in the obese group than in the non-obese group. RHI correlated positively with SVR (r=0.390, p=0.044) in obese subjects.
Conclusion: Our results indicate that both indices used for the detection of early atherosclerotic changes are influenced by vascular tone. Vascular resistance could influence CAVI and RHI results impairing their interpretation.