Symptomatic Atherosclerosis Research Articles

Submaximal primary angioplasty for symptomatic intracranial atherosclerosis: peri-procedural complications and long-term outcomes.

The aim of our study is to report the peri-procedural complications and long-term stroke recurrent rate of symptomatic intracranial atherosclerosis (ICAS) patients who underwent submaximal primary angioplasty. This is a retrospective analysis of consecutive patients in a single center who underwent submaximal primary angioplasty between January 1, 2012 and December 31, 2015. The peri-procedural complications and long-term outcomes are reported. Primary angioplasty was successfully performed in 129 patients (97.0%). The mean degree of pre-procedural stenosis was 81.9 ± 10.2%, and the degree of residual stenosis was 40.7 ± 19.1%. There were nine (6.8%) peri-procedural complications within 30days, including seven ischemic strokes, one subarachnoid hemorrhage, and one asymptomatic intracerebral hemorrhage. None of them resulted in death. One-year follow-up was available in 122 patients (91.7%). Three more ischemic strokes (2.3%) which were in the territory of the treated artery occurred between 30days and 1year. The 1-year stroke and death rate was 9.0%, including peri-procedural stroke. Kaplan-Meier analysis showed a 3-year stroke-free survival of 87.2%. Submaximal primary angioplasty can be performed with a low peri-procedural complication rate and relatively good clinical outcome at long-term follow-up for symptomatic ICAS patients.

Drug-coated balloons for the treatment of symptomatic intracranial atherosclerosis: initial experience and follow-up outcome

BackgroundThe optimal treatment for patients with symptomatic severe intracranial atherosclerotic disease is not well established. Angioplasty and stenting have been attempted, with controversial results, mainly attributed to perioperative complications and...

HOXA11-AS regulates diabetic arteriosclerosis-related inflammation via PI3K/AKT pathway.

This study aims to explore whether homeobox A11 antisense RNA (HOXA11-AS) could regulate inflammation induced by diabetic arteriosclerosis (DAA) via PI3K/AKT pathway. Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to detect expressions of HOXA11-AS and proinflammatory genes in carotid endarterectomy samples of symptomatic and asymptomatic atherosclerosis (AS) patients, diabetes mellitus (DM), and non-DM patients. The above-mentioned genes in DM animal model and non-DM animal model were also detected. We detected the expression of HOXA11-AS in vascular smooth muscle cells (VSMCs) treated with platelet-derived growth factor (PDGF) or PDGF inhibitor imatinib, respectively. Subsequently, we applied cell transfection technology to interfere with the expression of HOXA11-AS in VSMCs. In vascular endothelial cells (VECs) and VSMCs, we detected the effect of HOXA11-AS on the expressions of genes related to the proliferation, migration, and cell cycle. Then, VSMCs were treated with tumor necrosis factor-α (TNF-α), and the expression of HOXA11-AS was examined in VSMCs. The effect of HOXA11-AS on TNF-α-induced inflammation in VSMCs was detected as well. Finally, we analyzed the effect of HOXA11-AS on PDGF-induced activation of PI3K/AKT pathway in VSMCs and VECs. HOXA11-AS expression was markedly increased in carotid endarterectomy specimens of symptomatic AS patients compared to that of asymptomatic AS patients. Expression levels of HOXA11-AS and pro-inflammatory genes were significantly elevated in carotid endarterectomy specimens of DM patients. Similarly, HOXA11-AS expression was also significantly increased in carotid arteries of DM mice compared with that of non-DM mice. PDGF could upregulate HOXA11-AS expression in VSMCs, which was reversed by PDGF inhibitor imatinib. HOXA11-AS knockdown could reduce the expressions of the proliferation-associated gene (PCNA) and the cycle-related genes (p21, p53), and also inhibited the proliferation and migration of VSMCs induced by PDGF. HOXA11-AS was upregulated by TNF-α. HOXA11-AS knockdown remarkably downregulated expressions of inflammation-related genes in VSMCs induced by TNF-α. In VECs, low expression of HOXA11-AS can inhibit the expression of TNF-α-induced pro-inflammatory genes and PDGF-induced vascular inflammation-related genes. Low expression of HOXA11-AS inhibited PDGF-induced activation of PI3K/AKT pathway in VSMCs and VECs. HOXA11-AS may participate in DAA by activating the PI3K/AKT pathway to regulate inflammation in VSMCs and VECs.

Statin Pretreatment and Microembolic Signals in Large Artery Atherosclerosis.

Background and Purpose- Scarce data indicate that statin pretreatment (SP) in patients with acute cerebral ischemia because of large artery atherosclerosis may be related to lower risk of recurrent stroke because of a decreased incidence of microembolic signals (MES) during transcranial Doppler monitoring. Methods- We performed a systematic review and meta-analysis of available observational studies reporting MES presence/absence or MES burden, categorized according to SP status, in patients with acute cerebral ischemia because of symptomatic (≥50%) large artery atherosclerosis. In studies with partially-published data, authors were contacted for previously unpublished information. We also performed a sensitivity analysis of studies with data on MES burden categorized according to SP status, and an additional subgroup analysis in patients receiving higher-dose SP (atorvastatin 80 mg or rosuvastatin 40 mg daily). Results- Seven eligible study protocols were identified (610 patients, 54% with SP). SP was associated with a reduced risk of MES detection during transcranial Doppler monitoring (risk ratio=0.67; 95% CI, 0.45-0.98), with substantial heterogeneity between studies ( I2=52%). In studies reporting MES burden (n=4), a significantly lower number of MES were identified in patients with compared with those without SP (mean difference=-0.92; 95% CI, -1.64 to -0.19), with no evidence of heterogeneity between studies ( I2=49%). Subgroup analysis revealed that higher-dose SP reduced the risk of detecting MES (risk ratio=0.23; 95% CI, 0.06-0.88), with no evidence of heterogeneity between studies ( I2=0%). Conclusions- SP seems to be associated with a lower incidence and burden of MES in patients with acute cerebral ischemia because of large artery atherosclerosis.

Balloon-expandable stents for treatment of symptomatic middle cerebral artery stenosis: Clinical outcomes during long-term follow-up.

Insertion of a balloon-expandable stent (BES) in patients with symptomatic intracranial atherosclerosis is a treatment option for reperfusion therapy. In this study, we retrospectively reviewed clinical outcomes during long-term follow-up after insertion of balloon-expandable stents in patients with symptomatic middle cerebral artery (MCA) stenosis. Institutional review board approval was obtained for retrospective review of patient data. Thirty-four patients (15 men, 19 women; median age, 67.5 years) with symptomatic MCA stenosis underwent balloon-expandable stent insertion between June 2008 and December 2010. Patient records were reviewed for angiographic findings and clinical outcomes during long-term follow-up. Of these patients, 22 presented with acute ischemic stroke with underlying MCA atherosclerosis and had good clinical outcomes (modified Rankin Scale score (mRS): 0-2) after reperfusion therapy. Indications for stenting for the remaining 12 patients were recurrent transient ischemic attacks (TIAs) refractory to medical therapy and MCA stenosis greater than 70%. During the poststenting follow-up period, which ranged from 61 to 108 months (median, 67.5 months), a TIA occurred in five patients. Of these five patients, one experienced a complete reocclusion of the MCA stent, and three had symptomatic restenosis. The remaining 29 patients did not experience any further ischemic events or restenosis during the follow-up period. In our study, treatment with balloon-expandable stents in patients with symptomatic MCA stenosis resulted in low recurrence rates for both ischemic events and restenosis during long-term follow-up.

Symptomatic Intracranial Atherosclerosis: Natural History of Medical Management Beyond the Hyperacute Stage of Ischemic Stroke in the Post-SAMMPRIS Era

Background: A major cause of ischemic stroke (IS) worldwide, especially in Asia, is intracranial atherosclerotic stenosis (ICAS), which is also associated with the high risk of recurrent stroke.Objective: The aim of our study was to determine the natural history of symptomatic ICAS ischemic stroke (ICAS IS) patients.Materials and Methods: We collected data on acute ICAS IS patients beyond the hyperacute IS phase to determine stroke recurrence and mortality at a tertiary care neurology hospital. Data were collected on basic demographics and traditional risk factors such as hypertension, coronary artery disease, diabetes mellitus, tobacco abuse, and hyperlipidemia, and statistical analysis was done. The primary endpoint was to measure the unfavorable outcome as defined by recurrent stroke or death from any cause.Results: The mean follow-up time for the total 87 patients was 24.5 months. Nine patients (10.3%) had an unfavorable outcome in the follow-up period; 2 (2.3%) of them had recurrent IS. Age was a predictor of the unfavorable outcome ( P = .0025), whereas hyperlipidemia was present more in patients with the favorable outcome ( P = .033). There was a tendency for patients with poor outcomes to have a higher National Institutes of Health Stroke Scale at their onset of stroke.Conclusions: Aggressive medical treatment was associated with a relatively low risk of recurrent stroke in our ICAS IS population. This study provides groundwork for larger studies that can take into account clinical and newer imaging techniques to improve secondary prevention in ICAS IS patients.

IP127. Risk Factors for Major Adverse Clinical Events After Carotid Endarterectomy Based on Patient Age and Symptoms

Carotid endarterectomy (CEA) is a well-established surgical procedure in the treatment of symptomatic and asymptomatic carotid atherosclerosis. We reviewed the American College of Surgeons National Surgical Quality Improvement Program database to assess which factors contribute to major adverse clinical events (MACEs) in the 30-day postoperative period. The American College of Surgeons National Surgical Quality Improvement Program database was queried among all participating institutions for CEAs performed in 2011 to 2015. Patients’ demographic data, comorbid conditions, preprocedure medication use, and operative variables were analyzed using multivariate logistic regression analysis to determine predictors of postoperative MACEs. There were 17,888 patients who underwent CEA analyzed; the patients were grouped by age (<75 and ≥75 years old) and whether they presented symptomatically (SYM) or asymptomatically (AS) before the procedure. For AS patients <75 years, the rate of stroke, myocardial infarction (MI), death, and MACEs was 1.8%, 1.6%, 0.4%, and 3.6%, respectively; for patients ≥75 years, rates were 1.7%, 2.3%, 0.7%, and 4.3%. The rate of MI was significantly higher in older patients (P = .0133). The odds of postoperative stroke was 73% higher (P < .0011) in diabetics, 57% higher (P = .0109) with American Society of Anesthesiologists (ASA) score 4 or 5, and 34% higher with operative time >2.5 hours (P = .0189). SYM patients ≥75 years had 1.1 times higher risk of postoperative stroke if they had insulin-dependent diabetes (P = .0148). Reintubation and reoperation were associated with increased risk of postoperative stroke in both age groups, whether SYM or AS (P < .0001), as well as postoperative MI (P < .0001). AS patients <75 years had higher likelihood of postoperative MI if they had history of congestive heart failure (P = .0257) and operative time >2.5 hours (P = .0033). SYM patients ≥75 years had 46% higher likelihood of postoperative MI if operative time >2.5 hours (P = .0023). Mortality was higher in AS patients <75 years with ASA score 4 or 5 (P = .0006) and those ≥75 years (P = .0072) and in patients who were reintubated (P < .0001). In SYM patients <75 years, the rate of stroke, MI, death, and MACEs was 4.8%, 1.4%, 0.9%, and 6.3%, respectively. In those ≥75 years, rates were 4.9%, 2.6%, 1.6%, and 7.8%. Older patients had higher rates of MI and MACEs (P = .001 and P= .0103). SYM patients <75 years had higher mortality if they had chronic obstructive pulmonary disease (P = .0002) and diabetes (P = .0062). SYM patients of all ages had higher mortality with postoperative stroke or MI (P < 0.0001). Patients 75 years or older are at increased risk of postoperative MI after CEA regardless of symptomatic status. Diabetes, increased operative time, and ASA score 4 or 5 were associated with higher MACE rates among all age groups.

The Role of Colchicine in the Prevention of Cerebrovascular Ischemia.

Despite the proven efficacy of anti-thrombotic, lipid-lowering, anti-hypertensive therapies and lifestyle modification changes for secondary ischemic stroke prevention, the risk of recurrent stroke, coronary events and vascular death remains substantial even for patients treated with high rates of established secondary preventive medications. In the present review, we summarize available literature data on the association between systemic inflammation and symptomatic atherosclerosis including recurrent cerebral ischemia. We also highlight the potential role of colchicine in the suppression of atherosclerosis-induced inflammation, plaque stabilization and thromboembolism prevention. Accumulating evidence suggests that inflammation is of key importance in the pathophysiology of atherosclerotic plaque de-stabilization and thromboembolism, with inflammatory cells being involved in all stages of atherosclerosis development. Therefore, anti-inflammatory therapies targeting the atherosclerotic plaque inflammation may be important contributors in plaque stabilization and in the prevention of thromboembolic events. Colchicine is known to have multiple anti-inflammatory properties including inhibition of microtubule polymerization, leading to reduced secretion in monocyte-macrophages. Currently the randomized controlled CONVINCE trial is enrolling stroke patients to evaluate the effect of a daily low-dose of colchicine in reducing the rate of recurrent stroke and major vascular events. Inflammatory pathways seem to be key mediators in the development of atherosclerotic process, atheromatous plaque destabilization and thromboembolism. Colchicine as a novel therapeutic agent could be a safe and effective inhibitor of the inflammation cascade in patients with extra- or intracranial atherosclerosis or arteriolosclerosis, resulting in reduced vascular events.

Rola galektyny 3 jako markera diagnostycznego i prognostycznego w kardiologii

Galectin 3 (Gal-3) is a protein belonging to family lectins. Gal-3 is produced as a response to inflammatory mediators by several types of cells directly associated with atherosclerosis such as macrophages and endothelial cells. Galectin 3 represents a link between inflammation and fibrosis. Gal-3 is a biomarker associated with inflammation and cardiac fibrosis in patients with heart failure. Association of galectin 3 with cardiovascular risk factors suggest that it can be a promising marker of subclinical and symptomatic atherosclerosis. Previous research suggest that Gal-3 may be a useful diagnostics marker and prognostic factor in ischaemic heart disease and heart failure.

Do Nonalcoholic Fatty Liver Disease and Fetuin-A Play Different Roles in Symptomatic Coronary Artery Disease and Peripheral Arterial Disease?

Background and Aims: Nonalcoholic fatty liver disease (NAFLD) is strongly associated with both atherosclerotic cardiovascular disease (CVD) and Fetuin-A. However, the association of Fetuin-A with atherosclerosis is more controversial. We hypothesized that the pathogenic interplay of NAFLD, Fetuin-A and atherosclerosis varies based on arterial site. Accordingly, we aimed to assess NAFLD prevalence, Fetuin-A values and their relationship with symptomatic atherosclerosis occurring in different localizations: coronary artery disease (CAD) vs. peripheral arterial disease (PAD). Methods: One hundred and forty-nine consecutive patients with symptomatic atherosclerotic CVD were recruited: 45 with CAD diagnosed by coronary angiography and 104 with PAD detected by doppler-ultrasound and/or computed tomography angiography and/or angiography. NAFLD was diagnosed based on both ultrasonography and exclusion of competing etiologies. Serum Fetuin-A was measured with ELISA. Results: NAFLD was detected in 54% of the overall group, with higher rates in PAD (59%) than CAD (42%) patients. Median Fetuin-A values were 256 (111–662) μg/mL, higher in patients with CAD (378 (124−662) μg/mL) than those with PAD (236 (111−461) μg/mL). The main findings were: (1) CAD patients had higher Fetuin-A values and less frequently NAFLD than PAD patients; (2) NAFLD was positively associated with Fetuin-A values; however, this association was limited to CAD patients only; (3) Fetuin-A values were positively associated with both CAD and NAFLD. Conclusion: The pathogenic interplay of NAFLD, Fetuin-A and atherosclerosis probably varies according to the arterial site.

Quantitative assessment of symptomatic intracranial atherosclerosis and lenticulostriate arteries in recent stroke patients using whole-brain high-resolution cardiovascular magnetic resonance imaging

BackgroundIt has been shown that intracranial atherosclerotic stenosis (ICAS) has heterogeneous features in terms of plaque instability and vascular remodeling. Therefore, quantitative information on the changes of intracranial atherosclerosis and lenticulostriate arteries (LSAs) may potentially improve understanding of the pathophysiological mechanisms underlying stroke and may guide the treatment and work-up strategies. Our present study aimed to use a novel whole-brain high-resolution cardiovascular magnetic resonance imaging (WB-HRCMR) to assess both ICAS plaques and LSAs in recent stroke patients.MethodsTwenty-nine symptomatic and 23 asymptomatic ICAS patients were enrolled in this study from Jan 2015 through Sep 2017 and all patients underwent WB-HRCMR. Intracranial atherosclerotic plaque burden, plaque enhancement volume, plaque enhancement index, as well as the number and length of LSAs were evaluated in two groups. Enhancement index was calculated as follows: ([Signal intensity (SI)plaque/SInormal wall on post-contrast imaging] − [SIplaque/SInormal wall on matched pre-contrast imaging])/(SIplaque / SInormal wall on matched pre-contrast imaging). Logistic regression analysis was used to investigate the independent high risk plaque and LSAs features associated with stroke.ResultsSymptomatic ICAS patients exhibited larger enhancement plaque volume (20.70 ± 3.07 mm3 vs. 6.71 ± 1.87 mm3P = 0.001) and higher enhancement index (0.44 ± 0.08 vs. 0.09 ± 0.06 P = 0.001) compared with the asymptomatic ICAS. The average length of LSAs in symptomatic ICAS (20.95 ± 0.87 mm) was shorter than in asymptomatic ICAS (24.04 ± 0.95 mm) (P = 0.02). Regression analysis showed that the enhancement index (100.43, 95% CI − 4.02-2510.96; P = 0.005) and the average length of LSAs (0.80, 95% CI − 0.65-0.99; P = 0.036) were independent factors for predicting of stroke.ConclusionWB-HRCMR enabled the comprehensive quantitative evaluation of intracranial atherosclerotic lesions and perforating arteries. Symptomatic ICAS had distinct plaque characteristics and shorter LSA length compared with asymptomatic ICAS.

Abstract TP120: Elevated Lipoprotein-Associated Phospholipase A2 is Differentially Associated With Symptomatic Intracranial Atherosclerosis

Background and Objective: Intracranial atherosclerotic disease (ICAD) is a common etiology of stroke in China. Lipoprotein-associated phospholipaseA2 (Lp-PLA2), an inflammatory enzyme expressed in atherosclerotic plaques, has been linked to an increased risk of ischemic stroke. Relatively few studies have explored the relationship between Lp-PLA2 and various ischemic stroke subtypes. We aimed to determine the association between the serum Lp-PLA2 mass and the main types of symptomatic large vessel atherosclerosis. Methods: In this cross-sectional study, we reviewed data on 126 eligible acute ischemic stroke patients consecutively admitted to a single medical center in China from March 2014 to February 2016. Clinical symptoms, signs and traditional risk factors of cerebrovascular diseases were recorded. The level of serum lipids, homocysteine and glucose etc. were collected. Serum Lp-PLA2 and high-sensitivity C-reactive protein (hs-CRP) were measured. According to the results of CT angiography, patients were divided into four different groups: 1) no artery stenosis (N), 2) both intracranial and extracranial artery stenosis (B), 3) intracranial artery stenosis (I), 4) extracranial artery stenosis (E). The association of serum Lp-PLA2 and other inflammatory markers to ICAD were analyzed with Pearson correlation test. Results: Lp-PLA2 expression in the ICAD group was higher than other three groups (I vs. N vs. B vs. E: 112.22±66.79 ug/l vs. 81.70±38.50 ug/l vs.89.25±52.15 ug/l vs. 106.11± 57.76 ug/l, p=0.025). When Lp-PLA2 was above the median level, the presence of ICAD was higher than other three groups (Q3: 16[50.0%] vs. 1[3.1%] vs. 9[28.1%] vs. 6[18.8%], P=0.002; Q4: 15[48.4%] vs. 5[16.1%] vs. 8[25.8%] vs. 3[9.7%], P=0.014). In ICAD group, Lp-PLA2 mass was positively correlated with hs-CRP (r=0.899, P &lt;0.001), and inversely correlated with total cholesterol (r=-0.307, P =0.028) and apoliprotein B (r=-0.320, P =0.022). Conclusions: Lp-PLA2 is differentially associated with ICAD compared to extracranial artery stenosis or no stenosis, which suggests that inflammation may play a greater role in the pathophysiology of ICAD versus these other symptomatic stroke categories.

Abstract TP131: Intracranial Plaque Enhancement on Vessel Wall MRI and the Oral Microbiome

Introduction: Alterations in the oral microbiome are associated with the development of cardiovascular disease. Post-contrast plaque enhancement (PPE) on vessel wall MRI is associated with symptomatic intracranial atherosclerosis and increased risk of stroke recurrence, but the mechanism remains unknown. Hypothesis: We hypothesized that the oral microbiome in patients with PPE of the stroke parent artery would be distinct from those without PPE, offering insight into the pathophysiology of PPE. Methods: We conducted a prospective study of patients with ischemic stroke due to intracranial atherosclerosis, who underwent vessel wall MRI and oral swab within 14 days of stroke. MRI was interpreted by a blinded neuroradiologist and the oral microbiome was analyzed using validated genomic techniques. The diversity of bacterial species was tested with the Wilcoxon signed-rank test. Results: Thirty-two patients were included in our analysis, of which 20/32 had PPE (62%). No significant difference was found in bacterial species abundance between patients with or without PPE (p=0.745) (Figures 1+2), but 2/20 (10%) patients with PPE had elevated Mycoplasma species, which were absent in all the patients without PPE. Conclusions: Although we did not find an association between PPE and alterations in the oral microbiome, the identification of Mycoplasma in patients with PPE is of interest. Mycoplasma has been identified in histologic samples of ruptured atherosclerotic plaques. A larger study will be required to investigate this association and determine the impact of the oral microbiome on PPE when controlling for cardiovascular risk factors.

Frequency, Predictors, and Impact of Combined Antiplatelet Therapy on Venous Thromboembolism in Patients With Symptomatic Atherosclerosis.

Observational studies suggest that symptomatic atherosclerosis may be associated with risk of venous thromboembolism (VTE). Prior randomized studies have demonstrated a significant reduction in recurrent VTE with aspirin monotherapy. Whether VTE risk is associated with more severe symptomatic atherosclerosis and more intensive antiplatelet therapy reduces VTE risk beyond aspirin monotherapy is unknown. TRA2P-TIMI 50 (Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events-Thrombolysis in Myocardial Infarction) (vorapaxar) and PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction 54) (ticagrelor) were blinded, randomized placebo-controlled trials of antiplatelet therapy for the prevention of ischemic events in stable patients with symptomatic atherosclerosis. Two blinded vascular specialists systematically identified symptomatic venous thromboembolic events in both trials. Of 47 611 patients with stable vascular disease followed for 3 years in both studies there were 343 VTE events in 301 patients (Kaplan-Meier rate at 3 years, 0.9% for placebo). The risk of VTE was independently associated with age, body mass index, polyvascular disease, chronic obstructive pulmonary disease, and malignancy. The burden of atherosclerosis manifested as an increasing number of symptomatic vascular territories was associated with a graded increase in the 3-year rates of VTE (0.76% for 1, 1.53% for 2, and 2.45% for 3 territories). More intensive antiplatelet therapy (vorapaxar and ticagrelor pooled) significantly reduced the risk of VTE by 29% compared with background antiplatelet therapy, from 0.93% to 0.64% at 3 years (hazard ratio, 0.71; 95% confidence interval, 0.56-0.89; P=0.003). The rate of VTE in patients with atherosclerosis is ≈0.3% per year while on treatment with ≥1 antiplatelet agent, with increased risk independently associated with the number of symptomatic vascular territories. More intensive antiplatelet therapy reduces the risk of VTE. These data suggest a relationship between atherosclerosis burden and VTE risk, and they support inclusion of VTE as a prospective end point in long-term secondary prevention trials evaluating the risks and benefits of antiplatelet therapies in patients with atherosclerosis. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01225562.

Medical Treatment of Intracranial Atherosclerosis: An Update.

For patients with symptomatic intracranial atherosclerosis (ICAS), antithrombotic agents are the mainstay of therapy. Anticoagulation (warfarin) is not widely used since it is not more effective than aspirin and carries a high risk of bleeding. New oral anticoagulants are showing promise, but their use has not been investigated in appropriate clinical trials. Since the recurrent stroke risk is high with aspirin monotherapy, dual antiplatelets are considered in the early stage of symptomatic ICAS. Based on the Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) and Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) results, aspirin plus clopidogrel has been recommended. However, this combination was not superior to aspirin monotherapy in patients with ICAS in the CHANCE substudy. Progression of ICAS is common, and it is associated with recurrent strokes. In the Trial of Cilostazol in Symptomatic Intracranial Arterial Stenosis (TOSS) study, aspirin plus cilostazol was more effective than aspirin monotherapy in preventing progression. The TOSS II trial showed that the overall change in stenosis was better with aspirin plus cilostazol than with aspirin plus clopidogrel. Aside from antithrombotic therapy, risk factor management is critical for secondary prevention, and high blood pressure is clearly linked to recurrent stroke. However, blood pressure may have to be cautiously managed in the early stage of stroke. Considering that ICAS is the major cause of stroke worldwide, further investigations are needed to establish optimal management strategies for patients with ICAS.

Inverse relations of serum phosphatidylcholines and lysophosphatidylcholines with vascular damage and heart rate in patients with atherosclerosis

Background and aimsThe rapidly growing discipline of lipidomics allows the study of a wide spectrum of lipid species in body fluids and provides new insights into the pathogenesis of cardiovascular disease. We investigated serum phosphatidylcholine (PC) and lysophosphatidylcholine (lysoPC) species in relation to arterial stiffness, hemodynamics, and endothelial dysfunction in symptomatic patients with atherosclerosis and in healthy controls. Methods and resultsThirty-two patients with peripheral arterial disease (age 61.7 ± 9.0 years), 52 patients with coronary artery disease (age 63.2 ± 9.2 years), and 40 apparently healthy controls (age 60.3 ± 7.1 years) were studied. Serum levels of 90 glycerophospholipids were determined with the AbsoluteIDQ™ p180 kit (BIOCRATES Life Sciences AG, Innsbruck, Austria). The technique of applanation tonometry was used for non-invasive pulse wave analysis and carotid-femoral pulse wave velocity (cf-PWV) assessment. Decreased serum levels of several individual PC and lysoPC species (e.g., PC aa C28:1, PC aa C30:0, PC aa C32:2, PC ae C30:0 and PC ae C34:2, lysoPC a C18:2) were observed for the patient groups in comparison to the healthy subjects. In addition, a considerable number of PCs and lysoPCs were inversely related to either cf-PWV, heart rate, asymmetric dimethylarginine (ADMA) or ADMA/arginine for patients with symptomatic atherosclerosis but not for the controls. ConclusionWe found altered relationships between PC and lysoPC profiles, inflammation, and arterial function in atherosclerotic patients, compared to healthy subjects.

Detection of symptomatic carotid atherosclerosis from 18F-fluorodeoxyglucose and 18F-sodium fluoride positron emission tomography after stroke: A prospective study

Detection of symptomatic carotid atherosclerosis from 18F-fluorodeoxyglucose and 18F-sodium fluoride positron emission tomography after stroke: A prospective study

Symptomatic carotid atherosclerosis detection by positron emission tomography imaging

Symptomatic carotid atherosclerosis detection by positron emission tomography imaging

NGAL and MMP-9/NGAL as biomarkers of plaque vulnerability and targets of statins in patients with carotid atherosclerosis.

Neutrophil gelatinase associated lipocalin (NGAL) is expressed in atherosclerotic lesions and was recently implicated in the pathogenesis of cardiovascular pathologies. Statins are known to exert stabilizing effects on atherosclerotic plaque. The aims of our study were (1) to investigate the association of serum NGAL and metalloproteinase (MMP)-9/NGAL complex with the vulnerability of the atherosclerotic plaque, and (2) to reveal the effects of statin treatment on circulating NGAL and MMP-9/NGAL levels in patients with carotid artery stenosis. We examined the levels of NGAL and MMP-9/NGAL in blood samples from 136 patients with carotid artery stenosis by specific enzyme-linked immunosorbent assays. Patients with vulnerable plaques, as determined by ultrasound (plaques with decreased echogenicity) and histological analysis (type VI according to the classification of American Heart Association [AHA]), displayed the highest levels of NGAL (both p<0.0001) and MMP-9/NGAL complex (p=0.0004 and p=0.004, respectively). Moreover, patients with symptomatic carotid atherosclerosis had significantly higher NGAL levels compared to asymptomatic patients (p=0.0007). The statin-treated group (n=108) demonstrated lower NGAL (73.9 vs. 128.0 μg/L, p<0.0001) and MMP-9/NGAL (28.9 vs. 40.6 μg/L, p=0.046) as compared to the non-statin group (n=28). Furthermore, in multivariate regression analysis NGAL, but not MMP-9/NGAL levels, were independently associated with symptomatic carotid artery stenosis. In addition, statin treatment was independently associated with lower NGAL levels. Circulating NGAL and MMP-9/NGAL are associated with plaque vulnerability in patients with carotid artery stenosis. Statin treatment could contribute to plaque stabilization by reducing circulating NGAL and MMP-9/NGAL levels.

Carotid intraplaque hemorrhage on vessel wall MRI does not correlate with TCD emboli monitoring in patients with recently symptomatic carotid atherosclerosis.

Background Carotid intraplaque hemorrhage (IPH) seen on vessel wall MRI is associated with an increased risk of stroke or transient ischemic attack, as are microembolic signals (MES) detected by transcranial Doppler (TCD). We sought to examine the association between IPH and MES in acute stroke patients with symptomatic carotid atherosclerosis. Methods Through a retrospective chart review, we included patients from 2011 to 2013 with acute ischemic stroke due to carotid atherosclerosis of varying stenosis who had both 3D volumetric MRI of the neck and TCD emboli monitoring. Results Twenty-four patients met the inclusion criteria. Mean time from stroke to MRI was 1.4 ± 1.9 days and to TCD was 2.6 ± 2.4 days. MES was seen in 10 patients (42%) and IPH was present in seven patients (29%), but we did not find a relationship between MES and IPH ( p = 0.64). Conclusion In patients with recent acute ischemic stroke attributed to carotid atherosclerosis, we did not detect an association between the presence of IPH and MES. While this small study may be underpowered, an alternate explanation is that MES and IPH reflect vulnerable carotid atherosclerosis through different mechanisms. This untested concept warrants prospective study in a larger cohort.