Symptomatic Atherosclerosis Research Articles

Risk factors of arterial thrombotic events after unprovoked venous thromboembolism, and after cancer associated venous thromboembolism: A prospective cohort study

IntroductionThe increased risk of arterial thrombotic (ATE) after VTE, particularly when they are unprovoked or cancer-associated has been established. However, the risk factors of ATE after these VTE remain unclear. Material and methodsUsing cause-specific hazard regression models, we determined risk factors of ATE (myocardial infarction, ischemic stroke, acute limb ischemia, digestive tract ischemia, or renal ischemia) in 2242 patients with unprovoked VTE and in 914 patients with cancer-associated VTE from a multi-center prospective cohort. ResultsOf patients with unprovoked-VTE, 174 developed ATE (7.8%, incidence: 1.26 per 100 patient-years) during follow-up (median: 68 months). Among patients with cancer-associated VTE, 57 developed ATE (6.2%, incidence: 1.98 per 100 patient-years) during follow-up (median: 30 months). After multivariable analysis, the identified risk factors of ATE in patients with unprovoked-VTE were age > 65 years (vs. <50 years, HR 2.59, 95% CI: 1.56–4.29), past history of symptomatic atherosclerosis (HR 2.11, 95% CI: 1.40–3.19), and treatment with low molecule weight heparin (vs. vitamin K antagonists, HR: 2.26, 95% CI: 1.13–4.52). In patients with cancer-associated VTE, the identified risk factors of ATE were: past history of symptomatic atherosclerosis (HR: 3.13, 95% CI: 1.72–5.67), and ongoing anticoagulation at the diagnosis of VTE (HR: 2.77, 95% CI: 1.07–7.22). ConclusionsThe risk of ATE after unprovoked VTE and after cancer-associated VTE, is determined by some classic cardiovascular risk factors and appears to be influenced by anticoagulant treatment introduced for VTE, as well as the presence or absence of ongoing anticoagulation at the diagnosis of VTE.

Association of plaque enhancement on vessel wall MRI and the phosphodiesterase 4D variant with stroke recurrence in patients with symptomatic intracranial atherosclerosis.

Vessel wall MRI (VW-MRI) can be used to evaluate the nature of intracranial atherosclerosis (ICAS) plaque in vivo. Phosphodiesterase 4D (PDE4D) participates in stroke development. This study aims to explore the value of VW-MRI findings and the PDE4D genevariant in predicting stroke recurrence in patients with ICAS. We prospectively recruited 324 symptomatic ICAS patients. VW-MRI was performed to determine luminal and wall changes. PDE4D genesingle-nucleotide polymorphisms (SNPs)-namely, SNP32, SNP83, and SNP87-were determined by direct sequencing. The risk factors of stroke recurrence were analyzed using the multivariate Cox proportional hazards model. Of the 324 subjects, 97 (29.9%) experienced recurrent ischemic stroke during the follow-up period. A total of 254 patients (78.4%) showed plaque enhancement; 87 of these patients experienced stroke recurrence. The CT/CC genotype frequencies of PDE4D83 were significantly higher in participants with recurrent stroke than in patients without stroke recurrence (p = 0.019 and p < 0.001, respectively). However, the PDE4D32 and PDE4D87 variants were not correlated with recurrent stroke. Multivariate analysis showed that plaque enhancement from VW-MRI (HR 4.52, 95% CI 2.35-8.73, p < 0.001) and the PDE4D83 variant (HR 7.43, 95% CI 1.75-31.87, p = 0.005) were independently correlated with stroke recurrence. Kaplan-Meier curves showed significant differences in stroke recurrence rates between the plaque-enhanced group and the non-enhanced group (p < 0.001) and between the PDE4D83 variant carriers and noncarriers (p = 0.002). Plaque enhancement on VW-MRI and the presence of the PDE4D83 variant are associated with ischemic stroke recurrence in subjects with symptomatic ICAS.

The effectiveness of enterprise stent use on the treatment of intracranial atherosclerosis disease.

To examine the clinical outcome of Enterprise stent in patients with severe and symptomatic intracranial atherosclerosis. Twenty-five patients who underwent Enterprise stenting between January 2012 and March 2019 were included in this study. Exclusion criteria were previous intracranial stenting and inadequate follow-up. Technical success rates of the procedures were recorded. Clinical outcome was evaluated with pre- and post-treatment modified Rankin Scale scores. The patients were monitored for 18months clinically and for 14.3months radiologically. The mean age of the 15 males and 10 females was 61.6 ± 8.19. Of these 25 patients, 6 (24%) were in the anterior system and 19 (76%) were in posterior system. The mean degree of pre-treatment stenosis was 86.4% ± 7 with the mean lesion length of 12.5 ± 7.5mm. The residual stenosis rate was 23.8% ± 8.81. Technical success rate was 100%. There were two major complications within the first 30 days (8%). Late major complications (after 30days) occurred in one case (4%). Stent restenosis was detected in two patients (8%). No intracranial bleeding or mortality was observed. In this single-center study, we achieved high technical success and tolerable complication rates. Enterprise stent may be a good treatment alternative for severe intracranial stenosis especially in patients resistant to medical treatment when correct patient selection is made. However, further randomized controlled studies, including more cases should be carried out.

PCSK9 inhibition in patients with acute stroke and symptomatic intracranial atherosclerosis: protocol for a prospective, randomised, open-label, blinded end-point trial with vessel-wall MR imaging

IntroductionDual antiplatelet therapy and high-intensity statins are the mainstay treatment in patients with acute stage, symptomatic intracranial atherosclerotic stenosis (ICAS). Alirocumab is a monoclonal antibody that can inhibit proprotein convertase...

Stroke Prevention in Symptomatic Large Artery Intracranial Atherosclerosis Practice Advisory: Report of the AAN Guideline Subcommittee.

To review treatments for reducing the risk of recurrent stroke or death in patients with symptomatic intracranial atherosclerotic arterial stenosis (sICAS). The development of this practice advisory followed the process outlined in the American Academy of Neurology Clinical Practice Guideline Process Manual, 2011 Edition, as amended. The systematic review included studies through November 2020. Recommendations were based on evidence, related evidence, principles of care, and inferences. Clinicians should recommend aspirin 325 mg/d for long-term prevention of stroke and death and should recommend adding clopidogrel 75 mg/d to aspirin for up to 90 days to further reduce stroke risk in patients with severe (70%-99%) sICAS who have low risk of hemorrhagic transformation. Clinicians should recommend high-intensity statin therapy to achieve a goal low-density lipoprotein cholesterol level <70 mg/dL, a long-term blood pressure target of <140/90 mm Hg, at least moderate physical activity, and treatment of other modifiable vascular risk factors for patients with sICAS. Clinicians should not recommend percutaneous transluminal angioplasty and stenting for stroke prevention in patients with moderate (50%-69%) sICAS or as the initial treatment for stroke prevention in patients with severe sICAS. Clinicians should not routinely recommend angioplasty alone or indirect bypass for stroke prevention in patients with sICAS outside clinical trials. Clinicians should not recommend direct bypass for stroke prevention in patients with sICAS. Clinicians should counsel patients about the risks of percutaneous transluminal angioplasty and stenting and alternative treatments if one of these procedures is being contemplated.

Predictors of Recurrence in Symptomatic Large Artery Atherosclerosis and Cryptogenic Strokes—A Comparative Study

Background and Purpose: Ischemic stroke has highest recurrence risk in the first-year, ranging from 5.7% to 14%, depending on etiology, with highest reported following cardioembolism and large artery atherosclerosis (LAA), while it is not negligible in cryptogenic strokes. We evaluated the utility of clinical, imaging parameters along with electrographic and echocardiographic biomarkers of atrial dysfunction in 2 etiological groups, namely LAA and cryptogenic strokes and compared the predictors of recurrence risk at 1 year. Methodology: All acute ischemic strokes admitted to Comprehensive Stroke Care Centre, Department of Neurology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, India for 1 year (July 2019 till June 2020) with 1 year completed follow-up were screened from electronic records. Strokes secondary to LAA and undetermined cause were compared for their clinical, imaging, and cardiac variables to predict risk of recurrence in the first year. Results: Of the 179 patients, 93 had strokes secondary to LAA and 86 had cryptogenic strokes (CS). Seventy-five patients had more than 1 event at presentation/follow-up. Recurrence risk did not differ between the 2 etiological subgroups at 1 year. Hypertension ( P = .016), multiple territory strokes ( P = .02), and dilated left ventricle (LA) chamber ( P = .047) were independently associated with recurrence risk in the entire cohort as well as within the undetermined group. Early hospitalization within 48 h reduced the overall recurrence risk ( P = .01), thus emphasizing the role of early etiological evaluation and initiation of secondary prevention in reducing future events, irrespective of etiology. Conclusion: In optimally managed LAA and cryptogenic strokes, presence of hypertension, multiterritorial infarcts, and dilated LA chambers increases the recurrence risk pointing to a likely cardiac substrate itself contributing to future stroke risk.

Abstract TP255: Lymphocytes And Platelets In Extracted Thrombus May Indicate The Etiology Of The Thrombus. Results From The Itacat Multicentric Registry.

Aim: We performed a histological and immune analysis of the clot in acute stroke patients to detect surrogates of stroke etiology. Methods: We conducted a prospective observational study of consecutive patients with acute stroke who underwent thrombectomy that obtained extracted thrombus (ITACAT study). Several staining were performed to evaluate red blood cells/fibrin (hematoxylin/eosin), platelets (CD61) and leucocytes (CD4, CD8 and CD20). All patients received CT angio to detect extra/intracranial vascular stenosis and 30-day cardiac monitoring to diagnose AF. According to TOAST classification the thrombi were classified in cardioembolic etiology CE (T-CE), due to symptomatic atherosclerosis (T-AT) and without any cause (T-CRYP). We excluded strokes due to double cause or incomplete workup. Results: Of the 117 patients: 30 were T-AT, 55 were T-CE and 32 were T-CRYP. T-AT patients were younger: T-AT 68 years (60-77) Vs. T-CE 75 years (68-80) Vs. T-CRYP 72 years (55-81) (p=0.034). T-AT group had higher percentage of CD4: T-AT 6.52% (4-13) Vs. T-CE (3.31% (12.9) Vs .T-CRYP 3.72% (1.5-12) (p=0.015) and lower percentage of CD61: T-AT 51.18% (34-68) Vs. CE 64.70% (19.56) Vs. CRYP 70.3% (19) (p=0.001). There were no correlation between CD4 and platelets. Both CD4 OR 1.05 (1-1.10) (p=0.020) and CD61 (OR 0.96 (0.94-0.98) (p=0.01) independently predicted T-AT from the age. Final analysis (n=400 cases) will be ended in September 2021. Conclusions: Patients with high percentage of CD4 and low percentage of CD61 are related to atherosclerosis etiology.

Association between symptomatic intracranial atherosclerotic disease and the integrity of the circle of Willis

The relationship between the severity of intracranial atherosclerotic disease and the circle of Willis integrity is unclear. In this brief report, we investigate the associations between symptomatic intracranial atherosclerotic disease and the integrity of the circle of Willis. Patients with symptomatic intracranial atherosclerosis were enrolled and underwent intracranial artery magnetic resonance vessel wall imaging and time-of-flight angiography. The presence or absence of an intracranial atherosclerotic plaque and its maximum wall thickness and stenosis were evaluated. The presence or absence of the A1 segment of the bilateral anterior cerebral arteries (from the internal carotid artery to the anterior communicating artery segment is called anterior cerebral artery A1 segment), and anterior communicating artery, the P1 segment of the bilateral posterior cerebral arteries (The P1 segment of the posterior cerebral artery is a horizontally outward segment), and bilateral posterior communicating arteries were determined. The associations of the intracranial plaque features with the integrity of the circle of Willis were analyzed. Of the 110 recruited subjects (57.2 ± 11.1 years; 65% males), 51 had intracranial plaques, and 44 had stenosis. In patients with bilateral A1 and P1 segments (n = 85), intracranial stenosis was more severe in patients with an anterior communicating artery than those without an anterior communicating artery (19.7% ± 21.7% vs. 1.4% ± 3.3%, p = 0.046). In patients with bilateral A1 and P1 segments and an anterior communicating artery (n = 79), intracranial stenosis was more severe in patients with posterior communicating arteries than those without posterior communicating arteries (27.9% ± 23.7% vs. 13.5% ± 17.9%, p = 0.007). The odds ratio of intracranial stenosis was 1.214 (95% confidence interval (CI), 1.054-1.398; p = 0.007) in discriminating for the presence of posterior communicating arteries in patients with bilateral A1 and P1 segments and an anterior communicating artery after adjusting for confounding factors. The severity of intracranial atherosclerosis was independently associated with the presence of posterior communicating arteries in patients with a complete anterior part of the circle of Willis.

Risk Factors for Asymptomatic and Symptomatic Intracranial Atherosclerosis Determined by Magnetic Resonance Vessel Wall Imaging in Chinese Population: A Case-Control Study.

Background and PurposeThe association between risk factors and intracranial atherosclerosis disease (ICAD) determined by magnetic resonance (MR) vessel wall imaging in Chinese population has not been investigated. The aim of this study was to investigate the associations of conventional vascular risk factors with asymptomatic and symptomatic ICAD using MR vessel wall imaging in Chinese population.MethodsThe study population was recruited from two cohort studies of ICASMAP and CAMERA comprised 104 symptomatic ICAD subjects (57.1 ± 11.1 years; 35.6% females), 51 asymptomatic ICAD subjects (70.1 ± 8.4 years; 50.0% females) and 418 controls (58.0 ± 13.3 years; 61.0% females) defined as asymptomatic subjects without ICAD on MR vessel wall imaging. We compared the vascular risk factors between the three groups using a multivariate logistic regression analysis.ResultsCompared with controls, there was a significant positive association between age (OR: 1.07, 95% CI: 1.03–1.10, p < 0.001) and hypertension (OR: 3.03, 95% CI: 1.45–6.36, p = 0.003) and asymptomatic ICAD. There was a positive association of smoking (OR: 3.41, 95% CI: 1.57–7.42, p = 0.001), hypertension (OR: 7.43, 95% CI: 3.81–14.49, p < 0.001) and diabetes (OR: 3.54, 95% CI: 1.93–6.49, p < 0.001) and an inverse association of high-density lipoprotein (HDL) (p < 0.017) with symptomatic ICAD. Compared to asymptomatic ICAD, there was a significant inverse association of age (OR: 0.86, 95% CI: 0.81–0.92, p < 0.001) and HDL (p < 0.001) with symptomatic ICAD.ConclusionOld age and hypertension are associated with asymptomatic ICAD and smoking, hypertension, diabetes and lower HDL are associated with an increased risk of symptomatic ICAD in Chinese population.Clinical Trial RegistrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT03417063.

Association between Short-Term Blood Pressure Variability and Intracranial Atherosclerotic Plaque Vulnerability: A High-Resolution Magnetic Resonance Imaging Study.

Aim: short-term blood pressure variability (BPV) as a risk factor of atherosclerosis and cardiovascular events has been investigated. However, its association with atherosclerotic plaque vulnerability remains unknown. The objective of this study was to determine the association between short-term BPV and intracranial atherosclerotic plaque vulnerability. Methods: this is a cross-sectional analysis of 267 ischemic stroke patients with symptomatic intracranial atherosclerosis (mean age, 65±12 years old; 60.3% male), which were prospectively recruited in a comprehensive stroke center. Systolic and diastolic BP SD, CV, and BP variability ratio (BPVR) from 24 hours, daytime, and nighttime were calculated from 24-h ambulatory blood pressure monitoring, intracranial atherosclerotic plaque burden and vulnerability were evaluated by high-resolution magnetic resonance vessel wall imaging. Logistic regression analysis was used to locate the correlation between short-term BPV and plaque vulnerability. Results: a total of 36.3% subjects presented with intraplaque hemorrhage (IPH) in this study. Multivariate logistic regression suggested that nighttime diastolic BP CV and 24-h BPVR were associated with intracranial IPH independently after adjusted for cardiovascular risk factors, odds ratio (OR) and 95% confidence interval (CI) for per SD BPV changes were 1.418 (1.051, 1.914) and 0.731 (0.548, 0.976), respectively, and this association also independent of atherosclerosis burden and 24-h mean systolic BP level. Further subgroup analysis by age and hypertension history demonstrated that the statistical correlation could only establish in the elder, and subjects with hypertension. Conclusion: nighttime diastolic BP CV and 24-h BPVR were associated with intracranial IPH independently, especially in the elderly and subjects with hypertension.

EP.WE.593Cardiovascular risk modification in patients admitted for vascular surgical intervention

Abstract Introduction Management of cardiovascular risk is fundamental for patients with symptomatic atherosclerosis to reduce both medium and long-term cardiovascular morbidity and mortality. All patients admitted for operative vascular intervention with atherosclerotic arterial disease should be prescribed appropriate secondary prevention. Methods This was a single-cycle retrospective audit in a patient population undergoing operative intervention for symptomatic atherosclerotic arterial disease in a single regional vascular unit in June 2020. Episodes of care were examined for the prescription of an antiplatelet agent and statin. Results There were 81 procedures identified. The majority of patients were male and the mean age was 63-years. A diagnosis of diabetes was common. Antiplatelet agents were only prescribed to 48 (59%) and statins to 61 (75%). There was no clear pattern that could be defined between elective and emergency admissions [antiplatelet prescription 24 (71%) and 23 (49%); statin prescription 27 (79%) and 34 (72%)], or arterial reconstruction and major limb amputation [antiplatelet prescription 28 (76%) and 19 (45%); statin prescription 31 (84%) and 28 (67%)]. Conclusion It is a concern that a significant proportion of patients did not have antiplatelet and/or statin therapy prescribed. This implies failure of both primary and secondary care. In secondary care the medicines reconciliation process should be augmented with regular review of the prescription.

Analysis of antithrombotic therapy for symptomatic lower extremity atherosclerosis disease

Analysis of antithrombotic therapy for symptomatic lower extremity atherosclerosis disease

Adipose tissue induces trained innate immunity in patients with obesity

Abstract Introduction Obesity is the most prevalent modifiable risk factor for atherosclerotic cardiovascular disease and is characterized as a chronic inflammatory disease. Cells of the innate immune system, especially monocytes and macrophages, play a pivotal role in the various stages of atherosclerosis, although it still remains elusive why the strong inflammatory response persists in time. We recently showed that cells of the innate immune system, such as monocytes, can adopt a long-term immunological memory. Upon brief stimulation with atherogenic stimuli, monocytes demonstrate an enhanced long-term pro-inflammatory and pro-atherogenic phenotype. This is termed trained immunity and is mediated via epigenetic and metabolic reprogramming. The clinical relevance of these findings was verified in patients with symptomatic atherosclerosis, in which circulating monocytes showed a trained immune phenotype. Purpose As various adipose tissue-related particles, including pro-inflammatory cytokines and fatty acids, are capable of inducing trained immunity in vitro, we hypothesized that adipose tissue from obese subjects might induce training in peripheral monocytes, thereby contributing to the increased risk of atherosclerotic CVD in these patients. In line with this hypothesis, it is unclear whether chronic inflammation sustains after a previous period of obesity despite significant weight loss. Methods We obtained blood from 25 patients with obesity before and 6 months after bariatric surgery. Monocyte subsets and activation phenotype were studied using flow cytometry. Cytokine production capacity of isolated PBMCs was studied after ex vivo stimulation with several infectious and metabolic stimuli and we characterized isolated monocytes using transcriptomics. Next, we obtained visceral (VAT) and subcutaneous adipose tissue (SAT) biopsies from 10 patients. Using our established in vitro model for trained immunity, we co-incubated healthy human monocytes with the adipose tissue biopsies for 24 hours in a trans-well set-up. After 24 hours, the adipose tissue was removed and monocytes were rested. On day 6, the cells were re-stimulated for 24 hours with a second stimulus and cytokine production and the transcriptome of the macrophages was analyzed. Results Both SAT and VAT obtained from patients with obesity can induce a long-term memory in healthy human monocytes, as demonstrated by an increased cytokine production capacity 6 days after co-incubation. Interestingly, VAT induced a higher cytokine response compared to SAT. Analysis of the inflammatory phenotype of peripheral cells before and after bariatric surgery is currently ongoing. Conclusions Adipose tissue-secreted metabolites, particularly secreted by VAT, have the potential to induce persistent innate immune cell activation. Our further analyses will show whether the secretion of these molecules and the activation of the innate immune system persists upon weight loss. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Dutch Heart Foundation

Elevated lipoprotein(a) level predicts repeated peripheral revascularization

Abstract Background Despite high-intensity lipid-lowering therapy, there is a residual risk of cardiovascular events that could be associated with lipoprotein(a) [Lp(a)]. Data about the role of Lp(a) in the development of significant stenosis after carotid and lower extremity artery revascularization are lacking. Purpose To evaluate the relationship of Lp(a) level with repeated revascularization due to restenosis or de novo stenosis after endovascular or surgery repair of carotid and lower limb arteries. Methods The study included 258 patients (209 men and 49 women, mean age 67 years) who underwent revascularization of carotid and/or arteries of lower extremities for symptomatic stenotic atherosclerosis. Restenosis or de novo stenosis has been assessed by ultrasonography or angiography. History and physical examination have been performed to identify atherosclerosis risk factors. Lipids, C-reactive protein, Lp(a) concentrations were measured in blood serum. Results During 3 years follow-up, repeated revascularization due to restenosis or de novo stenosis was registered in 111 patients. Hyperlipoproteinemia(a) [Lp(a) ≥30 mg/dL] was associated with an increased risk of repeated revascularization with hazard ratio 2.9; 95% confidence interval 2.0–4.2, p&amp;lt;0.01 (figure). C-reactive protein and other clinical and laboratory variables did not differ in patients with and without repeated peripheral revascularization. According to Cox regression analysis adjusted for all risk factors, hyperlipoproteinemia(a) remained an independent predictor of severe restenosis or de novo stenosis of carotid and lower extremity arteries and was associated with a threefold increased risk of repeated revascularization. Conclusions In a three-year prospective study of patients after peripheral revascularization, Lp(a) level ≥30 mg/dL was shown as an independent risk factor for repeated revascularization. Funding Acknowledgement Type of funding sources: None. Survival analysis

Atherosclerosis risk factors may be underestimated in patients with pulmonary hypertension associated with congenital heart disease – results of Polish snapshot registry

Abstract Introduction Classic risk factors of atherosclerosis may contribute to cardiovascular (CV) risk in patients (pts) with pulmonary hypertension associated with congenital heart disease (PAH-CHD), but their prevalence is poorly studied. Purpose We evaluated a large cohort of Polish PAH-CHD patients (PAHpts) treated with specific therapies with regard to prevalence of classic risk factors for atherosclerosis. Methods A multicenter observational snapshot registry was conducted under the auspices of Polish Cardiac Society to study PAH pts, identified in centers treating &amp;gt;5 such pts in years 2008–2018. The analysis included 250 PAH-CHD pts, including non-corrected CHD – predominantly Eisenmenger Syndrome (Gr. 1, 224 pts, mean age 42±2 years, 63% females) and pts after heart disease correction (Gr. 2, 26 pts, mean age 42±6.5 years, 62% females). The incidence of classic CV risk factors was compared in both groups. Results The prevalence of risk factors was considerable considering young age of the cohort and statistically similar in both groups (Figure). Hypertension was present in 14% in Gr. 1 and 15% in Gr. 2. The incidence of diabetes was comparable in both groups (3% vs. 4%). Hyperlipidemia was nearly numerically twice as frequent in Gr. 1 (23% vs. 12%, p=0.18). Current smokers (1%) were only present in Gr. 1, while history of smoking was 4% in both groups. Symptomatic atherosclerosis of peripheral arteries was twice as frequent in Gr. 1 (8% vs. 4%, p=0,71). There was no difference regarding prior stroke (3,6% vs 4%, p=0,63). Chronic kidney disease and atrial fibrillation were one and a half more often in Gr. 1 (respectively, 12% vs. 8%, p=0,81; 12% vs. 8%, p=0.75). Mean heart rate was 72±2 bpm in Gr. 1 and 77±7 bpm in Gr. 2. Gastrointestinal bleeding was reported only in Gr. 1 (2.7%). SCORE calculated risks were low due to low age, but high risk was identified in 9.3% of Gr. 1 and 20% of Gr. 2 (p=0.096). Conclusions Based on our data from national survey, classic atherosclerosis CV risk factors are not uncommon in the population of relatively young patients with PAH-CHD, parallel to improved longevity. Selected pts from both groups present with elevated risk of death from atherosclerotic complications. This finding may influence the overall mortality risk in PAH-CHD population and reflects new challenges in management despite progress in specific therapies of pulmonary hypertension. Funding Acknowledgement Type of funding sources: None. Figure 1

Decreased CSF Dynamics in Treatment-Naive Patients with Essential Hypertension: A Study with Phase-Contrast Cine MR Imaging.

Arterial sclerosis resulting from hypertension slows CSF transportation in the perivascular spaces, showing the intrinsic relationship between the CSF and the blood vasculature. However, the exact effect of hypertension on human CSF flow dynamics remains unclear. The present study aimed to evaluate CSF flow dynamics in treatment-naive patients with essential hypertension using phase-contrast cine MR imaging. The study included 60 never-treated patients with essential hypertension and 60 subjects without symptomatic atherosclerosis. CSF flow parameters, such as forward flow volume, forward peak velocity, reverse flow volume, reverse peak velocity, average flow, and net flow volume, were measured with phase-contrast cine MR imaging. Differences between the 2 groups were assessed to determine the independent determinants of these CSF flow parameters. Forward flow volume, forward peak velocity, reverse flow volume, reverse peak velocity, and average flow in the patients with hypertension significantly decreased (all, P < .05). Increasing systolic blood pressure was significantly associated with lower forward flow volume (β = -0.44 mL/mL/mm Hg; 95% CI, -0.83 to -0.06 mL/mL/mm Hg), forward peak velocity (β = -0.50 cm/s/mm Hg; 95% CI, -0.88 to -0.12 cm/s/mm Hg), reverse flow volume (β = -0.61 mL/mL/mm Hg; 95% CI, -0.97 to -0.26 mL/mL/mm Hg), reverse peak velocity (β = -0.55 cm/s/mm Hg; 95% CI, -0.91-0.18 cm/s/mm Hg), and average flow (β = -0.50 mL/min/mm Hg; 95% CI, -0.93 to -0.08 mL/min/mm Hg). The CSF flow dynamics in patients with hypertension are decreased, and increasing systolic blood pressure is strongly associated with lower CSF flow dynamics.

Potential Association between Distal Deep Vein Thrombosis and Asymptomatic Atherosclerosis.

Background Several studies have previously reported an association between idiopathic proximal deep vein thrombosis (DVT) and atherosclerosis, but whether spontaneous distal DVT is associated with asymptomatic atherosclerosis is still unknown. Methods Ultrasonography of the carotid arteries was done for plaque detection and intima-media thickness (IMT) evaluation, and the ankle-brachial index (ABI) in 116 patients with spontaneous DVT and without symptomatic atherosclerosis. Fifty-seven patients (M/F 19/38, age range 54–78 years) had distal DVT and 59 (M/F 24/35, age range 51–73 years) had proximal DVT. A group of 57 (M/F 21/36, age range 64–70 years) matched subjects acted as controls. Results No significant difference was found in carotid plaques between patients with distal or proximal DVT versus controls ( p > 0.05 in all comparisons). Carotid IMT (mean ± SD) was significantly increased in patients with distal (1.00 ± 0.20 mm) and proximal (0.98 ± 0.16 mm) DVT versus controls (0.88 ± 0.15 mm, p <0.01 in both comparisons). An ABI £ 0.9 was found in 3/57 (5.3%) and 5/59 (8.5%) patients with distal and proximal DVT, respectively versus no controls with abnormal ABI. Conclusion Our results revealed that there may be an association between spontaneous distal DVT and asymptomatic atherosclerosis, and confirmed the known association between idiopathic proximal DVT and asymptomatic atherosclerosis. Larger studies are needed to confirm our results and to evaluate their clinical implications.

Dose-Dependent Association of Inflammatory Cytokines with Carotid Atherosclerosis in Transient Ischaemic Attack: Implications for Clinical Trials

Introduction: The 5-year recurrence risk after ischaemic stroke and transient ischaemic attack (TIA) is 25–30%. Although inflammation may be a target for prevention trials, the contribution of plaque inflammation to acute cerebrovascular events remains unclear. We investigated the association of acute inflammatory cytokines and high-sensitivity C-reactive protein (CRP) with recently symptomatic carotid atherosclerosis in a prospective cohort study. Methods: Blood and Imaging markers of TIA BIO-TIA) is a multicentre prospective study of imaging and inflammatory markers in patients with TIA. Exclusion criteria were infection and other co-morbid illnesses associated with inflammation. CRP and serum cytokines (interleukin [IL]-6, IL-1β, IL-8, IL-10, IL-12, interferon-γ [IFN-γ] and tumour necrosis factor-α [TNF-α]) were measured. All patients had carotid imaging. Results: Two hundred and thirty-eight TIA cases and 64 controls (TIA mimics) were included. Forty-nine (20.6%) cases had symptomatic internal carotid artery stenosis. Pro-inflammatory cytokine levels increased in a dose-dependent manner across controls, TIA without carotid stenosis (CS), and TIA with CS (IL-1β, p_trend = 0.03; IL-6, p_trend < 0.0001; IL-8, p_trend = 0.01; interferon (IFN)-γ, p_trend = 0.005; TNF-α, p_trend = 0.003). Results were unchanged when DWI-positive cases were excluded. On multivariable linear regression, only age (p = 0.01) and CS (p = 0.04) independently predicted log-IL-6. On multivariable Cox regression, CRP was the only independent predictor of 90-day stroke recurrence (adjusted hazard ratio per 1-unit increase 1.03 [95% CI: 1.01–1.05], p = 0.003). Conclusion: Symptomatic carotid atherosclerosis was associated with elevated cytokines in TIA patients after controlling for other sources of inflammation. High-sensitivity CRP was associated with recurrent ischaemic stroke at 90 days. These findings implicate acute plaque inflammation in the pathogenesis of cerebral thromboembolism and support a rationale for randomized trials of anti-inflammatory therapy for stroke patients, who were excluded from coronary trials.

Circumferential segmental vessel-wall enhancement on black blood MRI in patients referred for the evaluation of vasculopathy

BackgroundHigh resolution intracranial vessel wall magnetic resonance imaging, or black blood MRI, has recently gained traction as an adjunct to computed tomography angiography, magnetic resonance angiography, and digital subtraction angiography in the characterization of atherosclerosis, vasculitides, and inflammatory changes in the aneurysm wall. However, the occurrence of uniform circumferential segmental arterial vessel wall enhancement (CSWE) in patients without these diagnoses has not previously been studied. The purpose of this study is twofold: 1) to evaluate the prevalence of CSWE in the major intracranial arteries in patients without vasculitides, symptomatic atherosclerosis, or aneurysmal subarachnoid hemorrhage and 2) to determine the association, if any, between such enhancement and risk factors for cerebrovascular atherosclerotic disease. Materials & methodsA retrospective study of vessel wall magnetic resonance imaging examinations was performed to evaluate for CSWE in 26 patients without known vessel wall pathology such as aneurysms or vasculitides and intracranial hemorrhage. Further evaluation of CSWE association with major intracranial atherosclerotic disease risk factors including hypertension, hyperlipidemia, diabetes mellitus and cigarette smoking was performed. Results and conclusion46% of the cohort of patients demonstrated CSWE. Among the patients with CSWE, there was increased prevalence of CSWE in the posterior circulation vasculature with particular predilection to the V4 vertebral artery segments (92%), although there was greater association of anterior circulation CSWE with risk factors for atherosclerosis. Patients with anterior circulation CSWE also demonstrated the most number of segments with CSWE. We therefore propose that CSWE, particularly in the anterior circulation, may portend early atherosclerosis.

Molecular Biomarkers Associated with Early-Onset Symptomatic Intracranial Atherosclerosis.

PurposePrevious studies have shown a rising incidence of early-onset symptomatic intracranial atherosclerosis (sICAS), which has brought a severe economic burden to social development. This study aimed to evaluate the molecular biomarkers associated with early-onset sICAS and to seek possible intervention strategies for early prevention.Patients and MethodsWe consecutively recruited patients with sICAS and divided them into two groups based on age: early-onset sICAS group as age ≤60 years old and late-onset sICAS group as age >60 years old. We collected and compared the demographic data and laboratory results of each group. A bivariate logistic regression model was applied to evaluate the independent molecular biomarkers of early-onset sICAS.ResultsA total of 1007 subjects with sICAS were enrolled in this study, comprising 519 patients in the early-onset sICAS group and 488 patients in the late-onset sICAS group. Bivariate logistic regression analysis demonstrated an increased level of white blood cell, platelet, albumin globulin ratio, free triiodothyronine, and a decreased level of total bile acid, urea nitrogen, high-density lipoprotein, homocysteine, and fibrinogen in the early-onset sICAS group when compared to the late-onset group.ConclusionOur study showed the relevance between early sICAS and circulating levels of different molecular biomarkers. Detection of these related molecular biomarkers may provide a simple way for early sICAS preventions in the future.