Diabetes Mellitus and Clinical Outcomes in Carotid Artery Revascularization Using Second-Generation, MicroNet-Covered Stents: Analysis from the PARADIGM Study.

Introduction: Carotid artery stenting (CAS) using conventional (single-layer) stents is associated with worse clinical outcomes in diabetes mellitus (DM) vs. non-DM patients: an effect driven largely by lesion-related adverse events. CAS outcomes with MicroNet-covered stents (MCS) in diabetic patients have not been evaluated. Aim: To compare short- and long-term clinical outcomes and restenosis rate in DM vs. non-DM patients with carotid stenosis treated using MCS. Materials and Methods: In a prospective study in all-comer symptomatic and increased-stroke-risk asymptomatic carotid stenosis, 101 consecutive patients (age 51-86 years, 41% diabetics) underwent 106 MCS-CAS. Clinical outcomes and duplex ultrasound velocities were assessed periprocedurally and at 30 days/12 months. Results: Baseline characteristics of DM vs. non-DM patients were similar except for a higher prevalence of recent cerebral symptoms in DM. Type 1 and type 1+2 plaques were more prevalent in DM patients (26.7% vs. 9.8%, p = 0.02; 62.2% vs. 37.7%, p = 0.01). Proximal embolic protection was more prevalent in DM (60% vs. 36%; p = 0.015). 30-day clinical complications were limited to a single periprocedural minor stroke in DM (2.4% vs. 0%, p = 0.22). 12-month in-stent velocities and clinical outcomes were not different (death rate 4.8% vs. 3.3%; p = 0.69; no new strokes). Restenosis rate was not different (0% vs. 1.7%, p = 0.22). Conclusions: MCS may offset the adverse impact of DM on periprocedural, 30-day, and 12-month clinical complications of CAS and minimize the risk of in-stent restenosis. In this increased-stroke-risk cohort, adverse event rate was low both in DM and non-DM. Further larger-scale clinical datasets including extended follow-ups are warranted.

Highly-calcific carotid lesions endovascular management in symptomatic and increased-stroke-risk asymptomatic patients using the CGuard™ dual-layer carotid stent system: Analysis from the PARADIGM study.

OBJECTIVES: To assess feasibility, safety, angiographic, and clinical outcome of highly-calcific carotid stenosis (HCCS) endovascular management using CGuard™ dual-layer carotid stents. BACKGROUND: HCCS has been a challenge to carotid artery stenting (CAS) using conventional stents. CGuard combines a high-radial-force open-cell frame conformability with MicroNet sealing properties. METHODS: The PARADIGM study is prospectively assessing routine CGuard use in all-comer carotid revascularization patients; the focus of the present analysis is HCCS versus non-HCCS lesions. Angiographic HCCS (core laboratory evaluation) required calcific segment length to lesion length ≥2/3, minimal calcification thickness ≥3 mm, circularity (≥3 quadrants), and calcification severity grade ≥3 (carotid calcification severity scoring system [CCSS]; G0-G4). RESULTS: One hundred and one consecutive patients (51-86 years, 54.4% symptomatic; 106 lesions) received CAS (16 HCCS and 90 non-HCCS); eight others (two HCCS) were treated surgically. CCSS evaluation was reproducible, with weighted kappa (95% CI) of 0.73 (0.58-0.88) and 0.83 (0.71-0.94) for inter- and intra-observer reproducibility respectively. HCCS postdilatation pressures were higher than those in non-HCCS; 22 (20-24) versus 20 (18-24) atm, p = .028; median (Q1-Q3). Angiography-optimized HCCS-CAS was feasible and free of contrast extravasation or clinical complications. Overall residual diameter stenosis was single-digit but it was higher in HCCS; 9 (4-17) versus 3 (1-7) %, p = .002. At 30 days and 12 months HCCS in-stent velocities were normal and there were no adverse clinical events. CONCLUSION: CGuard HCCS endovascular management was feasible and safe. A novel algorithm to grade carotid artery calcification severity was reproducible and applicable in clinical study setting. Larger HCCS series and longer-term follow-up are warranted.

Impaired plasma clot lysis and its determinants in patients with obstructive sleep apnea syndrome.

Evidence indicates that hypercoagulability and impaired fibrinolysis have been observed in patients with obstructive sleep apnea syndrome (OSAS). It is unclear which factors determine prolonged fibrin clot lysis in OSAS. One hundred and sixty-five consecutive patients suspected of OSAS underwent overnight polysomnography. Prior to polysomnography, we determined plasma clot lysis time (CLT), plasminogen activator inhibitor (PAI)-1 antigen, activated thrombin-activatable fibrinolysis inhibitor (TAFIa), plasmin, and antiplasmin. OSAS was diagnosed in 110 (66.7%) patients, including 35 (31.8%) with severe OSAS, 26 (23.6%) with moderate OSAS, and 49 (44.6%) mild OSAS. Compared with 55 (33.3%) individuals in whom OSAS was not confirmed, OSAS patients had prolonged CLT (+12.8%), associated with higher PAI-1 antigen (+18.1%) (after adjustment for age, diabetes, and body mass index; both P < 0.01) and similar levels of TAFIa, plasmin, or antiplasmin. PAI-1, TAFIa, and CLT correlated positively with apnea/hypopnea index, which reflects the severity of OSAS (R = 0.66, P < 0.001; R = 0.29, P = 0.002; R = 0.55, P = 0.001, respectively), and with other polysomnography parameters, with the most potent correlations observed for desaturation index. Regression analysis adjusted for potential confounders showed that in OSAS, CLT was independently predicted by apnea/hypopnea index (B = 0.29, P = 0.002), PAI-1 (B = 0.42, P < 0.001), and TAFIa (B = 0.81, P = 0.044), whereas both PAI-1 and TAFIa were predicted only by desaturation index (B = 0.24, P = 0.002; and B = 0.14, P = 0.001, respectively). The severity of OSAS is closely associated with hypofibrinolysis measured in a global plasma-based assay, driven largely by PAI-1. Attenuated fibrinolysis might contribute to high risk of thromboembolic events in this disease.

Novel PARADIGM in carotid revascularisation: Prospective evaluation of All-comer peRcutaneous cArotiD revascularisation in symptomatic and Increased-risk asymptomatic carotid artery stenosis using CGuard™ MicroNet-covered embolic prevention stent system.

AIMS: Our aim was to determine (1) periprocedural and 30-day clinical safety and efficacy of the CGuard MicroNet-covered embolic prevention carotid stent system (MN-EPS) in routine use for unselected carotid stenosis (CS) patients undergoing CAS, as well as (2) feasibility of MN-EPS post-dilatation optimisation to minimise residual stenosis after CAS. METHODS AND RESULTS: This was a non-industry-funded, prospective academic study in all-referrals-tracked symptomatic and asymptomatic CS. In asymptomatic lesions, intervention was mandated only in case of increased stroke risk CS features. There was independent neurologist evaluation before CAS, at 48 hours and 30 days. There was external source data verification, angiographic core lab, and statistical analysis. Over 11 months, 108 referrals were recommended by the NeuroVascular Team for revascularisation: 101 (51-86 years, 55 symptomatic, evolving stroke in nine) underwent 106 (100% MN-EPS use) neuroprotection device-assisted (46% proximal, 54% distal) CAS; CEA was performed in seven. MN-EPS device success was 99.1%. Angiographic diameter stenosis was reduced from 83±9% to 6.7±5% (p<0.001). No MN-EPS foreshortening/elongation occurred (30 mm long was 29.82±0.68 mm; 40 mm long was 39.89±0.59 mm). The periprocedural death/major stroke/MI rate was 0%. One event, with no change in NIHSS or modified Rankin Scale and no clinical sequel, was adjudicated by the clinical events committee as minor stroke (0.9%). By 30 days there were no new events (0%). CONCLUSIONS: These increased risk consecutive patient data (1) indicate safety and efficacy of routine MN-EPS use in achieving endovascular reconstruction across all-comer CS lesion subsets, and (2) are consistent with MN-EPS protection against cerebral events extending throughout the stent healing period.

Association between the -1562 C/T MMP-9 polymorphism and cerebrovascular disease in a Polish population.

BACKGROUND AND PURPOSE: Matrix metalloproteinase 9 (MMP-9) is an endopeptidase degrading extracellular matrix. There is growing evidence that changes in extracellular matrix play an important role in vascular pathology, especially in cardiovascular and cerebrovascular disease. Previous studies have demonstrated that MMP-9 activity is controlled by --1562 C/T polymorphism. Genotypes with T allele (CT, TT) have higher enzymatic activity. Thus, this polymorphism could be responsible for the higher risk for cerebrovascular disease and death. The aim of this study was to assess the significance of MMP-9 polymorphism as a risk factor for cerebrovascular disease in a Polish population. MATERIAL AND METHODS: A total of 775 consecutive patients with a diagnosis of cerebrovascular disease (ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage) admitted to the Stroke Unit, Jagiellonian University, Krakow, Poland between 2000 and 2004 were studied and compared with 766 matched controls. The polymorphism was studied by polymerase chain reaction (PCR) and restricted enzyme digestion. RESULTS: Among 418 patients with ischaemic stroke of various aetiologies and among 146 patients with primary intracerebral haemorrhage and 211 patients with subarachnoid haemorrhage due to ruptured intracranial aneurysm, statistical analysis did not show a significant difference between occurrence of CC, CT, TT genotypes or C and T alleles in patients with stroke of various aetiology compared with controls. CONCLUSIONS: We found no association between the -1562 C/T MMP-9 polymorphism and ischaemic stroke, subarachnoid haemorrhage or spontaneous intracerebral haemorrhage in the studied Polish population.

The C(-1562)T polymorphism of the MMP-9 gene and the risk of sporadic amyotrophic lateral sclerosis.

BACKGROUND AND PURPOSE: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of multiple and poorly understood aetiopathogenesis. Genetic factors involved in the pathogenesis of sporadic ALS still remain unknown. A candidate gene might be matrix metalloproteinase-9 gene (MMP-9) - a member of the matrix metalloproteinase family capable of degrading elements of the extracellular matrix. Recent data suggest that MMP-9 may be involved in the pathophysiology of ALS. MMP-9 levels and activity are influenced by the -1562 C/T polymorphism of the MMP-9 gene. We have studied the association between the -1562 C/T polymorphism of the MMP-9 gene and the risk of sporadic ALS. MATERIAL AND METHODS: We included 228 patients with a definite or probable diagnosis of sporadic ALS and 428 healthy controls matched for age and sex. The diagnosis of sporadic ALS was established according to El Escorial criteria. The polymorphism was studied by polymerase chain reaction (PCR) and restricted enzyme digestion. RESULTS: Distribution of genotypes and alleles of the MMP-9 gene between sporadic ALS cases and controls did not differ significantly: C/C - 168 (73.7%) vs. 304 (71.0%), C/T - 53 (23.2%) vs. 118 (27.6%), T/T - 7 (3.1%) vs. 6 (1.4%), respectively and alleles: C - 389 (85.3%) vs. 726 (84.8%), T - 67 (14.7 %) vs. 130 (15.2%), respectively. CONCLUSION: The polymorphism -1562 C/T of the MMP-9 gene is not associated with the risk of sporadic amyotrophic lateral sclerosis in the studied population of Polish patients.

A1/A2 polymorphism of GpIIIa gene and a risk of aneurysmal subarachnoid haemorrhage.

Platelet glycoproteins are involved in pathophysiology of cerebrovascular diseases. The aim of this study was to investigate the association between the GpIIIa gene A1/A2 polymorphism and a risk of aneurysmal subarachnoid haemorrhage (SAH) in a Polish population. In a case-control study we genotyped 288 Caucasian patients with aneurysmal SAH and 457 age-, gender- and race-matched controls. The GpIIIa A1/A2 polymorphism was genotyped with RFLP technique. No difference was found in the distribution of the polymorphism between the cases and controls (cases: A1A1-201 (69.8%), A1A2-83 (28.8%) and A2A2-4 (1.4%) vs. controls: A1A1-323 (70.7%); A1A2-128 (28.0%); A2A2-6 (1.3%), P>0.05. In a multivariate analysis female gender (OR=1.950; 95%CI: 1.308-2.907), hypertension (OR=4.774; 95%CI: 3.048-7.478) and smoking (OR=2.034; 95%CI: 1.366-3.030), but not GpIIIa A1/A2 polymorphism, were independent risk factors for aneurysmal SAH. The GpIIIa A1/A2 polymorphism is not a risk factor of aneurysmal SAH in a Polish population.

Endoglin gene insertion polymorphism not associated with aneurysmal subarachnoid hemorrhage.

OBJECT: Data concerning an association between the ENG gene intronic insertion polymorphism and intracrahial aneurysms (IAs) remain inconsistent. In this study the authors investigated whether this polymorphism is associated with a subarachnoid hemorrhage (SAH) caused by a ruptured IA in a Polish population. METHODS: One hundred nineteen patients with aneurysmal SAH and 119 sex-matched healthy volunteers were studied. The insertion ENG gene polymorphism in intron 7 was identified using polymerase chain reaction-single-strand chain polymorphism method. The distribution of the insertion allele did not differ between the SAH (13%) and control (16%) cases (p = 0.36). The homozygous insertion/insertion genotype frequencies in these cases were 3.4 and 0.8%, respectively (p = 0.18). CONCLUSIONS: The authors failed to find an association between the intronic insertion polymorphism of the ENG gene and aneurysmal SAH in a Polish population.

Alpha1-antichymotrypsin gene (SERPINA3) A/T polymorphism as a risk factor for aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: The member 3 of clade A of serine proteinase inhibitors (SERPINA3), known previously as the alpha1-antichymotrypsin, is an acute phase protein, the levels of which increase in acute and chronic inflammation. The A/T polymorphism of the SERPINA3 gene influences expression of SERPINA3 protein. SERPINA3 can be related to aneurysmal subarachnoid hemorrhage (SAH) by influencing inflammation or by regulating cathepsin G activity. We studied the significance of SERPINA3 A/T polymorphism in patients with aneurysmal SAH compared with healthy controls. METHODS: A total of 180 patients with aneurysmal SAH and 263 healthy controls were genotyped for the SERPINA3 A/T polymorphism. Aneurysmal SAH was diagnosed by cranial computed tomography or lumbar puncture and digital subtraction angiography. SERPINA3 polymorphism was detected by polymerase chain reaction amplification and restriction enzyme digestion. RESULTS: The SERPINA3 genotype distribution in patients with aneurysmal SAH (AA-29 16.1%; AT-108 60.0%; TT-43 23.9%) differed significantly from controls (AA-70 26.6%; AT-123 46.8%; TT-70 26.6%; P=0.009). A logistic regression model showed that the presence of genotype with T allele (AT+TT; odds ratio [OR], 2.01; 95% CI, 1.19 to 3.38; P=0.009) or AA genotype (OR, 0.49; 95% CI, 0.30 to 0.84; P=0.009) of the SERPINA3 influences the risk for aneurysmal SAH independently from smoking, excessive alcohol consumption, and hypertension. CONCLUSIONS: The A/T polymorphism of SERPINA3 gene is associated with the risk factor for aneurysmal SAH.

II genotype of the angiotensin-converting enzyme gene increases the risk for subarachnoid hemorrhage from ruptured aneurysm.

BACKGROUND AND PURPOSE: Evidence exists in support of a role of genetic factors in susceptibility to aneurysmal subarachnoid hemorrhage (SAH) in humans. Meta-analysis of 2 previous studies showed that the I allele of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism was a weak, but significant, risk factor for aneurysmal SAH. Moreover, a recent study has shown that the local renin-angiotensin system (RAS) is involved in the development of intracranial aneurysm. The aim of this study was to investigate the association between ACE I/D polymorphism and a risk for aneurysmal SAH in a Polish population. METHODS: Ninety patients with aneurysmal SAH (mean age: 48.9+/-14.0 years) and 128 healthy controls matched for age and sex were genotyped for the ACE I/D polymorphism. Aneurysmal SAH was diagnosed by cranial computed tomography and/or lumbar puncture and digital subtraction angiography. ACE gene polymorphism was detected by polymerase chain reaction amplification of the intron 16-specific I/D fragments, 490-bp and 190-bp, respectively. RESULTS: The ACE genotype distribution in patients with aneurysmal SAH (II, 52.2%; ID, 15.6%; DD, 32.2%) differed significantly from controls (II, 23.4%; ID, 50.8%; DD, 25.8%) (P<0.001). A logistic regression model showed that the II genotype of ACE gene was independent from female sex and smoking as a risk factor for aneurysmal SAH (OR, 4.57; 95% CI, 2.35 to 8.90). CONCLUSIONS: Here we report that II genotype of ACE gene is a risk factor for aneurysmal SAH.

[Depressive symptoms following ischemic stroke]. / Objawy depresyjne po udarze niedokrwiennym mózgu.

Depressed mood and other depressive symptoms frequently seen after cerebral stroke contribute to an unfavorable prognosis in this patient population. Identification of the subgroup of patients at increased risk for depressive symptoms is a prerequisite of early treatment. In the study aimed at evaluation of post-stroke depressive symptoms prevalence and risk factors participants were 766 consecutive patients with ischemic cerebral infarction, admitted in the years 1997-2000 to the Stroke Unit, Neurology Department in Cracow. Data concerning depressive symptoms, demographic characteristics and clinical variables were obtained from medical records. Depressive symptoms during the hospitalization were found in 19% of cases. Younger age, neurological deficits and previous history of psychiatric disorders were independent factors increasing the risk of post-stroke depressive symptoms. The study allowed to identify the subpopulation of stroke patients at risk for affective disorders following a cerebrovascular accident.