Relationship of arterial stiffness and baseline vascular burden with new lacunes and microbleeds: A longitudinal cohort study.

INTRODUCTION: Arterial stiffness may have a significant impact on the development of cerebral small vessel disease (cSVD). PATIENTS AND METHODS: We obtained pulse wave velocity (24-h PWV) by means of ambulatory blood pressure monitoring (ABPM) in patients with a recent small subcortical infarct (RSSI). Patients with known cardiac or arterial embolic sources were excluded. Lacunes, microbleeds, white matter hyperintensities and enlarged perivascular spaces at baseline were assessed in a brain MRI and included in a cSVD score. A follow-up MRI was obtained 2 years later and assessed for the appearance of new lacunes or microbleeds. We constructed both unadjusted and adjusted models, and subsequently selected the optimal models based on the area under the curve (AUC) of the predicted probabilities. RESULTS: Ninety-two patients (mean age 67.04 years, 69.6% men) were evaluated and 25 had new lacunes or microbleeds during follow-up. There was a strong correlation between 24-h PWV and age (r = 0.942, p < 0.001). cSVD was associated with new lacunes or microbleeds when adjusted by age, 24-h PWV, NT-proBNP and hypercholesterolemia (OR 2.453, CI95% 1.381-4.358). The models exhibiting the highest discrimination, as indicated by their area under the curve (AUC) values, were as follows: 1 (AUC 0.854) - Age, cSVD score, 24-h PWV, Hypercholesterolemia; 2 (AUC 0.852) - cSVD score, 24-h PWV, Hypercholesterolemia; and 3 (AUC 0.843) - Age, cSVD score, Hypercholesterolemia. CONCLUSIONS: cSVD score is a stronger predictor for cSVD progression than age or hemodynamic parameters in patients with a RSSI.

Sex and gender differences in acute stroke care: metrics, access to treatment and outcome. A territorial analysis of the Stroke Code System of Catalonia.

INTRODUCTION: Previous studies have reported differences in the management and outcome of women stroke patients in comparison with men. We aim to analyze sex and gender differences in the medical assistance, access to treatment and outcome of acute stroke patients in Catalonia. PATIENTS AND METHODS: Data were obtained from a prospective population-based registry of stroke code activations in Catalonia (CICAT) from January/2016 to December/2019. The registry includes demographic data, stroke severity, stroke subtype, reperfusion therapy, and time workflow. Centralized clinical outcome at 90 days was assessed in patients receiving reperfusion therapy. RESULTS: A total of 23,371 stroke code activations were registered (54% men, 46% women). No differences in prehospital time metrics were observed. Women more frequently had a final diagnosis of stroke mimic, were older and had a previous worse functional situation. Among ischemic stroke patients, women had higher stroke severity and more frequently presented proximal large vessel occlusion. Women received more frequently reperfusion therapy (48.2% vs 43.1%, p < 0.001). Women tended to present a worse outcome at 90 days, especially for the group receiving only IVT (good outcome 56.7% vs 63.8%; p < 0.001), but not for the group of patients treated with IVT + MT or MT alone, although sex was not independently associated with clinical outcome in logistic regression analysis (OR 1.07; 95% CI, 0.94-1.23; p = 0.27) nor in the analysis after matching using the propensity score (OR 1.09; 95% CI, 0.97-1.22). DISCUSSION AND CONCLUSION: We found some differences by sex in that acute stroke was more frequent in older women and the stroke severity was higher. We found no differences in medical assistance times, access to reperfusion treatment and early complications. Worse clinical outcome at 90 days in women was conditioned by stroke severity and older age, but not by sex itself.

NT-proBNP, cerebral small vessel disease and cardiac function in patients with a recent lacunar infarct.

NT-proBNP is produced from both atria and ventricles and it is increased in patients with cardiac disease. NT-proBNP is also associated with cerebral small vessel disease(cSVD) but there are no studies that had carried out a systematic evaluation of cardiac function in this specific setting. We conducted a prospective observational study in 100 patients within 30 days after a recent lacunar infarct by means of brain MRI, 24 h ambulatory blood pressure monitoring, transthoracic echocardiography, and plasmatic NT-proBNP. Global cSVD burden was quantified using a validated visual score (0 to 4) and dichotomized into 2 groups (0-2 or 3-4). Age (73.8 vs 63.5 years) and NT-proBNP (156 vs 76 pg/ml) were increased in patients with SVD 3-4, while daytime augmentation index normalized for the heart rate of 75 bpm (AIx75) (22.5 vs 25.6%) was decreased. The proportion of patients with left atrial enlargement, left ventricular hypertrophy, or septal e' velocity <7 cm/s was not different between both groups. NT-proBNP was increased in patients with left atrial enlargement (126 vs 88 pg/ml). In multivariate analysis, age (OR 1.129 CI 95% 1.054-1.209), daytime AIx75 (OR 0.91 CI 95% 0.84-0.987,) and NT-proBNP (OR 1.007 CI 95% 1.001-1.012,) were independently associated with cSVD score 3-4. In conclusion, as well as in other patients with cSVD we found an association between NT-proBNP and cSVD. This association was independent of cardiac function.

Determinants and Trends of the Use of Intravenous Thrombolysis for Minor Stroke: A Population-Based Study, 2016 to 2020.

BACKGROUND: We analyzed the main factors associated with intravenous thrombolysis (IVT) in patients with minor ischemic stroke. METHODS: Data were obtained from a prospective, government-mandated, population-based registry of stroke code patients in Catalonia (6 Comprehensive Stroke Centers, 8 Primary Stroke Centers, and 14 TeleStroke Centers). We selected patients diagnosed with ischemic stroke and National Institutes of Health Stroke Scale (NIHSS) ≤5 at hospital admission from January 2016 to December 2020. We excluded patients with a baseline modified Rankin Scale score of ≥3, absolute contraindication for IVT, unknown stroke onset, or admitted to hospital beyond 4.5 after stroke onset. The main outcome was treatment with IVT. We performed univariable and binary logistic regression analyses to identify the most important factors associated with IVT. RESULTS: We included 2975 code strokes; 1433 (48.2%) received IVT of which 30 (2.1%) had a symptomatic hemorrhagic transformation. Patients treated with IVT as compared to patients who did not receive IVT were more frequently women, had higher NIHSS, arrived earlier to hospital, were admitted to a Comprehensive Stroke Centers, and had large vessel occlusion. After binary logistic regression, NIHSS score 4 to 5 (odds ratio, 40.62 [95% CI, 31.73-57.22]; P<0.001) and large vessel occlusion (odds ratio, 16.39 [95% CI, 7.25-37.04]; P<0.001) were the strongest predictors of IVT. Younger age, female sex, baseline modified Rankin Scale score of 0, earlier arrival to hospital (<120 minutes after stroke onset), and the type of stroke center were also independently associated with IVT. The weight of large vessel occlusion on IVT was higher in patients with lower NIHSS. CONCLUSIONS: Minor stroke female patients, with higher NIHSS, arriving earlier to the hospital, presenting with large vessel occlusion and admitted to a Comprehensive Stroke Centers were more likely to receive intravenous thrombolysis.

Progression of Large Vessel Disease in Patients With Giant Cell Arteritis-Associated Ischemic Stroke: The Role of Vascular Imaging: A Case Series.

OBJECTIVE: Giant cell arteritis (GCA) can cause ischemic stroke (IS) due to the involvement of the internal carotid and vertebral arteries. The aim of our study is to describe the pattern of stroke recurrence in patients with GCA-related IS and the role of vascular imaging in the follow-up of these patients. METHODS: We conducted an observational study of 2417 consecutive patients diagnosed with IS and admitted to our hospital from January 2012 to December 2018. We reviewed patients with GCA-related IS and the relationship of erythrocyte sedimentation rate, C-reactive protein, vascular status, and clinical course. RESULTS: We found 4 patients with GCA-related IS among 2417 IS patients: 1 woman (25%); median age, 77.3 years (67-85 years). Mean follow-up was 3.6 years. Initial vascular workup showed vertebral artery stenosis in all of them and internal carotid artery stenosis in 2 patients. All patients were started on treatment with full-dose prednisone, associated with methotrexate in 2 cases. Follow-up color-coded duplex sonography disclosed progression of arterial stenoses in 3 patients who suffered a recurrent IS (days after index stroke; mean, 27.67 [SD, 10.97]) despite normal C-reactive protein and erythrocyte sedimentation rate values. CONCLUSIONS: Vascular imaging, especially with color-coded duplex sonography, could play a role in the follow-up of patients with GCA-related IS and identify those patients with higher risk of recurrent stroke.

Genome-Wide Association Study of VKORC1 and CYP2C9 on acenocoumarol dose, stroke recurrence and intracranial haemorrhage in Spain.

Acenocoumarol is an oral anticoagulant with significant interindividual dose variations. Variants in CYP2C9 and VKORC1 have been associated with acenocoumarol maintenance dose. We analysed whether any of the 49 polymorphisms in CYP2C9 and VKORC1 previously associated with acenocoumarol maintenance dose in a Genome-Wide Association study (GWAs) in Dutch population are associated with stroke recurrence, intracranial haemorrhage (ICH) and acenocoumarol maintenance dose in a Spanish population. We performed a GWAs using Human Core Exome-chip (Illumina) in 78 patients stroke patients treated with acenocoumarol for secondary prevention enrolled as part of the prospective investigator-initiated study (IIS) SEDMAN Study. Patients were followed-up a median of 12.8 months. Three and eight patients had recurrent stroke and ICH events, respectively. We found 14 of the 49 published variants associated with acenocoumarol maintenance dose (p < 0.05). Six polymorphisms were associated with stroke recurrence and four variants with ICH (p < 0.05). In conclusion, variants in VKORC1 and CYP2C9 are associated with acenocoumarol maintenance dose, stroke recurrence and ICH in a Spanish cohort. These results highlight the relevance of studying pharmacogenetics associated with efficacy and safety of anticoagulant drugs and justify studies with larger sample size and different ethnic populations.

GRECOS Project (Genotyping Recurrence Risk of Stroke): The Use of Genetics to Predict the Vascular Recurrence After Stroke.

BACKGROUND AND PURPOSE: Vascular recurrence occurs in 11% of patients during the first year after ischemic stroke (IS) or transient ischemic attack. Clinical scores do not predict the whole vascular recurrence risk; therefore, we aimed to find genetic variants associated with recurrence that might improve the clinical predictive models in IS. METHODS: We analyzed 256 polymorphisms from 115 candidate genes in 3 patient cohorts comprising 4482 IS or transient ischemic attack patients. The discovery cohort was prospectively recruited and included 1494 patients, 6.2% of them developed a new IS during the first year of follow-up. Replication analysis was performed in 2988 patients using SNPlex or HumanOmni1-Quad technology. We generated a predictive model using Cox regression (GRECOS score [Genotyping Reurrence Risk of Stroke]) and generated risk groups using a classification tree method. RESULTS: The analyses revealed that rs1800801 in the MGP gene (hazard ratio, 1.33; P=9×10-03), a gene related to artery calcification, was associated with new IS during the first year of follow-up. This polymorphism was replicated in a Spanish cohort (n=1.305); however, it was not significantly associated in a North American cohort (n=1.683). The GRECOS score predicted new IS (P=3.2×10-09) and could classify patients, from low risk of stroke recurrence (1.9%) to high risk (12.6%). Moreover, the addition of genetic risk factors to the GRECOS score improves the prediction compared with previous Stroke Prognosis Instrument-II score (P=0.03). CONCLUSIONS: The use of genetics could be useful to estimate vascular recurrence risk after IS. Genetic variability in the MGP gene was associated with vascular recurrence in the Spanish population.

Expresión de la proteína C reactiva en placas ateroscleróticas de carótida / Expression of C-reactive protein in atherosclerotic carotid plaques

Introducción. La proteína C-reactiva (PCR) es un marcador de inflamación y de pronóstico de la enfermedad cardiovascular. Además, esta proteína parece realizar funciones mediadoras de esta enfermedad, dado sus múltiples efectos proaterogénicos y su presencia en las lesiones ateroscleróticas. Material y métodos. En este estudio, se analizó la expresión de la PCR, mediante la reacción en cadena de la polimerasa a tiempo real, en las lesiones avanzadas de carótida obtenidas mediante endarterectomía. Además, mediante inmunohistoquímica, se analizó la expresión de esta proteína en estas lesiones ateroscleróticas avanzadas y en muestras de arteria carótida que se encontraban en diferentes estadios de progresión. Resultados. Los valores de ácido ribonucleico mensajero de PCR fueron significativamente más elevados en las lesiones ulceradas no complicadas, comparado con las lesiones ulceradas complicadas (p = 0,001) y fibrosas (p = 0,01). Mediante inmuno-histoquímica, se observó marcaje para PCR en las lesiones más avanzadas, principalmente en las células inflamatorias infiltradas y en vasos de nueva formación. En cambio, en lesiones más tempranas y en las arterias carótidas sanas no se encontró tinción para la PCR. Conclusión. La expresión de la PCR en las lesiones ateroscleróticas de carótida se induce en estadios medios y avanzados de la progresión, y puede estar implicada en la inflamación y la neovascularización que aparece en estos estadios, lo que conlleva riesgo de complicaciones hemorrágicas (AU)

Background. C-reactive protein (CRP) is an inflammatory and powerful marker of future vascular events. Recently, it has been proposed as a mediator molecule of atherosclerotic disease due to its multiple proatherogenic effects and its presence in atherosclerotic plaques. Material and methods. CRP expression was analyzed by real time polymerase chain reaction (PCR) in advanced carotid plaques. Furthermore, protein expression was analyzed by immunohistochemistry in carotid atherosclerotic lesions obtained by endarterectomy and in carotid samples in different phases of progression. Results. Analysis by real time PCR showed significantly higher levels of CRP in ulcerated non-complicated lesions as compared to complicated ulcerated lesions (p = 0.001) or fibrous lesions (p = 0.01). An immunohistochemistry assay for CRP showed that in advanced lesions, mainly infiltrated inflammatory cells and new vessels were stained. In contrast, no CRP staining was observed in early lesions and carotid artery controls. Conclusion. CRP expression in carotid atherosclerotic lesions is induced in moderated and advanced stages of plaque progression, suggesting a possible role of this molecule in inflammation and neovascularization and triggering atherothrombotic complications (AU)