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Growth patterns of four lines of mice selected for body conformation were analyzed with the logistic function, in order to provide baseline information about the relationship between asymptotic weight and maturing rate of body weight. Two lines were divergently selected favoring the phenotypic correlation between body weight and tail length (agonistic selection: CBi+, high body weight and long tail; CBi-, low body weight and short tail), whereas the other two lines were generated by a disruptive selection performed against the correlation between the aforementioned traits (antagonistic selection: CBi/C, high body weight and short tail; CBi/L, low body weight and long tail). The logistic parameters A (asymptotic weight) and k (maturing rate) behaved in CBi/C and CBi- mice and in CBi+ females as expected in terms of the negative genetic relationship between mature size and earliness of maturing. An altered growth pattern was found in CBi/L mice and in CBi+ males, because in the former genotype, selected for low body weight, the time taken to mature increased, whereas in the latter, selected for high body weight, there was a non-significant increase in the same trait. In accordance with the selective criterion, different sources of genetic variation for body weight could be exploited: one inversely associated with earliness of maturing (agonistic selection), and the other independent of maturing rate (antagonistic selection), showing that genetic variation of A is partly independent of k.

Cerebral small vessel disease (cSVD) is associated with increased blood-brain barrier (BBB) permeability. We sought to evaluate whether arterial stiffness might be associated with BBB permeability in patients with cSVD. We assessed BBB permeability using Dynamic Contrast-Enhanced MRI (DCE-MRI) in 29 patients that had suffered a recent small subcortical infarct (RSSI). BBB permeability in the whole brain (WB), gray matter (GM) and white matter (WM) was assessed with the parameter Ktrans. We used ambulatory blood pressure monitoring to measure 24-h systolic blood pressure (24-h SBP), diastolic blood pressure (24-h DBP), and pulse wave velocity (24-h PWV) both after stroke and following a 2-year follow-up. The differences between both measurements were calculated as Δ24-h SBP, Δ24-h DBP and Δ24-h PWV. DCE-MRI was acquired at a median (IQR) of 24 (19-27) months after stroke. Median age was 66.7 (9.7) years, and 24 (83%) patients were men. Median (IQR) Δ24-h PWV was 0.3 (-0.1, 0.5) m/s. WB-Ktrans, GM-Ktrans, and WM-Ktrans were associated with Δ24-h PWV (Spearman's, r [95% CI], WB 0.651 [0.363-0.839]; GM 0.657 [0.373-0.845], WM 0.530[0.197-0.777]) but not with Δ24-h SBP or Δ24-h DBP. These associations remained significant after adjustment with linear regression models, controlling for age, sex, body mass index, and Δ24-h SBP (b[95% CI], WB 0.725[0.384-1.127], GM 0.629 [0.316-1.369], WM 0.865 [0.455-0.892]) or Δ24-h DBP (b[95% CI], WM 0.707 [0.370-1.103], GM 0.643 [0.352-1.371], WM 0.772 [0.367-0.834]). Our results suggest that an increment on arterial stiffness in the months following a RSSI might increase BBB permeability., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

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., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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 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., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

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.

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., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

We aimed to evaluate brachial and central blood pressure (BP) estimates and biomarker levels in lacunar ischemic stroke (IS) and other IS subtypes (nonlacunar stroke). We studied 70 functionally independent subjects consecutively admitted to our institution after a first episode of IS. Subjects with previous heart failure were excluded. BP was measured at admission and during the subacute phase of stroke (5-7 days after stroke onset). Aortic pulse wave velocity (aPWV), augmentation index (AIx), and 24 h brachial and central BP (24h-ABPM) were measured by means of a Mobil-O-Graph device during the subacute phase of stroke. Determination of N-terminal prohormone of brain natriuretic peptide (NT-proBNP), urinary albumin excretion, and echocardiography were performed in all subjects. After adjusting for age and clinical severity, lacunar IS had significantly higher levels of BP at admission (systolic BP 173 ± 37 vs 153 ± 28 mmHg, p = 0.006; diastolic BP: 97 ± 21 vs 86 ± 16 mmHg, p = 0.035) and during the subacute phase of stroke (systolic BP 152 ± 23 vs 134 ± 19 mmHg, p = 0.001; diastolic BP: 84 ± 14 and 77 ± 10 mmHg, respectively; p = 0.038) but lower NT-proBNP levels (median: 36,277 vs 274 pg/mL, p = 0.009) than nonlacunar IS. Central BP, aPWV, and AIx were not different between lacunar and nonlacunar IS, neither the rate of target organ damage. In conclusion, patients with a first episode of lacunar IS have higher BP values at admission and during the subacute phase of stroke and lower levels of NT-proBNP, suggesting a closer relationship with hypertension of this IS subtype.

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.

Embolism of cardiac origin accounts for about 20% of ischemic strokes. Nonvalvular atrial fibrillation is the most frequent cause of cardioembolic stroke. Approximately 1% of population is affected by atrial fibrillation, and its prevalence is growing with ageing in the modern world. Strokes due to cardioembolism are in general severe and prone to early recurrence and have a higher long-term risk of recurrence and mortality. Despite its enormous preventive potential, continuous oral anticoagulation is prescribed for less than half of patients with atrial fibrillation who have risk factors for cardioembolism and no contraindications for anticoagulation. Available evidence does not support routine immediate anticoagulation of acute cardioembolic stroke. Anticoagulation therapy's associated risk of hemorrhage and monitoring requirements have encouraged the investigation of alternative therapies for individuals with atrial fibrillation. New anticoagulants being tested for prevention of stroke are low-molecular-weight heparins (LMWH), unfractionated heparin, factor Xa inhibitors, or direct thrombin inhibitors like dabigatran etexilate and rivaroxaban. The later exhibit stable pharmacokinetics obviating the need for coagulation monitoring or dose titration, and they lack clinically significant food or drug interaction. Moreover, they offer another potential that includes fixed dosing, oral administration, and rapid onset of action. There are several concerns regarding potential harm, including an increased risk for hepatotoxicity, clinically significant bleeding, and acute coronary events. Therefore, additional trials and postmarketing surveillance will be needed.