Elevated lipopolysaccharide level is largely driven by time since symptom onset in acute ischemic stroke: the impact on clinical outcomes.

BACKGROUND: Gut dysbiosis leading to increased intestinal barrier permeability and translocation of lipopolysaccharide (LPS) in the circulation has been demonstrated in patients with acute myocardial infarction and pulmonary embolism. OBJECTIVES: We investigated changes in circulating LPS concentrations in acute ischemic stroke (AIS) and their consequences, including prognosis. METHODS: We studied 98 AIS patients, aged 74 ± 12 years, including 74 (75.5%) thrombolysed individuals. We determined serum LPS and zonulin, a marker of gut permeability, along with protein carbonyl (PC), fibrin clot properties, and thrombin generation on admission, at 24 hours and 3 months. Stroke severity was assessed using the National Institutes of Health Stroke Scale. Stroke functional outcome using modified Rankin scale and stroke-related mortality were evaluated at 3 months. RESULTS: Serum LPS and zonulin levels on admission were associated with time since symptom onset (r = 0.57; P < .0001; and r = 0.40; P < .0001). Baseline LPS levels correlated with PC (r = 0.51; P < .0001) but not with coagulation and fibrinolysis markers. LPS levels increased at 24 hours in thrombolysed patients (P < .001) and correlated with the National Institutes of Health Stroke Scale score (r = 0.31; P = .002) and PC (r = 0.32; P = .0057). Both LPS and zonulin levels measured at 24 hours increased the odds of having unfavorable modified Rankin scale scores (odds ratio [OR], 1.22; 95% CI, 1.04-1.42; and OR, 2.36; 95% CI, 1.24-4.49 per unit). Elevated LPS level, but not zonulin, was associated with stroke-related mortality (OR, 1.26; 95% CI, 1.02-1.55 per unit). CONCLUSION: In AIS patients intestinal permeability is mainly driven by increasing time since the symptom onset. Our findings suggest that LPS, with a trend toward its further rise following thrombolysis, adversely affects neurologic functional outcomes and 3-month mortality.

Family History of Stroke Is Associated with Large- and Small-Vessel Etiology: A Systematic Review and Meta-Analysis.

BACKGROUND: Several studies have investigated the association between family history of stroke (FHS) and stroke etiology, recurrence, or mortality; however, the results have been discrepant. We conducted a systematic review with meta-analysis to further evaluate the associations. MATERIALS AND METHODS: We searched Scopus database using the term "family history" AND "stroke" up to December 2023 to identify observational studies and systematic reviews reporting both the prevalence of FHS and the rates of stroke etiology or recurrence or mortality. Case reports, series, and narrative reviews were excluded. We used odds ratio (OR) as a common measure of association and I2 to determine heterogeneity of effects across studies. RESULTS: We have identified 22 articles (130,999 patients, 53% female), which met the prespecified inclusion criteria. After pooling the results, FHS was associated with large-vessel (OR, 1.24, 95% CI [1.07-1.44]), as well as small-vessel (OR, 1.17, 95% CI [1.05-1.31]), but not cardioembolic stroke etiology (OR, 0.74, 95% CI [0.60-0.90]). There was no relationship between FHS and stroke recurrence (OR, 1.16, 96% CI [0.84-1.61]), nor mortality (0.94, 95% CI [0.63-1.41]). CONCLUSIONS: FHS is associated with large- and small-vessel stroke etiology, but not stroke recurrence or mortality. These findings might be useful to physicians caring for stroke patients in their everyday practice.

Altered fibrin clot phenotype in young adults with intracerebral hemorrhage of unknown cause: A case-control study.

BACKGROUND: Intracerebral hemorrhage (ICH) of undetermined etiology occurs infrequently in young and middle-aged adults. We hypothesized that slight decreases in coagulation factors and formation of less compact fibrin clots prone to faster lysis predispose to this type of ICH. METHODS: We recruited 44 consecutive patients aged <50 years following ICH of unknown cause at least 3 months since the event. Subjects free of ICH (n = 47) matched for age, sex, BMI, and hypertension served as the control group. We assessed plasma fibrin clot permeability, turbidity and fibrinolytic capacity, along with thrombin generation, coagulation factors (F) II, FV, FVII, FVIII, FIX, FX, FXI, antithrombin, and fibrinolysis proteins. RESULTS: ICH patients (median age 41 years, 45.5 % women) had 8.4 % lower FII (p = 0.0001) and 10.1 % lower FVII activity (p = 0.0003), 9.4 % higher antithrombin activity (p = 0.0004) and 13.5 % lower platelet count (p = 0.02). Other factors and thrombin generation did not differ between the two groups. The ICH survivors were characterized by impaired fibrin polymerization reflected by 10.1 % longer lag phase of the turbidimetry curve (p = 0.0002), decreased fiber density indicated by 11.8 % lower maximum absorbance (p = 0.004), as well as 11.1 % shorter clot lysis time (p = 0.014) and 10.0 % faster increase of maximal D-Dimer levels (p = 0.000001). CONCLUSIONS: We demonstrated a prohemorrhagic fibrin clot phenotype, along with lower FII, FVII and higher antithrombin activity in adults below 50 years of age who suffered from ICH of unknown cause, which might indicate novel mechanisms contributing to ICH in younger individuals.

Protein Carbonylation Contributes to Prothrombotic Fibrin Clot Phenotype in Acute Ischemic Stroke: Clinical Associations.

BACKGROUND: Acute ischemic stroke (AIS) is associated with enhanced oxidative stress and unfavorably altered fibrin clot properties. We investigated determinants of plasma protein carbonylation (PC) in AIS, its impact on the prothrombotic state, and prognostic value during follow-up. METHODS: We included 98 consecutive AIS patients aged 74±12 years (male:female ratio, 50:48 [51%:49%]) at the Neurology Center in Warsaw, Poland, between January and December 2014. As many as 74 (75.5%) patients underwent thrombolysis, and 24 were unsuitable for thrombolysis. We determined plasma PC, along with thrombin generation, fibrin clot permeability, and clot lysis time on admission, at 24 hours, and 3 months. Stroke severity was assessed using the National Institutes of Health Stroke Scale and stroke outcome with the modified Rankin Scale. Hemorrhagic transformation was assessed on the computed tomography scan within 48 hours from the symptom onset, while stroke-related mortality was evaluated at 3 months. RESULTS: On admission, PC levels (median, 4.61 [3.81-5.70] nM/mg protein) were associated with the time since symptom onset (r=0.41; P<0.0001) and with the National Institutes of Health Stroke Scale score (P=0.36; P=0.0003). Higher PC levels on admission correlated with denser fibrin clot formation and prolonged clot lysis time but not with thrombin generation. In thrombolysed patients, lower PC levels were observed after 24 hours (-34%) and at 3 months (-23%; both P<0.001). PC levels at baseline and after 24 hours predicted the modified Rankin Scale score >2 at 3 months (OR, 1.90 [95% CI, 1.21-3.00]; OR, 2.19 [95% CI, 1.39-3.44], respectively). Higher PC at baseline predicted hemorrhagic transformation of stroke (OR, 1.95 [95% CI, 1.02-3.74]) and stroke-related mortality (OR, 2.02 [95% CI, 1.08-3.79]), while higher PC at 24 hours predicted solely stroke-related mortality (OR, 2.11 [95% CI, 1.28-3.46]). CONCLUSIONS: Elevated plasma PC levels in patients with AIS, related to prothrombotic fibrin clot properties, are associated with stroke severity. Thrombolysis reduces the extent of PC. The current study suggests a prognostic value of PC in AIS.

Family history of stroke - a useful clue for the primary care physician and stroke neurologist: a narrative review.

Purpose: The heritability of ischemic stroke is a complex mechanism, involving the contribution of genetic traits and environmental factors, which is why in everyday practice clinicians often rely on the broad term "family history of stroke", defined as the case of any first-degree relative who has had a stroke. The aim of this review is to update the available data regarding family history of stroke in primary and secondary stroke prevention by searching the electronic Scopus database for the phrase TITLE-ABS-KEY ("family history" AND "stroke"). Views: A total of 140 articles met the pre-specified criteria and were included in the review. The prevalence of family history of stroke ranged from 37% in stroke-free individuals to 52% in patients with ischemic stroke. In primary prevention, family history of stroke was associated with increased risk of stroke, transient ischemic attack, stroke risk factors and stroke-like symptoms. In patients with ischemic stroke, it was more often associated with small- and large-vessel disease, though not with a cardioembolic etiology. Family history of stroke did not influence long-term functional outcomes after rehabilitation. In young stroke victims, it was related to symptom severity and the risk of a second stroke. Conclusions: Consideration of family history of stroke in everyday practice may carry useful information both for primary care physicians and stroke neurologists.

Voluntary Unemployment Is Associated With Increased Prevalence of Stroke and its Risk Factors in Middle-Aged Adults.

OBJECTIVE: The aim of the study is to investigate the association between the prevalence of stroke, its risk factors, and occupational status, with a differentiation between voluntary and involuntary unemployment. METHODS: This is a cross-sectional study, which included 3013 individuals aged 40 to 65 years. We compared the prevalence of stroke, comorbidities, self-reported stroke-like symptoms, healthy behaviors, and knowledge about stroke among the voluntarily and involuntarily unemployed versus the employed. RESULTS: Voluntary unemployment was associated with increased chances of stroke (odds ratio [OR], 1.92; 95% confidence interval [CI], 1.05-3.57), hypertension (OR, 1.18; 95% CI, 1.06-1.32), diabetes (OR, 1.16; 95% CI, 1.01-1.35), and obesity (OR, 1.16; 95% CI, 1.05-1.29). Involuntary job loss was associated with increased odds of hypertension (OR, 1.69; 95% CI, 1.16-2.50) and more frequent self-reported stroke-like symptoms. CONCLUSIONS: We found higher chances of stroke among the voluntarily unemployed middle-aged adults, presumably because of increased prevalence of hypertension, diabetes, and obesity.

Family History of Stroke is Associated with Greater Prevalence of Certain Risk Factors and Self-Reported Stroke Symptoms.

OBJECTIVES: Family history of stroke increases stroke risk, however mechanisms underlying this association remain unclear. We investigated whether family history of stroke is related to increased prevalence of stroke risk factors, unhealthy behaviors and self-reported stroke symptoms in middle-aged adults. MATERIALS AND METHODS: In a cross-sectional study conducted from November 2018 to January 2021 in 100 primary care facilities in Poland we evaluated adults aged 40-65 years (n = 2207, women 57.4%, median age 55 years) for stroke risk factors, healthy behaviors, family history of stroke, self-reported stroke symptoms and stroke knowledge using structured questionnaires. Patients were categorized based on family history of stroke defined as ≥1 first-degree relative with documented stroke. RESULTS: Family history of stroke was reported by 571 (25.9%) individuals who were older (median age 56 vs. 54 years, p = 0.00001) and after adjustment for age more frequently suffered from hypertension (61.5% vs. 53.7%, p = 0.024) and prior transient ischemic attack (2.1% vs. 0.9%, p = 0.019), but not other risk factors. However, they were less obese (34.5% vs. 39.1%, p = 0.03). Women, but not men, with family history of stroke (n = 339, 26.8%) had greater prevalence of atrial fibrillation (7.4% vs. 3.9%, p = 0.037). Family history of stroke was associated with higher prevalence of any self-reported stroke symptom (32.9% vs. 23.2%, p < 0.00001), but not with unhealthy dietary behaviors or low level of knowledge about stroke. CONCLUSIONS: Family history of stroke is associated with greater prevalence of certain risk factors and self-reported stroke symptoms, which indicates the need for closer surveillance of middle-aged individuals at risk.

Unbiased Profile of MicroRNA Expression in Ascending Aortic Aneurysm Tissue Appoints Molecular Pathways Contributing to the Pathology.

BACKGROUND: Complex etiopathogenesis of ascending aortic aneurysm suggests contribution of epigenetic mechanisms in its development. Several studies appointed microRNAs (miRs) as essential epigenetic factors in various human diseases; however, little is known about their role in ascending aortic aneurysm. Therefore, the aim of this study was to perform unbiased molecular screening of miRs expression in aneurysmal tissue and establish their functions on a transcriptional level. METHODS: Samples of ascending aortic tissue were obtained from 15 patients, and total RNA was isolated separately from aneurysmal and unaffected aortic tissue obtained from the same patient. Expression of the complete panel of human miRs was assessed by quantitative real-time polymerase chain reaction. Using bioinformatic tools, 13 genes were selected that were putatively regulated by overexpressed miRs. Expression level of transcripts were evaluated by quantitative real-time polymerase chain reaction and correlated with their targeting miRs. RESULTS: Overexpression of 10 miRs distinguished aneurysmal tissue from the unchanged one. These miRs were involved in cell senescence (miR-191-5p), maintenance of vascular integrity (miR-126-3p and miR-374-5p), nitric oxide-dependent vascular relaxation (miR-21-5p), smooth muscle differentiation, and contractility (miR-145- 3p, miR-29c-3p, miR-133a-3p, miR-186-5p, miR-143-3p, and miR-24-3p), and correlated with abundance of its miR targets. CONCLUSIONS: Altered expression of particular miRs selectively in the affected tissue indicate their role as factors that trigger pathways of aneurysmal transformation. Limited reparative properties due to overexpression of miR-191 may play a crucial role for aneurysm enlargement, whereas nitric oxide-dependent relaxation of vascular smooth muscle mediated by miR-21 offers an attractive explanation of the aneurysm's initiation, and is confirmed in experimental conditions.