Conventional Vascular Risk Factors Research Articles

Prevalence of stroke-related risk factors in Albania: a single-center experience.

Stroke, a prominent global cause of mortality and disability, is broadly categorized into ischemic and hemorrhagic types. An epidemiological survey of stroke and its risk factors can help identify individuals at higher risk and therefore promote stroke prevention strategies. The aim of this study was to estimate the current prevalence of stroke and evaluate stroke-associated risk factors in Albania. This was a single-center retrospective analysis conducted in Albania for the period from May 2015 to September 2021. Data were collected retrospectively through hospital records. Stroke was defined as sudden onset of a nonconvulsive and focal neurological deficit, and ischemic stroke was diagnosed using brain computed tomography (CT), magnetic resonance (MR) imaging, or both. We examined patient history characteristics encompassing demographics, stroke history, conventional vascular risk factors, and lifestyle-related risk factors. The mean age of the 3860 patients was 74.6 ±10.4 years, and 73.5% were men. The prevalence of carotid stenosis, arrhythmia, obesity, and hypertension was significantly higher in males than in females (p < 0.001). Out of the 3860 patients in the study cohort, 641 (16.6%) subjects died, while 335 (8.7%) patients achieved complete recovery. Hemiparesis was observed in 386 (10%) patients and hemiplegia in 868 (22.4%) patients. Our analysis underscores the male predominance (2.2 : 1) in stroke cases. Carotid and vertebral artery stenosis is a significant factor, emphasizing the life-saving potential of early intervention. Social and economic factors in Albania pose challenges, demanding comprehensive strategies. Prospective trials are crucial to explore intervention efficacy, and timing, and address socioeconomic impacts on timely stroke management.

Cohort profile: Beijing Healthy Aging Cohort Study (BHACS).

The Beijing Healthy Aging Cohort Study (BHACS) was established to supplement the limited data of a large representative cohort of older people based on the general population and was designed to evaluate the prevalence, incidence, and natural history of cognitive decline, functional disability, and conventional vascular risk factors. The aim was to determine the evolution of these conditions by estimating the rates and determinants of progression and regression to adverse outcomes, including dementia, cardiovascular events, cancer, and all-cause death. It can therefore provide evidence to help policy makers develop better policies to promote healthy aging in China. BHACS consisted of three cohorts (BLSA, CCHS-Beijing, and BECHCS) in Beijing with a total population of 11 235 (6281 in urban and 4954 in rural areas) and an age range of 55 years or older (55-101 years) with a mean age of 70.35 ± 7.71 years (70.69 ± 7.62 years in urban and 69.92 ± 7.80 years in rural areas). BHACS-BLSA conducted the baseline survey in 2009 with a multistage stratification-random clustering procedure for people aged 55 years or older; BHACS-CCHS-Beijing conducted the baseline survey in 2013-2015 with a stratified multistage cluster random sampling method for people aged 55 years or older; and BHACS-BECHCS conducted the baseline survey in 2010-2014 with two-stage cluster random sampling method for people aged 60 years or older. Data were collected through questionnaires, physical measurements, and laboratory analyses. Topics covered by BHACS include a wide range of physical and mental health indicators, lifestyles and personal, family, and socio-economic determinants of health. There are no immediate plans to make the cohort data freely available to the public, but specific proposals for further collaboration are welcome. For further information and collaboration, please contact the corresponding author Yao He (e-mail: yhe301@x263.net).

Association between Living Conditions and the Risk Factors, Etiology, and Outcome of Ischemic Stroke in Young Adults.

Objective In recent decades, living conditions have changed drastically. However, there are few data regarding the interaction between living conditions and the risk of ischemic stroke (IS) in young adults. The present study explored the association between living conditions or marital status and the risk factors, etiology, and outcome of IS in young adults. Methods We prospectively enrolled patients with incident IS who were 20-49 years old from 37 clinical stroke centers. We collected the demographic data, living conditions, marital status, vascular risk factors, disease etiology, treatment, and outcomes at discharge. A comparison group was established using the official statistics of Japan. We categorized patients into the two groups based on living conditions: solitary group and cohabiting group. Clinical characteristics were then compared between living conditions. Results In total, 303 patients were enrolled (224 men; median age at the onset: 44 years old). Significant factors associated with the incidence of IS were as follows: solitary status, body mass index >30 kg/m2, current smoking, heavy alcohol consumption, hypertension, diabetes mellitus, and dyslipidemia. Furthermore, in the solitary group, the proportions of men, unmarried individuals, and current smokers were significantly higher than in the cohabiting group. In addition, poor outcomes (modified Ranking Scale ≥ 4) of IS were more common in the solitary group than in the cohabiting group. Conclusion Our study showed that not only conventional vascular risk factors but also living conditions, especially living alone while unmarried, were independent risk factors for IS in young adults.

OA18 Small vessel and large vessel vasculitis due to rheumatoid vasculitis: a case of mononeuritis multiplex with pulseless foot leading to amputation

Abstract Introduction Rheumatoid vasculitis occurs in patients with longstanding severe seropositive rheumatoid arthritis. The incidence has reduced drastically with availability of more effective medication. Rheumatoid vasculitis primarily affects small and medium vessels, and rarely large vessels as well. Case description This 77-year-old lady with deforming seropositive rheumatoid arthritis was stable on methotrexate under the care of multiple Trusts for the last 30 years. Methotrexate had been stopped a year ago due to pancytopenia and she was started on prednisolone and hydroxychloroquine. While on these medications she flared with arthralgia and had difficulty in walking attributed to ankle synovitis. She was started on adalimumab, after 3 doses of which she developed widespread skin psoriasis leading to discontinuation. Subsequently, she was admitted to our Trust with left foot gangrene and was referred to rheumatology. Further questioning revealed that numbness in both lower limbs, inability to walk and frequent falls had started following the cessation of methotrexate. On examination, there was bilateral foot drop, worse on the right side. The left foot was gangrenous with diminished pulses in dorsalis pedis and posterior tibial arteries with preserved all other pulses. There was no vasculitic rash or nail fold infarcts. Psoriatic rash had resolved and there was no active synovitis in the joints. Nerve conduction test revealed severe ongoing axonal degenerative type sensory and motor polyneuropathy in the lower limbs without any upper limb involvement. CT angiogram showed multifocal stenoses, more so in the left common iliac, external iliac and superficial femoral artery. There were no conventional vascular risk factors such as hypertension, diabetes, dyslipidaemia or smoking, and there was no past history of cardiovascular disease. PET-CT scan did not reveal any features of vasculitis or aortitis. The vasculitis screening was negative including cryoglobulins. Initially she was on IV antibiotics for left foot cellulitis, hence she was managed with steroids without any potent immunosuppressive agents. Subsequently, she underwent left sided below knee amputation. After the wound had healed, she was started on IV rituximab with low-dose methotrexate and steroid taper. Discussion Although rare, rheumatoid vasculitis can cause significant morbidity and complications. Rheumatoid vasculitis tends to occur in patients with so-called ‘burnt-out’ RA and strongly associated with seropositivity. While it can affect many organ systems, skin and the peripheral nervous system are most frequently affected. Cutaneous vasculitis occurs in around 90% of patients and is the most common clinical manifestation. This includes parable purpura, leg ulcers and nailfold infarcts. It may lead to digital ischaemia, necrosis and gangrene if large vessels are involved. Another common manifestation is a vasculitic neuropathy due to involvement of the vaso nervorum. Around 40% have a sensory neuropathy and 20% have a mixed sensory motor neuropathy like the index patient. Ocular manifestations such as scleritis have been described and may be the first indication of rheumatoid vasculitis. Aortitis in rheumatoid vasculitis may present with aortic insufficiency and aneurysm formation. Pericarditis has also been described as a possible disease manifestation in patients with rheumatoid vasculitis. Our patient did not have any of these clinical features and the PET-CT scan was unremarkable, which could have been due to the steroids she was on prior to the scan. Clinically, there was pulseless gangrene of the left foot with CT angiogram showing multiple stenosis suggesting large vessel involvement in the absence of conventional vascular risk factors. Renal involvement in rheumatoid vasculitis is very rare. PAN like renal involvement and glomerulonephritis has been described. Our patient did not have any haematuria or any significant proteinuria, and imaging did not reveal any renovascular aneurysms. Isolated nailfold infarcts do not require any systemic treatment. Systemic involvement with rheumatoid vasculitis requires aggressive treatment with high-dose steroids with cyclophosphamide or rituximab. Our patient had neuropathy and gangrene of the left foot, hence she was started on rituximab accordingly. Key learning points Rheumatoid vasculitis is a rare but serious complication which can present with a vasculitic neuropathy/mononeuritis multiplex. Rarely, it can cause ischemia and gangrene. If there is systemic involvement, aggressive therapy with steroids, cyclophosphamide or rituximab is needed.

Is coronary artery calcium an independent risk factor for white matter hyperintensity?

BackgroundCardiovascular diseases have been considered the primary cause of disability and death worldwide. Coronary artery calcium (CAC) is an important indicator of the severity of coronary atherosclerosis. This study is aimed to investigate the relationship between CAC and white matter hyperintensity (WMH) in the context of diagnostic utility.MethodsA retrospective analysis was conducted on 342 patients with a diagnosis of WMH on magnetic resonance images (MRI) who also underwent chest computed tomography (CT) scans. WMH volumes were automatically measured using a lesion prediction algorithm. Subjects were divided into four groups based on the CAC score obtained from chest CT scans. A multilevel mixed-effects linear regression model considering conventional vascular risk factors assessed the association between total WMH volume and CAC score.ResultsOverall, participants with coronary artery calcium (CAC score > 0) had larger WMH volumes than those without calcium (CAC score = 0), and WMH volumes were statistically different between the four CAC score groups, with increasing CAC scores, the volume of WMH significantly increased. In the linear regression model 1 of the high CAC score group, for every 1% increase in CAC score, the WMH volume increases by 2.96%. After including other covariates in model 2 and model 3, the β coefficient in the high CAC group remains higher than in the low and medium CAC score groups.ConclusionIn elderly adults, the presence and severity of CAC is related to an increase in WMH volume. Our findings suggest an association between two different vascular bed diseases in addition to traditional vascular risk factors, possibly indicating a comorbid mechanism.

A neuropathologic feature of brain aging: multi-lumen vascular profiles

Cerebrovascular pathologies other than frank infarctions are commonly seen in aged brains. Here, we focus on multi-lumen vascular profiles (MVPs), which are characterized by multiple vessel lumens enclosed in a single vascular channel. Little information exists on the prevalence, risk factors, and co-pathologies of MVPs. Therefore, we used samples and data from the University of Kentucky Alzheimer’s Disease Research Center (n = 91), the University of Kentucky Pathology Department (n = 31), and the University of Pittsburgh Pathology Department (n = 4) to study MVPs. Age at death was correlated with MVP density in the frontal neocortex, Brodmann Area 9 (r = 0.51; p < 0.0001). Exploratory analyses were performed to evaluate the association between conventional vascular risk factors (e.g., hypertension, diabetes), cardiovascular diseases (e.g., heart attack, arrhythmia), and cerebrovascular disease (e.g., stroke); the only nominal association with MVP density was a self-reported history of brain trauma (Prevalence Ratio = 2.1; 95 CI 1.1–3.9, before correcting for multiple comparisons). No specific associations were detected between neuropathological (e.g., brain arteriolosclerosis) or genetic (e.g., APOE) variables and MVP density. Using a tissue clearing method called SeeDB, we provide 3-dimensional images of MVPs in brain tissue. We conclude that MVPs are an age-related brain pathology and more work is required to identify their clinical-pathological correlation and associated risk factors.

Risk Factors for Stroke in the Young (18–45 Years): A Case-Control Analysis of INTERSTROKE Data from 32 Countries

Background: It is not clear whether conventional vascular risk factors are responsible for most strokes in patients younger than 45 years of age. Our objective was to evaluate the association of common risk factors with stroke in individuals under 45 years. Methods: INTERSTROKE was a case-control study carried out in 32 countries between 2007 and 2015. Patients presenting within 5 days of symptom onset of a first stroke were enrolled as cases. Controls were age and sex matched to cases and had no history of stroke. Cases and controls underwent similar evaluations. Odds ratios (ORs) and population attributable risks (PARs) were calculated to determine the association of various risk factors with all stroke, ischemic stroke, and intracranial hemorrhage, for patients 45 years of age or younger. Findings: 1,582 case-control pairs were included in this analysis. The mean age of this cohort was 38.5 years (SD 6.32). Overall, 71% strokes were ischemic. Cardiac causes {OR: 8.42 (95% confidence interval [CI]: 3.01–23.5)}; binge drinking of alcohol (OR: 5.44 [95% CI: 1.81–16.4]); hypertension (OR: 5.41 [95% CI: 3.40–8.58]); ApoB/ApoA1 ratio (OR: 2.74 [95% CI: 1.69–4.46]); psychosocial stress (OR: 2.33 [95% CI: 1.01–5.41]); smoking (OR: 1.85 [95% CI: 1.17–2.94]); and increased waist-to-hip ratio (OR: 1.69 [95% CI: 1.04–2.75]) were the most important risk factors for ischemic stroke in these young cases. For intracerebral hemorrhage, only hypertension (OR: 9.08 [95% CI: 5.46–15.1]) and binge drinking (OR: 4.06 [95% CI: 1.27–13.0]) were significant risk factors. The strength of association and population attributable risk (PAR) for hypertension increased with age (PAR 23.3% in those <35 years of age, 50.7% in 35–45 years of age). Interpretation: Conventional risk factors such as hypertension, smoking, binge drinking of alcohol, central obesity, cardiac causes, dyslipidemia, and psychosocial stress are important risk factors for stroke in those younger than 45 years of age. Hypertension is the most significant risk factor in all age groups and across all regions and both stroke subtypes. These risk factors should be identified and modified in early adulthood to prevent strokes in young individuals.

Distinct lesion features and underlying mechanisms in patients with acute multiple infarcts in multiple cerebral circulations (P11-5.022)

<h3>Objective:</h3> To determine the etiology spectrum and lesion distribution patterns of patients with acute multiple infarcts in multiple cerebral circulations (AMIMCC) and provide guidance for treatment and prevention. <h3>Background:</h3> The etiologies and mechanisms of AMIMCC were complicated deserving clinical attention. <h3>Design/Methods:</h3> Patients with acute ischemic stroke were consecutively included in this study between June 2012 and Apr 2022. AMIMCC was defined as noncontiguous focal lesions located at more than one cerebral circulation with acute neurological deficits. We retrospectively analyzed the clinical and imaging characteristics and etiology spectrums between patients with AMIMCC and non-AMIMCC. Infarct lesion patterns on DWI and its relevance with the etiology were further discussed. <h3>Results:</h3> A total of 1213 patients were enrolled, of whom 145(12%) were diagnosed as AMIMCC. Compared with non-AMIMCC, AMIMCC patients manifested as younger age(P=.016), more often female(P=.001), less common for conventional vascular risk factors(P&lt;.05). The constitution of TOAST classification was significantly different between patients with AMIMCC and non-AMIMCC(P=0.000), with higher proportion of stroke of other determined cause(67.6%vs12.4%). Regarding the detailed etiology of AMIMCC, autoimmune or hematologic diseases were the most common(27.6%), followed by peri-procedural infarcts(15.2%), cardioembolism(13.1%), malignant tumor(11.7%), large artery atherosclerosis (10.3%), sudden drop in blood pressure(8.3%). Hypercoagulability and systemic hypoperfusion were the common underlying mechanisms of AMIMCC. Distinctive lesion distribution patterns were associated with stroke etiologies and mechanisms in AMIMCC patients. Sixty-five percent of the 20 patients diagnosed with SLE/APS and 52.9% of the 17 patients with malignant tumor tended to manifest as supratentorial infarcts. However, 68.4% of cardioembolism presented with both supratentorial and infratentorial infarct lesions. More than half of patients with SOC and SUC had intracranial or extracranial artery stenosis. <h3>Conclusions:</h3> The etiologies and mechanism of AMIMCC were complicated compared to non-AMIMCC. The distribution characteristics of infarct lesions might have important implications for identification of etiology in AMIMCC patients, further guiding and optimizing clinical diagnosis strategy. <b>Disclosure:</b> Ms. Sha has nothing to disclose. Mr. Han has nothing to disclose. Ms. Hong has nothing to disclose. Dr. Wu has nothing to disclose. Dr. Tang has nothing to disclose. Lixin Zhou has nothing to disclose. Yi-Cheng Zhu has nothing to disclose. Jun Ni has nothing to disclose.

Small-vessel disease in the brain

Cerebral small-vessels are generally located in the brain at branch points from major cerebral blood vessels and perfuse subcortical structures such as the white matter tracts, basal ganglia, thalamus, and pons. Cerebral small-vessel disease (CSVD) can lead to several different clinical manifestations including ischemic lacunar stroke, intracerebral hemorrhage, and vascular dementia. Risk factors for CSVD overlap with conventional vascular risk factors including hypertension, diabetes mellitus, and hypercholesterolemia, as well as genetic causes. As in cardiovascular disease, treatment of CSVD involves both primary and secondary prevention. Aspirin has not been established as a primary prevention strategy for CSVD among the general population; however, long-term antiplatelet therapy with aspirin alone continues to be the mainstay of secondary stroke prevention for non-cardioembolic ischemic stroke and high-risk TIA.

Distinct lesion features and underlying mechanisms in patients with acute multiple infarcts in multiple cerebral territories.

To determine the etiology spectrum and lesion distribution patterns of patients with acute multiple infarcts in multiple cerebral territories (AMIMCT) and provide guidance for treatment and prevention strategies in these patients. Patients with acute ischemic stroke diagnosed using diffusion-weighted imaging (DWI) were consecutively included in this study between June 2012 and Apr 2022. AMIMCT was defined as non-contiguous focal lesions located in more than one cerebral territory with acute neurological deficits. We retrospectively analyzed the clinical and imaging characteristics, etiology spectra and underlying mechanisms in patients with and without AMIMCT. Infarct lesion patterns on DWI and their relevance to etiology were further discussed. A total of 1,213 patients were enrolled, of whom 145 (12%) were diagnosed with AMIMCT. Patients with AMIMCT tended to be younger (P = 0.016), more often female (P = 0.001), and exhibited less common conventional vascular risk factors (P < 0.05) compared to those without AMIMCT. The constitution of the Trial of Org 10,172 in Acute Stroke Treatment classification was significantly different between patients with and without AMIMCT (P = 0.000), with a higher proportion of stroke of other determined causes (67.6% vs. 12.4%). For detailed etiologies, autoimmune or hematologic diseases were the most common (26.2%) etiologies of AMIMCT, followed by periprocedural infarcts (15.2%), cardioembolism (12.4%), tumor (12.4%), large artery atherosclerosis (10.3%), and sudden drop in blood pressure (8.3%). Hypercoagulability and systemic hypoperfusion are common underlying mechanisms of AMIMCT. Distinctive lesion distribution patterns were found associated with stroke etiologies and mechanisms in AMIMCT. Most of patients with large artery atherosclerosis (73.3%), autoimmune/hematologic diseases (57.9%) manifested the disease as multiple infarct lesions located in bilateral supratentorial regions. However, 66.7% of cardioembolism and 83.8% of cardiovascular surgery related stroke presented with both supratentorial and infratentorial infarct lesions. The etiologies and mechanisms of patients with AMIMCT were more complex than those without AMIMCT. The distribution characteristics of infarct lesions might have important implications for the identification of etiology and mechanism in the future, which could further guide and optimize clinical diagnostic strategies.

Acute Ischemic Stroke in Tubercular Meningitis Patients Without Conventional Vascular Risk Factors: A Retrospective Case Control Study.

Ischemic stroke is a common complication in patients with tubercular meningitis (TBM). However, the risk factors for Ischemic stroke in TBM patients are not fully understood, especially in those patients without conventional vascular risk factors. The aim of the present study was to explore the clinical features and independent risk factors for tubercular meningitis-related Ischemic stroke (TBMRIS). Tubercular meningitis patients with acute Ischemic stroke without conventional vascular risk factors were recruited between July 2010 and July 2020 as the TBMRIS group. Patients who solely had tubercular meningitis were recruited as the control group (TMB group). Demographic characteristics, clinical presentations, and cerebrospinal fluid (CSF) examinations were collected, and multiple logistic regression analysis was applied to analyse the independent risk factors for TBMRIS. A total of 70 TBMRIS patients and 70 TMB patients were enrolled. Most (82.86%) of the TBMRIS patients experienced Ischemic stroke events within 3 months after the diagnosis of tubercular meningitis. The multiple logistic regression analysis revealed that variation in red blood cell distribution width (RDW-CV), mean platelet volume (MVP), C-reactive protein (CRP), CSF glucose and Modified Research Council Grade II (MRC Grade II) were independent risk factors for TBRIS. The AUC of the identification model was 0.808, with a sensitivity of 68.60% and a specificity of 84.30%. This study revealed that RDW-CV, MVP, CRP, CSF glucose and MRC Grade II are potential independent risk factors for TBMRIS. The identification model established in this study may help monitor TBM patients who are at high risk of developing TBMRIS.

Morphological characteristics of symptomatic and asymptomatic carotid webs.

Carotid webs (CWs) are an increasingly recognized source of recurrent stroke among young patients without conventional vascular risk factors. There have been no previous studies demonstrating that specific web morphological characteristics correlate with a higher stroke risk. The authors aim to report distinct morphological features of symptomatic and asymptomatic CWs. The authors performed a cross-sectional study of patients with CWs detected on CT angiography (CTA) of the neck. Patients were categorized based on whether or not they presented with stroke ipsilaterally and if it was likely to be attributable to their web. The following CW morphological variables were recorded and compared based on CTA: length, thickness, angle, and the proportion of carotid bulb lumen occupied by the web (web-to-bulb ratio [WBR]). A total of 86 CWs were identified, 14 of which presented with stroke (16.3%). Patients presenting with stroke had webs that were significantly longer (4.18 mm vs 2.20 mm, p = 0.001) and were situated at more acute angles relative to the carotid wall (73.2° vs 94.9°, p = 0.004). Additionally, patients presenting with stroke had higher WBRs compared to the asymptomatic cohort (0.50 vs 0.36, p = 0.008). The optimal threshold associated with stroke was web length ≥ 3.1 mm (OR 15.2, 95% CI 3.73-61.8; p < 0.001), web angle ≤ 90.1° (OR 5.00, 95% CI 1.42-17.6; p = 0.012), and WBR ≥ 0.50 (OR 30.0, 95% CI 5.94-151; p < 0.001). Patients with CWs that occupy more than half of the diameter of the carotid bulb lumen and are situated at acute angles relative to the carotid wall are more likely to present with acute ischemic stroke. Additional studies are needed to determine the long-term outcomes of these lesions.

Risk stratification in symptomatic intracranial atherosclerotic disease with conventional vascular risk factors and cerebral haemodynamics

Background and purposeSymptomatic intracranial atherosclerotic stenosis (sICAS) is associated with a considerable risk of recurrent stroke despite contemporarily optimal medical treatment. Severity of luminal stenosis in sICAS and its haemodynamic...

Causes of ischemic stroke in young adults versus non-young adults: A multicenter hospital-based observational study.

BackgroundVery few comparative studies have focused on the differences in the causes of ischemic stroke between young adults and non-young adults. This study was performed to determine what causes of ischemic stroke are more important in young adults than in non-young adults using a large-scale multicenter hospital-based stroke registry in Fukuoka, Japan.Methods and resultsWe investigated data on 15,860 consecutive patients aged ≥18 years with acute ischemic stroke (mean age: 73.5 ± 12.4 years, 58.2% men) who were hospitalized between 2007 and 2019. In total, 779 patients were categorized as young adults (≤50 years of age). Although vascular risk factors, including hypertension, diabetes mellitus, and dyslipidemia, were less frequent in young adults than in non-young adults, the prevalence of diabetes mellitus and dyslipidemia in young adults aged >40 years were comparable to those of non-young adults. Lifestyle-related risk factors such as smoking, drinking, and obesity were more frequent in young adults than in non-young adults. As young adults became older, the proportions of cardioembolism and stroke of other determined etiologies decreased, but those of large-artery atherosclerosis and small-vessel occlusion increased. Some embolic sources (high-risk sources: arterial myxoma, dilated cardiomyopathy, and intracardiac thrombus; medium-risk sources: atrial septal defect, nonbacterial thrombotic endocarditis, patent foramen ovale, and left ventricular hypokinesis) and uncommon causes (vascular diseases: reversible cerebral vasoconstriction syndrome, moyamoya disease, other vascular causes, arterial dissection, and cerebral venous thrombosis; hematologic diseases: antiphospholipid syndrome and protein S deficiency) were more prevalent in young adults than in non-young adults, and these trends decreased with age.ConclusionsCertain embolic sources and uncommon causes may be etiologically important causes of ischemic stroke in young adults. However, the contribution of conventional vascular risk factors and lifestyle-related risk factors is not negligible with advancing age, even in young adults.

Pulmonary Tuberculosis-Related Ischemic Stroke: A Retrospective Case Control Study.

ObjectiveThere have been only a few studies of ischemic stroke in patients with pulmonary tuberculosis (pTB). This study aimed to explore the clinical features and the underlying pathogenesis of pulmonary tuberculosis-related ischemic stroke (TBRIS).MethodsActive pulmonary tuberculosis patients with acute ischemic stroke (without conventional vascular risk factors) were recruited as the TBRIS group. Patients who solely had active pulmonary tuberculosis were recruited as the control group (pTB group). Clinical data were collected, and multiple logistic regression analysis was applied to analyze the independent risk factors for TBRIS.ResultsA total of 179 TBRIS patients and 179 pTB patients were enrolled. Most (56.42%) of the TBRIS patients experienced the ischemic stroke events within 3 months after the diagnosis of tuberculosis. The multiple logistic regression analysis revealed that an increased mean platelet volume; elevated plasma D-dimer, C-reactive protein, and serum ferritin levels; and an increased monocyte percentage were independent risk factors for TBRIS. The AUC of the identification model was 0.778, with a sensitivity of 70.30% and a specificity of 78.90%.ConclusionThe findings in the present study suggested that most of the TBRIS patients experienced ischemic stroke within 3 months after the diagnosis of tuberculosis. And the more intensive immune response to the tuberculosis infection in the TBRIS group contributed to the initiation of platelet activation and to the development of a hypercoagulable state, which were attributed to the pathogenesis of TBRIS. Index of TBRIS equaling to 0.3234 facilitates clinicians to identify the pTB patients who were at higher risk for TBRIS, and allow physicians to take further effective measures to prevent ischemic stroke in patients with pTB. However, our findings will need to be confirmed by further studies.

Risk factors for hippocampal cavities in a marginally housed population.

Cavities in the hippocampus are morphological variants of uncertain significance. Aberrant neurodevelopment along with vascular and inflammatory etiologies have been proposed. We sought to characterize these cavities and their potential risk factors in a marginally housed population, with high rates of viral infection, addiction, and mental illness. (1) The volume of hippocampal cavities (HCavs) is greater in this highly multimorbid population compared to the general population. (2) Conventional vascular risk factors such as greater age and systolic blood pressure are associated with higher HCav volume. (3) Nonprescribed substance-related risk factors such as stimulant use or dependence, and smoking are associated with increased HCav volume independent of vascular risk factors. This is a retrospective analysis of an ongoing prospective study. We analyzed baseline data, including medical history, physical exam, psychiatric diagnosis, and MRI from a total of 375 participants. Hippocampal cavities were defined as spaces isointense to CSF on T1 MRI sequences, bounded on all sides by hippocampal tissue, with a volume of at least 1 mm3 . Risk factors were evaluated using negative binomial multiple regression. Stimulant use was reported by 87.3% of participants, with stimulant dependence diagnosed in 83.3% of participants. Prevalence of cavities was 71.6%, with a mean total bilateral HCav volume of 13.89 mm3 . On average, a 1 mmHg greater systolic blood pressure was associated with a 2.17% greater total HCav volume (95% CI=[0.57%, 3.79%], p=.0076), while each cigarette smoked per day trended toward a 2.69% greater total HCav volume (95% CI=[-0.87%, 5.54%], p=.058). A diagnosis of stimulant dependence was associated with a 95.6% greater total HCav volume (95% CI=[5.39%, 263.19%], p=.0335). Hypertension and diagnosis of stimulant dependence were associated with a greater total volume of HCav.

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.

Circulating Interleukin-6 Levels and Incident Ischemic Stroke: A Systematic Review and Meta-analysis of Prospective Studies.

Human genetic studies support a key role of interleukin-6 (IL-6) in the pathogenesis of ischemic stroke. However, there are only limited data from observational studies exploring circulating IL-6 levels as a risk factor for ischemic stroke. We set out to perform a systematic review and meta-analysis of aggregate data on cohort studies to determine the magnitude and shape of the association between circulating IL-6 levels and risk of incident ischemic stroke in the general population. Following the PRISMA guidelines, we systematically screened the PubMed search engine from inception to March 2021 for population-based prospective cohort studies exploring the association between circulating IL-6 levels and risk of incident ischemic stroke. We pooled association estimates for ischemic stroke risk with random-effects models and explored nonlinear effects in dose-response meta-analyses. Risk of bias was assessed with the Newcastle-Ottawa Scale (NOS). We used funnel plots and trim-to-fill analyses to assess publication bias. We identified 11 studies (n = 27,411 individuals; 2,669 stroke events) meeting our eligibility criteria. Mean age of all included participants was 60.5 years and 54.8% were female. Overall, quality of the included studies was high (median 8 out of 9 NOS points, interquartile range 7-9). In meta-analyses, 1 SD increment in circulating log-transformed IL-6 levels was associated with a 19% increase in risk of incident ischemic stroke over a mean follow-up of 12.4 years (relative risk 1.19; 95% confidence interval 1.10 to 1.28). A dose-response meta-analysis showed a linear association between circulating IL-6 levels and ischemic stroke risk. There was only moderate heterogeneity and the results were consistent in sensitivity analyses restricted to studies of low risk of bias and studies fully adjusting for demographic and vascular risk factors. The results also remained stable following adjustment for publication bias. Higher circulating IL-6 levels in community-dwelling individuals are associated with higher long-term risk of incident ischemic stroke in a linear pattern and independently of conventional vascular risk factors. Along with findings from genetic studies and clinical trials, these results provide additional support for a key role of IL-6 signaling in ischemic stroke.

Abstract P771: Monocyte-Chemoattractant Protein-1 Levels in Human Carotid Atherosclerosis Associate With Hallmarks of Plaque Vulnerability

Background: Monocyte chemoattractant protein-1 (MCP-1) is a chemokine recruiting monocytes to the atherosclerotic plaque. Experimental, genetic, and epidemiological data support a key role of MCP-1 in atherosclerosis. Yet, the translational potential of targeting MCP-1 signaling for lowering vascular risk is limited by the lack of data on plaque MCP-1 activity in human atherosclerosis. Methods: We measured MCP-1 levels in human plaque samples from 1,199 patients undergoing carotid endarterectomy from the Athero-Express Biobank. We explored associations of plaque MCP-1 levels with histopathological features of plaque vulnerability, clinical plaque instability (symptomatic vs. asymptomatic plaque), molecular markers of plaque inflammation and remodeling, and with incident vascular events up to three years after plaque removal. Results: MCP-1 plaque levels were associated with individual histopathological hallmarks of plaque vulnerability (large lipid core, low collagen, high macrophage burden, low smooth muscle cell burden, intraplaque hemorrhage), as well as with a cumulative vulnerability index (range 0-5, beta: 0.42, 95%CI: 0.30-0.53, p=5.4x10 -13 ) independently of age, sex, and conventional vascular risk factors. Furthermore, MCP-1 levels were higher among patients with symptomatic, as compared to asymptomatic plaques (p=0.0001) and were associated with the levels of pro-inflammatory cytokines involved in leukocyte adhesion, as well as with matrix metalloproteinase activity in the plaque. In the follow-up analyses, MCP-1 levels were associated with a higher risk of peri-procedural events (up to 30 days after surgery). Conclusions: Our findings highlight a role of MCP-1 in human plaque vulnerability, the leading mechanism underlying vascular events like stroke and myocardial infarction. As such, they suggest that interfering with MCP-1 signaling in patients with established atherosclerosis could lower vascular risk.

Stroke and Chronic Kidney Disease.

Chronic kidney disease (CKD) is strongly associated with the full spectrum of cerebrovascular disease including ischaemic and haemorrhagic stroke, small vessel disease, and vascular cognitive impairment. Shared conventional vascular risk factors such as age, hypertension, and diabetes mellitus may account for many of these associations, but novel renal-specific risk factors such as uraemia-related coagulopathy or endothelial dysfunction have also been proposed. In this chapter, we will explore the impact of CKD on stroke risk, mechanisms, and outcomes. We will also outline potential challenges and inequities in stroke care delivery and research for these patients along with some strategies to help improve stroke prevention and management for this high-risk group.