Predictors Of Cerebrovascular Disease Research Articles

Uncontrolled HIV and inflammation is associated with intracranial saccular aneurysm presence.

To study biomarkers of inflammation in cerebrovascular disease, exploring modifiable and non-modifiable biochemical and clinical risk factors associated with the presence of intracranial saccular aneurysms (ISAs) in an HIV-positive cohort. A cross-sectional community-based study was used to study blood biomarkers of inflammation as predictors of cerebrovascular disease, specifically the presence of ISAs in persons with HIV. Potential biochemical and clinical predictors of ISA presence were identified. Time of flight magnetic resonance angiography and magnetic resonance imaging data identified the presence of ISAs in an HIV-positive cohort. Quantitative assays for neuroinflammatory biomarkers were performed on plasma blood samples. Lasso regression models were used to identify neuroinflammatory biomarkers and clinical risk factors associated with ISAs. Eight of 72 participants had radiographically identified ISAs. ISAs were more common in non-Hispanic black participants (18.5% vs. 0% presence in nonblack patients). Participants with well controlled HIV (defined as CD4+ count >200 cells/ml and undetectable viral load at time of magnetic resonance imaging) had lower odds of ISAs (odds ratio: 0.19, 95% confidence interval 0.05-0.79) independent of age, sex, ethnicity and vascular risk factors. Macrophage inflammatory protein-1 p, an HIV- suppressive factor detected in participant blood samples, was inversely associated with aneurysm presence. Well controlled HIV is associated with fewer ISAs. The identification of non-modifiable and modifiable risk factors contributing to ISA formation may provide valuable insight to impact clinical practice and inform the pathophysiology underlying ISA formation.

Carotid intima-media thickness relative to cognitive impairment in dialysis patients, and their relationship with brain volume and cerebral small vessel disease.

Background:Carotid intima–media thickness (cIMT) is considered a risk factor for and predictor of cerebrovascular disease. In this study, we explored the contribution of cIMT to cognitive impairment (CI) in dialysis patients and the role of cerebral small vascular disease (CSVD) and brain atrophy in this process.Methods:Cognitive function was assessed using a comprehensive cognitive test battery. CSVD and brain volume were assessed by magnetic resonance imaging, and cIMT was measured by ultrasonography. Multivariable analysis and mediation were used to explore the relevant relationships among cIMT, CI, CSVD and brain volume.Results:Seventy-three dialysis patients were enrolled. Approximately 54.8% were diagnosed with increased cIMT. The increased cIMT group was older and had lower serum albumin and creatinine levels than the normal cIMT group. There was no difference in the CSVD prevalence between the different cIMT groups. Patients in the normal, unilaterally and bilaterally increased cIMT subgroups demonstrated a gradual decrease in brain-matter volume and degenerate cognitive function. cIMT was related to cognitive function and gray-/white-matter volume. Increased cIMT was associated with a significantly increased risk of a reduced Mini Mental State Examination/Montreal Cognitive Assessment score and Trail A/B time delay. Mediation analysis showed that CI was mediated by brain-matter volume but not by CSVD.Conclusion:Increased cIMT was an independent risk factor for impairment of global cognitive function, memory, and executive function. The impact of cIMT on cognition was not induced by CSVD but by brain atrophy. cIMT may be a useful tool for screening patients at high risk of CI in the dialysis population.

1478-P: Impact of Prior Cerebrovascular Disease (CVD) and Glucose Tolerance Status on Incident CVD in Japanese

Although both a glucose metabolism abnormality and prior cerebrovascular disease (CVD) are major predictors of CVD, few studies have compared their impact on a subsequent CVD event. Also, few studies evaluated risk of prediabetes separately from nondiabetic categories. Thus, the impact of diabetes mellitus (DM) on subsequent CVD compared to normal glucose tolerance (NGT) could have been underestimated. We analyzed a nationwide claims-based database of 290,865 participants in 2008-14. Participants were classified as having NGT, prediabetes or DM based on fasting plasma glucose, HbA1c and use of antihypoglycemic agents (185,648 with NGT; 87,867 with prediabetes; 17,350 with DM). Participants were also classified as with or without prior CVD based on ICD-10 and questionnaires (1,944 with prior CVD; 288,921 without prior CVD). Cox regression model showed that prediabetes and DM confers about 1.1- and 1.4-fold excess risk for CVD, respectively, compared to NGT without prior CVD. Prediabetes and DM does not increase risk for CVD compared to NGT with prior CVD (Table). Prior CVD confers a 4-7-fold excess risk for CVD regardless of glucose tolerance status. Hazard ratio of CVD in NGT with prior CVD was 4 times higher than in DM without prior CVD. This implies that prediabetes and DM increase CVD only in those without prior CVD. Prior CVD confers a higher risk for subsequent CVD regardless of glucose tolerance status. Disclosure D. Yanagisawa: None. K. Fujihara: None. T. Osawa: None. M. Kitazawa: None. M. Yamamoto: None. Y. Matsubayashi: None. N. Yamanaka: None. S. Kodama: None. H. Sone: Research Support; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Kowa Pharmaceutical Europe Co. Ltd., Kyowa Hakko Kirin Co., Ltd., Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Teijin Pharma Limited.

Serum klotho: a potential predictor of cerebrovascular disease in hemodialysis patients

BackgroundHemodialysis patients suffer from a serious threat of cerebrovascular disease. Klotho, as an aging-suppressor gene, contributes to protect on vascular calcification and oxidative stress, which are the risk factors of cerebrovascular disease. The purpose of the present study is to determine the relationship between serum klotho and cerebrovascular disease in patients receiving hemodialysis.MethodsSerum klotho levels of hemodialysis patients were measured by ELISA. Cerebrovascular diseases were diagnosed by CT or MRI scans. The cognitive function of hemodialysis patients with cerebrovascular disease were evaluated with a neuropsychological battery assessing domains of global cognition verbal memory, spatial memory, executive function and verbal fluency.ResultsEighty-eight patients were included, 57 ± 14 years, 63.64% male, 52.27% older than 60 years. Twenty-eight participants had cerebrovascular disease (23 cases had cerebral infarction, 5 cases had cerebral hemorrhage). The average level of serum klotho of all participants was 119.10 ± 47.29 pg/ml. The serum klotho level was significantly associated with cerebrovascular disease in hemodialysis patients (HR(95%CI) = 0.975(0.960–0.990), p = 0.001). The optimal cut-off value of serum klotho for predicting cerebrovascular disease in hemodialysis patients was 137.22 pg/ml, with a specificity of 96.4% and a sensitivity of 46.7%. But serum klotho was not an independent risk factor of cognitive impairment for hemodialysis patients with cerebrovascular disease (HR((95%CI) = 1.002(0.986–1.018), p = 0.776) or with cerebral infarction (HR(95%CI) = 1.005(0.987–1.023), p = 0.576).ConclusionsThe serum klotho level is a potential predictor of cerebrovascular disease in hemodialysis patients, but it is not an independent risk factor of cognitive impairment for hemodialysis patients with cerebrovascular disease.

Association Between Carotid Artery Function and Structure in the Northern Manhattan Study.

Carotid plaque (CP), carotid intima media thickness (cIMT), and stiffness (STIFF) are pre-clinical markers of atherosclerosis and predictors of cerebrovascular disease (CVD). We sought to investigate whether STIFF is a significant determinant of cIMT and CP, which may provide an insight into the mechanism by which STIFF adds to the risk of CVD. We analyzed 876 stroke-free subjects from the Northern Manhattan Study with available ultrasound measures. To obtain the associations with STIFF, we performed multivariable-adjusted regression, negative binomial regression (for CP number), and multinomial logistic regression (for plaque area). The mean age was 64 ± 9 years; 63% women and 65% Caribbean Hispanics. The mean cIMT was 0.93 ± 0.9 mm, the mean diastolic diameter 6.24 ± 0.94 mm, and STIFF 8.6 ± 6.2 ln mmHg. Prevalence of CP was 57%, and the mean total plaque area was 22.6 ± 23.0 mm2. STIFF was positively associated with cIMT but not with CP. There was an association between diastolic diameter and thick plaque. For each millimeter increase in diastolic diameter, there was about a 20% increased risk of having thick plaque (vs. no plaque). In longitudinal analyses, each millimeter increase in diastolic diameter was associated with a 37% increased risk of incident plaque. Increased STIFF was associated with increased cIMT and carotid artery dilatation with greater plaque burden. Increased cIMT and plaque burden represent vascular remodeling likely resulting from the two different age-related mechanisms, one that includes diffuse wall thickening (cIMT) with STIFF and another that incorporates focal atherosclerosis (plaque) with luminal dilatation.

Ocular fundus photography of patients with focal neurologic deficits in an emergency department.

We evaluated the frequency and predictive value of ocular fundus abnormalities among patients who presented to the emergency department (ED) with focal neurologic deficits to determine the utility of these findings in the evaluation of patients with suspected TIA and stroke. In this cross-sectional pilot study, ocular fundus photographs were obtained using a nonmydriatic fundus camera. Demographic, neuroimaging, and ABCD(2) score components were collected. Photographs were reviewed for retinal microvascular abnormalities. The results were analyzed using univariate statistics and logistic regression modeling. Two hundred fifty-seven patients presented to the ED with focal neurologic deficits, of whom 81 patients (32%) had cerebrovascular disease (CVD) and 144 (56%; 95% confidence interval: 50%-62%) had retinal microvascular abnormalities. Focal and general arteriolar narrowing increased the odds of clinically diagnosed CVD by 5.5 and 2.6 times, respectively, after controlling for the ABCD(2) score and diffusion-weighted imaging. These fundus findings also significantly differentiated TIA from non-CVD, even after controlling for the ABCD(2) score. Focal and general arteriolar narrowing were independent predictors of CVD overall, and TIA alone, even after controlling for the ABCD(2) score and diffusion-weighted imaging lesions. The inclusion of nonmydriatic ocular fundus photographs in the evaluation of patients presenting to the ED with focal neurologic deficits may assist in the differentiation of stroke and TIA from other causes of focal neurologic deficits.

LIBMAN-SACKS ENDOCARDITIS: DETECTION AND CHARACTERIZATION BY REAL TIME THREE-DIMENSIONAL TRANSESOPHAGEAL ECHOCARDIOGRAPHY

Libman-Sacks vegetations (LSV) are independent predictors of cerebrovascular disease in patients with systemic lupus erythematosus (SLE) and can be complicated with infective endocarditis, severe valve regurgitation, need for high risk valve surgery, and increased mortality. Thus, accurate detection

1053 ASSOCIATION BETWEEN DIABETES MELLITUS, HEPATIC STEATOSIS AND FIBROSIS IN CHRONIC HEPATITIS C PATIENTS IN TAIWAN

Background: Cerebrovascular disease is one of the leading causes of death worldwide. Hepatitis C virus (HCV) infection, a well-accepted causal agent for liver-related diseases, has been reported to increase the risk for atherothrombosis. However, the association between HCV infection and cerebrovascular diseases remains inconclusive and the dose-response relationship between serum HCVRNA levels and cerebrovascular death has never been elucidated. Methods: This study enrolled 23,665 residents aged between 30–65 years in community during 1991–1992. They were personally interviewed using structured questionnaires and provided blood samples for various serological and biochemical testing at study entry. Those who were seropositive for antibodies against HCV (anti-HCV) were examined for serum HCVRNA levels. HCV genotypes were determined in participants who had detectable serum HCVRNA. Cerebrovascular deaths of participants during follow-up were ascertained by computerized linkage with National Death Certification profiles from 1991 to 2007 (ICD-9: 430–438). Person-years at risk were calculated for each person as time from enrollment date to either the date of death, or to the end of 2007, whichever came first. Cox proportional hazards models were used to estimate relative risks and 95% confidence intervals for magnitude of HCV after adjustment of other risk factors. Results: There were 240 cerebrovascular deaths with 361,171 person-years of follow-up, giving a mortality of 66.5 per 100,000 person-years in this population. The cumulative risks for cerebrovascular death were 1.0% and 2.7% for anti-HCV seronegatives and anti-HCV seropositives (p < 0.001). Participants seropositive for anti-HCV had increased risk of cerebrovascular death, with a multivariate-adjusted relative risk (95% confidence interval) of 2.27 (1.56–3.30). Elevated serum HCVRNA levels increased the risk for cerebrovascular death with dose-response trend (p < 0.001). The adjusted relative risks were 1.52 (0.67– 3.44), 1.73 (0.43–6.98), 2.31 (1.25–4.25), and 3.45 (1.76– 6.75) in corresponding to participants with serum HCVRNA level <25 (undetectable), 25–<10, 10–<10, and ≥10 IU/mL, respectively, comparing with anti-HCV seronegatives. Using antiHCV seronegatives as reference group, the adjusted relative risks for cerebrovascular death were 3.58 (1.99–6.43) and 2.06 (1.05– 4.03) for participants with HCV genotype non-1 and genotype 1. Conclusions: HCV infection is an independent risk predictor of cerebrovascular diseases.

Increased risk of Alzheimer's disease in Type II diabetes: insulin resistance of the brain or insulin-induced amyloid pathology?

Type II diabetes mellitus (DM2) is associated with an increased risk of cognitive dysfunction and dementia. The increased risk of dementia concerns both Alzheimer's disease and vascular dementia. Although some uncertainty remains into the exact pathogenesis, several mechanisms through which DM2 may affect the brain have now been identified. First, factors related to the 'metabolic syndrome', a cluster of metabolic and vascular risk factors (e.g. dyslipidaemia and hypertension) that is closely linked to DM2, may be involved. A number of these risk factors are predictors of cerebrovascular disease, accelerated cognitive decline and dementia. Secondly, hyperglycaemia may be involved, through adverse effects of potentially 'toxic' glucose metabolites on the brain and its vasculature. Thirdly, insulin itself may be involved. Insulin can directly modulate synaptic plasticity and learning and memory, and disturbances in insulin signalling pathways in the periphery and in the brain have recently been implicated in Alzheimer's disease and brain aging. Insulin also regulates the metabolism of beta-amyloid and tau, the building blocks of amyloid plaques and neurofibrillary tangles, the neuropathological hallmarks of Alzheimer's disease. In this paper, the evidence for the association between DM2 and dementia and for each of these underlying mechanisms will be reviewed, with emphasis on the role of insulin itself.

Cerebrovascular Disease as a Complication of Cardiac Transplantation

Background and Objectives: To characterize the frequency, risk factors, clinical presentation and etiological subtypes of cerebrovascular diseases (CVD) following cardiac transplantation (CTX). Methods: In a retrospective review of our CTX database (period 1984–2002), we assessed demographic data, vascular risk factors, surgery and donor details. We classified ischemic stroke (IS) using the clinical criteria of the Oxfordshire Community Stroke Project and the etiological criteria of the TOAST study. Logistic regression analysis and survival curves were carried out. Results: CTX was performed in a total of 314 patients (age 46 ± 14 years, 78% male) and mean follow-up was 54 ± 57 months. Twenty-two patients (7%) presented CVD: hemorrhagic stroke in 12%, transient ischemic attack in 28% and IS in 60%. CVD were early postoperative (less than 2 weeks) in 20% of patients and late in 80%. The clinical presentation in patients with IS was total anterior circulation (23.1%), partial anterior (38.4%), lacunar (15.4%) and posterior circulation (23.1%), and the etiological classification was large artery atherosclerosis (15.4%), cardioembolism (14.4%), small vessel disease (15.4%), unusual causes (15.4%) and undetermined cause (38.4%). The only independent predictor of CVD was a prior CVD event with an odds ratio of 8.2 (95% CI, 2.2–30.2, p < 0.02). The estimated risk of CVD at 5 years was greater (p < 0.02) in patients with prior CVD (4.1%) than in those without (1.1%). Conclusions: CVD are a relatively frequent complication after CTX (7%) and usually occur in the late postoperative phase. CVD prior to transplantation increase the risk of CVD after this procedure.

Primitive reflexes in cerebrovascular disease: a community study of older people with stroke and carotid stenosis

To determine the prevalence of primitive reflexes (frontal release signs) in elderly community residents with cerebrovascular disease and to examine their relationship with neuropsychological and mood-related variables. Three groups of 25 people over 65 with anterior circulation stroke, transient ischaemic attack (TIA) and a control group were assessed using measures of generalized cognitive impairment, frontal lobe dysfunction, frontal release signs and mood-related variables. Predictors of cerebrovascular disease were examined further in stroke and TIA groups. Both stroke and TIA groups showed a higher mean score on the Frontal Release Signs Scale and a higher prevalence of most reflexes than the control group. Verbal fluency and DSM-IV depressive disorder were independent predictors of frontal release signs. TIAs may predispose to subtle neurological impairment, which may be mediated by frontal lobe damage. Their role in the pathogenesis of depression in later life requires further exploration.