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Purpose: To determine whether ocular motor cranial nerve (CN) palsy raises the risk of subsequent stroke in the general population. Methods: We investigated the association between ocular motor CN palsy and occurrence of stroke using the National Health Insurance Service-National Sample Cohort database from 2002 to 2013. We included individuals aged ≥ 20 years on January 1st, 2004, and excluded those having any paralytic strabismus, disorders in binocular movement, diplopia and any cerebrovascular diseases before entering the cohort. Incident ocular motor CN palsy was identified by diagnostic codes for third, fourth, and sixth nerve palsies. To determine the effect of incident ocular motor CN palsy on the occurrence of subsequent stroke, we used time-varying covariate Cox regression models. Model 1 included only incident third, fourth, and sixth nerve palsies as a time-varying covariate. Model 2 included Model 1 and defined demographic information. Model 3 included Model 2, comorbidity, co-medication, and the Charlson index score. Results: Among 727,689 individuals in the cohort, 1,633 patients developed ocular motor CN palsy and 17,657 patients suffered stroke. Cox regression models showed that development of ocular motor CN palsy was associated with an increased risk of subsequent stroke (hazard ratio [HR] = 4.65; 95% confidence intervals [CIs], 3.74–5.80 in Model 1), and the results were consistent even after adjusting for demographic factors and confounders in Model 2 and 3. Men, older age, and individuals not living in Seoul/Incheon area were associated with an increased risk of stroke, while individuals with higher income were associated with decreased risk of stroke in both Model 2 and 3. Sensitivity analyses using propensity score-based matching produced similar results in all three Models (HR = 1.95; 95% CI, 1.55–2.46 in Model 1, HR = 1.91; 95% CI, 1.52–2.41 in Model 2, and HR = 1.63; 95% CI, 1.29–2.06 in Model 3). Conclusions: The occurrence of ocular motor CN palsy is a significant risk factor of subsequent stroke even after adjusting for demographic factors and confounders in the general population. Physicians may need to educate patients with ocular motor CN palsy regarding the higher risk of future stroke. [ABSTRACT FROM AUTHOR]

Elevated levels of FGF23 in individuals with chronic kidney disease (CKD) are associated with adverse health outcomes, such as increased mortality, large vessel disease, and reduced white matter volume, cardiovascular and cerebrovascular events. Apart from the well-known link between cardiovascular (CV) risk factors, especially diabetes and hypertension, and cerebrovascular damage, elevated FGF23 is also postulated to be associated with cerebrovascular damage independently of CKD. Elevated FGF23 predisposes to vascular calcification and is associated with vascular stiffness and endothelial dysfunction in the general population with normal renal function. These factors may lead to microangiopathic changes in the brain, cumulative ischemia, and eventually to the loss of white matter fibers. The relationship between FGF23 and brain integrity in individuals without CKD has hitherto not been investigated. In this study, we aimed to determine the association between FGF23, and white matter integrity in a cohort of 50 participants with varying degrees of CV risk burden, using high resolution structural human brain connectomes constructed from MRI diffusion images. We observed that increased FGF23 was associated with axonal loss in the frontal lobe, leading to a fragmentation of white matter network organization. This study provides the first description of the relationship between elevated levels of FGF23, white matter integrity, and brain health. We suggest a synergistic interaction of CV risk factors and FGF23 as a potentially novel determinant of brain health. [ABSTRACT FROM AUTHOR]

Motivation: Obstructive sleep apnea (OSA) can impair cerebral vasoreactivity and is associated with an increased risk of cerebrovascular disease. Unfortunately, an easy-to-use, non-invasive, portable monitor of cerebral vasoreactivity does not exist. Therefore, we have evaluated the use of near-infrared diffuse correlation spectroscopy to measure the microvascular cerebral blood flow (CBF) response to a mild head-of-bed position change as a biomarker for the evaluation of cerebral vasoreactivity alteration due to chronic OSA. Furthermore, we have monitored the effect of two years of continuous positive airway pressure (CPAP) treatment on the cerebral vasoreactivity. Methodology: CBF was measured at different head-of-bed position changes (supine to 30° to supine) in sixty-eight patients with OSA grouped according to severity (forty moderate to severe, twenty-eight mild) and in fourteen control subjects without OSA. A subgroup (n = 13) with severe OSA was measured again after two years of CPAP treatment. Results: All patients and controls showed a similar CBF response after changing position from supine to 30° (p = 0.819), with a median (confidence interval) change of -17.5 (-10.3, -22.9)%. However, when being tilted back to the supine position, while the control group (p = 0.091) and the mild patients with OSA (p = 0.227) recovered to the initial baseline, patients with moderate and severe OSA did not recover to the baseline (9.8 (0.8, 12.9)%, p < 0.001) suggesting altered cerebral vasoreactivity. This alteration was correlated with OSA severity defined by the apnea-hypopnea index, and with mean nocturnal arterial oxygen saturation. The CBF response was normalized after two years of CPAP treatment upon follow-up measurements. Conclusion: In conclusion, microvascular CBF response to a head-of-bed challenge measured by diffuse correlation spectroscopy suggests that moderate and severe patients with OSA have altered cerebral vasoreactivity related to OSA severity. This may normalize after two years of CPAP treatment. [ABSTRACT FROM AUTHOR]

Background and objective: Changes in cerebral blood flow (CBF) immediately after cigarette smoking (CS) are still unclear. Our purpose was to evaluate the hemodynamic changes in each intracranial vessel after CS by using quantitative magnetic resonance angiography (MRA). Material and methods: Fifteen healthy male smokers less than 45 years old with more than 3 pack-year smoking history were enrolled in this study. The hemodynamic change in the vessels, represented by cerebral flow rate (CFR, ml/s) and flow velocity (FV, cm/s), was quantitatively measured in eleven vascular segments of the brain using phase-contrast MRA. Two sets of data at each vessel before and after CS were statistically analyzed by paired t-test. Three of 15 participants, as a control group, followed all the procedures but did not smoke. Results: Total CFR of the distal intracranial vessels (anterior, middle, and posterior cerebral arteries; ACA, MCA, and PCA) was significantly reduced after CS by 7.3% (847 vs. 785 ml/s, p = 0.024). Such flow changes were statistically more significant in the anterior circulation (ACA and MCA) compared to the posterior circulation (PCA). All distal intracranial vessels did not have significant FV change while peak systolic velocity and mean velocity dropped 7.4 and 4.3% and pulsatility index decreased 10.9% in the internal carotid artery. Regarding cross-sectional areas, all distal intracranial vessels showed diminished, and only MCA had a statistical significance (9.9 vs. 9.3 mm2, p = 0.016). Conclusions: There was a significant decrease of CFR after CS especially in the anterior circulation of twelve young male smokers. Considering the changes of FV and cross-sectional area all together, it can be suggested that cerebrovascular impedance increased after CS especially at the main trunk level of the distal intracranial vessels (ACA, MCA, and PCA). [ABSTRACT FROM AUTHOR]

Tinnitus mostly results from central and peripheral auditory pathology. Chronic kidney disease (CKD) is a major risk factor for cerebrovascular disease. However, no studies have evaluated the association between tinnitus and CKD. The aim of this study is to investigate the risk of tinnitus in patients with CKD. This retrospective cohort study was conducted using Taiwan National Health Insurance Research Database from 2000 to 2010. We established a CKD group (n = 185,430) and a non-CKD comparison group (n = 556,290) to investigate the incidence of tinnitus. Cox proportional hazard regression analysis was used to evaluate the effects of CKD on tinnitus risk. The results showed CKD significantly increased the risk of tinnitus (adjusted hazard ratio, 3.02; 95% CI, 2.655–3.456, P<0.001). A subgroup analysis revealed the increase in risk of tinnitus is more in CKD patients with heart failure (adjusted hazard ratio, 9.975; 95% CI, 5.001–18.752) and diabetes mellitus (adjusted hazard ratio, 3.712; 95% CI, 2.856–5.007). Furthermore, compared to non-CKD patients, the risk of tinnitus was increased 4.586-fold (95% CI, 2.399–6.7) in CKD patients with dialysis and 2.461-fold (95% CI, 1.033–3.454) in CKD patients without dialysis. This study is the first to report that CKD is associated with an increased risk of tinnitus. Among CKD cohort, patients with dialysis are at a higher risk of tinnitus than those without dialysis. [ABSTRACT FROM AUTHOR]

Background: Patients who develop herpes zoster or herpes zoster ophthalmicus may be at risk for cerebrovascular and cardiac complications. We systematically reviewed the published literature to determine the association between herpes zoster and its subtypes with the occurrence of cerebrovascular and cardiac events. Methods/Results: Systematic searches of PubMed (MEDLINE), SCOPUS (Embase) and Google Scholar were performed in December 2016. Eligible studies were cohort, case-control, and self-controlled case-series examining the association between herpes zoster or subtypes of herpes zoster with the occurrence of cerebrovascular and cardiac events including stroke, transient ischemic attack, coronary heart disease, and myocardial infarction. Data on the occurrence of the examined events were abstracted. Odds ratios and their accompanying confidence intervals were estimated using random and fixed effects models with statistical heterogeneity estimated with the I2 statistic. Twelve studies examining 7.9 million patients up to 28 years after the onset of herpes zoster met our pre-defined eligibility criteria. Random and fixed effects meta-analyses showed that herpes zoster, type unspecified, and herpes zoster ophthalmicus were associated with a significantly increased risk of cerebrovascular events, without any evidence of statistical heterogeneity. Our meta-analysis also found a significantly increased risk of cardiac events associated with herpes zoster, type unspecified. Conclusions: Our results are consistent with the accumulating body of evidence that herpes zoster and herpes zoster ophthalmicus are significantly associated with cerebrovascular and cardiovascular events. [ABSTRACT FROM AUTHOR]

Patients with kidney disease (KD) are at increased risk for cerebrovascular disease (CVD) and CVD patients with KD have worse outcomes. We aimed to determine the representation of KD patients in major randomized controlled trials (RCTs) of CVD interventions. We searched MEDLINE for reports of major CVD trials published through February 9, 2017. We excluded trials that did not report mortality outcomes, enrolled fewer than 100 participants, or were subgroup, follow-up, or post-hoc analyses. Two independent reviewers performed study selection and data extraction. We included 135 RCTs randomizing 194,977 participants. KD patients were excluded in 48 (35.6%) trials, but were less likely to be excluded from trials of class I/II recommended interventions (n = 7; 15.9%; p = 0.001) and more likely to be excluded in trials with registered protocols (45.5% vs. 22.4%; p = 0.007). Exclusion was lower in trials supported by academic or governmental grants compared to industry or combined funding (21.2% vs. 42.0% and 47.8%; p = 0.033 and 0.028, respectively). Among trials excluding KD patients, 24 (50.0%) used serum creatinine, 7 (14.6%) used estimated glomerular filtration rate or creatinine clearance, 7 (14.6%) used renal replacement therapy, and 19 (39.6%) used non-specific kidney-related criteria. Only 4 (3.0%) trials reported baseline renal function. No trials prespecified or reported subgroup analyses by baseline renal function. Although 19 (14.1%) trials reported the incidence of acute kidney injury, no trial examined adverse event rates according to renal function. In summary, more than one third of major CVD trials excluded patients with KD, primarily based on serum creatinine or non-specific criteria, and outcomes were not stratified by renal parameters. Therefore, purposeful efforts to increase inclusion of KD patients in CVD trials and evaluate the impact of renal function on efficacy and safety are needed to improve the quality of evidence for interventions in this vulnerable population. [ABSTRACT FROM AUTHOR]

The risk of death is increased for persons with epilepsy. The literature on causes of death in epilepsy is based mainly on cohorts with epilepsy of mixed aetiologies. For clinical purposes and improved understanding of mortality in different epilepsies, more information is needed on mortality in epilepsies of specific causes. In poststroke epilepsy (PSE), seizures occur in a setting of vascular disease and high mortality rates. The extent to which epilepsy contributes to mortality in this patient group is poorly understood. We therefore aimed to describe causes of death (COD) in PSE on a national scale. A previously identified cohort of 7740 patients with epilepsy or seizures after a stroke in 2005–2010 was investigated. A total of 4167 deaths occurred before the end of 2014. The standardized mortality ratio for the study cohort was 3.56 (95% CI: 3.45–3.67). The main underlying causes of death were disorders of the circulatory system (60%) followed by neoplasms (12%). Diseases of the nervous system were the sixth leading underlying COD (3%), and epilepsy or status epilepticus was considered the underlying COD in approximately a similar proportion of cases as neurodegenerative disorders (0.9% and 1.1%, respectively). Epilepsy was considered a contributing COD in 14% of cases. Our findings highlight the importance of optimal management of vascular morbidity in patients with PSE. The large proportion of patients with epilepsy as a contributing COD indicate the need of high ambitions also regarding the management of seizures in patients with PSE. [ABSTRACT FROM AUTHOR]

Introduction: Cerebral microbleed (CMB) is a potent risk factor for overt cerebrovascular disease. Although some studies indicated the possible role of renal dysfunction as a risk factor of CMB, the findings could not be generalized. This study aimed to investigate the association between renal dysfunction and cerebral microbleed (CMB) in neurologically healthy adults. Materials and methods: A total of 2,518 subjects who underwent brain MRI as part of health screening were involved in the study. CMBs were defined as well-demarcated focal areas of low signal intensity with associated blooming on the T2-weighted MRI measuring less than 5mm in diameter. The glomerular filtration rate (GFR) was estimated using the Modification of Diet in Renal Disease formula. Kidney function was classified as normal (≥90), mild (60 to 89.9), moderate (30 to 59.9), and severe (<30 mL/min/1.73 m2) renal dysfunction according to the GFR. Results: The mean age of the participants was 57.5 ± 8.3 years (ranged 40 to 79), and 1,367 subjects (54.3%) were male. The mean GFR level was 81.5 ± 15.5, and the prevalence of CMB was 4.1% (n = 103). Subjects with CMB demonstrated a higher proportion of moderate-to-severe renal dysfunction than those without CMB (15.5% vs. 5.0%, p < 0.001). In the multivariate logistic regression analysis, moderate-to-severe renal dysfunction showed a significant association with CMB (adjusted odd ratio = 2.63; p = 0.008). Furthermore, a decrease in the GFR level was associated with an increasing trend of the presence of CMB (p for trend = 0.031) and number of CMB lesions (p for trend = 0.003). Conclusions: Renal dysfunction was significantly associated with the presence of CMB in neurologically healthy adults. More studies are needed to evaluate if treatment of kidney disease and risk factor modification may prevent further progress of CMB. [ABSTRACT FROM AUTHOR]

Objective: Thyroid disorders are well known to be associated with cardiovascular diseases. Some studies have shown that the negative effects of thyroid disorders are partially reversible after adequate treatment. The aim of this analysis was to assess the risk of incident ischemic cerebrovascular diseases in study participants treated for thyroid dysfunctions in a population-based cohort study. Methods: For the presented analyses data from 8564 male and 8714 female individuals aged 25 to 74 years of the MONICA/KORA cohort were used (median follow-up 14.0 years). A combined binary variable “thyroid disorder” (TDC) was created utilizing data on self-reported physician-treated thyroid disorders and information about medication use. To examine the association between TDC and incident ischemic cerebrovascular events, we performed multiple adjusted Cox proportional hazard regression models and calculated hazard ratios and corresponding 95% confidence intervals (HR, 95%CI). Results: During follow-up between 1984 and 2008/2009, 514 incident fatal and non-fatal ischemic cerebrovascular events occurred in men and 323 in women. At baseline, 3.5% of men and 15.6% of women reported TDC. In the fully adjusted model, males who reported TDC had a significantly reduced risk of ischemic cerebrovascular events (HR = 0.52, 95%CI = 0.29–0.92). A similar result was obtained in men, when we utilized information on thyroid hormones use only. For the total study population and for women with TDC we found no association with ischemic cerebrovascular events. Conclusions: In our longitudinal analyses subjects with treated thyroid diseases had no increased risk of incident ischemic cerebrovascular events. Surprisingly in males, even a significantly reduced risk of incident ischemic cerebrovascular events was found, a result that deserves further clarification. [ABSTRACT FROM AUTHOR]

Background: Improved medical care over more than five decades has markedly increased life expectancy, from 12 years to approximately 60 years, in people with Down syndrome (DS). With increased survival into late adulthood, there is now a greater need for the medical care of people with DS to prevent and treat aging-related disorders. In the wider population, acquired cardiovascular diseases such as stroke and coronary heart disease are common with increasing age, but the risks of these diseases in people with DS are unknown. There are no population-level data on the incidence of acquired major cerebrovascular and coronary diseases in DS, and no data examining how cardiovascular comorbidities or risk factors in DS might impact on cardiovascular event incidence. Such data would be also valuable to inform health care planning for people with DS. Our objective was therefore to conduct a population-level matched cohort study to quantify the risk of incident major cardiovascular events in DS. Methods and Findings: A population-level matched cohort study compared the risk of incident cardiovascular events between hospitalized patients with and without DS, adjusting for sex, and vascular risk factors. The sample was derived from hospitalization data within the Australian state of Victoria from 1993–2010. For each DS admission, 4 exact age-matched non-DS admissions were randomly selected from all hospitalizations within a week of the relevant DS admission to form the comparison cohort. There were 4,081 people with DS and 16,324 without DS, with a total of 212,539 person-years of observation. Compared to the group without DS, there was a higher prevalence in the DS group of congenital heart disease, cardiac arrhythmia, dementia, pulmonary hypertension, diabetes and sleep apnea, and a lower prevalence of ever-smoking. DS was associated with a greater risk of incident cerebrovascular events (Risk Ratio, RR 2.70, 95% CI 2.08, 3.53) especially among females (RR 3.31, 95% CI 2.21, 4.94) and patients aged 50 years old. The association of DS with ischemic strokes was substantially attenuated on adjustment for cardioembolic risk (RR 1.93, 95% CI 1.04, 3.20), but unaffected by adjustment for atherosclerotic risk. DS was associated with a 40–70% reduced risk of any coronary event in males (RR 0.58, 95% CI 0.40, 0.84) but not in females (RR 1.14, 95% CI 0.73, 1.77). Conclusions: DS is associated with a high risk of stroke, expressed across all ages. Ischemic stroke risk in DS appears mostly driven by cardioembolic risk. The greater risk of hemorrhagic stroke and lower risk of coronary events (in males) in DS remain unexplained. [ABSTRACT FROM AUTHOR]

Background and Purpose: Some prior studies have linked ambient temperature with risk of cerebrovascular events. If causal, the pathophysiologic mechanisms underlying this putative association remain unknown. Temperature-related changes in cerebral vascular function may play a role, but this hypothesis has not been previously evaluated. Methods: We evaluated the association between ambient temperature and cerebral vascular function among 432 participants ≥65 years old from the MOBILIZE Boston Study with data on cerebrovascular blood flow, cerebrovascular resistance, and cerebrovascular reactivity in the middle cerebral artery. We used linear regression models to assess the association of mean ambient temperature in the previous 1 to 28 days with cerebrovascular hemodynamics adjusting for potential confounding factors. Results: A 10°C increase in the 21-day moving average of ambient temperature was associated with a 10.1% (95% confidence interval [CI], 2.2%, 17.3%) lower blood flow velocity, a 9.0% (95% CI, 0.7%, 18.0%) higher cerebrovascular resistance, and a 15.3% (95%CI, 2.7%, 26.4%) lower cerebral vasoreactivity. Further adjustment for ozone and fine particulate matter (PM2.5) did not materially alter the results. However, we found statistically significant interactions between ambient temperature and PM2.5 such that the association between temperature and blood flow velocity was attenuated at higher levels of PM2.5. Conclusions: In this elderly population, we found that ambient temperature was negatively associated with cerebral blood flow velocity and cerebrovascular vasoreactivity and positively associated with cerebrovascular resistance. Changes in vascular function may partly underlie the observed associations between ambient temperature and risk of cerebrovascular events. [ABSTRACT FROM AUTHOR]

Deformities in the Circle of Willis (CoW) can significantly increase the risk of cerebrovascular disease in humans. However, the molecular mechanisms underlying these deformities have not been understood. Based on our previous studies, variations in the CoW of gerbils are hereditary. A normal CoW is observed in approximately 60% of gerbils, a percentage that also applies to humans. Thus, gerbil is an ideal experimental model for studying variations in the CoW. To study the mechanisms underlying these variations, we selected genes associated with different types of the CoW using suppression subtractive hybridization (SSH). After evaluating the efficiency of SSH using quantitative real-time polymerase chain reaction (qPCR) on subtracted and unsubtracted cDNA and Southern blotting on SSH PCR products, 12 SSH libraries were established. We identified 4 genes (CST3, GNAS, GPx4 and PFN2) associated with variations in the CoW. These genes were identified with qPCR and Western blotting using 70 expressed sequence tags from the SSH libraries. Cloning and sequencing allowed us to demonstrate that the 4 genes were closely related to mouse genes. We may assume that these 4 genes play an important role in the development of variations in the CoW. This study provides a foundation for further research of genes related to development of variations in the CoW and the mechanisms of dysmorphosis of cerebral vessels. [ABSTRACT FROM AUTHOR]

Background: Pulmonary hypertension (PH) was recently recognized as a common complication of end-stage renal disease (ESRD) that causes an increased risk of mortality. Epidemiological data for this disorder in earlier stages of chronic kidney disease (CKD) and its association with cardiovascular (CV) morbidity are scarce. Methods: We retrospectively analyzed 2,351 Chinese CKD patients with complete clinical records and echocardiography data between Jan 2008 and May 2012. The patients were divided into the following 6 groups: CKD Stages 1–4; Stage 5 for those not on or initiated on hemodialysis for <3 months; and Stage 5D for the patients undergoing hemodialysis for ≥3 months. The prevalence of PH and CV morbidity was investigated, and their association was evaluated with a logistic regression model. Results: PH was detected in 426 patients (18.1%). Mild, moderate and severe PH was diagnosed in 12.1%, 4.9% and 1.1% of the patients, respectively. Severe PH was detected in CKD Stages 5 and 5D. CV morbidity was found in 645 patients (27.4%). Compared with the non-PH group, the PH group had a higher risk for cardiac disease but not for cerebrovascular disease risk. PH severity was associated with cardiac morbidity risk [odds ratio (95% CI) for mild PH: 1.79 (1.30–2.47); moderate PH: 2.75 (1.73–4.37); severe PH: 3.90 (1.46–10.42)]. Conclusions: Our study showed for the first time the epidemiology profile of PH across the spectrum of CKD. Mild-to-moderate PH occurs with more frequency in advanced CKD, and severe PH is scarce in non-ESRD CKD. PH in CKD is associated with cardiac but not cerebrovascular disease, with increasing cardiac morbidity seen with increasing PH severity. Evidence from prospective studies addressing PH in this population is needed to predict cardiac events. [ABSTRACT FROM AUTHOR]

Arterial ischemia and hemorrhage are associated with bevacizumab, an inhibitor of vascular endothelial growth factor that is widely used to treat many types of cancers. As specific types of arterial ischemia and hemorrhage, cerebrovascular events such as central nervous system (CNS) ischemic events and CNS hemorrhage are serious adverse events. However, increased cerebrovascular events have not been uniformly reported by previous studies. New randomized controlled trials (RCTs) have been reported in recent years and we therefore conducted an up-to-date meta-analysis of RCTs to fully characterize the risk of cerebrovascular events with bevacizumab. We searched the databases of PubMed, Web of Science, and the American Society of Clinical Oncology conferences to identify relevant clinical trials up to February 2014. Eligible studies included prospective RCTs that directly compared patients with cancer treated with and without bevacizumab. A total of 12,917 patients from 17 RCTs were included in our analysis. Patients treated with bevacizumab had a significantly increased risk of cerebrovascular events compared with patients treated with control medication, with a relative risk of 3.28 (95% CI, 1.97–5.48). The risks of CNS ischemic events and CNS hemorrhage were increased compared with control, with RRs of 3.22 (95% CI, 1.71–6.07) and 3.09 (95% CI, 1.36–6.99), respectively. Risk varied with the bevacizumab dose, with RRs of 3.97 (95% CI, 2.15–7.36) and 1.96 (95% CI, 0.76–5.06) at 5 and 2.5 mg/kg/week, respectively. Higher risks were observed in patients with metastatic colorectal cancer (RR, 6.42; 95% CI, 1.76–35.57), and no significant risk was observed in other types of tumors. In conclusion, the addition of bevacizumab significantly increased the risk of cerebrovascular events compared with controls, including CNS ischemic events and CNS hemorrhage. The risk may vary with bevacizumab dose and tumor type. [ABSTRACT FROM AUTHOR]

Objective: To examine the associations of combined lifestyle factors and physical conditions with cerebrovascular diseases (CBVD) mortality, after accounting for competing risk events, including death from cardiovascular diseases, cancers and other diseases. Methods: Data on 2010 subjects aged over 55 years were finally analyzed using competing risk models. All the subjects were interviewed by the Beijing Longitudinal Study of Aging (BLSA), in China, between 1 January 1992 and 30 August 2009. Results: Elderly females were at a lower risk of death from CBVD than elderly males (HR = 0.639, 95% CI = 0.457–0.895). Increasing age (HR = 1.543, 95% CI = 1.013–2.349), poor self-rated health (HR = 1.652, 95% CI = 1.198–2.277), hypertension (HR = 2.201, 95% CI = 1.524–3.178) and overweight (HR = 1.473, 95% CI = 1.013–2.142) or obesity (HR = 1.711, 95% CI = 1.1754–2.490) was associated with higher CBVD mortality risk. Normal cognition function (HR = 0.650, 95% CI = 0.434–0.973) and living in urban (HR = 0.456, 95% CI = 0.286–0.727) was associated with lower CBVD mortality risk. Gray’s test also confirmed the cumulative incidence (CIF) of CBVD was lower in the ‘married’ group than those without spouse, and the mortality was lowest in the ‘nutrition sufficient’ group among the ‘frequent consumption of meat group’ and the ‘medial type group’ (P value<0.001). Conclusions: CBVD mortality was associated with gender, age, blood pressure, residence, BMI, cognitive function, nutrition and the result of self-rated health assessment in the elderly in Beijing, China. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to investigate prospectively whether MRI plaque imaging can identify patients with asymptomatic carotid artery stenosis who have an increased risk for future cerebral events. MRI plaque imaging allows categorization of carotid stenosis into different lesion types (I–VIII). Within these lesion types, lesion types IV–V and VI are regarded as rupture-prone plaques, whereas the other lesion types represent stable ones. Methods: Eighty-three consecutive patients (45 male (54.2%); age 54–88 years (mean 73.2 years)) presenting with an asymptomatic carotid stenosis of 50–99% according to ECST-criteria were recruited. Patients were imaged with a 1.5-T scanner. T1-, T2-, time-of-flight-, and proton-density weighted studies were performed. The carotid plaques were classified as lesion type I–VIII. Clinical endpoints were ischemic stroke, TIA or amaurosis fugax. Survival analysis and log rank test were used to ascertain statistical significance. Results: Six out of 83 patients (7.2%) were excluded: 4 patients had insufficient MR image quality; 1 patient was lost-to-follow-up; 1 patient died shortly after the baseline MRI plaque imaging. The following results were obtained by analyzing the remaining 77 patients. The mean time of follow-up was 41.1 months. During follow-up, n = 9 (11.7%) ipsilateral ischemic cerebrovascular events occurred. Only patients presenting with the high-risk lesion types IV–V and VI developed an ipsilateral cerebrovascular event versus none of the patients presenting with the stable lesion types III, VII, and VIII (n = 9 (11.7%) vs. n = 0 (0%) during follow-up). Event-free survival was higher among patients with the MRI-defined stable lesion types (III, VII, and VIII) than in patients with the high-risk lesion types (IV–V and VI) (log rank test P<0.0001). Conclusions: MRI plaque imaging has the potential to identify patients with asymptomatic carotid stenosis who are particularly at risk of developing future cerebral ischemia. MRI could improve selection criteria for invasive therapy in the future. [ABSTRACT FROM AUTHOR]

Background: Studies on the association of stroke risk to dietary glycemic index (GI) and glycemic load (GL) have produced contrasting results. Objective: To investigate the relation of dietary GI and GL to stroke risk in the large EPIC-Italy cohort (EPICOR) recruited from widely dispersed geographic areas of Italy. Design: We studied 44099 participants (13,646 men and 30,453 women) who completed a dietary questionnaire. Multivariable Cox modeling estimated adjusted hazard ratios (HRs) of stroke with 95% confidence intervals (95%CI). Over 11 years of follow-up, 355 stroke cases (195 ischemic and 83 hemorrhagic) were identified. Results: Increasing carbohydrate intake was associated with increasing stroke risk (HR = 2.01, 95%CI = 1.04–3.86 highest vs. lowest quintile; p for trend 0.025). Increasing carbohydrate intake from high-GI foods was also significantly associated with increasing stroke risk (HR 1.87, 95%CI = 1.16–3.02 highest vs. lowest, p trend 0.008), while increasing carbohydrate intake from low-GI foods was not. Increasing GL was associated with significantly increasing stroke risk (HR 2.21, 95%CI = 1.16–4.20, highest vs. lowest; p trend 0.015). Dietary carbohydrate from high GI foods was associated with increased both ischemic stroke risk (highest vs. lowest HR 1.92, 95%CI = 1.01–3.66) and hemorrhagic stroke risk (highest vs. lowest HR 3.14, 95%CI = 1.09–9.04). GL was associated with increased both ischemic and hemorrhagic stroke risk (HR 1.44, 95%CI = 1.09–1.92 and HR 1.56, 95%CI = 1.01–2.41 respectively, continuous variable). Conclusions: In this Italian cohort, high dietary GL and carbohydrate from high GI foods consumption increase overall risk of stroke. [ABSTRACT FROM AUTHOR]

Objective: To investigate the relationship between sex hormones and the risk of vascular disease in elderly men and to evaluate the advantages and disadvantages of testosterone replacement. Methods: A total of 337 men, aged 60 to 91 years, were enrolled in this single-center, cross-sectional study, and their sex hormone levels were assessed. Linear and logistic regression analyses were utilized to compare the sex hormone levels between patients with and without vascular disease. The nonparametric K-sample test was used for inter-group comparisons. Results: Aging and abnormal metabolism were both significantly associated with an increased risk of vascular diseases and changes in sex hormone levels. Primary linear and logistic regression analyses showed no significant differences in sex hormone concentrations between patients with and without vascular diseases after adjusting for age. Logistic regression with abnormal metabolism as categorical variable showed that free testosterone (FT) and free estradiol (FE2) had significant relationships with CEVD risk (P<0.05). In further regression with all metabolic continuous variables included, the testosterone/estradiol (T/E2) ratio replaced FT and FE2 (P<0.05). Trend line analyses showed that T/E2 actually had a binomial linear correlation with the risk of cerebrovascular disease; its best protective effect occurred at values of 0.13–0.15, with an OR value extremely close to those of FT and FE2 (0.23 vs. 0.24–0.25). Conclusion: T/E2 balance plays a key role in the relationship between sex hormones and the risk of cerebrovascular disease. The balance between T and E2 may be more important than their absolute quantities. Extremely low T/E2 and inappropriately high T/E2 ratio can both harm the brain blood vessels. Careful consideration should be given before beginning testosterone replacement treatment, and supplementing with estrogen seems to be a good way to protect blood vessels of the brain in elderly men. [ABSTRACT FROM AUTHOR]

Elevated homocysteine is an important risk factor that increases cerebrovascular and neurodegenerative disease morbidity. In mammals, B vitamin supplementation can reduce homocysteine levels. Whether, and how, hibernating mammals, that essentially stop ingesting B vitamins, maintain homocysteine metabolism and avoid cerebrovascular impacts and neurodegeneration remain unclear. Here, we compare homocysteine levels in the brains of torpid bats, active bats and rats to identify the molecules involved in homocysteine homeostasis. We found that homocysteine does not elevate in torpid brains, despite declining vitamin B levels. At low levels of vitamin B6 and B12, we found no change in total expression level of the two main enzymes involved in homocysteine metabolism (methionine synthase and cystathionine β-synthase), but a 1.85-fold increase in the expression of the coenzyme-independent betaine-homocysteine S-methyltransferase (BHMT). BHMT expression was observed in the amygdala of basal ganglia and the cerebral cortex where BHMT levels were clearly elevated during torpor. This is the first report of BHMT protein expression in the brain and suggests that BHMT modulates homocysteine in the brains of hibernating bats. BHMT may have a neuroprotective role in the brains of hibernating mammals and further research on this system could expand our biomedical understanding of certain cerebrovascular and neurodegenerative disease processes. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a complex polygenic inflammatory disease associated with accelerated atherosclerosis and increased risk of cardiovascular (CV) disease. Previous genome-wide association studies have described SMAD3 rs17228212 polymorphism as an important signal associated with CV events. The aim of the present study was to evaluate for the first time the relationship between this gene polymorphism and the susceptibility to CV manifestations and its potential association with the presence of subclinical atherosclerosis assessed by the evaluation of carotid intima-media thickness (cIMT) in patients with RA. Methods:One thousand eight hundred and ninety-seven patients fulfilling classification criteria for RA were genotyped for SMAD3 rs17228212 gene polymorphism through TaqMan genotyping assay. Also, subclinical atherosclerosis determined by the assessment of cIMT was analyzed in a subgroup of these patients by carotid ultrasonography. Results:No statistically significant differences were observed when allele frequencies of RA patients with or without CV events were compared. Nevertheless, when RA patients were stratified according to anti-cyclic citrullinated peptide (anti-CCP) status, we found that in RA patients who were negative for anti-CCP antibodies, the presence of C allele of SMAD3 rs17228212 polymorphism conferred a protective effect against the risk of cerebrovascular accident (CVA) after adjustment for demographic and classic CV risk factors (HR [95%CI]=0.36 [0.14–0.94], p=0.038) in a Cox regression model. Additionally, correlation between the presence of C allele of SMAD3 rs17228212 polymorphism and lower values of cIMT was found after adjustment for demographic and classic CV risk factors (p-value=0.0094) in the anti-CCP negative RA patients. Conclusions:Our results revealed that SMAD3 rs17228212 gene variant is associated with lower risk of CVA and less severe subclinical atherosclerosis in RA patients negative for anti-CCP antibodies. These findings may have importance to establish predictive models of CV disease in RA patients according to anti-CCP status. [ABSTRACT FROM AUTHOR]