Xiangyan Chen

Apolipoprotein E ε4 Allele Is Associated with Vascular Dementia

Background/Aims: The apolipoprotein E (ApoE) exon 4 polymorphism has been associated with vascular dementia (VaD) risk. Since not all studies confirm this finding, we explored this association in a case-control study. Methods: We genotyped ApoE in 144 VaD patients and 251 controls. Results: VaD patients were more likely than controls to have ApoE Ε3/Ε4 or Ε4/Ε4 genotypes: 23.6% versus 15.1%, odds ratio (OR) = 1.7, p = 0.036. This association remained significant after adjustment for age, sex, hypertension and diabetes by multiple logistic regression: OR = 1.9, p = 0.030. The association of Ε3/Ε4 or Ε4/Ε4 genotypes with VaD was strong among people with hypertension (OR = 2.9, p = 0.007) or diabetes (OR = 6.5, p = 0.011). The association was absent among people without hypertension (OR = 1.1, p = 0.79) or diabetes (OR = 1.3, p = 0.43). Conclusion: This interaction with hypertension and diabetes should be examined in other studies to confirm or refute this observation.

The Frequency and Determinants of Calcification in Intracranial Arteries in Chinese Patients Who Underwent Computed Tomography Examinations

Background: Intracranial artery calcification is common but the prevalence and determinants are not well established. We aim to describe the prevalence and location of calcification in intracranial arteries according to brain multi-detector-row computed tomography (MDCT) images, and to investigate its correlation with potential risk factors. Methods: We studied consecutive men and women referred for brain CT in December 2004. All patients received a questionnaire regarding their medical history related to atherosclerosis, including traditional risk factors of atherosclerosis, serum chemistry values and inflammatory markers. All CT examinations were done with a 16-slice MDCT and the severity of intracranial artery calcification was categorized. Results: Four hundred and ninety patients aged 1.4–101 years (62.92 ± 19.04; mean ± SD) were included in our study. There were 340 patients (69.4%) who had intracranial artery calcification. The highest prevalence of intracranial artery calcification was seen in the internal carotid artery (60%), followed by vertebral artery (20%), middle cerebral artery (5%) and basilar artery (5%). Patients with calcification were significantly older than those without calcification (p < 0.001). A significantly higher prevalence of calcification was present among patients with hypertension (p < 0.001), diabetes (p < 0.001), renal failure (p < 0.05), atrial fibrillation (p < 0.05), smoking (p < 0.05), hyperlipidemia (p < 0.001), ischemic heart disease (p < 0.05) and ischemic stroke (p < 0.001). Mean values of serum phosphate, serum urea and CRP level were also significantly higher in patients with intracranial artery calcification (p < 0.05, respectively), and there was a trend that patients with intracranial calcification had a higher white blood cell count (p = 0.070). Stepwise multiple logistic regression showed age (RR = 2.795 per 10 years), a history of ischemic stroke (RR = 3.915), and white blood cell count (RR = 1.107) to be independently associated with intracranial artery calcification. Conclusions: Calcification of the intracranial arteries is associated with age, history of ischemic stroke and white blood cell count. Further prospective studies to investigate the clinical significance of intracranial artery calcification are needed.

Cortical and frontal atrophy are associated with cognitive impairment in age-related confluent white-matter lesion

Objective Although age-related confluent white-matter lesion (WML) is an important substrate for cognitive impairment, the mechanisms whereby WML induces cognitive impairment are uncertain. The authors investigated cognitive predictors in patients with confluent WML. Methods Among 100 patients with ischaemic stroke with confluent WML on MRI, the authors assessed executive function and global cognition by the Mattis Dementia Rating Scale—Initiation/Perseveration Subscale (MDRS I/P) and Mini-Mental State Examination (MMSE), respectively. All volumetric measures were corrected for intracranial volume. The authors investigated the association between basic demography, vascular risk factors, APOE status, WML volume, infarct measures (volume, number, location), microbleed number, atrophy measures (global, central, regional) and cognitive performance. The authors also performed Pittsburgh Compound B (PIB) imaging among seven cognitive impaired patients with stroke. Results WML was no longer related to cognitive performance after adding atrophy into regression equations. Multivariate regression models showed that cortical grey matter volume independently accounted for performance on both the MDRS I/P (β=0.241, p=0.045) and MMSE (β=0.243, p=0.032). Models examining frontal subregions revealed that volumes of both left (β=0.424, p<0.001) and right (β=0.219, p=0.045) lateral frontal orbital gyri predicted MDRS I/P, whereas education (β=0.385, p<0.001) and left lateral frontal orbital gyrus (β=0.222, p=0.037) predicted MMSE. Volumes of WML and cognitively relevant brain regions were significantly associated. Seven patients with PIB imaging showed no uptake pattern typical of Alzheimers disease, suggesting a predominantly vascular aetiology for the cognitive impairment and brain changes in these patients. Conclusions Cognitive impairment in patients with confluent WML is mediated by global and frontal cortical atrophy.

External Counterpulsation Augments Blood Pressure and Cerebral Flow Velocities in Ischemic Stroke Patients With Cerebral Intracranial Large Artery Occlusive Disease

Background and Purpose— External counterpulsation (ECP) is a novel noninvasive method used to improve the perfusion of vital organs, which may benefit ischemic stroke patients. We hypothesized that ECP may augment cerebral blood flow of ischemic stroke patients via induced hypertension. Methods— We recruited ischemic stroke patients with cerebral intracranial large artery occlusive disease and healthy elderly controls into this study. Bilateral middle cerebral arteries of subjects were monitored using transcranial Doppler. Flow velocity changes before, during, and after ECP were, respectively, recorded for 3 minutes while continuous beat-to-beat blood pressure data were recorded. Cerebral augmentation index was the increase in percentage of middle cerebral artery mean flow velocity during ECP compared with baseline. Transcranial Doppler data were analyzed based on ipsilateral or contralateral to the infarct side. Results— ECP significantly increased mean blood pressure of stroke patients and controls. During ECP, middle cerebral artery mean flow velocities of stroke patients increased on both ipsilateral and contralateral sides when compared with baseline (ipsilateral cerebral augmentation index, 9.64%; contralateral cerebral augmentation index, 9%; both P<0.001), but there was no increase in difference between the 2 sides when compared with each other. Mean flow velocities of controls did not change under ECP. After ECP, blood pressure and flow velocity of stroke patients returned to baseline level. Conclusion— ECP provides a new method of cerebral blood flow augmentation in ischemic stroke by elevation of blood pressure. Flow augmentation induced by ECP suggests the improvement of cerebral perfusion and collateral supply from infarct ipsilateral and contralateral sides.

Associations of apolipoprotein E exon 4 and lipoprotein lipase S447X polymorphisms with acute ischemic stroke and myocardial infarction

Abstract Background: Because apolipoprotein E (apoE) and lipopoprotein lipase (LPL) polymorphisms interact with each other and with other factors to affect lipid metabolism, we sought to determine their separate and combined effects in association with ischemic vascular disease. Methods: We performed a case-control study of 816 subjects: 246 acute ischemic stroke patients, 234 acute myocardial infarction patients, and 336 controls. APOE exon 4 and LPL S447X genotypes were determined. Results: APOE ɛ2 and ɛ4 homozygotes were increased in stroke (4.5% vs. 1.0%, p=0.008), while in myocardial infarction the ɛ4 allele was increased (12.6% vs. 9.5%, p=0.006) but ɛ2 was decreased (3.7% vs. 12.1%, p=0.000006). For subjects with either APOE ɛ2 or ɛ4 alleles, LPL X alleles were increased in vascular disease (OR=2.2, p=0.01). LPL X alleles displayed opposite tendencies toward association with disease when subjects were divided by sex, smoking, or APOE genotype. Meta-analysis and regression analysis of previous studies supported the sex and smoking dichotomies. Conclusion: This is the first report of an association of vascular disease with an interaction of APOE exon 4 and LPL S447X genotypes. Therefore, APOE genotypes and LPL S447X interactions with apoE, sex, and smoking may affect the risk of myocardial infarction and ischemic stroke.

Methylenetetrahydrofolate reductase gene A222V polymorphism and risk of ischemic stroke

Abstract The 5,10-methylenetetrahydrofolate reductase (MTHFR) gene 677C→T polymorphism causes an A222V amino acid change which affects MTHFR enzyme activity and can increase homocysteine, a vascular disease risk factor. This polymorphism was examined for association with stroke. In a case-control study of 241 ischemic stroke patients and 304 controls in Hong Kong, the V allele increased in stroke [28% vs. 20%, odds ratio (OR) 1.5, p=0.003]. A lack of significance for the increase in the VV genotype (7.5% vs. 4.6%, OR 1.7, p=0.16) may be due to its rarity in this region. V-allele carriers had more severe strokes (according to the NIH stroke scale). The association of the V allele with stroke occurred mostly in women or older subjects and was due to decreasing V allele frequency with age, as seen in other studies. This V frequency decline with age might be due to a loss of V-carrying controls from a higher risk of cancer, vascular disease, bone fracture, and kidney failure when folate is sparse. Examination of previous studies revealed that the association of VV genotype with stroke appeared stronger in Japan than elsewhere, possibly due to dietary differences. Perhaps folate supplementation for stroke prevention would particularly benefit VV individuals in such high-risk regions.

Validation of the ABCD2 Score to Identify the Patients With High Risk of Late Stroke After a Transient Ischemic Attack or Minor Ischemic Stroke

Background and Purpose— The ABCD2 score is able to predict the short-term risk of stroke after a transient ischemic attack/minor stroke. We aimed to explore its predictive value for long-term recurrent stroke. Methods— Consecutive patients with a transient ischemic attack/minor stroke, hospitalized during a 2-year period, were followed up to document any further stroke and death stratified by a 7-point ABCD2 score. Result— A total of 490 patients were followed for an average of 40.5 months (SD, 10.7 months). Further stroke were identified in 76 (15.5%) patients and 62 (12.7%) patients died during follow-up. Multivariate Cox regression analysis showed that an ABCD2 score >4 was found to be an independent risk factor for further stroke (hazard ratio, 2.27; 95% CI, 1.36 to 3.80) and for death (hazard ratio, 1.68; 95% CI, 0.99 to 2.85). Conclusions— In addition to predicting short-term stroke risk, ABCD2 score is a useful tool to predict long-term stroke risk after a transient ischemic attack or minor ischemic stroke.

Autonomic dysfunction in different subtypes of post-acute ischemic stroke.

OBJECTIVESnCentral autonomic impairment is frequent in ischemic stroke at acute or chronic stages. The mechanism by which these symptoms occur in patients with ischemic stroke has not been elucidated. This study sought to investigate cardiovascular autonomic function in patients with different subtypes of post-acute ischemic stroke.nnnMETHODSn77 ischemic stroke patients [50 patients with large-artery atherosclerosis (LAA) and 27 patients with small-vessel occlusion (SVO), average 6 months after stroke onset] and 37 elderly controls were recruited. All performed Ewings battery autonomic function tests and power spectral analysis of heart rate variability (HRV).nnnRESULTSnStroke patients with both LAA and SVO had significantly lower low frequency power spectral density than controls. The prevalence of autonomic dysfunction in both groups (82.0% patients with LAA and 63.0% with SVO) was higher than that in controls (21.6%). Patients with LAA showed impairment of all parasympathetic tests (all P<0.05) and one of the sympathetic tests (mean fall in systolic blood pressure on standing: P = 0.058) and those with SVO only showed impairment in two parasympathetic tests (heart rate response to deep breathing: P = 0.010; heart rate response to standing: P = 0.004) in comparison with controls. Patients with LAA had significantly more impairment than those with SVO in some autonomic parameters (Valsalva ratio: P = 0.039; mean fall in systolic blood pressure on standing: P = 0.015).nnnCONCLUSIONSnIrrespective of the subtype of the ischemia, post-acute stroke patients showed a parasympathetic cardiac deficit. Additionally, parasympathetic and sympathetic cardiovascular modulations were more severely impaired in patients with LAA.

Middle Cerebral Artery Stenosis Increased the Risk of Vascular Disease Mortality among Type 2 Diabetic Patients

Background: In Chinese populations, middle cerebral artery (MCA) stenosis is the most commonly identified intracranial vascular lesion, and has been shown to be associated with an increased risk of secondary stroke mortality, but has yet to be reported for primary events. We assess whether asymptomatic MCA stenosis is associated with mortality in Chinese type 2 diabetic patients. Methods: The presence of MCA stenosis was determined by transcranial Doppler and mortality data were collated in the Hong Kong Death Registry. Cox proportional hazards regression was used to determine if the MCA stenosis (n = 272, 53.7% 2-vessel disease) in 2,197 diabetics was associated with all-cause or vascular disease mortality, including after adjustment for conventional vascular risk factors. Anthropometric and fasting biochemical parameters were compared between diabetic patients with MCA stenosis and without evidence of stenosis. Results: A total of 191 deaths were identified (30.9% of vascular disease origin) during a follow-up of 18,279 patient years over 8.32 years. After adjustment for age, gender and diabetes duration, the hazard ratios for vascular mortality for 1- and 2-vessel disease were 2.47 (95% CI = 1.13–5.38) and 4.47 (95% CI = 2.24–8.82), p < 0.001 for trend, for increasing vascular mortality with increasing severity of cerebrovascular involvement, but 0.81 (95% CI = 0.45–1.47) and 2.23 (95% CI = 1.45–1.47), p = 0.001 for trend, for all-cause mortality. For vascular mortality, further adjustments for anthropometric and fasting biochemical parameters, or existing disease and treatment history increased the hazard ratios for 1-vessel disease slightly but attenuated the risk for 2-vessel disease evidently, 2.81 (95% CI = 1.10–7.16) and 2.85 (95% = CI 1.11–7.33), p = 0.026. Conclusion: The presence of MCA stenoses was an independent predictor of vascular mortality in these diabetics. More aggressive treatment of risk factors in these subjects merits further evaluation.

The age-related white matter changes scale correlates with cognitive impairment

Background and purpose:u2002 Age‐related white matter changes (ARWMC) are closely associated with cognitive impairment. Although the ARWMC scale has been widely used to grade white matter changes (WMC) severity, the correlation between this scale and cognitive impairment has not been studied. We aimed to validate the ARWMC scale against cognition in patients with stroke.