Chyi-Huey Bai

Genetic variants of connexin37 are associated with carotid intima-medial thickness and future onset of ischemic stroke

BACKGROUNDnCarotid intima-medial thickness (IMT) is a surrogate marker of subclinical atherosclerosis. This study aimed to investigate the impacts of genetic variants on IMT and future development of ischemic stroke in a cohort, followed by an independent replication study.nnnMETHODSnB-mode carotid ultrasound was performed among 3330 healthy adults in the CVDFACT cohort study, and the genetic effects of atherosclerosis-related genes including connexin37 (GJA4), C-reactive protein (CRP), paraoxonase (PON1), adiponectin (ACDC), angiotensin-converting enzyme (ACE), beta-adrenergic receptor (ADRB1, ADRB2), antithrombin III (SERPINC1), and kinesin family member 6 (KIF6) were evaluated by a multivariate regression model, adjusting for traditional vascular risk factors. Study subjects were prospectively followed for the development of ischemic stroke to assess the prognostic impacts of these genetic variants. An independent case-control study was performed to replicate the genetic association from the cohort study.nnnRESULTSnThe T allele of connexin37 C1019T polymorphism significantly affected IMT (β=0.014, p=0.013) after adjusting for traditional risk factors. During an average follow-up period of 10.7 years, 80 patients with ischemic stroke (2.4%) were identified. The connexin37 1019T allele was significantly associated with an increased rate of ischemic stroke under an additive model, with hazard ratios (HR) of 2.83 (95% confidence interval, 1.2-6.66) and 1.69 (95% confidence interval, 1.06-2.71), comparing TT and CT genotype with CC, respectively. After Cox analysis, age (HR, 1.78 every 10 years), diabetes mellitus (HR, 2.63), hypertension (HR, 2.08), and the T allele of C1019T polymorphism of GJA4 (HR, 1.69) were identified as independent predictors of ischemic stroke. The relationship between T allele of C1019T polymorphism of GJA4 gene and ischemic stroke was also confirmed by an independent association study.nnnCONCLUSIONnConnexin 37 genetic variants significantly affect carotid IMT and contribute to future development of ischemic stroke.

Increased risk of stroke among patients with ankylosing spondylitis: a population-based matched-cohort study

AbstractnAnkylosing spondylitis (AS) is a chronic inflammatory rheumatic disease. Although two prior studies detected increased prevalence ratios of cerebrovascular disease among AS patients, the results of the two studies investigating AS and stroke are in conflict. Therefore, the present cohort study set out to estimate the risk of subsequent stroke in AS patients compared with matched controls using a population-based dataset in Taiwan. This investigation analyzed administrative claims data sourced from the Taiwan National Health Insurance Database. Our study consisted of a study cohort comprising 1,479 AS patients and a comparison cohort of 5,916 subjects without AS. Cox proportional hazards regressions were performed to estimate the risk of subsequent stroke during the follow-up period. We also conducted additional analyses investigating the risk of subsequent stroke by gender and pharmaceutical prescription. After adjusting for chronic lower respiratory diseases, type 2 diabetes mellitus, hypertension, hyperlipidemia, renal disease, coronary heart disease, atrial fibrillation, income, and urbanization, compared with comparison patients, the hazard ratio for subsequent stroke among patients with AS was 2.3 (95xa0% CI 1.9–2.8). We also stratified our results by both gender and pharmaceutical prescription, but did not find a statistically significant difference for the risk of subsequent stroke either between men and women, or between AS patients taking various pharmaceutical regimens and the overall AS population. This is the first study to report an increased hazard ratio for subsequent stroke among AS patients when compared with matched comparison patients without AS.n

Increased risk of stroke among patients with Crohn’s disease: a population-based matched cohort study

BackgroundCrohn’s disease (CD) is one type of inflammatory bowel disease (IBD) that has been speculated to share prognostic factors with the development of stroke. There is controversial information in the literature regarding the association between CD and stroke. The present cohort study estimated the risk of subsequent stroke among CD patients compared with matched comparison subjects drawn from a population-based dataset in Taiwan.MethodThis study drew data from the Taiwan National Health Insurance Database to conduct a historical cohort study. The study cohort comprised 3309 CD patients, and the comparison cohort comprised 13,236 subjects without an IBD. Cox proportional hazards regressions were performed to estimate the risk of subsequent stroke during the follow-up period. We also conducted additional analyses stratifying by age group and gender.ResultsAfter adjusting for selected medical co-morbidities and recent prescriptions of selected pharmaceuticals, the hazard ratio (HR) for subsequent stroke among patients with CD was found to be 1.911 (95xa0% confidence interval (CI)u2009=u20091.65–2.22) that of comparison subjects. While we did not detect an association between stroke and CD among patients aged 30–40xa0years, we did detect increased risks for stroke among CD patients aged 40–50xa0years (HRu2009=u20092.29) and those aged over 50xa0years (HRu2009=u20091.88). We also found women (HRu2009=u20092.39) to be at a greater risk than men (HRu2009=u20091.50).ConclusionThis study reports an increased HR for subsequent stroke among CD patients when compared to matched comparison patients without IBD in an Asian population.

Increased risk of stroke among patients with ulcerative colitis: a population-based matched cohort study.

BackgroundThe risk of venous thromboembolism (VTE) and the development of atherosclerosis are increased in patients with inflammatory bowel disease (IBD). Ulcerative colitis (UC) is one type of IBD; however, there is controversy in the literature regarding the association between UC and stroke. The present cohort study estimated the risk of subsequent stroke among UC patients compared with that among matched comparison subjects drawn from a population-based data set in Taiwan.MethodsThis investigation analyzed administrative claims data sourced from the Taiwan National Health Insurance Database. Our study consisted of a study cohort comprising 516 UC patients and a comparison cohort of 2,579 subjects without IBD. Cox proportional hazards regressions were performed to estimate the risk of subsequent stroke during the follow-up period. We also conducted additional analyses investigating the risk of subsequent stroke by age group and gender.ResultsAfter adjusting for selected medical co-morbidities and recent prescriptions of selected pharmaceuticals, the hazard ratio (HR) for subsequent stroke among patients with UC was 2.045 (95xa0% confidence interval (CI)u2009=u20091.374–3.043) than that among comparison subjects. While we did not detect an association between stroke and UC among patients aged 30–40 or 40–50xa0years, we did detect increased risks for stroke among UC patients aged over 50xa0years (HRu2009=u20092.045). We also found the association to remain significant for both men (HRu2009=u20092.153) and women (HRu2009=u20092.750).ConclusionsThis study detected an increased HR for subsequent stroke among Taiwanese UC patients when compared to that among matched comparison patients without IBD.

Common carotid artery end-diastolic velocity is independently associated with future cardiovascular events:

Background Carotid ultrasound is widely used to measure haemodynamic parameters, such as intima-media thickness and blood flow velocities (i.e. peak-systolic velocity [PSV], end-diastolic velocity [EDV], and resistive index [RI]). However, the association between blood flow velocities and cardiovascular events remains unclear. Design and methods Baseline data, including quantitative ultrasonography, were obtained from 3146 adults as part of the Cardiovascular Diseases Risk Factor Two-Township Study. Occurrence of ischaemic heart disease (IHD) and stroke was determined from insurance claims and death certificates. The hazard ratio (HR) of CVD (IHD and stroke combined) was calculated for EDV and PSV of the common carotid artery using Cox models. Net reclassification index and integrated discrimination index were used to evaluate the capacity of EDV to predict IHD, stroke, and CVD. Results Median follow-up was 12.8 years. There were 220 cases of IHD and 247 cases of stroke. The HR (95% CI) for CVD from univariate analysis was 4.54 (3.51–5.85) for EDV <15u2009cm/s relative to EDVu2009≥u200920u2009cm/s (pu2009<u20090.0001), and 3.23 (2.51–4.15) for PSVu2009<u200965u2009cm/s relative to PSVu2009≥u200980u2009cm/s (pu2009<u20090.0001). The HR (95% CI) for CVD from multivariate analysis was 1.66 (1.22–2.26) for EDVu2009<u200915u2009cm/s relative to EDVu2009≥u200920u2009cm/s, and 1.39 (1.03–1.89) for PSVu2009<u200965u2009cm/s relative to PSVu2009≥u200980u2009cm/s. EDV slightly but significantly improved prediction of CVD (integrated discrimination index 0.56%, pu2009=u20090.016). Conclusions Low common carotid EDV and PSV were independently associated with future CVD, and EDV improved the prediction of future CVD. More prospective studies are required in different ethnic groups to understand the significance and implication of these findings.

Improved predictive ability of the Montreal Cognitive Assessment for diagnosing dementia in a community-based study

IntroductionWe compared the predictive ability of the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) to diagnose dementia in a community-based study.MethodsA total of 276 people aged 60xa0years or older were enrolled. All of the participants were administered face-to-face interview questionnaires and MoCA and MMSE examinations. The receiver operating characteristic curve method and area under curve were performed to assess the predictive ability for diagnosing dementia.ResultsThe 276 participants had a mean age of 67.9u2009±u20096.1xa0years and mean education duration of 11.4u2009±u20094.0xa0years. In general, the MoCA yielded higher AUCs (0.891) with favorable sensitivity (78xa0%) and excellent specificity (94xa0%) compared with the MMSE in differentiating the participants with and without dementia in either the total sample or all subgroups.ConclusionOur study determined a higher predictive ability in the MoCA than in the MMSE for diagnosing dementia according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria in a community-based sample with a broader range of education level.

Epistasis analysis for estrogen metabolic and signaling pathway genes on young ischemic stroke patients.

Background Endogenous estrogens play an important role in the overall cardiocirculatory system. However, there are no studies exploring the hormone metabolism and signaling pathway genes together on ischemic stroke, including sulfotransferase family 1E (SULT1E1), catechol-O-methyl-transferase (COMT), and estrogen receptor α (ESR1). Methods A case-control study was conducted on 305 young ischemic stroke subjects aged ≦ 50 years and 309 age-matched healthy controls. SULT1E1 -64G/A, COMT Val158Met, ESR1 c.454−397 T/C and c.454−351 A/G genes were genotyped and compared between cases and controls to identify single nucleotide polymorphisms associated with ischemic stroke susceptibility. Gene-gene interaction effects were analyzed using entropy-based multifactor dimensionality reduction (MDR), classification and regression tree (CART), and traditional multiple regression models. Results COMT Val158Met polymorphism showed a significant association with susceptibility of young ischemic stroke among females. There was a two-way interaction between SULT1E1 -64G/A and COMT Val158Met in both MDR and CART analysis. The logistic regression model also showed there was a significant interaction effect between SULT1E1 -64G/A and COMT Val158Met on ischemic stroke of the young (P for interactionu200a=u200a0.0171). We further found that lower estradiol level could increase the risk of young ischemic stroke for those who carry either SULT1E1 or COMT risk genotypes, showing a significant interaction effect (P for interactionu200a=u200a0.0174). Conclusions Our findings support that a significant epistasis effect exists among estrogen metabolic and signaling pathway genes and gene-environment interactions on young ischemic stroke subjects.

Microstructural White Matter Tissue Characteristics Are Modulated by Homocysteine: A Diffusion Tensor Imaging Study

Homocysteine level can lead to adverse effects on the brain white matter through endothelial dysfunction, microstructural inflammation, and neurotoxin effects. Despite previously observed associations between elevated homocysteine and macroscopic structural brain changes, it is still unknown whether microstructural associations of homocysteine on brain tissue properties can be observed in healthy subjects with routine MRI. To this end, we investigated potential relationships between homocysteine levels and microstructural measures computed with diffusion tensor imaging (DTI) in a cohort of 338 healthy participants. Significant positive correlations were observed between homocysteine levels and diffusivity measures in the bilateral temporal WM, the brainstem, and the bilateral cerebellar peduncle. This is the first study demonstrating that DTI is sufficiently sensitive to relate microstructural WM properties to homocysteine levels in healthy subjects.

Significant Synergistic Effect of Peroxisome Proliferator–Activated Receptor γ C-2821T and Diabetes on the Risk of Ischemic Stroke

OBJECTIVE To explore the relationship between the genetic polymorphisms of PPARγ (Pro12Ala, C1431T, and C-2821T) and the risk of ischemic stroke and to investigate whether these genetic polymorphisms of PPARγ would modify the risk of ischemic stroke among patients with hypertension or diabetes. RESEARCH DESIGN AND METHODS The case-control study was conducted with 537 ischemic stroke patients and 537 control subjects. A structured questionnaire was used to collect information on conventional cardiovascular risk factors and laboratory results. The genetic polymorphisms of PPARγ were determined by PCR–restriction fragment–length polymorphism. RESULTS A significant interaction was seen between the −2821C allele and diabetes but not between this allele and hypertension. A markedly elevated risk of ischemic stroke (odds ratio 9.7) was found in the subjects with diabetes and the −2821C allele compared with that in those without these two risk factors. CONCLUSIONS The −2821C allele of PPARγ was a strong predictor of ischemic stroke for diabetic patients.

J-014 C-REACTIVE PROTEIN, AN INFLAMMATION MARKER, PREDICTS THE DEVELOPMENT OF HYPERTWNSION AND ISCHEMIC STROKE IN TAIWANESE POPULATION

Background Inflammation has been associated with cardiovascular events and mortality, using C-reactive protein (CRP) as a marker. However, few studies simultaneously examined its short-term effect for the development of hypertension and long-term effect for future ischemic stroke. We examined the hypotheses on whether CRP can independently predict the development of hypertension and ischemic stroke (IS) in the Chinese population in Taiwan. Methods The study population was those recruited in cycle 2 (1990–1993) of the CVDFACTS study and was followed to 1994–1997 for development of hypertension and to Dec 31, 2002 for future ischemic stroke. A total of 2113 normal blood pressure residents without diabetes were enrolled for studying incident hypertension and 3658 free of stroke individuals were recruited for future ischemic stroke. Three datasets were used to ascertain the status of ischemic stroke, including national health insurance dataset, death registry, and medical records. Results During the 3-year follow-up for development of hypertension and an average of 10.6-year follow-up for future ischemic stroke, there were 145 incident hypertension and 148 first-ever ischemic stroke events, respectively. The incidence rates of hypertension by tertiles of CRP were 3.1%, 6.3%, and 11.0% in that order (p for trend <.0001). The IS incidence rates by tertiles were 1.15, 4.04, and 6.54 per 1000 person-year (p for trend<.0001). In multivariate model baseline CRP significantly predicted incidence of hypertension and future IS. Comparing with the lowest group, the relative risks for incident hypertension were 1.35 (0.80–2.29) and 1.72 (1.0–2.88) for the middle and upper tertiles, respectively. Those for the future ischemic stroke were 1.87 (1.03–3.41) and 1.97 (1.08–3.61). Conclusions Inflammation may precede the development of hypertension and ischemic stroke in the Taiwanese population.