Intake of potassium- and magnesium-enriched salt improves functional outcome after stroke: a randomized, multicenter, double-blind controlled trial.

Background: Stroke is one of the leading causes of mortality and neurologic deficits. Management measures to improve neurologic outcomes are in great need. Our previous intervention trial in elderly subjects successfully used salt as a carrier for potassium, demonstrating a 41% reduction in cardiovascular mortality by switching to potassium-enriched salt. Dietary magnesium has been associated with lowered diabetes and/or stroke risk in humans and with neuroprotection in animals.Objective: Because a large proportion of Taiwanese individuals are in marginal deficiency states for potassium and for magnesium and salt is a good carrier for minerals, it is justifiable to study whether further enriching salt with magnesium at an amount near the Dietary Reference Intake (DRI) amount may provide additional benefit for stroke recovery.Design: This was a double-blind, randomized controlled trial comprising 291 discharged stroke patients with modified Rankin scale (mRS) ≤4. There were 3 arms: 1) regular salt (Na salt) (n = 99), 2) potassium-enriched salt (K salt) (n = 97), and 3) potassium- and magnesium-enriched salt (K/Mg salt) (n = 95). The NIH Stroke Scale (NIHSS), Barthel Index (BI), and mRS were evaluated at discharge, at 3 mo, and at 6 mo. A good neurologic performance was defined by NIHSS = 0, BI = 100, and mRS ≤1.Results: After the 6-mo intervention, the proportion of patients with good neurologic performance increased in a greater magnitude in the K/Mg salt group than in the K salt group and the Na salt group, in that order. The K/Mg salt group had a significantly increased OR (2.25; 95% CI: 1.09, 4.67) of achieving good neurologic performance compared with the Na salt group. But the effect of K salt alone (OR: 1.58; 95% CI: 0.77, 3.22) was not significant.Conclusions: This study suggests that providing the DRI amount of magnesium and potassium together long term is beneficial for stroke patient recovery from neurologic deficits. This trial was registered at clinicaltrials.gov as NCT02910427.

Low cholesterol level associated with severity and outcome of spontaneous intracerebral hemorrhage: Results from Taiwan Stroke Registry.

The relationship between cholesterol level and hemorrhagic stroke is inconclusive. We hypothesized that low cholesterol levels may have association with intracerebral hemorrhage (ICH) severity at admission and 3-month outcomes. This study used data obtained from a multi-center stroke registry program in Taiwan. We categorized acute spontaneous ICH patients, based on their baseline levels of total cholesterol (TC) measured at admission, into 3 groups with <160, 160-200 and >200 mg/dL of TC. We evaluated risk of having initial stroke severity, with National Institutes of Health Stroke Scale (NIHSS) >15 and unfavorable outcomes (modified Rankin Scale [mRS] score >2, 3-month mortality) after ICH by the TC group. A total of 2444 ICH patients (mean age 62.5±14.2 years; 64.2% men) were included in this study and 854 (34.9%) of them had baseline TC <160 mg/dL. Patients with TC <160 mg/dL presented more often severe neurological deficit (NIHSS >15), with an adjusted odds ratio [aOR] of 1.80; 95% confidence interval [CI], 1.41-2.30), and 3-month mRS >2 (aOR, 1.41; 95% CI, 1.11-1.78) using patients with TC >200 mg/dL as reference. Those with TC >160 mg/dL and body mass index (BMI) <22 kg/m2 had higher risk of 3-month mortality (aOR 3.94, 95% CI 1.76-8.80). Prior use of lipid-lowering drugs (2.8% of the ICH population) was not associated with initial severity and 3-month outcomes. A total cholesterol level lower than 160 mg/dL was common in patients with acute ICH and was associated with greater neurological severity on presentation and poor 3-month outcomes, especially with lower BMI.

Blood Pressure, Carotid Flow Pulsatility, and the Risk of Stroke: A Community-Based Study.

BACKGROUND AND PURPOSE: High blood pressure is a major cause of cardiovascular events, and carotid flow pulsatility may be associated with cardiovascular events. However, the combined effect of blood pressure and flow pulsatility on the development of stroke remains unclear. Therefore, we investigated the combined influence of central blood pressure and pulsatility index (PI) on the incidence of stroke. METHODS: Baseline data from 2033 adults (≥30 years) without stroke history in the Cardiovascular Disease Risk Factor Two-Township Study were linked to incident stroke. Common carotid flow PI was calculated by peak systolic velocity, end-diastolic velocity, and mean vessel velocity, which were measured in the common carotid artery. Hazard ratios for the risk of total stroke resulting from high central systolic blood pressure (CSBP) and high PI were calculated with Cox proportional hazard models. RESULTS: Over a median follow-up of 9.81 years, 132 people incurred stroke events. The incidence rates of stroke were 1.3, 6.4, and 13.2 per 1000 person-years for tertile groups of CSBP (P for trend<0.05) and 4.3, 7.0, and 9.4 per 1000 person-years for tertile groups of PI (P for trend<0.05). Compared with the first tertile of CSBP, hazard ratios were 4.88 (95% confidence interval, 2.29-10.43) for the second tertile and 10.42 (5.05-21.53) for the third tertile. Hazard ratios of PI were 2.18 (1.39-3.42; third tertile) and 1.64 (1.02-2.63; second tertile) compared with the first tertile. The individuals with a high CSBP and high PI had a 13-fold higher stroke risk compared with those with low CSBP and low PI (13.2; 1.75-99.71) after adjusting for age, sex, and traditional cardiovascular risk. CONCLUSIONS: CSBP and common carotid PI jointly and independently predicted future stroke. Carotid flow pulsatility may play an important role in the development of stroke.

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 <15 cm/s relative to EDV ≥ 20 cm/s (p < 0.0001), and 3.23 (2.51-4.15) for PSV < 65 cm/s relative to PSV ≥ 80 cm/s (p < 0.0001). The HR (95% CI) for CVD from multivariate analysis was 1.66 (1.22-2.26) for EDV < 15 cm/s relative to EDV ≥ 20 cm/s, and 1.39 (1.03-1.89) for PSV < 65 cm/s relative to PSV ≥ 80 cm/s. EDV slightly but significantly improved prediction of CVD (integrated discrimination index 0.56%, p = 0.016). 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.

Onset headache predicts good outcome in patients with first-ever ischemic stroke.

BACKGROUND AND PURPOSE: The study aimed to assess whether onset headache is an ominous sign in patients with first-ever ischemic stroke. METHODS: A large population of ischemic stroke patients was obtained from the Taiwan Stroke Registry. Stroke subtypes were classified by the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) criteria. On the basis of the International Classification of Headache Disorders, second version, onset headache was defined as a new headache that developed at the onset of ischemic stroke. Clinical features and impact on stroke outcomes, including in-hospital stroke in evolution, changes in National Institutes of Health Stroke Scale on discharge, and Barthel index and modified Rankin scale ≤6 months after stroke were compared between those with and without onset headache. RESULTS: Among 11 523 patients with first-ever ischemic stroke, 848 had onset headache (7.4%). Patients with specific cause, large-artery atherosclerosis, or cardioembolism were more likely to have onset headache. Patients with onset headache were younger, predominantly female, and more likely to have posterior circulation ischemic lesions. Compared with patients without onset headache, those with onset headache had a lower frequency of stroke in evolution (4.5% versus 6.7%; adjusted relative risk, 0.64; 95% confidence interval, 0.52-0.79), greater improvement in National Institutes of Health Stroke Scale score on discharge (0.08 versus -0.20; P=0.02), higher mean Barthel index scores (86.5±20.0 versus 83.9±23.3; adjusted difference, 1.43; 95% confidence interval, 0.28-2.89), and a lower frequency of modified Rankin scale higher than 2 (27.6% versus 31.5%; adjusted relative risk, 0.85; 95% confidence interval, 0.72-0.95) at 1-month follow-up. There was also a trend for better functional outcome in 3- and 6-month follow-ups. CONCLUSIONS: By adopting standard classification criteria, this large-scale study demonstrated that onset headache was associated with modest but significantly better outcomes after ischemic stroke.

Common carotid end-diastolic velocity and intima-media thickness jointly predict ischemic stroke in Taiwan.

BACKGROUND AND PURPOSE: In Asian populations, few studies investigated the association between stroke and common carotid artery intima-media thickness (IMT). Our previous case-control studies showed that low end-diastolic velocity (EDV) in common carotid artery, a potential hemodynamic marker of intracranial resistance, was associated with ischemic stroke. Therefore, we investigated the relationship between both EDV and IMT and incident ischemic stroke in an Asian population. METHODS: Baseline data from 3175 adults (30 years or older) in the Cardiovascular Diseases Risk Factor Two-Township Study were linked to incidental ischemic stroke status derived from insurance claims and death certificate records. Hazard ratios for risk of ischemic stroke for high IMT and low EDV values measured in common carotid artery were calculated using Cox proportional hazard models. RESULTS: With 9.85 years (median) of follow-up, 184 persons had ischemic stroke develop. Compared with the first tertile of IMT, hazard ratios were 2.03 (95% confidence intervals, 1.27-3.25) for the second tertile and 3.87 (95% confidence intervals, 2.36-5.69) for the third tertile. Hazard ratios of EDV were 5.31 (95% confidence intervals, 3.52-7.99; first tertile) and 1.94 (95% confidence intervals, 1.21-3.09; second tertile) compared with the third tertile. The individuals with high IMT and low EDV had >2-fold ischemic stroke risk compared to those with low IMT and high EDV (2.10; 95% confidence intervals, 1.35-3.26) after adjusting for age, sex, and traditional cardiovascular risk. CONCLUSIONS: Common carotid IMT and EDV jointly and independently predicted future ischemic stroke in this Taiwanese population. More prospective studies are required in various ethnic groups to understand the significance and implication of the current findings, particularly with respect to EDV.

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

BACKGROUND: Carotid 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. METHODS: B-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. RESULTS: The T allele of connexin37 C1019T polymorphism significantly affected IMT (ß=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. CONCLUSION: Connexin 37 genetic variants significantly affect carotid IMT and contribute to future development of ischemic stroke.

Shorter GT repeat polymorphism in the heme oxygenase-1 gene promoter has protective effect on ischemic stroke in dyslipidemia patients.

BACKGROUND: The microsatellite polymorphism of heme oxygenase (HO)-1 gene promoter has been shown to be associated with the susceptibility to ischemic event, including coronary artery disease (CAD), myocardial infarction, and peripheral vascular disease. We aimed to examine whether the length of (GT)(n) repeats in HO-1 gene promoter is associated with ischemic stroke in people with CAD risk factors, especially low level of HDL. METHODS: A total of 183 consecutive firstever ischemic stroke inpatients and 164 non-stroke patients were screened for the length of (GT)(n) repeats in HO-1 promoter. The long (L) and short (S) genotype are defined as the averaged repeat number >26 and <==26, respectively. RESULTS: Stroke patients tended to have more proportions of hypertension, diabetics and genotype L, than those of genotype S. Patients with genotype L of HO-1 gene promoter have higher stroke risk in comparison with genotype S especially in dyslipidemia individuals. The significant differences on stroke risk in multivariate odds ratios were found especially in people with low HDL-C levels. CONCLUSIONS: Subjects carrying longer (GT)(n) repeats in HO-1 gene promoter may have greater susceptibility to develop cerebral ischemic only in the presence of low HDL-C, suggesting the protective effects in HO-1 genotype S in the process of ischemic stroke, particularly in subjects with poor HDL-C status.

Rapid identification and susceptibility testing using the VITEK 2 system using culture fluids from positive BacT/ALERT blood cultures.

BACKGROUND AND PURPOSE: In order to reduce the turnaround time for laboratory diagnosis of bacteremia, the efficacy of identification and antimicrobial susceptibility testing using samples taken directly from positive BacT/ALERT standard aerobic and standard anaerobic blood culture bottles was evaluated. METHODS: 160 positive blood culture bottles were examined and incubated at 35 degrees C in 5% carbon dioxide for 4-24 h, and an aliquot of the culture fluid was Gram stained. Samples containing Gram-negative bacilli were inoculated on VITEK 2 ID-GNB (identification-Gram-negative bacilli) and AST (antimicrobial susceptibility testing)-GN04 cards, and those containing Gram-positive cocci were inoculated on ID-GPC (identification-Gram-positive cocci) and AST-P526 cards. The same samples were also examined by the standard method, involving subculture from positive BacT/ALERT standard blood culture bottles. RESULTS: Eighty seven of 97 Gram-negative bacilli (89.7%) and 21 of 63 Gram-positive cocci (33.3%) were correctly identified to the species level. For antimicrobial susceptibility testing, the direct method had an overall error rate of 5.4% for Gram-negative bacilli, with 0.9% very major, 0.9% major, and 3.6% minor discrepancies compared to the standard method. The overall error rate in antimicrobial susceptibility testing for the 13 Staphylococcus spp. was 10.3%, with 6.0% very major, 2.6% major, and 1.7% minor discrepancies. CONCLUSION: These data suggest that VITEK 2 cards inoculated with samples taken directly from positive Bact/ALERT blood culture bottles would provide acceptable identification and antimicrobial susceptibility testing results for Gram-negative bacilli, but not for Gram-positive cocci. Compared to the standard method, the direct method would reduce turnaround time by at least 24 h.

[Guidelines for the general management of patients with acute ischemic stroke].

The content of the second edition of "Guideline for General Management of Patients with Acute Ischemic Stroke" was amended from the first edition of that of the Taiwan Stroke Society in 2002. The format of the guideline followed the common unified instruction for the project of "The establishment of clinical guidelines for the top 10 payments diseases of the National Health Insurance at the departments of inpatients, emergency and outpatients" as recommended by the National Health Research Institutes (NHRI). The guideline was revised after several official meetings of local experts, as well as citation from the latest updated guidelines of the United States and the European Stroke academic groups. Before editing notice, the final evaluation was performed by the review team of the NHRI. Application of the guideline is dedicated or designated to the patients with acute ischemic stroke, and which is applied only limited to the general management. Guidelines for subacute or chronic phase, or the specific treatment for ischemic stroke patients will be published in separated articles. Management of most of the needs for patients with acute ischemic stroke must be completed in a very short period of time. It is recommended that hospitals providing stroke service to set up stroke unit, and to organize an integrated stroke team consisting of specialists from multiple disciplines. Upon arrival to the hospitals, patients should undergo the brain computed tomography, and related examinations and assessment as soon as possible to guide the choice of treatment reference for acute intervention. Intravenous recombinant tissue plasminogen activator treatment within three hours is effective in reducing disability for patients with acute ischemic stroke. Ischemic stroke patients with or without persistent symptoms should start antiplatelet therapy immediately, generally aspirin. Dose-adjusted warfarin (INR range of 2.0-3.0) is recommended for ischemic stroke patients with persistent or paroxysmal atrial fibrillation to prevent secondary embolism. The routine use ofheparin and drugs theoretically preventing further brain injury, including steroids, neuroprotectants, plasma volume expanders, barbiturates, and streptokinase, has not been proven benefits for recommendation.

Lower blood flow velocity, higher resistance index, and larger diameter of extracranial carotid arteries are associated with ischemic stroke independently of carotid atherosclerosis and cardiovascular risk factors.

PURPOSE: To investigate the association between diameter and flow velocity of the carotid arteries and ischemic stroke. METHODS: Peak systolic velocity, end diastolic velocity, Pourcelot resistance index, blood flow volume, luminal diameter, and carotid plaque burden were measured and compared in 240 ischemic stroke (IS) patients without history of stroke, 163 chronic stable IS patients, and 236 nonstroke controls (age, >or=40 years). Data were also compared between stroke subtypes (large artery atherosclerosis, lacunar, cardioembolic, or undetermined origin). RESULTS: Acute as well as chronic stable IS patients had significantly lower flow velocities and flow volume, higher resistance index than nonstroke controls in the common carotid artery (CCA), internal carotid artery and external carotid artery, and larger common carotid artery diameter. The differences were found across all IS subtypes and in stroke patients with as well as without carotid plaque. Comparisons between these subgroups showed significant differences in end diastolic velocity, resistance index, flow velocity, and diameter that were more prominent in the CCA. After adjusting for carotid plaque and cardiovascular risk factors, the associations between the above-mentioned parameter and stroke remained significant. CONCLUSIONS: Stroke patients in acute as well as chronic stable phase appeared to have larger CCA diameters, lower carotid flow velocities and volume, and higher resistance index than nonstroke patients independently of extracranial carotid atherosclerosis. These findings need to be confirmed by a prospective study.

High titer of anticardiolipin antibody is associated with first-ever ischemic stroke in Taiwan.

BACKGROUND AND PURPOSE: The association between anticardiolipin antibody (aCL) and ischemic stroke is controversial, and there are few case-control studies of Asian populations. The aim of this study, therefore, was to determine whether aCL is an independent risk factor for ischemic stroke in Taiwanese patients over the age of 40 years. METHODS: Both the IgG and IgM isotypes of aCL were measured in 273 patients (> 40 years of age) hospitalized for first-ever ischemic stroke and in 181 non-stroke controls. Results were defined as: negative (< 10 IgG phospholipid units [GPL] or < 7.5 IgM phospholipid units [MPL]); low positive (10-20 GPL or 7.5-15 MPL); or, high positive (> 20 GPL or > 15 MPL). Odds ratios (OR) were estimated by logistic regression with adjustment for potential confounders. RESULTS: A high positive IgG aCL was present in 4.4% of the stroke patients and 1.2% of the controls. Age- and sex-adjusted analysis showed a borderline association between a high positive level for aCL IgG titer and stroke, with an OR of 4.01 (95% CI 0.87-18.37; p = 0.0739). Final analysis, with adjustments for age, sex, hypertension, diabetes, tobacco smoking, atrial fibrillation, left ventricular hypertrophy and hyperlipidemia, revealed an OR of 5.25 (95% CI 1.06-25.89; p = 0.0419). CONCLUSIONS: The results of this study suggest that elevated titer of aCL IgG (> 20 GPL) is associated with first-ever ischemic stroke in Taiwanese patients aged over 40 years. High positive aCL titer is related to ischemic stroke after adjustment for conventional cerebrovascular risk factors, indicating that it is probably an independent risk factor for ischemic stroke.