Hyung-Min Kwon

Frequency, Risk Factors, and Outcome of Coexistent Small Vessel Disease and Intracranial Arterial Stenosis: Results From the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) Trial

IMPORTANCEnIntracranial arterial stenosis (ICAS) and small vessel disease (SVD) may coexist. There are limited data on the frequency and risk factors for coexistent SVD and the effect of SVD on stroke recurrence in patients receiving medical treatment for ICAS.nnnOBJECTIVEnTo investigate the frequency and risk factors for SVD and the effect of SVD on stroke recurrence in patients with ICAS.nnnDESIGN, SETTING, AND PARTICIPANTSnA post hoc analysis of the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) study, a prospective, multicenter clinical trial. Among 451 participants, 313 (69.4%) had baseline brain magnetic resonance imaging scans read centrally for SVD that was defined by any of the following: old lacunar infarction, grade 2 to 3 on the Fazekas scale (for high-grade white matter hyperintensities), or microbleeds. Patient enrollment in SAMMPRIS began November 25, 2008, and follow-up ended on April 30, 2013. Data analysis for the present study was performed from May 13, 2014, to July 29, 2015.nnnMAIN OUTCOMES AND MEASURESnRisk factors in patients with vs without SVD and the association between SVD and other baseline risk factors with any ischemic stroke and ischemic stroke in the territory of the stenotic artery determined using proportional hazards regression.nnnRESULTSnOf 313 patients, 155 individuals (49.5%) had SVD noted on baseline magnetic resonance imaging. Variables that were significantly higher in patients with SVD, reported as mean (SD), included age, 63.5 (10.5) years (Pu2009<u2009.001), systolic blood pressure, 149 (22) mm Hg (Pu2009<u2009.001), glucose level, 130 (50) mg/dL (Pu2009=u2009.03), and lower Montreal Cognitive Assessment scores (median, ≥24 [interquartile range, 20-26]; Pu2009=u2009.02).Other significant variables were the number of patients with diabetes mellitus (88 of 155 [56.8%]; Pu2009=u2009.003), coronary artery disease (46 [29.7%]; Pu2009=u2009.004), stroke before the qualifying event (59 [38.1%]; Pu2009<u2009.001), old infarct in the territory of the stenotic intracranial artery (88 [56.8%]; Pu2009<u2009.001), and receiving antithrombotic therapy at the time of the qualifying event (109 [70.3%]; Pu2009=u2009.005). The association between SVD and any ischemic stroke was nearly significant in the direction of a higher risk (18 [23.7%]); Pu2009=u2009.07) for patients with SVD. On bivariate analysis, SVD was not associated with an increased risk on multivariable analyses (hazard ratio, 1.7 [95% CI, 0.8-3.8]; Pu2009=u2009.20). In addition, SVD was not associated with an increased risk of stroke in the territory on either bivariate or multivariable analyses.nnnCONCLUSIONS AND RELEVANCEnAlthough SVD is common in patients with ICAS, the presence of SVD on baseline magnetic resonance imaging is not independently associated with an increased risk of stroke in patients with ICAS.nnnTRIAL REGISTRATIONnclinicaltrials.gov Identifier: NCT00576693.

Elevated neutrophil to lymphocyte ratio and ischemic stroke risk in generally healthy adults

Elevated neutrophil to lymphocyte ratio (NLR) has been reported as a marker for chronic inflammation, associated with poor prognosis in ischemic stroke patients, but there has been no study that investigated its association with ischemic stroke risk. This study was conducted to investigate elevated NLR as an independent risk factor for ischemic stroke incidence. Our retrospective cohort study included 24,708 generally healthy subjects aged 30–75 who received self-referred health screening at Seoul National University Hospital. Data on ischemic stroke incidence was retrieved from national medical claims registry. Median follow-up time was 5.9 years (interquartile range 4.2 years). Adjusted for major cardiovascular risk factors, compared to subjects with NLR<1.5, subjects with 2.5≤NLR<3.0, 3.0≤NLR<3.5, and NLR≥3.5 had elevated risk for ischemic stroke incidence with aHR (95% CI) of 1.76 (1.09–2.84), 2.21 (1.21–4.04), and 2.96 (1.57–5.58), respectively. NLR showed significant improvement in discrimination for ischemic stroke incidence compared to traditional cardiovascular risk factors (C-index 0.748 vs. 0.739, P = 0.025). There was significant net improvement in reclassification in Framingham risk for ischemic stroke incidence after addition of NLR, with IDI 0.0035 (P<0.0001), and NRI 6.02% (P = 0.0015). This reclassification for ischemic stroke incidence by NLR was markedly pronounced among subjects with atrial fibrillation with CHA2DS2-VASc<2 (NRI 42.41%, P = 0.056). Our study suggests elevated NLR to be an independent risk factor for ischemic stroke incidence in generally healthy adults. Future studies are needed to validate our results and further assess how subjects with elevated NLR should be managed within current guidelines.

Leukoaraiosis is associated with pneumonia after acute ischemic stroke

BackgroundStroke-associated pneumonia (SAP) is common in patients with acute ischemic stroke, and several risk factors have been reported. However, the relationship between underlying leukoaraiosis (LA) and SAP has not been addressed.MethodsWe collected consecutive patients with acute ischemic stroke within 24xa0h of symptom onset. SAP was defined as the lower respiratory tract infection within the first 7xa0days after stroke onset, according to the modified Centers for Disease Control and Prevention criteria. LA was graded using the Fazekas scale in both the periventricular and subcortical areas. We evaluated LA burden by summing the grade and dichotomized into mild LA (0–2) or severe LA (3–6). Relationship between LA and SAP was analyzed by binary logistic regression analysis with variables of Pu2009<u20090.05 in univariate analysis.ResultsThree hundred eight consecutive patients were enrolled, and SAP developed in 44 patients (14%). Univariate analysis revealed that SAP correlated with age, initial NIHSS score, atrial fibrillation, impaired consciousness, dysphagia, severe LA and hyperlipidemia. On multivariate analysis, severe LA [adjusted OR (aOR)u2009=u20094.41, 95% CIu2009=u20092.04–9.55, Pu2009<u20090.001 remained independent predictors of SAP after adjusted confounders.ConclusionsIn this study, LA was an independent predictor of SAP. This observation needs to be confirmed in suitably-designed, prospective studies.

High neutrophil to lymphocyte ratio is associated with white matter hyperintensity in a healthy population

High neutrophil to lymphocyte ratio (NLR) is correlated with the occurrence, morbidity and mortality of cerebrovascular disease as a marker of systemic inflammation. However, its effect on cerebral white matter hyperintensity (WMH) is unclear. We investigated high NLR burden as a surrogate marker of WMH volume in a healthy population. Healthy subjects with voluntary health check-ups between January 2006 and December 2013, including brain MRI and laboratory examination, were collected. WMH volumes were rated quantitatively. A total of 2875 subjects were enrolled, and the mean volume of WMH was 2.63±6.26mL. In multivariate linear regression analysis, NLR [β=0.191, 95% confidence interval (CI)=0.104 to 0.279, P<0.001] remained significant after adjusting for confounders. Age (β=0.049, 95% CI=0.045 to 0.054, P<0.001), hypertension (β=0.191, 95% CI=0.101 to 0.281, P<0.001), diabetes (β=0.153, 95% CI=0.045 to 0.261, P=0.006), and extracranial atherosclerosis (β=0.348, 95% CI=0.007 to 0.688, P=0.045) were also significant independently from NLR. Additionally, the high NLR group (NLR≥1.52) was related to male sex, hypertension, diabetes, current smoking, extracranial atherosclerosis, silent brain infarct, and high WMH volumes. In conclusion, high NLR is associated with larger WMH volumes in a healthy population. Assessment of NLR may be helpful in detecting cerebral WMH burdens in high risk groups.

The correlation between cerebral arterial pulsatility and cognitive dysfunction in Alzheimer's disease patients

BACKGROUNDnPotential role of vascular dysfunction has been suggested in the pathogenesis of Alzheimers disease (AD). Previous cross-sectional studies have demonstrated relations between abnormal transcranial Doppler (TCD) parameters and cognitive impairment. We aimed to investigate the associations between longitudinal changes of TCD parameters and cognitive decline in patients with AD.nnnMETHODSnWe have enrolled patients with mild to moderate AD who aged 60 to 79years. Mean flow velocity and pulsatility index (PI) of anterior (ACA), middle (MCA), and posterior (PCA) cerebral arteries were evaluated. Cognitive functions were assessed using mini-mental state examination (MMSE), clinical dementia rating sum of boxes (SOB), and Alzheimers Disease Assessment Scale (ADAS-cog), which was further categorized as praxis, language, and memory subscores. TCD and cognitive assessments were followed up 1year later, and the longitudinal changes (Δ) between the baseline and follow-up measurements were evaluated.nnnRESULTSnA total of 51 patients completed the follow-up evaluations (baseline age 71.5years, MMSE 21.2). In the baseline evaluations, high PI values of ACA and MCA were associated with poor MMSE score, ADAS-cog total, memory, and praxis subscores. After 1year, the increases of ACA and MCA PI were correlated with the aggravation of ADAS language subscore, and ΔACA PI was also correlated with ΔSOB. The decrease in mean flow velocity of ACA was associated with aggravation of ADAS-cog praxis score.nnnCONCLUSIONSnThere was significant correlation between longitudinal changes of TCD parameters and cognitive dysfunction in patients with mild to moderate AD. Serial assessment of TCD may provide useful information regarding to the disease progression.

Association between Helicobacter pylori Infection and Cerebral Small Vessel Disease

Background Small vessel disease is an important cause of cerebrovascular diseases and cognitive impairment in the elderly. There have been conflicting results regarding the relationship between Helicobacter pylori infection and ischemic stroke. This study aimed to examine the association between H. pylori infection and cerebral small vessel disease. Methods The study included 1,117 patients who underwent brain magnetic resonance imaging and H. pylori identification between 2005 and 2013 at Health Promotion Center, Seoul National University Hospital. Multivariable logistic regression analysis was used to assess the association between H. pylori infection and small vessel disease with adjustment for age, sex, hypertension, diabetes mellitus, dyslipidemia, body mass index, smoking status, problem drinking, and antiplatelet use. Results The adjusted odds ratios (aORs) for the association between H. pylori infection and silent brain infarction and cerebral microbleeds were 1.03 (95% confidence interval [CI], 0.66-1.61) and 0.70 (95% CI, 0.38-1.28), respectively. The aORs for silent brain infarction and cerebral microbleeds were 0.81 (95% CI, 0.44-1.44) and 0.59 (95% CI, 0.30-1.18) in patients aged <65 years and 1.59 (95% CI, 0.78-3.22) and 1.89 (95% CI, 0.38-9.33) in those aged >65 years, respectively. Moreover, the aORs for silent brain infarction and cerebral microbleeds were 0.96 (95% CI, 0.54-1.71) and 0.74 (95% CI, 0.33-1.69) in H. pylori-infected patients without atrophic gastritis and 0.89 (95% CI, 0.48-1.62) and 0.99 (95% CI, 0.43-2.27) in those with atrophic gastritis, respectively. Conclusion No association between H. pylori infection and small vessel disease was observed. H. pylori-induced inflammation may not be a risk factor for microcirculatory damage in the brain.

Effects of Temperature and Pressure on Acute Stroke Incidence Assessed Using a Korean Nationwide Insurance Database

Background and Purpose Many studies have evaluated the association between weather and stroke, with variable conclusions. Herein we determined the relationships between daily meteorological parameters and acute stroke incidence in South Korea. Methods Patients with acute stroke (2,894) were identified by standard sampling of a nationwide insurance claims database from January to December 2011. We used multiple Poisson regression analyses of stroke incidence and meteorological parameters (mean temperature, diurnal temperature change, temperature differences over the preceding 24 hours, atmospheric pressure, humidity, wind speed, and physiologically equivalent temperature) to calculate the relative risk of stroke incidence associated with meteorological parameters. Results There were no seasonal variations in the incidences of ischemic (2,176) or hemorrhagic (718) stroke. Temperature change during the day was positively correlated with ischemic stroke in men (relative risk [RR] 1.027; 95% confidence interval [CI] 1.006–1.05) and older patients (≥65 years) (RR 1.031, 95% CI 1.011–1.052). Temperature differences over the preceding 24 hours had a negative correlation with all strokes (RR 0.968, 95% CI 0.941–0.996), especially among older women. Diurnal variation of atmospheric pressure was also significantly associated with the incidence of ischemic stroke (age<65 years, RR 1.051, 95% CI 1.011–1.092; age≥65 years, RR 0.966, 95% CI 0.936–0.997). Conclusions Diurnal temperature change, temperature differences over the preceding 24 hours, and diurnal variation of atmospheric pressure were associated with daily stroke incidence. These findings may enhance our understanding of the relationship between stroke and weather.

Distal hyperintense vessel sign is associated with neurological deterioration in acute ischaemic stroke

The aim was to evaluate the relationship between distal hyperintense vessel sign (HVS) and early neurological deterioration (END) in acute ischaemic stroke with large vessel steno‐occlusion.

High neutrophil to lymphocyte ratios predict intracranial atherosclerosis in a healthy population

BACKGROUND AND AIMSnAlthough atherosclerosis has been shown to be an inflammatory disease, intracranial atherosclerosis (ICAS) has not been well addressed. The purpose of this study was to evaluate the relationship between the neutrophil to lymphocyte ratio (NLR) and the presence of ICAS lesions in a generally healthy population.nnnMETHODSnA consecutive series of subjects, who voluntarily visited for health check-ups between January 2006 and December 2013, were selected. Brain magnetic resonance imaging, brain magnetic angiography (MRA), and blood cell count data were assessed. ICAS was defined as an occlusion or more than 50% stenosis of intracranial vessels, as observed on brain MRA images. NLR was calculated based on absolute neutrophil and lymphocyte counts.nnnRESULTSnA total of 2842 subjects were evaluated, and 76 ICAS cases were found. The median NLR was 1.52 [1.17-2.01]. In multivariate analysis, NLR remained an independent predictor of ICAS [adjusted OR (aOR)u202f=u202f1.72, 95% confidence interval (CI)u202f=u202f1.01-2.95, pu202f=u202f0.048]. Age (aORu202f=u202f1.08, 95% CIu202f=u202f1.05-1.11, pu202f<u202f0.001) and hypertension (aORu202f=u202f1.81, 95% CIu202f=u202f1.11-2.94, pu202f=u202f0.017) were also significant factors for ICAS independent of NLR. Regarding ICAS burdens, NLR was significantly higher when the number of ICAS lesions (pu202f=u202f0.017) or occlusive ICAS lesions (pu202f=u202f0.005) was increased in a dose-response manner.nnnCONCLUSIONSnA high NLR was associated with both prevalence and burdens of ICAS in a healthy population.

Clinical relevance of abnormal neuroimaging findings and long‐term risk of stroke recurrence

Previous studies have revealed that the predictors of short‐ and long‐term stroke recurrence are different. We designed a comprehensive stroke recurrence (CSR) model, composed of demographic, clinical and radiological findings, to predict long‐term ischaemic stroke recurrences.