Lipid on stroke in intracranial artery atherosclerotic stenosis: a mediation role of glucose.

Objective: Expanding on previous investigations, this study aims to elucidate the role of lipid metabolism disorders in the development of intracranial atherosclerotic stenosis (ICAS) and the determination of stroke risk. The primary objective is to explore the connections between lipid parameters and acute ischemic stroke (AIS), while also examining the potential mediating influence of fasting glucose levels. Methods: Retrospectively, we collected data from symptomatic ICAS patients at the First Affiliated Hospital of Soochow University, including their baseline information such as medical histories and admission blood biochemical parameters. Stenotic conditions were evaluated using magnetic resonance imaging, computed tomography angiography, or digital subtraction angiography. The associations between lipid parameters and AIS risks were investigated via multivariate logistic regression analysis. Results: A total of 1103 patients with symptomatic ICAS were recruited, among whom 441 (40.0%) suffered new ischemic events during hospitalization. After adjusting for confounding factors, the RCS curves exhibited a dose-response relationship between the atherogenic index of plasma (AIP), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and AIS. Further multivariate analysis revealed significant associations between these parameters and AIS. Furthermore, mediation analysis indicated that fasting blood glucose (FBG) acted as a mediator in the association between lipid parameters (AIP, TC, and TG) and AIS. Conclusion: Higher lipid parameters in ICAS patients, particularly AIP, TC, and TG, were associated with an increased AIS risk. Additionally, FBG may mediate stroke risk in ICAS patients, highlighting the need for further exploration of underlying mechanisms.

Causal relationship between C-reactive protein and ischemic stroke caused by atherosclerosis: A Mendelian randomization study.

OBJECTIVES: This study investigates the association between C-reactive protein (CRP) and ischemic stroke caused by large artery atherosclerosis (LAA). METHODS: Five Mendelian Randomization (MR) methodologies were used for two-sample analyses: Inverse Variance Weighting (IVW), MR-Egger regression, Weighted Median (WM), Simple Mode, and Weighted Mode. CRP exposure data were obtained from aggregated summary statistics from a meta-analysis of genome-wide association studies (GWAS) in individuals of European ancestry (n = 343,524; UK Biobank). Stroke data were used as the outcome, with specific dataset details for relevant subtypes (cases = 40,585, controls = 406,111). RESULTS: In the CRP GWAS dataset, selected single nucleotide polymorphisms (SNPs) as instrumental variables (IVs) showed genome-wide significance and a causal relationship with CRP, particularly in relation to LAA stroke. IVW indicated a robust causal connection between CRP and LAA stroke (Beta = 0.151, SE = 0.055, P = 0.006). The WM approach supported this relationship (Beta = 0.176, SE = 0.082, P = 0.033). However, MR-Egger regression suggested a potential absence of a causal link (Beta = 0.098, SE = 0.077, P = 0.206), with minimal influence from horizontal pleiotropy (Intercept = 0.0029; P = 0.317). The Simple mode found no significant association (Beta = 0.046, SE = 0.217, P = 0.834), while the Weighted mode revealed a significant causal association (Beta = 0.138, SE = 0.059, P = 0.020) between CRP and LAA stroke. CONCLUSIONS: MR analysis provides evidence for a potential causal relationship between CRP and an increased risk of LAA stroke.

The role of triglyceride-glucose index in the differential diagnosis of atherosclerotic stroke and cardiogenic stroke.

OBJECTIVE: This study aims to investigate the role of the triglyceride glucose (TyG) index in differentiating cardiogenic stroke (CE) from large atherosclerotic stroke (LAA). METHOD: In this retrospective study, patients with acute ischemic stroke were recruited from the First Affiliated Hospital of Soochow University, Lianyungang Second People's Hospital and Lianyungang First People's Hospital. Their general data, medical history and laboratory indicators were collected and TyG index was calculated. Groups were classified by the TyG index quartile to compare the differences between groups. Logistic regression was utilized to assess the relationship between the TyG index and LAA. The receiver operating characteristic curve (ROC) curve was used to evaluate the diagnostic efficiency of the TyG index in differentiating LAA from CE. RESULT: The study recruited 1149 patients. After adjusting for several identified risk factors, groups TyG-Q2, TyG-Q3, and TyG-Q4 had a higher risk of developing LAA compared to group TyG-Q1(odds ratio (OR) = 1.63,95% confidence interval (CI) = 1.11-2.39, OR = 1.72,95%CI = 1.16-2.55, OR = 2.06,95%CI = 1.36-3.09). TyG has certain diagnostic value in distinguishing LAA from CE(AUC = 0.595, 95%CI0.566-0.623;P<0.001). CONCLUSION: Summarily, the TyG index has slight significance in the identification of LAA and CE; it is particularly a marker for their preliminary identification.

Short-term glycemic variability and intracranial atherosclerotic plaque stability assessed by high-resolution MR vessel wall imaging in type 2 diabetes mellitus.

OBJECTIVE: To investigate the relationship between short-term glycemic variability in patients with T2DM and the vulnerability of intracranial atherosclerotic plaques using HR-MR-VWI. MATERIALS AND METHODS: In total, 203 patients with acute ischemic stroke (AIS)/transient ischemia (TIA) combined with T2DM were enrolled. All of them underwent HR-MR-VWI during the period between July 2020 and July 2023. 203 patients were divided into groups with higher (1,5-AG≤ 30.7 µmol/L) and lower (1,5-AG> 30.7 µmol/L) short-term glycemic variability. Patients were also divided into the T1WI and non-T1WI hyperintensity groups. Associated factors(FBG, HbA1c, and 1,5-AG)for the T1WI hyperintensity were analyzed by binary logistic regression. We used the area under the curve (AUC), while the sensitivity and specificity were calculated at the optimal threshold. The Delong test was employed to compare the quality of the AUC of the predictors. RESULTS: The group with higher short-term glycemic variability had a higher incidence of the hyperintensity on T1WI, higher degree of enhancement, higher degree of stenosis and smaller lumen area (P < 0.05). The T1WI hyperintensity group had higher HbA1c levels, higher hemoglobin levels and lower 1,5-AG levels(P < 0.05). 1,5-AG (OR = 0.971, 95 % CI: 0.954∼0.988, P = 0.001), HbA1c (OR=1.305, 95 % CI: 1.065∼1.598, P = 0.01) and male sex (OR = 2.048, 95 % CI: 1.016∼4.128, P = 0.045)/(OR=2.102, 95 % CI: 1.058∼4.177, P = 0.034) were independent risk factors for the hyperintensity on T1WI. 1,5-AG demonstrated enhanced performance and yielded the highest AUC of the receiver operator characteristic curve (AUC = 0.726), with sensitivity and specificity values of 0.727 and 0.635 respectively. CONCLUSION: 1,5-AG, HbA1c and male sex are independent predictors of intracranial plaques with T1WI hyperintensity, the greater short-term glycemic variability, the higher incidence of vulnerable plaques.

Albumin levels and cerebral collateral circulation in patients with acute ischemic stroke due to intracranial arteriosclerotic: A propensity score-matched analysis.

Cerebral collateral circulation (CC) is associated with the recurrence and severity of acute ischemic stroke (AIS), and early identification of poor CC is helpful for the prevention of AIS. In this study we evaluated the association between serum albumin levels and CC in AIS using logistic regression. Propensity score (PS) matching was used to eliminate the effect of confounders, and restricted cubic splines (RCS) were employed to explore potential nonlinear associations between albumin and CC. In unadjusted logistic regression analysis, lower albumin (OR = 0.85, 95% CI = 0.79-0.92) was associated with poor CC, and after adjusting for covariates, the odds of lower albumin for poor CC compared to good CC were 0.86 (95% CI = 0.79-0.94). In the PS cohort, the association of albumin with CC was consistent with those of the original cohort. RCS results showed a linear relationship between albumin and CC (P values of .006 and .08 for overall and nonlinear associations, respectively). The results of this study suggest that lower serum albumin is independently associated with an increased risk of poor CC, which may serve as an effective predictive indicator for poor CC in patients with severe intracranial atherosclerotic stenosis.

Association of albumin levels with the risk of intracranial atherosclerosis.

OBJECTIVE: Intracranial artery stenosis from atherosclerosis is one of the etiologies of ischemic stroke. There is a correlation between serum albumin level and atherosclerosis. We aimed to investigate whether serum albumin level is related to intracranial atherosclerosis and its significance. METHODS: A retrospective analysis of 150 individuals who underwent cervical cerebral angiography after admission, including clinical data, imaging data, and laboratory data. Since atherosclerosis cannot be used as a good quantitative indicator, we choose the degree of arterial stenosis to reflect atherosclerosis. SPSS 24 software was used for data analysis, and P < .05 was considered statistically significant. RESULTS: Univariate analysis showed that age, diabetes, and serum albumin level were risk factors for intracranial atherosclerosis (P < .05). Multivariate analysis showed that diabetes and serum albumin levels were independent risk factors for intracranial atherosclerosis (P< 0.05). The average serum albumin level in the non-severe group was 39.80 g/L, and the average serum albumin level in the severe group was 37.60 g/L. The area under the ROC curve of serum albumin was 0.667 (95%CI 0.576-0.758, P = .001), the cutoff value was 0.332176, the sensitivity was 75.9%, and the specificity was 57.3%. CONCLUSION: Serum albumin level is an independent risk factor for intracranial atherosclerosis, and provides a new direction for clinical prevention and treatment.

Lipid Levels and Short-Term Risk of Recurrent Brain Infarcts in Symptomatic Intracranial Stenosis.

OBJECTIVES: Hyperlipidemia is a strong risk factor for intracranial atherosclerotic disease (ICAD) and clinical stroke recurrence. We explored the effect of serum lipid levels on subclinical infarct recurrence in the Mechanisms of earlY Recurrence in Intracranial Atherosclerotic Disease (MYRIAD) study. MATERIALS AND METHODS: We included enrolled MYRIAD patients with lipid measurements and brain MRI at baseline and brain MRI at 6-8 weeks. Infarct recurrence was defined as new infarcts in the territory of the symptomatic artery on brain MRI at 6-8 weeks compared to baseline brain MRI. We assessed the association between baseline total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) levels and recurrent infarct at 6-8 weeks using multivariable logistic regression. RESULTS: Among 74 patients (mean age 64.2±12.9 years, 59.5% were white, 60.8% men), 20 (27.0%) had new or recurrent infarcts. Mean HDL-C (37.2 vs. 43.9 mg/dL, P=0.037) was lower and TG (113.5 vs. 91.3 mg/dL, P=0.008) was higher while TC (199.8 vs. 174.3 mg/dL, P=0.061) and LDL-C (124.3 vs. 101.2 mg/dL, P=0.053) were nominally higher among those with recurrent infarcts than those without. LDL-C (adj. OR 1.022, 95% CI 1.004-1.040, P=0.015) and TG (adj. OR 1.009, 95% CI 1.001-1.016, P=0.021) were predictors of recurrent infarct at 6-8 weeks adjusting for other clinical and imaging factors. CONCLUSIONS: Baseline cholesterol markers can predict early infarct recurrence in patients with symptomatic ICAD. More intensive and rapid lipid lowering drugs may be required to reduce risk of early recurrence.

Plasma Lipid Profiling Contributes to Untangle the Complexity of Moyamoya Arteriopathy.

Moyamoya arteriopathy (MA) is a rare cerebrovascular disorder characterized by ischemic/hemorrhagic strokes. The pathophysiology is unknown. A deregulation of vasculogenic/angiogenic/inflammatory pathways has been hypothesized as a possible pathophysiological mechanism. Since lipids are implicated in modulating neo-vascularization/angiogenesis and inflammation, their deregulation is potentially involved in MA. Our aim is to evaluate angiogenic/vasculogenic/inflammatory proteins and lipid profile in plasma of MA patients and control subjects (healthy donors HD or subjects with atherosclerotic cerebrovascular disease ACVD). Angiogenic and inflammatory protein levels were measured by ELISA and a complete lipidomic analysis was performed on plasma by mass spectrometry. ELISA showed a significant decrease for MMP-9 released in plasma of MA. The untargeted lipidomic analysis showed a cumulative depletion of lipid asset in plasma of MA as compared to HD. Specifically, a decrease in membrane complex glycosphingolipids peripherally circulating in MA plasma with respect to HD was observed, likely suggestive of cerebral cellular recruitment. The quantitative targeted approach demonstrated an increase in free sphingoid bases, likely associated with a deregulated angiogenesis. Our findings indicate that lipid signature could play a central role in MA and that a detailed biomarker profile may contribute to untangle the complex, and still obscure, pathogenesis of MA.

Association of triglyceride-glucose index and high-sensitivity C-reactive protein with asymptomatic intracranial arterial stenosis: A cross-sectional study.

BACKGROUND AND AIMS: Triglyceride-glucose index (TyG) and high-sensitivity C-reactive protein (hsCRP) have been shown to play important roles in the pathophysiological mechanisms of atherogenesis. However, the cumulative value of TyG and hsCRP in identifying asymptomatic intracranial arterial stenosis (aICAS), as well as its severity and numerical burden, is uncertain. This study seeks to fill this knowledge gap. METHODS AND RESULTS: This study included 1938 participants aged ≥40 years who were free of stroke or transient ischemic attack. All participants were classified into four groups based on the participants' TyG and hsCRP levels, including low-TyG and low-hsCRP, low-TyG and high-hsCRP, high-TyG and low-hsCRP, and high-TyG and high-hsCRP groups. The presence of aICAS was screened via transcranial Doppler ultrasound and confirmed by magnetic resonance angiography. The TyG was calculated as ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. We used multinomial logistic regression analysis to investigate the cumulative value of TyG and hsCRP on identifying the severity of aICAS or its numerical burden. After adjustment for conventional confounders, isolated high-hsCRP, isolated high-TyG, and high-TyG combined with high-hsCRP were independently associated with moderate-to-severe aICAS. Compared with the low-TyG and low-hsCRP group, participants with high-TyG and high-hsCRP had a 2.6 times higher odds ratio (OR) of having a single moderate-to-severe aICAS and a 3.3 times higher OR of having multiple moderate-to-severe aICASs. CONCLUSION: The cumulative value of TyG and hsCRP may better identify moderate-to-severe aICAS as well as its numerical burden.

Determinants and Outcomes of Asymptomatic Intracranial Atherosclerotic Stenosis.

BACKGROUND: Intracranial atherosclerotic stenosis (ICAS) is one of the most common causes of stroke worldwide and confers a high risk of stroke recurrence, despite aggressive management of risk factors. OBJECTIVES: This study identified the role of risk factors and risk of vascular events in subjects with asymptomatic ICAS for improved risk stratification. METHODS: Stroke-free participants in the NOMAS (Northern Manhattan Study) trial, prospectively followed since 1993, underwent a brain magnetic resonance angiogram from 2003 to 2008. The study rated stenosis in 11 brain arteries as: 0: no stenosis; 1: <50% or luminal irregularities; 2: 50%-69%; and 3: ≥70% stenosis or flow gap. The study ascertained vascular events during the post-magnetic resonance imaging (MRI) period. Proportional odds regression quantified the association of pre-MRI exposures, and proportional hazard adjusted models were built to identify the risk of events in the post-MRI period. RESULTS: The included sample included 1,211 participants from NOMAS (mean age: 71 ± 9 years; 59% women; 65% Hispanic; 45% had any stenosis). Older age (OR: 1.02 per year; 95% CI: 1.01 to 1.04), hypertension duration (OR: 1.01 per year; 95% CI: 1.00 to 1.02), higher number of glucose-lowering drugs (OR: 1.64 per each medication; 95% CI: 1.24 to 2.15), and high-density lipoprotein (OR: 0.96 per mg/dL; 95% CI: 0.92 to 0.99) were associated with ICAS. The highest event risk was noted among participants with ICAS ≥70% (5.5% annual risk of vascular events; HR: 2.1; 95% CI:1.4 to 3.2; compared with those with no ICAS). CONCLUSIONS: ICAS is an imaging marker of established atherosclerotic disease in stroke-free subjects, and incidental diagnosis of ICAS should trigger a thorough assessment of vascular health.

The aptamer BT200 blocks von Willebrand factor and platelet function in blood of stroke patients.

The effect of conventional anti-platelet agents is limited in secondary stroke prevention, and their effects are blunted under high shear stress in the presence of increased levels of circulating von Willebrand factor (VWF). VWF is critically involved in thrombus formation at sites of stenotic extracranial/intracranial arteries. A third generation anti-VWF aptamer (BT200) has been generated which could be useful for secondary stroke prevention. To characterize the effects of BT200 in blood of patients with large artery atherosclerosis stroke (LAA). Blood samples were obtained from 33 patients with acute stroke or transient ischemic attack to measure inhibition of VWF activity and VWF-dependent platelet function. Patients who received clopidogrel or dual antiplatelet therapy did not differ in VWF dependent platelet function tests from aspirin treated patients. Of 18 patients receiving clopidogrel with or without aspirin, only 3 had a prolonged collagen adenosine diphosphate closure time, and none of the patients had ristocetin induced aggregation in the target range. BT200 concentration-dependently reduced median VWF activity from 178 to < 3%, ristocetin induced platelet aggregation from 40U to < 10U and prolonged collagen adenosine diphosphate closure times from 93 s to > 300 s. Baseline VWF activity correlated (r = 0.86, p < 0.001) with concentrations needed to reduce VWF activity to < 20% of normal, indicating that BT200 acts in a target concentration-dependent manner. Together with a long half-life supporting once weekly administration, the safety and tolerability observed in an ongoing phase I trial, and the existence of a reversal agent, BT200 is an interesting drug candidate.

SNP rs2043211 (p.C10X) in CARD8 Is Associated with Large-Artery Atherosclerosis Stroke in a Chinese Population.

SNP rs2043211 in CARD8 was found to have significant association with ischemic stroke. This study aimed to explore the possible association between rs2043211 and large-artery atherosclerosis stroke in Chinese and explain the possible mechanism. In total, 716 large-artery atherosclerosis stroke patients and 1088 controls were included in the study. Co-dominant, dominant, and recessive genetic models were constructed to evaluate the relationship between rs2043211 and large-artery atherosclerosis stroke risk by odds ratios with 95% confidence intervals. Stratified and interaction analyses were also done. We selected another 111 large-artery atherosclerosis stroke patients and measured the CARD8 levels in their plasma samples by enzyme-linked immunosorbent assay. Participants who carry T/T genotype have a higher risk of large-artery atherosclerosis stroke compared with those carry A/T or A/A genotypes (odds ratio = 1.35, 95% confidence intervals 1.03-1.77, P = 0.029). The higher risk for the T/T genotype is still notable in female, people with hypertension, and people without diabetes. In the interaction analysis, compared to the non-hypertensive participants with the wild homozygote type A/A, the hypertensive participants with the A/T+T/T homozygote had 3.27-fold increased risk (odds ratio = 3.27, 95% confidence intervals 2.33-4.60). The A/A group had lower CARD8 levels in plasma than the A/T and T/T group (P < 0.001). Further bioinformatics prediction indicated that the rs2043211 could significantly influence the mRNA secondary structure and protein expression of CARD8 (eQTL P = 9.8 × 10-198). The rs2043211 is probably a novel biomarker for large-artery atherosclerosis stroke in Chinese.

Plasma lipidomic analysis of sphingolipids in patients with large artery atherosclerosis cerebrovascular disease and cerebral small vessel disease.

BACKGROUND: Sphingolipids mainly consist of ceramides (Cer), sphingomyelins (SM) and glycosphingolipids. Sphingolipids are related with coronary heart disease and metabolic disease, but there're few studies about cerebrovascular disease. The purpose was to detect sphingolipids in plasma of patients with large artery atherosclerosis (LAA) cerebrovascular disease and cerebral small vessel disease (CSVD) to explore the similarities and differences of pathogenesis of the two subtypes. METHODS: 20 patients with LAA cerebrovascular disease, 20 patients with age-related CSVD, 10 patients with Fabry disease and 14 controls were enrolled from October 2017 to January 2019. Ultra-high performance liquid chromatography-quadruple-time-of-flight mass spectrometry/mass spectrometry was used to determine sphingolipids. Univariate combined with multivariate analysis was used for comparison. Receiver operating characteristic curves were used to determine sensitivities and specificities. RESULTS: 276 sphingolipids were detected, including 39 Cer, 3 ceramide phosphates, 72 glycosphingolipids and 162 SM. (1) Cer (d36:3), Cer (d34:2), Cer (d38:6), Cer (d36:4) and Cer (d16:0/18:1) were increased in LAA; SM (d34:1), Cer (d34:2), Cer (d36:4), Cer (d16:0/18:1), Cer (d38:6), Cer (d36:3) and Cer (d32:0) were increased in age-related CSVD. (2) Cer (d36:4) and SM (d34:1) were increased in age-related CSVD compared with LAA. (3) Total trihexosyl ceramides were increased in Fabry group compared with control (P<0.05); SM (d34:1) was increased in Fabry group. CONCLUSIONS: Ceramides are increased in both LAA and age-related CSVD, which may be related to similar risk factors and pathophysiological process of arteriosclerosis; SM is increased in both age-related CSVD and Fabry disease, suggesting that increased SM may be associated with CSVD. Glycosphingolipids, trihexosylceramides in particular, are increased in Fabry disease.

Importance of lipid ratios for predicting intracranial atherosclerotic stenosis.

BACKGROUND: This study aims to investigate the association of lipid ratios with intracranial atherosclerotic stenosis (ICAS) in a Chinese population. METHODS: This cross-sectional study included 658 consecutive patients with ischemic stroke. Intracranial and extracranial arteries were evaluated for atherosclerotic stenosis using digital subtraction angiography or computed tomography angiography. Lipid ratios [total cholesterol (TC)/high-density lipoprotein-cholesterol (HDL-C), triglycerides (TG)/HDL-C, low-density lipoprotein-cholesterol (LDL-C)/HDL-C, non-high-density lipoprotein-cholesterol (non-HDL-C)/HDL-C, remnant cholesterol (RC)/HDL-C, apolipoprotein B (apo B)/apolipoprotein A-I (apo A-I), and apo B/HDL-C] were calculated. RESULTS: The TC/HDL-C, LDL-C/HDL-C, RC/HDL-C, non-HDL-C/HDL-C, apo B/HDL-C and apo B/apo A-I ratios (all P < 0.05) were significantly associated with ICAS but not with extracranial atherosclerotic stenosis after adjustment for confounding factors. Receiver operating characteristic (ROC) curves analysis revealed that the apo B/apo A-I ratio had the largest area under the ROC curve (AUC) among lipid levels alone and for lipid ratios (AUC = 0.588). Lipid ratios had higher AUC values than those for lipid levels alone for the identification of ICAS. CONCLUSION: The TC/HDL-C, LDL-C/HDL-C, RC/HDL-C, non-HDL-C/HDL-C apo B/HDL-C, and apo B/apo A-I ratios were significantly related to ICAS risk. Compared with the other variables tested, the apo B/apo A-I ratio appeared to be a better discriminator for identifying ICAS risk in stroke patients.

Association between kidney disease measures and intracranial atherosclerosis: The ARIC study.

OBJECTIVE: To test the association between reduced kidney function (assessed by estimated glomerular filtration rate [eGFR] and cystatin C [CysC]) and kidney damage (assessed by urinary albumin-to-creatinine ratio [ACR]) and intracranial atherosclerotic disease (ICAD) by high-resolution vessel wall MRI (VWMRI) in the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS). METHODS: We conducted a cross-sectional analysis of ARIC participants with data on kidney measures and VWMRI in 2011 to 2013. The main outcomes were presence of intracranial plaques and luminal stenosis. Multivariable models were adjusted for demographics, cardiovascular risk factors, and use of antithrombotic medications. RESULTS: A total of 1,762 participants (mean ± SD age, 76.3 ± 5.3) were included. eGFR based on CysC (eGFRcysc) <60 mL/min/1.73 m2 (vs ≥60 mL/min/1.73 m2) was associated with plaque presence (adjusted odds ratio [OR] 1.29, 95% confidence interval [CI] 1.04-1.60), any detectable stenosis (adjusted OR 1.31, 95% CI 1.04-1.63), and >70% stenosis or occlusion (adjusted OR 2.15, 95% CI 1.32-3.50). Neither ACR nor CysC showed statistically significant associations with ICAD features in adjusted models. In adjusted multinomial models, participants with eGFRcysc <60 mL/min/1.73 m2 (vs ≥60 mL/min/1.73 m2) had an increased OR of 1.41 (95% CI 1.06-1.87) for having 1 plaque (vs none) but no significant increase for multiple plaques; ACR ≥30 was associated with moderate (50%-70%) stenosis (OR 2.01, 95% CI 1.14-3.55) vs absent or less than 50% stenosis. CONCLUSION: In community-dwelling older adults, reduced kidney function or elevated kidney damage was associated with ICAD measured by VWMRI. This finding may help to better identify a population at high risk for ICAD.

Serum Uric Acid Levels and Risk of Intracranial Atherosclerotic Stenosis: A Cross-Sectional Study.

Elevated serum uric acid (SUA) has been reported to be associated with an increased risk of cardiovascular diseases, but the role of SUA in intracranial atherosclerosis remains unclear. To investigate the association between SUA and intracranial atherosclerotic stenosis (ICAS), we evaluated 1522 subjects (305 with ICAS, 1217 without ICAS) with magnetic resonance angiography (MRA). Subjects were classified into ten groups according to the deciles of the SUA level. The rate of ICAS reached a minimum in the seventh decile (6.0-6.3 mg/dL; reference group). After adjusting for confounding factors, multivariate logistic regression analysis demonstrated that both low SUA level (≤ 3.8 mg/dL; OR, 2.34; 95% CI, 1.29-4.39; p = 0.006) and high SUA level (≥ 7.8 mg/dL; OR, 2.10; 95% CI, 1.15-3.92; p = 0.017) conferred greater risk for ICAS. In multivariable analysis with a quadratic model which used SUA as a continuous variable, a U-shaped association between SUA and the rate of ICAS was confirmed (α > 0; p < 0.001). The estimated SUA level associated with the lowest rate of ICAS was 6.2 mg/dL. In conclusion, our findings suggest a U-shaped association between ICAS and SUA.

Association between serum bilirubin and asymptomatic intracranial atherosclerosis: results from a population-based study.

INTRODUCTION: The effects of bilirubin on asymptomatic intracranial atherosclerosis (aICAS) remain uncertain. OBJECTIVES: To investigate the association between bilirubin and aICAS in rural-dwelling Chinese people. METHODS: This population-based study included 2013 participants from the Kongcun Town Study, which aimed to investigate the prevalence of aICAS in people aged ≥ 40 years who were free of stroke and hepatic and gall disease history. Baseline data were collected via interviews, clinical examinations, and laboratory tests. Total bilirubin (Tbil), direct bilirubin (Dbil), and indirect bilirubin (Ibil) levels were divided into high-concentration group and low-concentration group, respectively. We diagnosed aICAS and moderate-to-severe aICAS (m-saICAS) (≥ 50% stenosis) by integrating transcranial Doppler ultrasound with magnetic resonance angiography. The association between bilirubin and aICAS, as well as m-saICAS, was analyzed using logistic regression. RESULTS: Of the 2013 participants, those in the high-concentration group of Tbil (odds ratio (OR), 0.50; 95% confidence interval (CI), 0.42-0.87), Dbil (OR 0.60, 95%CI 0.41-0.87), and Ibil (OR 0.67; 95%CI 0.47-0.97) had a lower risk of aICAS than those in the low-concentration group after adjusting all confounders. The high concentrations of Tbil, Dbil, and Ibil were also negatively associated with m-saICAS. After stratification according to age, Tbil, Dbil, and Ibil were significantly negatively associated with aICAS among participants aged ≥ 60 years. CONCLUSION: Tbil, Dbil, and Ibil might be independent protective factors for aICAS and moderate-to-severe aICAS in rural-dwelling Chinese people, especially among older participants aged ≥ 60 years.

Apolipoprotein B/AI ratio as an independent risk factor for intracranial atherosclerotic stenosis.

To investigate the relation of higher apolipoprotein B/apolipoprotein AI (apoB/AI) ratio with the risk of suffering intracranial atherosclerotic stenosis (ICAS) in both stroke and non-stroke population, we enrolled 1138 patients with acute ischemic stroke (359 with ICAS, 779 without ICAS) and 1072 non-stroke controls (239 with ICAS, 833 without ICAS) into the study. ICAS was defined as atherosclerotic stenosis >50% or the occlusion of the several main intracranial arteries. ApoB/AI ratio of patients with ICAS was significantly higher than those of individuals without ICAS in both stroke group and non-stroke groups. Increased ratio of apoB/AI was an independent risk factor for ICAS in both stroke group (OR 2.80, 95% CI 1.45-5.42, p=0.002) and non-stroke groups (OR 3.38, 95% CI 1.61-7.12, p<0.001). Compared with the lowest quartile, the third (Stroke OR=1.71, 95%CI, 1.11-2.63, p=0.014; Non-stroke OR=1.71, 95%CI, 1.04-2.82, p=0.033) and forth quartiles (Stroke OR=2.06, 95%CI, 1.27-3.35, p=0.003; Non-stroke OR=2.00, 95%CI, 1.16-3.49, p=0.012) were independent risk factors for ICAS in both stroke (p value for trend=0.001)) and non-stroke (p value for trend=0.006) groups. In summary, increased apoB/AI ratio was a valuable independent risk factor for ICAS in stroke patients as well as in non-stroke controls.

Elevated homocysteine as an independent risk for intracranial atherosclerotic stenosis.

To investigate the association of homocysteine concentration with intracranial atherosclerotic stenosis (ICAS), we assessed 933 acute ischemic stroke patients (346 with ICAS, 587 without ICAS) and 798 non-stroke controls (175 with ICAS, 623 without ICAS) with magnetic resonance angiography (MRA). Homocysteine concentration was found to be significantly higher in participants with ICAS than those without ICAS. In logistic regression analyses, homocysteine concentration was significantly associated with ICAS both in patients (OR: 1.04; 95% CI: 1.01-1.08; P=0.008) and controls (OR: 1.10; 95% CI: 1.06-1.15; P<0.001) for 1 µmol/L increment in homocysteine. Compared with the lowest quartile, the second (OR:1.53; 95% CI: 1.01-2.33), third (OR:1.71; 95% CI: 1.14 -2.60) and fourth (OR:2.48; 95%CI: 1.63-3.81) quartiles were independent predictors of ICAS in patients (P for trend<0.001); the third (OR:1.99; 95% CI: 1.18-3.40) and fourth (OR:2.36; 95%CI: 1.38-4.10) quartiles were independent predictors of ICAS in controls (P for trend<0.001). Hence, elevated homocysteine might be an independent risk for ICAS.

Decreased Antiatherogenic Protein Levels are Associated with Aneurysm Structure Alterations in MR Vessel Wall Imaging.

OBJECTIVE: Thickened intracranial aneurysm wall with atherosclerotic remodeling is a part of its degenerative scenario. Current magnetic resonance (MR)-vessel wall imaging enables the detection of atherosclerotic wall thickening as aneurysm wall enhancement. The purpose of this study was to examine the correlation between identified atherosclerotic remodeling in vessel wall imaging, and systemic atherosclerosis-related risk factors. METHODS: A total of 39 aneurysms in 38 consecutive patients scheduled to undergo microsurgical clipping or endovascular coiling of intracranial aneurysms were prospectively evaluated. All patients underwent aneurysm MR-vessel wall imaging and the presence of aneurysm wall enhancement on contrast-enhanced vessel wall imaging was evaluated. The relationship between aneurysm wall enhancement and patient demographic data, aneurysm morphology and atherosclerosis-related risk factors including blood laboratory data were assessed. RESULTS: Aneurysm wall enhancement was detected in 19 of 39 intracranial aneurysms (48.7%). The maximum diameter of the intracranial aneurysm (P < .01), apolipoprotein A2 (P < .01) and apolipoprotein C2 (P = .01) was significantly associated with the presence of aneurysm wall enhancement. In multivariate logistic regression analyses, the maximum diameter of the intracranial aneurysm (odds ratio: 1.67, 95% confidence interval: 1.17-3.05) and decreased apolipoprotein A2 (odds ratio: 0.62, 95% confidence interval: 0.34-0.97) was significantly correlated with aneurysm wall enhancement. CONCLUSIONS: Rather than atherosclerotic factors, antiatherogenic proteins reduction was associated with aneurysm wall enhancement in vessel wall imaging. To elucidate antiatherogenic factors might to help find out promoting factor of unruptured intracranial aneurysms instability.