S-EPMC5647639 - Association of Systolic Blood Pressure with Progression of Symptomatic Intracranial Atherosclerotic Stenosis. - OmicsDI

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Association of Systolic Blood Pressure with Progression of Symptomatic Intracranial Atherosclerotic Stenosis.

ABSTRACT: BACKGROUND AND PURPOSE:Elevated blood pressure (BP) is associated with greater severity of intracranial atherosclerotic stenosis (ICAS) and increased risk of ischemic stroke. Because little is known about the relationship of maintained BP level with progression of symptomatic ICAS (sICAS), we evaluated the independent association of maintained systolic BP (SBP) with risk of sICAS progression. METHODS:We analyzed the Trial of cilOstazol in Symptomatic intracranial Stenosis 2, which evaluated 402 stroke patients with sICAS (mean age, 64.5±11.3 years; male, 52.2%). Study participants were categorized into four groups according to mean SBP level: low-normal (<120 mm Hg), normal to high-normal (120 to 139 mm Hg), high (140 to 159 mm Hg), and very-high (?160 mm Hg). Progression of sICAS was defined as worsening in the degree of stenosis by ?1 grade on the 7-month magnetic resonance angiography follow-up. RESULTS:sICAS progression was observed in 52 (12.9%) subjects. Percentages of sICAS progression by mean SBP category showed a J-shape pattern: low-normal (21.4%), normal to high-normal (10.7%), high (11.4%), and very-high (38.9%). In multivariable analysis, compared to the normal to high-normal SBP group, odds ratios (95% confidence intervals) were low-normal, 1.88 (0.62-5.67); high, 1.06 (0.47-2.37); and very-high, 8.75 (2.57-29.86). Rate of sICAS progression by 10-mm Hg strata showed a similar pattern to findings from mean SBP category (9.47; 2.58-34.73 for SBP ?160 mm Hg). CONCLUSIONS:Among individuals with a recent ICAS stroke, very-high SBP level during the short-term period after the index stroke was associated with significantly greater odds of sICAS progression.

SUBMITTER: Park JH

PROVIDER: S-EPMC5647639 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Association of Systolic Blood Pressure with Progression of Symptomatic Intracranial Atherosclerotic Stenosis.

Park Jong-Ho JH Ovbiagele Bruce B Hong Keun-Sik KS Kwon Sun U SU

Journal of stroke 20170929 3

<h4>Background and purpose</h4>Elevated blood pressure (BP) is associated with greater severity of intracranial atherosclerotic stenosis (ICAS) and increased risk of ischemic stroke. Because little is known about the relationship of maintained BP level with progression of symptomatic ICAS (sICAS), we evaluated the independent association of maintained systolic BP (SBP) with risk of sICAS progression.<h4>Methods</h4>We analyzed the Trial of cilOstazol in Symptomatic intracranial Stenosis 2, which ...[more]

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Project description:ObjectiveAcute ischemic stroke (AIS) is characterized by high rates of morbidity, disability, mortality, and recurrence, often leaving patients with varying degrees of sequelae. Symptomatic intracranial atherosclerotic stenosis (sICAS) is a significant contributor to AIS pathogenesis and recurrence. The formation and progression of sICAS are influenced by pathways such as lipid metabolism and inflammatory response. Given its high risk of clinical recurrence, timely assessment of intracranial vascular stenosis in AIS is crucial for diagnosing sICAS, treating stroke, and preventing stroke recurrence.MethodsFourteen AIS patients were divided into stenosis and control groups based on the presence or absence of intracranial vessel stenosis. Initially, 4D Label-free proteome quantification technology was employed for mass spectrometry analysis to identify differential proteins between the groups. Subsequently, functional enrichment analysis, including GO classification, KEGG pathway, and Domain, revealed trends related to differential proteins. The STRING (v.11.5) protein interaction network database was used to identify differential protein interactions and target proteins. Finally, parallel reaction monitoring (PRM) validated the selected target proteins.ResultsMass spectrometry identified 1,096 proteins, with 991 being quantitatively comparable. Using a p-value <0.05 and differential expression change thresholds of >1.3 for significant up-regulation and < 1/1.3 for significant down-regulation, 46 differential proteins were identified: 24 significantly up-regulated and 22 significantly down-regulated. PRM experiments validated five proteins related to lipid metabolism and inflammatory response: namely alpha-2-macroglobulin (A2M), lipopolysaccharide-binding protein (LBP), cathepsin G (CTSG), cystatin (CST)3, and fatty acid-binding protein (FABP)1.ConclusionThe detection of changes in these five proteins in AIS patients can aid in the diagnosis of sICAS, inform stroke treatment, and assist in preventing stroke recurrence. Moreover, it can contribute to the development of drugs for preventing AIS recurrence by integrating traditional Chinese and Western medicine.

Project description:Although genome-wide association studies (GWAS) have identified hundreds of complex trait loci, the pathomechanisms of most remain elusive. Studying the genetics of risk factors predisposing to disease is an attractive approach to identify targets for functional studies. Intracranial aneurysms (IA) are rupture-prone pouches at cerebral artery branching sites. IA is a complex disease for which GWAS have identified five loci with strong association and a further 14 loci with suggestive association. To decipher potential underlying disease mechanisms, we tested whether there are IA loci that convey their effect through elevating blood pressure (BP), a strong risk factor of IA. We performed a meta-analysis of four population-based Finnish cohorts (n(FIN)? = ?11 266) not selected for IA, to assess the association of previously identified IA candidate loci (n ?=? 19) with BP. We defined systolic BP (SBP), diastolic BP, mean arterial pressure, and pulse pressure as quantitative outcome variables. The most significant result was further tested for association in the ICBP-GWAS cohort of 200 000 individuals. We found that the suggestive IA locus at 5q23.2 in PRDM6 was significantly associated with SBP in individuals of European descent (p(FIN) ?=? 3.01E-05, p(ICBP-GWAS) ?= ?0.0007, p(ALL)? = ?8.13E-07). The risk allele of IA was associated with higher SBP. PRDM6 encodes a protein predominantly expressed in vascular smooth muscle cells. Our study connects a complex disease (IA) locus with a common risk factor for the disease (SBP). We hypothesize that common variants in PRDM6 can contribute to altered vascular wall structure, hence increasing SBP and predisposing to IA. True positive associations often fail to reach genome-wide significance in GWAS. Our findings show that analysis of traditional risk factors as intermediate phenotypes is an effective tool for deciphering hidden heritability. Further, we demonstrate that common disease loci identified in a population isolate may bear wider significance.

Project description:BackgroundIntracranial atherosclerotic plaque causing mild luminal stenosis might lead to acute ischemic events. However, the difference between culprit and nonculprit lesions is unclear, as are the factors associated with favorable treatment outcomes.PurposeTo quantify characteristics of intracranial atherosclerosis with mild luminal stenosis and to identify factors associated with lesion type (culprit or nonculprit) and with clinical outcomes.Study typeProspective POPULATION: 293 patients who had acute stroke with mild luminal stenosis (<50%) in the middle cerebral or basilar artery.Field strength/sequence3.0 T higher resolution magnetic resonance imaging (hrMRI) of intracranial arteries and whole brain MR images.AssessmentMorphological and compositional analysis of plaques was performed. This included assessment of plaque volume, plaque burden, remodeling ratio, eccentricity, intraplaque hemorrhage, and enhancement ratio. Clinical outcomes were assessed according to the modified Rankin Scale (mRS) at day 90, with a favorable outcome being defined as a 90-day mRS ≤2.Statistical testsThe odds ratios (ORs) with 95% confidence intervals (CIs) were calculated by a logistic regression model.ResultsHypertension (OR 5.2; 95% CI 2.6-10.3; P < 0.05) and hrMRI enhancement ratio (OR 2.7; 95% CI 1.4-5.1; P < 0.05) were independently associated with lesion type. Patients without hypertension had significantly more (P < 0.05) favorable outcomes (124/144) than patients with hypertension (97/149). Most hypertensive patients without any previous blood pressure control (54/63) had a favorable outcome. However, these patients were significantly younger (P < 0.05) than those with adequate blood pressure control. After adjusting for all significant characteristics, hypertension duration (OR 1.19; 95% CI 1.09-1.29; P < 0.05), hypertension management (OR 2.49; 95% CI 1.18-5.26; P < 0.05), and enhancement ratio (OR 0.01; 95% CI 0.001-0.157; P < 0.05) were found to be independent high-risk factors for outcome prediction. DATA CONCLUSION: hrMRI provided incremental value over traditional risk factors in identifying higher risk intracranial atherosclerosis with mild luminal stenosis.Level of evidence2 TECHNICAL EFFICACY: Stage 2.

Project description:Objective Acute ischemic stroke is a group of diseases characterized by high morbidity, high disability, high mortality, and high recurrence, and most patients are left with varying degrees of sequelae. Symptomatic intracranial atherosclerotic stenosis (sICAS) is a major cause of acute ischemic stroke pathogenesis, and its formation and progression are influenced by a combination of pathways including lipid metabolism and inflammatory response. sICAS has a high risk of clinical recurrence. Therefore, timely and effective assessment of intracranial vascular stenosis in acute ischemic stroke is particularly important for the diagnosis of sICAS, the treatment of stroke and the prevention of stroke recurrence.Method The aim of this study was to screen for unique differential proteins that are closely associated with sICAS in patients with acute ischemic stroke. Fourteen patients with acute ischemic stroke were included and divided into stenosis and control groups according to whether the intracranial vessels were stenosed or not. First, mass spectrometry was applied to all patients included using 4D Label-free proteome quantification technology to obtain the differential proteins between the two groups. Secondly, functional enrichment analysis using GO classification, KEGG pathway, Domain and other bioinformatics libraries were used to obtain differential protein-related enrichment trends. Then, the STRING (v.11.5) protein interaction network database was applied for comparison to obtain the differential protein interactions and corresponding target proteins. Finally, PRM was applied to validate the selected target proteins.Result 1096 proteins were obtained by mass spectrometry, of which the number of quantitatively comparable proteins was 991. When P value<0.05, a change in differential expression of more than 1.3 was used as the change threshold for significant up-regulation and less than 1/1.3 was used as the change threshold for significant down-regulation, resulting in a total of 46 differential proteins screened, of which 24 proteins were significantly up-regulated and 22 proteins were significantly down-regulated. In PRM experiments, five proteins involved in lipid metabolism and inflammatory response have been validated, namely A2M ,LBP, CTSG,CST3,FABP1.Conclusion By detecting the changes of these five proteins in acute ischemic stroke patients, we can provide a basis for the diagnosis of sICAS, the treatment of stroke and the prevention of stroke recurrence, and also help to promote the development of drugs for the prevention of acute ischemic stroke recurrence by combining Chinese and Western medicine.