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Comorbidities associated with different levels of total cholesterol in male and female acute ischemic stroke patients.

ABSTRACT:

Abstract

Men and women differ in their clinical risk factors with respect to various predictors of severity in acute ischemic stroke (AIS). High cholesterol is a risk factor for AIS and the mechanism by which high cholesterol levels lead to an AIS is well established. However, the specific relationship between demographic, clinical risk factors, total cholesterol, and the resulting gender difference in AIS patients is yet to be investigated. This study recruited AIS patients between January 2000 and June 2016 classified into normal, borderline or high total cholesterol (TC). Normal was defined as ?200?mg/dl, borderline 200 to 239?mg/dl and high ?240?mg/dl based on Adult Treatment Panel III (ATP III) Guidelines for the classification of TC levels. The logistic regression model was used to predict clinical risk factors associated within men and women AIS patients with different levels of TC. A total of 3532 AIS patients presented with normal TC, 760 patients with borderline TC and 427 patients with high TC. The high total cholesterol group was more likely to be women with increasing age (OR?=?1.028, 95% CI, 1.006-1.052, P?=?.014), body mass index (BMI) (OR?=?1.052, 95% CI, 1.004-1.102, P?=?.033), and high-density lipoprotein cholesterol (HDL-C) (OR?=?1.039, 95% CI, 1.019-1.060, P?

SUBMITTER: Brechtel L

PROVIDER: S-EPMC7769330 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Comorbidities associated with different levels of total cholesterol in male and female acute ischemic stroke patients.

Brechtel Leanne L Poupore Nicolas N Stoikov Teodora T Roley Laurie Theriot LT Emerson John F JF Nathaniel Thomas T

Medicine 20201201 52

<h4>Abstract</h4>Men and women differ in their clinical risk factors with respect to various predictors of severity in acute ischemic stroke (AIS). High cholesterol is a risk factor for AIS and the mechanism by which high cholesterol levels lead to an AIS is well established. However, the specific relationship between demographic, clinical risk factors, total cholesterol, and the resulting gender difference in AIS patients is yet to be investigated. This study recruited AIS patients between Janu ...[more]

PMID: 33350783

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Project description:BackgroundSpecific clinical risk factors may contribute to improving or worsening neurological functions in acute ischemic stroke (AIS) patients pre-treated with a combined cholesterol reducer and recombinant tissue plasminogen activator (rtPA) therapy. In this study, clinical risk factors associated with good or poor presenting neurological symptoms in ischemic stroke patients with prior cholesterol reducer use, specifically a statin and rtPA therapy was investigated.MethodsRetrospective data for baseline clinical and demographic data for patients with AIS taking cholesterol reducers prior to rtPA treatment from January 2010 to June 2016 in a regional stroke center was analyzed. Improving (NIHSS score ≤ 7) or worsening (NIHSS score > 7) of neurologic functions were the determined measures of treatment outcome. Multivariate logistic regression models identified demographic and clinical factors associated with worsening or improving neurologic functions.ResultsAdjusted multivariate analysis showed that in an AIS population with a combined rtPA and cholesterol reducer medication history, increasing age (OR = 1.032, 95% CI, 1.015-1.048, P < 0.001) and atrial fibrillation (OR = 1.859, 95% CI, 1.098-3.149, P = 0.021) demonstrated a likely association with worsening neurologic functions, while direct admission (OR = 0.411, 95% CI, 0.246-0.686, P = 0.001) and being Caucasian (OR = 0.496, 95% CI, 0.297-0.827, P = 0.007) showed an association with improving or progressing neurologic functions.ConclusionA prior cholesterol reducer, namely a statin, plus rtPA combination may be associated with worsening neurological function for elderly AIS patients with atrial fibrillation, while Caucasians directly admitted to a neurology unit are more likely to show an association with progress or improvements in neurologic functions. While combining statin with rtPA treatment may facilitate worsening neurologic functions in elderly AIS patients with atrial fibrillation, they should not be denied of this therapy. The decision to combine statin and rtPA for AIS patients with atrial fibrillation can be done after clinical stabilization following appropriate clinical management.

Project description:Background: Cerebral small vessel disease (SVD) is generally considered as a cause of stroke, disability, gait disturbances, vascular cognitive impairment, and dementia. The aim of this study was to investigate whether the total SVD burden can be used to predict functional outcome in patients with acute ischemic stroke. Methods: From April 2017 to January 2018, consecutive patients with acute ischemic stroke who underwent baseline MRI scan were evaluated. The functional outcome was assessed using the modified Rankin Scale (mRS) at 90 days and defined as i) excellent outcome (mRS ≤ 1) and ii) good outcome (mRS ≤ 2). Brain MRI was performed and assessed for lacunes, white matter hyperintensities (WMH), and enlarged perivascular spaces (EPVS). The total SVD burden was calculated based on lacunes, WMH, and EPVS and then summed up to generate an ordinal "total SVD burden" (range 0-3). Bivariate logistic regression models were used to identify the association between SVD and functional outcome. Results: A total of 416 patients were included in the final analysis; 44.0, 33.4, 19.2, and 3.4% of the patients had 0, 1, 2, and 3 features of SVD, respectively. In regard to individual SVD feature, lacunes (OR: 0.48, 95% CI: 0.32-0.71; OR: 0.49, 95% CI: 0.31-0.77) and WMH (OR: 0.53, 95% CI: 0.34-0.82; OR: 0.53, 95% CI: 0.33-0.85) were negatively associated with excellent outcome and good outcome. As to the total burden of SVD, three SVD features had strongest negative associations with functional outcomes (excellent outcome, OR: 0.13, 95% CI: 0.03-0.48; good outcome, OR: 0.18, 95% CI: 0.06-0.54). After adjustment for potential confounders, a high SVD burden (3 features, OR: 0.07, 95% CI: 0.01-0.41) and the score of total SVD burden (OR: 0.64, 95% CI: 0.44-0.93) remained negatively associated with excellent outcome. Conclusion: Total SVD burden negatively associated with functional outcome at 3 months in patients with acute ischemic stroke and is superior to individual SVD feature in prediction of functional outcome. MRI-based assessment of total SVD burden is highly valuable in clinical management of stroke victims and could help guide the allocation of resources to improve outcome.

Project description:Background. Women account for 60% of all stroke deaths and are more often permanently disabled than men, despite their higher observed stroke incidence. Considering the clinical population affected by stroke, an obvious drawback is that many pre-clinical and clinical studies only investigate young males. To improve therapeutic translation from bench to bedside, we believe that it is advantageous to include both sexes in experimental models of stroke. The aims of this study were to identify early cerebral vascular responses to ischemic stroke in females, compare the differential gene expression patterns with those seen in males, and identify potential new therapeutic targets. Results. Transient middle cerebral artery occlusion (tMCAO) was used to induce stroke in both female and male rats, the middle cerebral arteries (MCAs) were isolated 3 hours post reperfusion and RNA was extracted. Affymetrix whole transcriptome expression profiling was performed on female (n = 12) MCAs to reveal differentially expressed genes. In total, 1076 genes had an increased expression and 879 genes a decreased expression in the occluded MCAs as compared with the control MCAs from female rats. An enrichment of genes related to apoptosis, regulation of transcription, protein autophosphorylation, inflammation, oxidative stress, and tissue repair and recovery were seen in the occluded MCA. The high expression genes chosen for qPCR verification (Adamts4, Olr1, JunB, Fosl1, Serpine1, S1pr3, Ccl2 and Socs3) were all shown to be upregulated in the same manner in both females and males after tMCAO (p < 0.05; n = 23). When comparing the differentially expressed genes in female MCAs (occluded and non-occluded) with our previous findings in males after tMCAO, a total of 297 genes overlapped (all groups had 32 genes in common). Conclusions. The cascades of processes initiated in the vasculature following reperfusion are complex. Dynamic gene expression alterations were observed in the occluded MCAs, and to a less pronounced degree in the non-occluded MCAs. Dysregulation of inflammation and blood-brain barrier breakdown are possible pharmacological targets. The sample of genes (<1% of differentially expressed genes) validated for this microarray did not reveal any sex differences.

Dataset Information

Comorbidities associated with different levels of total cholesterol in male and female acute ischemic stroke patients.

Abstract

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Comorbidities associated with different levels of total cholesterol in male and female acute ischemic stroke patients.

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