Sex differences in clinical risk factors in obese ischemic stroke patients with a history of smoking.

Clinical risk factors associated obesity and smoking, as well as their combined effect, are not fully understood. This study aims to determine sex differences in risk factors in a population of acute ischemic stroke (AIS) patients who are obese and with a history of previous or current smoking. METHODS: A retrospective analysis of risk factors in male and female AIS patients with baseline data of obesity and current or previous history of smoking, smoking, and obesity alone was determined. The primary predictor and outcome are risk factors associated with male and female AIS patients. Baseline risk factors were analyzed using a multivariate regression analysis to determine specific risk factors linked with the combined effect of obesity and current or previous history of smoking''. RESULTS: Male obese AIS patients who are current or previous smokers were more likely to be older patients(OR = 1.024, 95% CI, 1.022-1.047, P = 0.033) that present with coronary artery disease (OR = 1.806, 95% CI, 1.028-3.174, P = 0.040), a history of alcohol use (OR = 2.873, 95% CI, 1.349-6.166, P = 0.006), elevated serum creatinine (OR = 4.724, 95% CI, 2.171-10.281, P < 0.001) and systolic blood pressure (OR = 1.029, 95% CI, 1.011-1.047, P < 0.002). Females were more associated with depression (OR = 0.432, 95% CI, 0.244-0.764, P = 0.004), previous TIA (OR = 0.319, 95% CI, 0.142-0.714, P < 0.005), and higher levels of HDL (OR = 0.938, 95% CI, 0.915-0.962, P < 0.001). CONCLUSION: Our results reveal sex differences in risk factors in obese AIS patients with a current or past history of smoking. This finding emphasizes the need to develop management strategies to improve the care of obese AIS patients who are either current or former smokers.

Risk Factors Associated With Exclusion of Obese Patients Ischemic Stroke With a History of Smoking From Thrombolysis Therapy.

The objective of this study is to determine risk factors that may contribute to exclusion decision from recombinant tissue plasminogen activator (rtPA) in patients with acute ischemic stroke (AIS) with a combined current or history of smoking and obesity. This study was conducted on data from 5469 patients with AIS collected from a regional stroke registry. Risk factors associated with inclusion or exclusion from rtPA were determined using multivariate logistic regression analysis. The adjusted odds ratios and 95% confidence interval for each risk factor were used to predict the increasing odds of an association of a specific risk factor with exclusion from rtPA. In the adjusted analysis, obese patients with AIS with a history of smoking (current and previous) excluded from rtPA were more likely to present with carotid artery stenosis (OR = 0.069, 95% CI 0.011-0.442), diabetes (OR = 0.604, 95% CI 0.366-0.997), higher total cholesterol (OR = 0.975, 95% CI 0.956-0.995), and history of alcohol use (OR = 0.438, 95% CI 0.232-0.828). Higher NIHSS score (OR = 1.051, 95% CI 1.017-1.086), higher triglycerides (OR = 1.004, 95% CI 1.001-1.006), and higher high-density lipoprotein (OR = 1.028, 95% CI 1.000-1.057) were associated with the inclusion for rtPA. Our findings reveal specific risk factors that contribute to the exclusion of patients with AIS with a combined effect of smoking and obesity from rtPA. These findings suggest the need to develop management strategies to improve the use of rtPA for obese patients with AIS with a history of smoking.

Riding the wave: a quantitative report of electrocardiogram utilization for myocardial infarction confirmation.

The purpose of this study was to generate a quantitative profile of electrocardiograms (ECGs) for confirming surgical success of permanent coronary artery ligation. An ECG was recorded at baseline, and 0, 1, and 5 min after ligation and analyzed using iWorkx LabScribe software. Cohort 1 (C57Bl6/J, n = 8/sex) was enrolled to determine ECG characteristics that were confirmed in cohort 2 (C57Bl6/J, n = 6/sex; CD8-/-n = 6 males/4 females). Of the 16 mice in cohort 1, 12 (6/sex) had an infarct ≥35% and four mice (2/sex) had <35% based on 2,3,5-triphenyltetrazolium chloride staining. After ligation, the QRS complex and R-S amplitude were significantly different compared with baseline. No differences were observed in the R-S amplitude between mice with infarcts ≥35% versus <35% at any time point, whereas the QRS complex was significant 1 min after ligation. Receiver operating characteristic (ROC) curve linked changes in the QRS complex but not the R-S amplitude at 1 and 5 min with surgical success. Data were normalized to baseline values to calculate fold change. ROC analysis of the normalized QRS data indicated strong sensitivity and specificity for infarcts ≥35%; normalized R-S amplitude remained nonsignificant. With a cutoff generated by ROC analysis of cohort 1 (>80% sensitivity; >90% specificity), the non-normalized QRS complex of cohort 2 had an 86% success rate (2 false positives; 1 false negative). The normalized data had a 77% success rate (2 false positives; 3 false negatives). Neither sex nor genotype was associated with false predictions (P = 0.18). Our data indicate that the area under the QRS complex 1 min after ligation can improve reproducibility in MI surgeries.NEW & NOTEWORTHY Our study describes a quantitative method for using an electrocardiogram (ECG) to determine which animals have infarcts that reflect coronary artery ligation. Using a quantitative ECG, investigators will have the benefit of having real-time feedback during the procedure, which will ultimately decrease the amount of time investigators spend performing experiments. This overall increase in efficiency will help investigators decrease animal numbers used due to better surgical outcomes.

Chronic Porphyromonas gingivalis lipopolysaccharide induces adverse myocardial infarction wound healing through activation of CD8+ T cells.

Oral and gum health have long been associated with incidence and outcomes of cardiovascular disease. Periodontal disease increases myocardial infarction (MI) mortality by sevenfold through mechanisms that are not fully understood. The goal of this study was to evaluate whether lipopolysaccharide (LPS) from a periodontal pathogen accelerates inflammation after MI through memory T-cell activation. We compared four groups [no MI, chronic LPS, day 1 after MI, and day 1 after MI with chronic LPS (LPS + MI); n = 68 mice] using the mouse heart attack research tool 1.0 database and tissue bank coupled with new analyses and experiments. LPS + MI increased total CD8+ T cells in the left ventricle versus the other groups (P < 0.05 vs. all). Memory CD8+ T cells (CD44 + CD27+) were 10-fold greater in LPS + MI than in MI alone (P = 0.02). Interleukin (IL)-4 stimulated splenic CD8+ T cells away from an effector phenotype and toward a memory phenotype, inducing secretion of factors associated with the Wnt/ß-catenin signaling that promoted monocyte migration and decreased viability. To dissect the effect of CD8+ T cells after MI, we administered a major histocompatibility complex-I-blocking antibody starting 7 days before MI, which prevented effector CD8+ T-cell activation without affecting the memory response. The reduction in effector cells diminished infarct wall thinning but had no effect on macrophage numbers or MertK expression. LPS + MI + IgG attenuated macrophages within the infarct without effecting CD8+ T cells, suggesting these two processes were independent. Overall, our data indicate that effector and memory CD8+ T cells at post-MI day 1 are amplified by chronic LPS to potentially promote infarct wall thinning.NEW & NOTEWORTHY Although there is a well-documented link between periodontal disease and heart health, the mechanisms are unclear. Our study indicates that in response to circulating periodontal endotoxins, memory CD8+ T cells are activated, resulting in an acceleration of macrophage-mediated inflammation after MI. Blocking activation of effector CD8+ T cells had no effect on the macrophage numbers or wall thinning at post-MI day 1, indicating that this response was likely due in part to memory CD8+ T cells.

Organized Chaos: Deciphering Immune Cell Heterogeneity's Role in Inflammation in the Heart.

During homeostasis, immune cells perform daily housekeeping functions to maintain heart health by acting as sentinels for tissue damage and foreign particles. Resident immune cells compose 5% of the cellular population in healthy human ventricular tissue. In response to injury, there is an increase in inflammation within the heart due to the influx of immune cells. Some of the most common immune cells recruited to the heart are macrophages, dendritic cells, neutrophils, and T-cells. In this review, we will discuss what is known about cardiac immune cell heterogeneity during homeostasis, how these cell populations change in response to a pathology such as myocardial infarction or pressure overload, and what stimuli are regulating these processes. In addition, we will summarize technologies used to evaluate cell heterogeneity in models of cardiovascular disease.