Common Variants Associated With Expression Contribute to Carotid Plaque Vulnerability, but Not to Cardiovascular Disease in Humans.

Oncostatin M (OSM) signaling is implicated in atherosclerosis, however the mechanism remains unclear. We investigated the impact of common genetic variants in and its receptors, and , on overall plaque vulnerability, plaque phenotype, intraplaque and expression, coronary artery calcification burden and cardiovascular disease susceptibility. We queried Genotype-Tissue Expression data and found that rs13168867 (C allele) was associated with decreased expression and that rs10491509 (A allele) was associated with increased expression in arterial tissues.

Sclerostin Downregulation Globally by Naturally Occurring Genetic Variants, or Locally in Atherosclerotic Plaques, Does Not Associate With Cardiovascular Events in Humans.

Inhibition of sclerostin increases bone formation and decreases bone resorption, leading to increased bone mass, bone mineral density, and bone strength and reduced fracture risk. In a clinical study of the sclerostin antibody romosozumab versus alendronate in postmenopausal women (ARCH), an imbalance in adjudicated serious cardiovascular (CV) adverse events driven by an increase in myocardial infarction (MI) and stroke was observed. To explore whether there was a potential mechanistic plausibility that sclerostin expression, or its inhibition, in atherosclerotic (AS) plaques may have contributed to this imbalance, sclerostin was immunostained in human plaques to determine whether it was detected in regions relevant to plaque stability in 94 carotid and 50 femoral AS plaques surgically collected from older female patients (mean age 69.

The age- and sex-specific composition of atherosclerotic plaques in vascular surgery patients.

Background And Aims: The sex- and age-related differences in the composition of iliofemoral atherosclerotic plaques are largely unknown. Therefore, the aim of the current study is to gain insight into plaque composition across strata of age and sex in a large cohort of vascular surgery patients.

Methods: Peripheral atherosclerotic plaques of patients who underwent iliofemoral endarterectomy (n = 790) were harvested between 2002 and 2014.

Cerebral Small Vessel Disease in Standard Pre-operative Imaging Reports Is Independently Associated with Increased Risk of Cardiovascular Death Following Carotid Endarterectomy.

Objective: Cerebral white matter lesions (WMLs) and lacunar infarcts are surrogates of cerebral small vessel disease (SVD). WML severity as determined by trained radiologists predicts post-operative stroke or death in patients undergoing carotid endarterectomy (CEA). It is unknown whether routine pre-operative brain imaging reports as part of standard clinical practice also predict short and long term risk of stroke and death after CEA.

Exercise reduces inflammatory cell production and cardiovascular inflammation via instruction of hematopoietic progenitor cells.

A sedentary lifestyle, chronic inflammation and leukocytosis increase atherosclerosis; however, it remains unclear whether regular physical activity influences leukocyte production. Here we show that voluntary running decreases hematopoietic activity in mice. Exercise protects mice and humans with atherosclerosis from chronic leukocytosis but does not compromise emergency hematopoiesis in mice.

Preoperative hypertension is associated with atherosclerotic intraplaque hemorrhage in patients undergoing carotid endarterectomy.

Background And Aims: Both hypertension and atherosclerotic plaque characteristics such as intraplaque hemorrhage (IPH) are associated with cardiovascular events (CVE). It is unknown if hypertension is associated with IPH. Therefore, we studied if hypertension is associated with unstable atherosclerotic plaque characteristics in patients undergoing carotid endarterectomy (CEA).

Validation of randomized controlled trial-derived models for the prediction of postintervention outcomes in chronic limb-threatening ischemia.

Background: Chronic limb-threatening ischemia (CLTI) represents the most severe form of peripheral artery disease and has a large impact on quality of life, morbidity, and mortality. Interventions are aimed at improving tissue perfusion and averting amputation and secondary cardiovascular complications with an optimal risk-benefit ratio. Several prediction models regarding postprocedural outcomes in CLTI patients have been developed on the basis of randomized controlled trials to improve clinical decision-making.

The Impact of Diabetes and Time on the Atherosclerotic Plaque and Cardiovascular Outcome in Patients Undergoing Iliofemoral Endarterectomy.

Objective: The incidence of diabetes is rapidly increasing and diabetes is associated with an increased risk of peripheral artery disease. Recent studies have shown a time dependent decline in vulnerable plaque features and secondary cardiovascular events in iliofemoral endarterectomy (IFE) patients. IFE patients with diabetes have a high risk of cardiovascular events.

Circulating CD14CD16 classical monocytes do not associate with a vulnerable plaque phenotype, and do not predict secondary events in severe atherosclerotic patients.

Aims: Mouse studies have established distinct monocyte subtypes that participate in the process of atherosclerotic lesion formation. The pro-inflammatory Ly6C monocyte subtype actively contributes to murine plaque progression and destabilization. Also in humans, different peripheral monocyte subtypes have been identified, of which the CD14CD16 classical monocyte is suggested to display similar pro-atherosclerotic properties as the murine Ly6C subtype.

A single preoperative blood test predicts postoperative sepsis and pneumonia after coronary bypass or open aneurysm surgery.

Background: Major surgery comes with a high risk for postoperative inflammatory complications. Preoperative risk scores predict mortality risk but fail to identify patients at risk for complications following cardiovascular surgery. We therefore assessed the value of preoperative red cell distribution width (RDW) as a predictor for pneumonia and sepsis after cardiovascular surgery and studied the relation of RDW with hematopoietic tissue activity.

Smoking is Associated to DNA Methylation in Atherosclerotic Carotid Lesions.

Background: Tobacco smoking is a major risk factor for atherosclerotic disease and has been associated with DNA methylation (DNAm) changes in blood cells. However, whether smoking influences DNAm in the diseased vascular wall is unknown but may prove crucial in understanding the pathophysiology of atherosclerosis. In this study, we associated current tobacco smoking to epigenome-wide DNAm in atherosclerotic plaques from patients undergoing carotid endarterectomy.

Testosterone to oestradiol ratio reflects systemic and plaque inflammation and predicts future cardiovascular events in men with severe atherosclerosis.

Aims: The effects of testosterone on cardiovascular disease (CVD) as reported in literature have been ambiguous. Recently, the interplay between testosterone and oestradiol as assessed by testosterone/oestradiol (T/E2) ratio was suggested to be better informative on the normal physiological balance. Considering the role in CVD, we hypothesized that a low T/E2 ratio in men with CVD is associated with increased inflammation, a more unstable plaque and a worse cardiovascular outcome.

Lung volumes identify an at-risk group in persons with prolonged secondhand tobacco smoke exposure but without overt airflow obstruction.

Introduction: Exposure to secondhand smoke (SHS) is associated with occult obstructive lung disease as evident by abnormal airflow indices representing small airway disease despite having preserved spirometry (normal forced expiratory volume in 1 s-to-forced vital capacity ratio, FEV/FVC). The significance of lung volumes that reflect air trapping in the presence of preserved spirometry is unclear.

Methods: To investigate whether lung volumes representing air trapping could determine susceptibility to respiratory morbidity in people with SHS exposure but without spirometric chronic obstructive pulmonary disease, we examined a cohort of 256 subjects with prolonged occupational SHS exposure and preserved spirometry.

Impaired kidney function is associated with intraplaque hemorrhage in patients undergoing carotid endarterectomy.

Background And Aims: Previously, we showed that patients undergoing carotid endarterectomy have an increased risk for major atherosclerotic events in the presence of moderate or poor kidney function. Acceleration of vascular inflammatory responses is considered to be causally involved in progression of atherogenesis and poor outcome in chronic kidney disease patients. The association between kidney function and plaque composition has not been thoroughly investigated yet.

Atherosclerotic plaque characteristics are not associated with future cardiovascular events in patients undergoing iliofemoral endarterectomy.

Background: Plaque characteristics such as intraplaque hemorrhage (IPH) have been associated with secondary cardiovascular events (CVE) in patients undergoing carotid endarterectomy. In addition, carotid plaques containing macrophage infiltration or a large lipid core size were associated with less restenosis. It is currently unknown whether iliofemoral plaque histopathologic characteristics are predictive for secondary CVE in patients with peripheral arterial disease undergoing iliofemoral endarterectomy.

Modeling vascular inflammation and atherogenicity after inhalation of ambient levels of ozone: exploratory lessons from transcriptomics.

Background: Epidemiologic studies have linked inhalation of air pollutants such as ozone to cardiovascular mortality. Human exposure studies have shown that inhalation of ambient levels of ozone causes airway and systemic inflammation and an imbalance in sympathetic/parasympathetic tone.

Methods: To explore molecular mechanisms through which ozone inhalation contributes to cardiovascular mortality, we compared transcriptomics data previously obtained from bronchoalveolar lavage (BAL) cells obtained from healthy subjects after inhalational exposure to ozone (200 ppb for 4 h) to those of various cell samples from 11 published studies of patients with atherosclerotic disease using the Nextbio genomic data platform.

Circulating GDF-15 levels predict future secondary manifestations of cardiovascular disease explicitly in women but not men with atherosclerosis.

Background: Elevated serum levels of growth differentiation factor-15 (GDF-15), is an established risk factor for a range of cardiovascular diseases. We aimed to evaluate the predictive value of plasma GDF-15 as a biomarker for secondary cardiovascular events (CVE) in patients with atherosclerosis undergoing carotid endarterectomy (CEA). Secondly, we determined whether plasma GDF-15 was associated with carotid plaque characteristics.

Biobanking in carotid artery disease: translation to clinical practice.

Biobanking of atherosclerotic tissue samples has contributed to our understanding of vascular occlusive disease. The careful examination of atherosclerotic plaques derived during vascular surgery or autopsies helped shape our minds in understanding the underlying substrate of arterial thrombosis. This review will outline concepts of progression of atherosclerotic disease that have been based on descriptions of human plaque pathology.

Secondhand Tobacco Smoke and COPD Risk in Smokers: A COPDGene Study Cohort Subgroup Analysis.

Background: Exposure to secondhand tobacco smoke (SHS) can be a risk factor for chronic obstructive pulmonary disease (COPD), but its role among relatively heavy smokers with potential co-exposure to workplace vapors, gas, dust, and fumes (VGDF) has not been studied.

Methods: To estimate the contribution of SHS exposure to COPD risk, taking into account smoking effects and work-related exposures to VGDF, we quantified SHS based on survey responses for 1400 ever-employed subjects enrolled in the COPDGene study, all current or former smokers with or without COPD. Occupational exposures to VGDF were quantified based on a job exposure matrix.