leptin and Carotid-Stenosis

Stroke is an important cause of morbidity and mortality, and is an economic burden. Diabetes and obesity are two important modifiable risk factors for stroke. Patients with diabetes have a higher incidence of stroke and a poorer prognosis after stroke. Risk-factor modification is the most important aspect of prevention of stroke in diabetes and obesity. This includes lifestyle modifications and different therapeutic modalities to control conditions, such as diabetes, hypertension, dyslipidemia and arrhythmia. Recent landmark studies have shown the beneficial effects of statins in diabetic patients even with close to normal or normal low-density lipoprotein cholesterol. Obesity, which is a risk factor for diabetes, hypertension and hyperlipidemia has been shown to be an independent risk factor for stroke. Increased leptin, dysregulation of adipocyte proteins, increased insulin resistance and C-reactive protein may be factors involved in the increased incidence of cardiovascular morbidity and mortality directly related to obesity. Visceral fat is a much bigger health risk than subcutaneous fat. Lifestyle interventions and pharmacotherapeutic agents have been used to manage obesity. In morbidly obese patients, surgical intervention seems to be the best method of treatment with a long-lasting favorable metabolic outcome. In the 21st Century, with the advanced medical knowledge and the therapeutic modalities available, it should be possible to reduce the incidence of stroke associated with diabetes and obesity.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Atrial Fibrillation; Blood Glucose; Cardiovascular Agents; Carotid Stenosis; Diabetes Mellitus; Diabetic Angiopathies; Diabetic Nephropathies; Diabetic Retinopathy; Dyslipidemias; Humans; Hypertension; Insulin Resistance; Ischemic Attack, Transient; Leptin; Life Style; Lipoproteins; Obesity; Plasminogen Activator Inhibitor 1; Risk Factors; Smoking; Stroke

Leptin is an adipokine, known to be associated with oxidative stress, inflammation, and atherogenesis. Leptin plays an essential role in atheromatosis-associated inflammatory cascade through stimulation of inflammatory mediators such as soluble intracellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1). However, little is known about this association in patients with atherosclerosis and severe internal carotid artery (ICA) stenosis undergoing carotid endarterectomy (CEA). Our objective was to evaluate the variations of serum leptin levels, as well as sICAM-1 and sVCAM-1 levels in these patients during the process of CEA and 24 hours postoperatively.. The study group enrolled 50 patients undergoing CEA for ICA stenosis (> 70%). Serum leptin, sICAM-1 and sVCAM-1 plasma concentration measurements were performed at 4 distinct time points: before clamping of the ICA, 30 minutes after clamping of the ICA, 60 minutes after declamping of ICA and 24 hours postoperatively.. Leptin was significantly decreased during CEA, but an overshooting in its levels was observed at 24 hours after the operation. Both sICAM-1 and sVCAM-1 initially followed the pattern of leptin changes but after completing CEA and up to 24 hours postoperatively a steep increase in their levels was not established. sVCAM-1 and sICAM-1 correlated with indices of oxidative stress at peak inflammatory burden.. Leptin is a circulating marker of carotid atherosclerosis. Oxidative stress and expression of sVCAM-1 and sICAM-1 on vascular endothelial cells are key features in the pathophysiological process of atherosclerosis.

Topics: Aged; Carotid Stenosis; Case-Control Studies; Endarterectomy, Carotid; Female; Gene Expression Regulation; Humans; Intercellular Adhesion Molecule-1; Leptin; Male; Middle Aged; Oxidative Stress; Prospective Studies; Vascular Cell Adhesion Molecule-1

As endocrine organ, adipose tissue may modulate inflammatory response by releasing a wide range of mediators, known as adipocytokines. Due to the complex balance between pro- and anti-inflammatory activity their pathophysiological and prognostic role in cardiovascular (CV) diseases still remains debated. Here, we consider the potential associations of circulating adipocytokines adiponectin, leptin and their ratio (LAR), with metabolic and inflammatory profiles in 217 patients with severe carotid stenosis. A prospective analysis investigating their predictive role toward acute coronary syndromes (ACS) was also drawn over a 12-month follow-up period. Serum leptin was positively associated with fasting insulinemia and HOMA-IR, but not with lipid profile and inflammation. Conversely, adiponectin was negatively associated with glucose, insulin, HOMA-IR, triglycerides and both systemic and intraplaque inflammatory markers whereas a positive association with high-density lipoprotein cholesterol (HDL-c) was observed. Accordingly, a significant association with metabolic profile was reported for LAR. According to the cut-off point identified by ROC curve, adiponectin values≤2.56μg/mL were correlated with a higher risk of ACS occurrence at 12months' follow-up (p-value for Log Rank test=0.0003). At Cox regression analysis the predictive ability of low serum adiponectin was confirmed also after adjustment for age, male gender and diabetes. In conclusion, adiponectin may be considered a biomarker of metabolic compensation, inversely associated with chronic low-grade inflammation. Circulating adiponectin is also associated with lower risk of adverse CV events in patients with severe carotid stenosis.

Topics: Acute Coronary Syndrome; Adiponectin; Aged; Area Under Curve; Biomarkers; Blood Glucose; Carotid Stenosis; Down-Regulation; Female; Humans; Inflammation Mediators; Insulin; Kaplan-Meier Estimate; Leptin; Lipids; Male; Middle Aged; Multivariate Analysis; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Prospective Studies; Reproducibility of Results; ROC Curve; Severity of Illness Index; Time Factors

The rupture of unstable carotid atherosclerotic plaques is one of the main causes of cerebrovascular ischemic events. There is need for circulating markers that can predict plaque instability and risk of stroke. Proinflammatory chemerin, leptin, and resistin, along with anti-inflammatory adiponectin, are adipokines with direct influence on vascular function. We investigated the association of circulating adipokines with carotid plaque instability and cerebrovascular symptomatology.. Neurologically symptomatic and asymptomatic patients (n=165) scheduled for carotid endarterectomy were recruited. Fasting blood samples were collected preoperatively; adiponectin and leptin levels were determined by radioimmunoassay; and chemerin and resistin levels were measured by enzyme-linked immunosorbent assays. The instability of plaque specimens was assessed using gold-standard histological classifications. Chemerin was significantly associated with plaque instability. The fully adjusted model, accounting for age, sex, body mass index, high-sensitivity C-reactive protein, type 2 diabetes mellitus, and circulating adiponectin, leptin, and resistin, yielded an odds ratio of 0.991 (95% confidence interval 0.985-0.998) for plaque instability per unit increase in chemerin. High leptin levels were significantly associated with presence of specific features of plaque instability. In subjects with type 2 diabetes mellitus, resistin levels were significantly elevated in symptomatic when compared with asymptomatic subjects (P=0.001) and increased the risk of cerebrovascular symptomatology (adjusted odds ratio 1.264, 95% confidence interval 1.004-1.594).. Low chemerin and high resistin levels were associated with carotid disease severity, suggesting that these adipokines may act as potential markers for plaque instability and stroke risk. Future studies are needed to assess causation between circulating adipokines and plaque instability.

Topics: Adiponectin; Aged; Biomarkers; Carotid Stenosis; Cerebrovascular Disorders; Chemokines; Chi-Square Distribution; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Enzyme-Linked Immunosorbent Assay; Female; Humans; Intercellular Signaling Peptides and Proteins; Leptin; Logistic Models; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Plaque, Atherosclerotic; Predictive Value of Tests; Prognosis; Resistin; Risk Assessment; Risk Factors; Rupture, Spontaneous; Severity of Illness Index

Patients with psoriasis may have an increased risk of cardiovascular disease.. We sought to evaluate the potential association between subclinical atherosclerosis and psoriasis by measuring the intima-media wall thickness (IMT) of the common carotid artery (CCA) in patients with psoriasis and evaluating its correlation with serum leptin and resistin levels.. The mean IMT (MIMT) of the CCA and leptin, resistin, triglyceride (TG), and total cholesterol levels in serum were determined in 60 patients and 60 healthy sex- and age-matched control subjects.. Compared with the healthy control subjects, patients with psoriasis had significantly higher MIMT of the CCA and higher levels of serum leptin, resistin, TG, and total cholesterol. In addition, MIMT of the CCA was positively correlated with serum leptin, resistin, TG, and total cholesterol levels in patients with psoriasis.. This was a cross-sectional single-center study, and we could not evaluate additional biomarkers such as adipokine or adiponectin because of our restricted facilities.. Although serum leptin, resistin, TG, and total cholesterol levels and MIMT of the CCA were significantly increased in patients with psoriasis, MIMT of the CCA was also positively correlated with these biomarkers. Therefore, psoriasis could be an independent risk factor for subclinical atherosclerosis.

Topics: Adolescent; Adult; Age Distribution; Aged; Aged, 80 and over; Atherosclerosis; Biomarkers; Carotid Intima-Media Thickness; Carotid Stenosis; Case-Control Studies; Comorbidity; Female; Humans; Incidence; Leptin; Male; Middle Aged; Prognosis; Psoriasis; Resistin; Risk Assessment; Severity of Illness Index; Sex Distribution; Statistics, Nonparametric; Young Adult

Topics: Aged; Biomarkers; Carotid Stenosis; Endarterectomy, Carotid; Enzyme-Linked Immunosorbent Assay; Humans; Immunohistochemistry; Leptin; Middle Aged; Phenotype; Plaque, Atherosclerotic; Risk Factors

Obesity is a risk factor for atherosclerotic vascular disease. Altered adipokine secretion, including increased production of nicotinamide phosphoribosyltransferase (Nampt) and retinol binding protein 4 (RBP4) may link adipose tissue dysfunction to cardiovascular complications.. We determined Nampt and RBP4 serum concentrations in 193 consecutive patients with carotid stenosis prior to carotid endarterectomy (CEA) in relation to recently experienced ischemic events, markers of atherosclerosis and obesity, as well as anthropometric and clinical characteristics.. Nampt but not RBP4 was significantly higher in symptomatic patients who experienced an ischemic event within 6 months before surgery compared to asymptomatic patients (p=0.001). In multivariate regression analysis Nampt was the only independent predictor of symptomatic carotid stenosis. Nampt correlated with peripheral leukocyte blood count (p<0.0001) and with the number of macrophages/foam cells within carotid plaques (p=0.042). However, Nampt and RBP4 serum concentrations did not correlate with the maximum percentage of carotid stenosis.. Our data suggest circulating Nampt as an independent predictor of recently experienced ischemic events in patients with carotid stenosis despite the lack of an association between Nampt and carotid atherosclerosis severity.

Topics: Adiponectin; Aged; Asymptomatic Diseases; Atherosclerosis; Carotid Stenosis; Endarterectomy, Carotid; Female; Humans; Ischemia; Leptin; Male; Nicotinamide Phosphoribosyltransferase; Obesity; Retinol-Binding Proteins, Plasma

Obesity is associated with accelerated atherosclerosis. Adipokines may directly influence vessel wall homeostasis by influencing the function of endothelial cells, arterial smooth muscle cells, and modulating inflammation. Recently, visceral adipose tissue-derived serpin (vaspin) was identified as a novel adipokine related to obesity and its metabolic consequences. However, the regulation of vaspin serum concentrations in human atherosclerosis is unknown. We therefore assessed vaspin serum concentrations in 107 consecutive patients with carotid stenosis undergoing carotid endarterectomy (CEA) in relation to severity of atherosclerosis, measures of obesity and circulating markers of obesity and atherosclerosis. Vaspin serum concentrations were significantly lower in patients with carotid stenosis who experienced an ischemic event within 3 months before surgery compared to asymptomatic patients. However, circulating vaspin was not associated with measures of atherosclerosis severity as maximum percentage stenosis. Vaspin serum concentrations were indistinguishable before and after CEA. We found a significant correlation between vaspin and leptin serum concentrations supporting previous results that vaspin closely reflects body fat mass. In conclusion, our data show that low vaspin serum concentrations correlate with recently experienced ischemic events in patients with carotid stenosis despite the lack of an association between circulating vaspin and parameters of atherosclerosis severity.

Topics: Aged; Angiography, Digital Subtraction; Biomarkers; Brain Ischemia; Carotid Stenosis; Endarterectomy, Carotid; Female; Humans; Leptin; Linear Models; Male; Multivariate Analysis; Obesity; Predictive Value of Tests; Risk Assessment; Risk Factors; Serpins; Severity of Illness Index; Treatment Outcome

Carotid artery lesions from symptomatic patients are characterized by inflammation and neovascularization. The adipokine leptin promotes angiogenesis and activates inflammatory cells, and the leptin receptor (ob gene-encoded receptor), ObR, is expressed in advanced atherosclerotic lesions. The present study quantitatively analyzed ObR messenger RNA (mRNA) expression and immunoreactivity in carotid artery plaques from symptomatic and asymptomatic persons. Plaque angiogenesis, gene expression of vascular endothelial growth factor (VEGF), and macrophage density were also analyzed.. Carotid endarterectomy specimens were collected from 26 patients undergoing surgery for hemispheric cerebrovascular symptoms (n = 13) or progressive asymptomatic internal carotid stenosis (n = 13). A representative sample, including part of the most active site, was collected from each lesion and evaluated by real-time polymerase chain reaction analysis for ObR(long) and ObR(common) isoforms, VEGF(165), and macrophage adhesion molecule-1 (Mac-1) mRNA, and by immunohistochemistry for ObR, von Willebrand factor (vWF), and CD68 antigen expression.. All plaques exhibited advanced atherosclerosis (American Heart Association class IV through VI). Transcript levels were preferentially elevated in symptomatic plaques for ObR(long) (P = .0006) and ObR(common) (P = .033), with a simultaneous upregulation of VEGF(165) (P = .001) and Mac-1 mRNA expression (P = .003). Immunohistochemical analysis confirmed a significant increase of ObR antigen levels (P = .011) and CD68-positive inflammatory cells (P = .049) in symptomatic plaques, whereas neovascularization, evident in all plaques, was similar in both groups (P = .7).. The ObR(long) and ObR(common) genes are upregulated and their protein preferentially synthesized in clinically symptomatic carotid plaques. Moreover, ObR expression is positively correlated with augmentation of gene transcripts related to macrophage density and neovascularization. These data suggest that ObR(long) and ObR(common) may be linked with histologic features of carotid plaque instability, which are associated with cerebral ischemic symptoms.

Topics: Aged; Biomarkers; C-Reactive Protein; Carotid Stenosis; Cerebrovascular Disorders; Female; Humans; Immunohistochemistry; Interleukin-6; Leptin; Macrophage-1 Antigen; Macrophages; Male; Middle Aged; Neovascularization, Pathologic; Polymerase Chain Reaction; Protein Isoforms; Receptors, Leptin; RNA, Messenger; Up-Regulation; Vascular Endothelial Growth Factor A

The evaluation of the leptin:adiponectin ratio (L:A) has been suggested as an atherosclerotic index in patients with type 2 diabetes and a useful parameter to assess insulin resistance in patients with and without diabetes.. We investigated, therefore, the relationship between L:A ratio and intima media thickness (IMT), an independent predictor of cardiovascular disease, in 110 healthy males.. L:A ratio was significantly correlated to body mass index, waist, hip, waist-to-hip ratio, systolic blood pressure, IMT, high-density lipoprotein, apolipoprotein A-I, glucose, and the homeostasis model of insulin resistance-revised. No significant correlation was observed with age, diastolic blood pressure, low-density lipoprotein, triglycerides, apolipoprotein B, ApoB/ApoA-I ratio, insulin, alanine transaminase, gamma-glutamyl-transferase, and resistin. In addition, when the relationship between IMT and adiponectin or leptin alone was analyzed, only leptin plasma levels significantly associated with IMT (r=0.301, P<0.01). In a multiple regression analysis including in the statistical model the risk factors known to affect IMT (age, systolic blood pressure, diastolic blood pressure, high-density lipoprotein cholesterol, triglycerides, total cholesterol, body mass index, glucose, and L:A ratio), we observed that only age, L:A, and glucose were independent predictors of IMT. As expected, obese subjects (body mass index >30 kg/m(2)) showed a significantly higher L:A ratio compared with nonobese subjects (1.20 versus 0.42, respectively, P<0.001); in addition, subjects with the metabolic syndrome showed a significantly higher L:A ratio level (0.79) compared with subjects without (0.52) (P<0.01).. We show here that the L:A ratio is a powerful independent predictor of IMT in healthy subjects and correlates with several anthropometric, metabolic, and clinical parameters better than each single adipokine.

Topics: Adiponectin; Adult; Aged; Biomarkers; Carotid Artery, Common; Carotid Stenosis; Humans; Leptin; Male; Middle Aged; Predictive Value of Tests; Regression Analysis; Tunica Media