leptin and Carotid-Artery-Diseases

Atherosclerosis is a complex disease with various intermediate phenotypes that are themselves complex and influenced by many factors. Through the use of carotid ultrasound techniques, the intermediate stages of vascular disease can be imaged and studied for association with potential genetic determinants. In this article we review the most recent available data (reports published since 2004) on the genetic determinants of atherosclerosis, as measured by one-, two-, and three-dimensional ultrasonography of the carotid arteries. In general, associations are disparate and modest. For intima-media thickness, promising associations have been found for both TNFRSF1A R92Q and PPARG P12A, but associations also differed in the same individuals depending on the specific ultrasound trait studied (eg, linear intima-media thickness versus total plaque volume in carotid arteries). Some of the challenging issues for future studies include accounting for gene-environment interactions, sex-specific associations, and the distinctiveness of different carotid ultrasound measures.

Topics: Carotid Artery Diseases; Genetic Predisposition to Disease; Genetic Variation; Humans; Leptin; Phenotype; Polymorphism, Genetic; Receptors, Tumor Necrosis Factor, Type I; Tunica Intima; Tunica Media; Ultrasonography

Unstable carotid plaques cause cerebral emboli. Leptin promotes atherosclerosis and vessel wall remodeling. We hypothesized that carotid atherosclerotic lesion instability is associated with local leptin synthesis.. Carotid endarterectomy plaques from symptomatic (n=40) and asymptomatic patients with progressive stenosis (n=38) were analyzed for local expression of leptin, tumor necrosis factor (TNF)-α, and plasminogen activator inhibitor type 1. All lesions exhibited advanced atherosclerosis inclusive of thick- and thin-cap fibroatheromas or lesion rupture. Symptomatic lesions exhibited more plaque ruptures and macrophage infiltration (P=0.001 and P=0.05, respectively). Symptomatic plaques showed preferential leptin, TNF-α, and plasminogen activator inhibitor type 1 transcript (P=0.03, P=0.04, and P=0.05, respectively). Leptin mRNA and antigen in macrophages and smooth muscle cells were confirmed by in situ hybridization and immunohistochemistry. Plasma leptin levels were not significantly different between groups (P=1.0), whereas TNF-α was significantly increased in symptomatic patients (P=0.006). Human aortic smooth muscle cell culture stimulated by TNF-α, lipopolysaccharide, or lipoteichoic acid revealed 6-, 6.7-, and 6-fold increased secreted leptin antigen, respectively, at 72 hours (P<0.05).. Neurologically symptomatic patients overexpress leptin mRNA and synthesize leptin protein in carotid plaque macrophages and smooth muscle cells. Local leptin induction, presumably by TNF-α, could exert paracrine or autocrine effects, thereby contributing to the pathogenesis of lesion instability.. URL: www.Clinicaltrials.gov. Unique identifier: NCT00449306.

Topics: Adult; Aged; Aged, 80 and over; Carotid Artery Diseases; Endarterectomy, Carotid; Female; Humans; Immunohistochemistry; In Situ Hybridization; Intracranial Embolism; Leptin; Male; Middle Aged; Myocytes, Smooth Muscle; Plaque, Atherosclerotic; Plasminogen Activator Inhibitor 1; Real-Time Polymerase Chain Reaction; Tumor Necrosis Factor-alpha

This research aimed to combine serum NLR-pyrin domain containing 1 (NLRP1) levels and collateral circulation to assess ischemic stroke patients and predict the prognoses of the patients. This present prospective observational study enrolled 196 ischemic stroke patients. All patients underwent CTA as well as digital subtraction angiography (DSA) to assess collateral circulation by American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR). In addition, we collected serum samples from 100 patients with carotid atherosclerosis as controls. The serum NLRP1, tumor necrosis factor α (TNF-α), interleukin (IL)-6, IL-1β and C-reactive protein (CRP) levels were measured by enzyme-linked immunosorbent assay (ELISA). The age, BMI, sex, smoke condition, diastolic blood pressure, systolic blood pressure, National Institutes of Health Stroke Scores (NIHSS), modified Rankin Scale (mRS) scores, imaging indicators and the levels of triglyceride, total cholesterol (TC), low-density leptin cholesterol (LDLC), high-density leptin cholesterol of all subjects were recorded. All data used SPSS 18.0 to statistical analyses. The serum levels of NLRP1 were remarkably enhanced in the ischemic stroke patients compared with the carotid atherosclerosis patients. The NIHSS score, the mRS score after 90 days and the levels of NLRP1, CRP, TNF-α IL-6 and IL-1β of ischemic stroke patients in the ASITN/SIR grade 0 to 2 group were remarkably elevated than the ischemic stroke patients in ASITN/SIR grade 3 to 4 group. Spearman analysis supported that a positive correlation existed among the NLRP1, CRP, IL-6, TNF-α, and IL-1β levels. The NIHSS score, infarct volume and the levels of NLRP1, IL-6, TNF-α, and IL-1β of ischemic stroke patients in the mRS score ≥ 3 group were remarkably elevated than the ischemic stroke patients in the mRS score ≤ 2 group. ASITN/SIR grade and NLRP1 could be potential diagnostic biomarkers of poor prognosis of ischemic stroke patients. It was found that NLRP1, ASITN/SIR grade, infarct volume, NIHSS, IL-6, and IL-1β were the risk factors for bad prognosis of ischemic stroke patients. This study showed that the serum NLRP1 levels were remarkably decreased in ischemic stroke patients. In addition, the serum NLRP1 levels and ASITN/SIR grade could predict the prognosis of ischemic stroke patients.

Topics: Brain Ischemia; Carotid Artery Diseases; Cholesterol; Clinical Relevance; Collateral Circulation; Computed Tomography Angiography; Humans; Infarction; Interleukin-6; Ischemic Stroke; Leptin; NLR Proteins; Stroke; Tumor Necrosis Factor-alpha

Atherosclerosis is the main cause for most cardiovascular diseases, and new biomarkers for this condition are always needed. Peptidase M20 domain containing 1 (PM20D1) is associated with both lipid metabolism and obesity. However, no study focuses on the role of PM20D1 in carotid atherosclerosis.. The present study aimed to investigate the role of PM20D1 in carotid atherosclerosis patients.. The present prospective observational study contained a total of 231 carotid atherosclerosis patients, who went to our department between July 2018 and December 2019. Blood samples and medical characteristics were also obtained from 231 healthy individuals with the same body mass index distribution of carotid atherosclerosis patients. Serum PM20D1 was determined using enzyme-linked immunosorbent assay. Clinical and demographic characteristics of all patients were collected, including age, sex, body mass index and medical history. Levels of C-reactive protein, tumor necrosis factor, homocysteine, as well as total cholesterol, triglyceride, high-density leptin cholesterol and low-density leptin cholesterol were recorded. Statistical analysis was conducted using the SPSS software, with p<0.05 as statistically different.. Serum PM20D1 levels were markedly lower in carotid atherosclerosis patients when compared to the healthy control, which were significantly lower in severe carotid atherosclerosis patients and carotid atherosclerosis/stroke patients. Patients with unstable plaques showed markedly lower PM20D1 when compared to patients with stable plaques. No significant difference was found among carotid atherosclerosis patients with different body mass index. Patients with higher PM20D1 levels showed significantly lower expression of C-reactive protein, tumor necrosis factor, homocysteine, triglyceride, total cholesterol and low-density leptin cholesterol. PM20D1 was negatively correlated with C-reactive protein, tumor necrosis factor, homocysteine, total cholesterol and low-density leptin cholesterol in carotid atherosclerosis patients, and could be used as a biomarker for severe carotid atherosclerosis patients or carotid atherosclerosis patients with stroke. Sex, tumor necrosis factor, homocysteine and PM20D1 were risk factors for carotid atherosclerosis.. PM20D1 was decreased in carotid atherosclerosis patients and was associated with severity, plaque stability, and levels of C-reactive protein, tumor necrosis factor, homocysteine, triglyceride, total cholesterol and low-density leptin cholesterol in carotid atherosclerosis patients.. A aterosclerose é a principal causa da maioria das doenças cardiovasculares, e novos biomarcadores para essa condição são sempre necessários. O domínio da peptidase M20 contendo 1 (PM20D1) está associado ao metabolismo lipídico e à obesidade. No entanto, nenhum estudo se concentra no papel do PM20D1 na aterosclerose carotídea.. O objetivo deste estudo foi investigar o papel do PM20D1 em pacientes com aterosclerose carotídea.. Estudo observacional prospectivo conduzido com um total de 231 pacientes com aterosclerose carotídea que estiveram em nosso departamento entre julho de 2018 e dezembro de 2019. Amostras de sangue e dados médicas foram obtidos de outros 231 indivíduos saudáveis com o mesmo índice de massa corporal (IMC) dos pacientes com aterosclerose carotídea. O PM20D1 sérico foi determinado por ensaio imunossorvente ligado a enzima (ELISA). As características clínicas e demográficas de todos os pacientes foram listadas, incluindo idade, sexo biológico, IMC e histórico médico. Os níveis de proteína C reativa (PCR), fator de necrose tumoral, homocisteína, colesterol total, triglicerídeos, leptina-colesterol de alta densidade e leptina-colesterol de baixa densidade foram registrados. Realizou-se análise estatística no software SPSS, com p<0,05 considerado estatisticamente significante.. Os níveis séricos de PM20D1 foram marcadamente mais baixos em pacientes com aterosclerose carotídea comparados aos controles saudáveis, sendo significativamente mais baixos em pacientes com aterosclerose carotídea grave e pacientes com aterosclerose carotídea/acidente vascular cerebral. Pacientes com placas instáveis apresentaram PM20D1 marcadamente menor quando comparados a pacientes com placas estáveis. Nenhuma diferença significativa foi encontrada entre pacientes com aterosclerose carotídea com diferentes IMC. Pacientes com níveis mais elevados de PM20D1 apresentaram expressão significativamente menor de PCR, fator de necrose tumoral, homocisteína, triglicerídeos, colesterol total e colesterol de baixa densidade. PM20D1 correlacionou-se negativamente com PCR, fator de necrose tumoral, homocisteína, colesterol total e leptina de baixa densidade em pacientes com aterosclerose carotídea, podendo ser usado como biomarcador para pacientes com aterosclerose carotídea grave ou com aterosclerose carotídea e acidente vascular cerebral. Sexo biológico, fator de necrose tumoral, homocisteína e PM20D1 foram considerados fatores de risco para aterosclerose carotídea.. O PM20D1 estava diminuído em pacientes com aterosclerose carotídea e foi associado com gravidade, estabilidade da placa, níveis de PCR, fator de necrose tumoral, homocisteína, triglicerídeos, colesterol total e colesterol de baixa densidade em pacientes com aterosclerose carotídea.

Topics: Amidohydrolases; Biomarkers; C-Reactive Protein; Carotid Artery Diseases; Cholesterol; Homocysteine; Humans; Leptin; Peptide Hydrolases; Plaque, Atherosclerotic; Risk Factors; Stroke; Triglycerides; Tumor Necrosis Factors

Information regarding the effect of leptin on the vasculature in young healthy adults at risk for cardiovascular disease development is limited. We therefore examined the associations between measures of subclinical atherosclerosis (carotid intima-media thickness, carotid cross-sectional wall area), large artery stiffness (pulse wave velocity) and a measure of endothelial dysfunction (von Willebrand factor [vWF]) with leptin in young healthy men and women.. In a cross-sectional study in South Africa involving 820 normotensive individuals (337 men and 483 women) aged 20-30 years, we measured carotid intima-media thickness, carotid cross-sectional wall area, pulse wave velocity, vWF from citrated plasma and leptin from serum.. Despite sevenfold higher leptin in women than men (P < 0.001), only in young healthy men, we observed negative, independent associations between measures of carotid wall thickness (carotid intima-media thickness: R. In young healthy men, we found a beneficial inverse association between measures of carotid wall thickness and circulating leptin, thereby supporting a potential vascular protective role of leptin.

Topics: Adult; Black People; Body Composition; Carotid Arteries; Carotid Artery Diseases; Carotid Intima-Media Thickness; Cross-Sectional Studies; Exercise; Humans; Leptin; Male; Prospective Studies; Pulse Wave Analysis; Regression Analysis; South Africa; Vascular Stiffness; White People; Young Adult

Carotid artery calcifications (CAC) and high carotid artery intima-media thickness (cIMT) are associated with low bone mineral density (BMD) by unknown mechanisms in postmenopausal women. Leptin, adiponectin and estradiol may mediate these associations. Our aim was to study the relationships of the aforementioned factors to bone health (BMD) and carotid atherosclerosis (CAC and cIMT).. Participants (n = 290, mean age 73.6 years) for this cross-sectional OSTPRE-BBA study (Kuopio Osteoporosis Risk Factor and Prevention - Bone, Brain and Atherosclerosis) were randomly selected from the OSTPRE cohort in 2009. Femoral neck and total body BMDs, trunk and total body fat mass were measured with dual-energy X-ray absorptiometry, and cIMT (mm) and CAC (no/yes) were measured with B-type ultrasound. Free estradiol, adiponectin and leptin were measured from serum samples.. Circulating estradiol levels were associated with leptin (β = 0.131, p < 0.001), but not with adiponectin (p > 0.05), when adjusted for total body fat mass. There were no associations between estradiol tertiles and BMDs, or with cIMT or CAC. Adiponectin levels were inversely associated with femoral neck BMD (p = 0.019, β = -0.138) and total body BMD (p = 0.009, β = -0.142), adjusted for total body fat mass, age, current smoking and estradiol, but showed no relationship with CAC or cIMT. Leptin levels were not associated with BMDs or cIMT; but the odds ratio was 1.5 between the CAC and leptin quartiles (p = 0.014), adjusted for total body fat mass, age, statin use and calcium intake.. The adipokines are associated with vascular calcification and low BMD. Moreover, estradiol was not independently associated with BMD or CAC.

Topics: Adipokines; Adiponectin; Aged; Body Composition; Bone Density; Carotid Artery Diseases; Carotid Intima-Media Thickness; Cross-Sectional Studies; Estradiol; Female; Humans; Leptin; Osteoporosis, Postmenopausal; Postmenopause; Vascular Calcification

The aim of this study was to evaluate the relationship between body composition, metabolic profile, adipokines, and carotid intima-media thickness (cIMT) in young survivors of childhood acute lymphocytic leukemia (ALL).. This cross-sectional study compared 55 ALL survivors, of chronological age between 15 years and 24 years, assigned into two groups according to the exposure to cranial radiation therapy (CRT; 25 irradiated and 30 nonirradiated) with 24 leukemia-free controls, and assessed body fat mass (dual-energy X-ray absorptiometry), computed tomography scan-derived abdominal adipose tissue, lipid profile, blood pressure (BP), adipokines, and cIMT by a multiple regression analysis.. Treatment with CRT had an effect on all of the variables derived from the computed tomography scan: visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) (P<0.050). In a multiple linear regression model, cIMT positively correlated with exposure to CRT (P=0.029), diastolic BP (P=0.016), and leptin-to-adiponectin ratio (P=0.048), while negatively related to SAT (P=0.007).. In young survivors of childhood ALL, CRT modified the distribution of fat and played a critical role in determining cIMT. Leptin-to-adiponectin ratio, a biomarker of abdominal obesity and metabolic syndrome, and diastolic BP also influenced cIMT, a marker of subclinical atherosclerosis. Nonetheless, adiposity-associated vascular disease might be attenuated by SAT. Changes in body fat must be evaluated in this group of patients in the early course of survivorship in order to avoid premature cardiovascular disease associated with atherosclerosis. Yet, further research as regards the possible protective effect of SAT on vascular disease is warranted.

Topics: Absorptiometry, Photon; Adiponectin; Adiposity; Adolescent; Biomarkers; Carotid Artery Diseases; Carotid Intima-Media Thickness; Case-Control Studies; Cranial Irradiation; Cross-Sectional Studies; Female; Humans; Intra-Abdominal Fat; Leptin; Linear Models; Male; Multivariate Analysis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Predictive Value of Tests; Risk Factors; Subcutaneous Fat; Survivors; Tomography, X-Ray Computed; Treatment Outcome; Young Adult

An increased frequency of atherosclerosis (ATH) in systemic lupus erythematosus (SLE) is well-documented but not fully explained by the presence of traditional cardiac risk factors. Several nontraditional biomarkers, including proinflammatory high-density lipoprotein (piHDL) and leptin, have been individually associated with subclinical ATH in SLE. The aim of this study was to examine whether these and other biomarkers can be combined into a risk profile, the Predictors of Risk for Elevated Flares, Damage Progression, and Increased Cardiovascular Disease in Patients with SLE (PREDICTS), that could be used to better predict future progression of ATH.. In total, 210 patients with SLE and 100 age-matched healthy control subjects (all women) participated in this prospective cohort study. The longitudinal presence of carotid plaque and intima-media thickness (IMT) were measured at baseline and followup (mean ± SD 29.6 ± 9.7 months).. At followup, carotid plaque was present in 29% of SLE patients. Factors significantly associated with plaque, determined using Salford Predictive Modeling and multivariate analysis, included age ≥48 years (odds ratio [OR] 4.1, P = 0.002), high piHDL function (OR 9.1, P < 0.001), leptin levels ≥34 ng/dl (OR 7.3, P = 0.001), plasma soluble TWEAK levels ≥373 pg/ml (OR 28.8, P = 0.004), and history of diabetes (OR 61.8, P < 0.001). Homocysteine levels ≥12 μmoles/liter were also a predictor. However, no single variable demonstrated an ideal combination of good negative predictive values (NPVs), positive predictive values (PPVs), sensitivity, and specificity. A high-risk PREDICTS profile was defined as ≥3 positive biomarkers or ≥1 positive biomarker plus a history of diabetes; for high-risk SLE patients, the PPV was 64%, NPV was 94%, sensitivity was 89%, and specificity was 79%. In multivariate analysis, SLE patients with the high-risk profile had 28-fold increased odds for the longitudinal presence of plaque (P < 0.001) and increased progression of IMT (P < 0.001).. A high-risk PREDICTS score confers 28-fold increased odds of the presence of any current, progressive, or acquired carotid plaque, both in patients with SLE and in control subjects, and is significantly associated with higher rates of IMT progression.

Topics: Adiponectin; Adult; Age Factors; Apolipoprotein A-I; Atherosclerosis; Biomarkers; Carotid Arteries; Carotid Artery Diseases; Carotid Intima-Media Thickness; Case-Control Studies; Cholesterol, HDL; Cholesterol, LDL; Cohort Studies; Cytokine TWEAK; Diabetes Complications; Diabetes Mellitus; Disease Progression; Female; Homocysteine; Humans; Leptin; Longitudinal Studies; Lupus Erythematosus, Systemic; Middle Aged; Multivariate Analysis; Odds Ratio; Plaque, Atherosclerotic; Predictive Value of Tests; Prospective Studies; Risk Assessment; Risk Factors; Sensitivity and Specificity; Tumor Necrosis Factors

We examined the relationship between plasma adipokine concentrations and ultrasound measures of vascular health in 100 HIV-infected adults on antiretroviral therapy. Leptin was positively correlated with flow-mediated dilation of the brachial artery and negatively with carotid intima-media thickness. These relationships were independent of traditional risk factors and trunk fat in women but not men. Neither adiponectin nor resistin was associated with either measure of vascular health.

Topics: Absorptiometry, Photon; Adipokines; Adult; Anti-HIV Agents; Body Mass Index; Brachial Artery; Carotid Arteries; Carotid Artery Diseases; Enzyme-Linked Immunosorbent Assay; Female; HIV Infections; Humans; Leptin; Male; Middle Aged; Obesity; Resistin; Risk Factors; Ultrasonography

Adiponectin and leptin are likely involved in the pathophysiology of rheumatoid arthritis (RA) and therefore potential new therapeutic targets. Adiponectin inhibition could be expected to enhance cardiovascular metabolic risk. However, it is unknown whether RA changes the influence of adipokines on cardiovascular metabolic risk. We determined whether RA impacts on the independent relationships of circulating leptin and adiponectin concentrations with cardiovascular risk factors and carotid intima-media thickness (cIMT) in 277 black African subjects from a developing population; 119 had RA. RA impacted on the relationships of adiponectin concentrations with lipid concentrations and blood pressure, independent of confounders including adiposity (interaction P < 0.05). This translated into an association of adiponectin concentrations with more favorable lipid variables including HDL cholesterol (P = 0.0005), non-HDL cholesterol (P = 0.007), and triglyceride (P = 0.005) concentrations, total cholesterol-HDL cholesterol (P = 0.0002) and triglycerides-HDL cholesterol (P = 0.0003) ratios, and higher systolic (P = 0.0006), diastolic (P = 0.0004), and mean blood pressure (P = 0.0007) in RA but not non-RA subjects. Leptin was not associated with metabolic risk after adjustment for adiposity. The cIMT did not differ by RA status, and adipokine concentrations were unrelated to atherosclerosis. This study suggests that leptin and adiponectin inhibition may not alter overall cardiovascular risk and disease in RA.

Topics: Adipokines; Adiponectin; Aged; Arterial Pressure; Arthritis, Rheumatoid; Atherosclerosis; Cardiovascular Diseases; Carotid Artery Diseases; Carotid Intima-Media Thickness; Cholesterol, HDL; Female; Humans; Leptin; Male; Middle Aged; Risk Factors

The adipocyte-derived hormone leptin plays a key role in the regulation of food intake and energy expenditure. Recent studies have suggested that leptin is also involved in the pathogenesis of obesity-associated atherosclerosis and cardiovascular disease. In this study, we investigated the associations of leptin and the soluble leptin receptor (sOb-R) with atherosclerosis in patients with type 2 diabetes.. Three hundred seventeen type 2 diabetic subjects were enrolled in this cross-sectional study. Fasting plasma leptin and sOb-R concentrations were measured by enzyme-linked immunosorbent assays. The intima-media thickness (IMT) of the common carotid artery was measured by ultrasound.. The IMT was significantly associated with sOb-R concentrations, age, diabetes duration, serum creatinine (sCre) levels, and systolic blood pressure (SBP), but not with leptin concentrations or the leptin/sOb-R ratio. The concentrations of leptin (r=0.478, p<0.001) and the sOb-R (r= -0.404, p<0.001) and the leptin/sOb-R ratio (r=0.501, p<0.001) were strongly correlated with IMT in subjects treated with insulin for glycemic control, but not in those treated with diet alone or oral hypoglycemic agents. Multiple regression analysis, including age, sex, diabetes duration, body mass index, SBP, HbA1c, triglycerides, LDL-cholesterol, sCre, smoking, and insulin therapy, revealed that plasma leptin and the leptin/sOb-R ratio were independently associated with IMT in subjects treated with insulin.. Plasma leptin and the leptin/sOb-R ratio are associated with atherosclerosis in patients with type 2 diabetes on insulin therapy, and these associations were independent of obesity and other cardiovascular risk factors.

Topics: Adipocytes; Adult; Aged; Aged, 80 and over; Atherosclerosis; Cardiovascular Diseases; Carotid Arteries; Carotid Artery Diseases; Carotid Intima-Media Thickness; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Humans; Leptin; Male; Middle Aged; Obesity; Receptors, Leptin

Adipokines are markers of insulin resistance and play a role in the atherosclerotic process. The association of adipokines with the macrovascular complications of type 1 diabetes mellitus (DM) needs to be determined. The aim of this study was to measure serum adiponectin, leptin, and resistin levels in type 1 DM patients and investigate their relationship with carotid intima media thickness (CIMT), a clinical marker of atherosclerosis.. Seventy-five type 1 DM patients and 115 sex and age-matched healthy controls were included in the study. Serum adiponectin, leptin, and resistin levels were measured by the enzyme-linked immunosorbent assay (ELISA method). CIMT was assessed by Doppler ultrasonography.. Adiponectin levels in diabetics were higher (25.8±14.8 μg/mL vs. 5.5±7.3 μg/mL; P<0.0001) and leptin levels were lower than controls (9.4±6.2 ng/mL vs. 12.8±8.6 ng/mL; P=0.01). Resistin levels were also higher in the diabetic group compared to controls (2.1±1.4 ng/mL vs. 1.6±0.8 ng/mL; P=0.04). Adiponectin was correlated negatively with CIMT (r=-0.24, P=0.03), age (r=-0.30, P=0.02), BMI (r=-0.33, P=0.02), waist-to-hip ratio (WHR) (r=-0.38, P=0.01) and positively with creatinine (r=0.44, P=0.004). Leptin levels were correlated with total cholesterol (r=0.53, P=0.01) and high-density lipoprotein (HDL) (r=0.67, P=0.001). Resistin was correlated with CIMT (r=0.24, P=0.03) and systolic blood pressure (r=0.48, P=0.009). Multivariate analysis revealed resistin and creatinine to be independent predictors of CIMT among adiponectin, leptin, resistin, WHR, glycosylated hemoglobin (HbA1c), and creatinine.. Increased adiponectin correlates negatively and resistin positively with CIMT in type 1 diabetic patients, but adjusting for other known predictors reveals only resistin to be associated with subclinical atherosclerosis in this group of patients.

Topics: Adipokines; Adiponectin; Adult; Blood Glucose; Blood Pressure; Body Mass Index; Carotid Artery Diseases; Carotid Intima-Media Thickness; Case-Control Studies; Chi-Square Distribution; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Enzyme-Linked Immunosorbent Assay; Female; Glycated Hemoglobin; Humans; Leptin; Lipids; Male; Resistin; Risk Assessment; Risk Factors; Turkey; Ultrasonography, Doppler; Waist Circumference; Young Adult

The adipocytokines adiponectin and leptin have been suggested as risk factors for cardiovascular disease, including stroke, acting through atherosclerosis. However, studies have provided conflicting results in underpowered cohorts with some suggesting that the leptin:adiponectin ratio is a better predictor of risk. We examined these associations with carotid intima-media thickness (IMT), a marker of early atherosclerosis and arterial remodeling and an independent predictor of stroke. We also examined association between genetic variants in the leptin and adiponectin genes and IMT.. Adiponectin and leptin levels were determined in 990 individuals from the community Carotid Atherosclerosis Progression Study. Five variants in the gene encoding adiponectin and 7 in the gene encoding leptin were genotyped and their effects on circulating levels assessed. Both were then correlated with IMT.. Adiponectin levels negatively correlated with IMT (-0.079, P=0.013). There was no correlation between leptin levels or leptin:adiponectin ratio and IMT. Two variants in the ADIPOQ gene encoding adiponectin were associated with altered adiponectin levels, 1 of which (rs266729) was associated with IMT. There was also an interaction with body mass index (P=0.019) with the association being present in obese subjects (P=0.02).. Our results support a causal role for adiponectin in early carotid IMT and suggest it may act through interaction with obesity. In contrast, we found no evidence of a role for leptin and no evidence that leptin:adiponectin ratio is a better predictor of risk that adiponectin levels alone.

Topics: Adiponectin; Adult; Aged; Biomarkers; Body Mass Index; Carotid Artery Diseases; Genetic Variation; Humans; Leptin; Middle Aged; Obesity; Polymorphism, Genetic; Risk Factors; Tunica Intima; Tunica Media

To characterize clinicopathogenetically factors influencing development of early chronic kidney disease (CKD) and impairment of other target organs in obese patients.. The examination of 86 obese patients (64 males and 22 females, mean age 44 +/- 11 years) included standard clinical tests, test for albuminuria, calculation of glomerular filtration rate (GFR) by MDRD formula, ultrasound investigation of the carotid arteries to detect atherosclerotic lesion of the carotid arteries, assessment of insulin resistance - IR (plasma concentration of insulin before meal and blood C-peptide, HOMA-index), test for plasma adipokinins (leptin, adiponectin).. Significant direct correlations were found between blood plasma leptin concentration, body mass index (BMI), plasma concentration of insulin and C-peptide, HOMA index, adiponectinemia and albuminuria. CKD patients have significantly higher than patients free of CKD levels of IR markers, waist circumference, BMI, leptinemia (38.2 +/- 28.8 and 21.6 +/- 19.8 ng/ml, respectively; p < 0.01). Obstructive sleep apnea syndrome was associated with higher IR and albuminuria, significantly lower estimated GFR (81 +/- 2 and 95 +/- 2 ml/min/1.73 m2, respectively; p < 0.05). Ultrasound evidence for atherosclerotic lesions of the carotid arteries was associated with a significant increase in blood plasma concentration of C-peptide, reduction of adiponectinemia (14.9 +/- 10.8 and 32.5 +/- 22.5 mcg/ml; p < 0.01), a rise in proportion fasting insulinemia/adiponectinemia (1.6 +/- 1.2 and 0.6 +/- 0.8, respectively; p < 0.05) and reduction of estimated GFR (86 +/- 19 and 102 +/- 25 ml/min/1.73 m2, respectively; p = 0.001).. In obesity, CKD at early stages develops in parallel with atherosclerotic lesion of the carotid arteries, which correlates with progression of leptinemia, IR and attenuation of organ-protecting properties of adiponectin.

Topics: Adiponectin; Atherosclerosis; Biomarkers; Carotid Artery Diseases; Chronic Disease; Female; Humans; Insulin Resistance; Kidney Diseases; Leptin; Male; Obesity

The leptin:adiponectin ratio (L:A ratio) is an independent predictor of carotid intima-media thickness (CIMT).. To evaluate whether the leptin:high-molecular-weight adiponectin ratio (L:HA ratio) is associated with CIMT in the general population.. We investigated the relationship between the L:HA ratio and CIMT in 233 Japanese study participants (106 men and 127 women).. After adjustment for confounding factors, CIMT was significantly correlated with the log L:HA ratio (beta = 0.11, p = 0.014) in men, whereas no correlation was observed in women (beta = 0.01, p = 0.50).. The L:HA ratio is closely correlated with CIMT in men, but not in women.

Topics: Adiponectin; Adult; Aged; Aged, 80 and over; Carotid Arteries; Carotid Artery Diseases; Female; Humans; Leptin; Linear Models; Male; Middle Aged; Multivariate Analysis; Sex Factors; Tunica Intima; Tunica Media; Ultrasonography

High leptin and low ghrelin are associated with the metabolic syndrome (MS).. Ghrelin, leptin (RIA kits), and insulin-like growth factor I (IGF-I) (ELISA kit) concentrations of the population-based cohort of 1045 subjects and their interactions with metabolic parameters were analysed. Intima-media thickness (IMT) was measured with carotid ultrasound.. The interaction between leptin and ghrelin on the MS was significant (P = 0.011). An additive effect of high leptin and low ghrelin on metabolic disturbances was observed: low ghrelin concentration (adjusted for age and sex) (P < 0.001) was associated with the MS and type 2 diabetes in the highest but not in the lower leptin quartiles. In the highest leptin quartile, ghrelin concentrations decreased linearly when the number of International Diabetes Federation MS criteria met (P < 0.01) increased. Ghrelin-leptin relation was independently associated with carotid IMT (P < 0.005). The independent positive association (P < 0.01) between the plasma ghrelin quartile and the carotid IMT was evident in the lowest IGF-I quartile.. Low ghrelin is associated with MS and type 2 diabetes in the presence of insulin and leptin resistance. Ghrelin-leptin relation is associated with early atherosclerosis. The interaction between IGF-I and ghrelin modifies the association of ghrelin with early atherosclerosis.

Topics: Adult; Carotid Artery Diseases; Case-Control Studies; Diabetes Mellitus, Type 2; Female; Ghrelin; Humans; Insulin-Like Growth Factor I; Leptin; Male; Metabolic Syndrome; Middle Aged; Tunica Intima; Tunica Media

Topics: Adiponectin; Aged; Aged, 80 and over; Biomarkers; Carotid Arteries; Carotid Artery Diseases; Female; Humans; Leptin; Middle Aged; Tunica Intima; Tunica Media

Elevated leptin levels are thought to contribute to the individual cardiovascular risk, however, the role of leptin in the pathogenesis of atherosclerosis remains unclear. The aim of our study was to elucidate the effects of leptin on growth of human vascular smooth muscle cells (VSMC) and leptin receptor expression. By establishing a new quantitative real-time PCR for leptin receptor (ObR) isoforms we showed that the short isoforms of ObR were expressed in a 10- to 27-fold excess compared to the long isoform in cultured human VSMCs. Incubation of VSMCs with 100 ng/ml leptin downregulated the short isoforms significantly, whereas the long isoform was not influenced. Increasing leptin concentrations of 50 and 100 ng/ml significantly reduced the cell number of VSMCs compared to untreated controls. Our findings suggest a role for leptin in vascular smooth muscle cell growth, associated to a downregulation of leptin receptor isoforms.

Topics: Aged; Aorta; Carotid Artery Diseases; Carotid Artery, Internal; Cell Proliferation; Cell Survival; Cells, Cultured; Dose-Response Relationship, Drug; Down-Regulation; Female; Growth Inhibitors; Humans; Iliac Artery; Leptin; Male; Middle Aged; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Polymerase Chain Reaction; Protein Isoforms; Receptors, Cell Surface; Receptors, Leptin; RNA, Messenger

The aging process is characterized by a number of gradual changes in circulating hormone concentrations as well as a gradual increase in the degree of atherosclerosis. The authors studied whether serum hormone levels are related to atherosclerosis of the carotid artery in independently living, elderly men. In 1996, 403 men (aged 73-94 years) were randomly selected from the general population of Zoetermeer, the Netherlands. Carotid artery intima-media thickness was determined. Serum concentrations of testosterone; estrone; estradiol; dehydroepiandrosterone and dehydroepiandrosterone sulfate; insulin-like growth factor I (IGF-I) (total and free) and its binding proteins IGFBP-1, IGFBP-2, and IGFBP-3; and leptin were measured. After the authors adjusted for age, serum testosterone, estrone, and free IGF-I were inversely related to intima-media thickness. The strength of these relations was as powerful in subjects with as in those without prevalent cardiovascular disease. Serum estradiol; dehydroepiandrosterone sulfate; total IGF-I, IGFBP-1, IGFBP-2, and IGFBP-3; and leptin showed no association. These findings suggest that endogenous testosterone, estrone, and free IGF-I levels may play a protective role in the development of atherosclerosis in aging men.

Topics: Aged; Aged, 80 and over; Aging; Arteriosclerosis; Carotid Artery Diseases; Case-Control Studies; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Estrone; Humans; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor Binding Protein 2; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Leptin; Linear Models; Male; Netherlands; Prevalence; Risk Factors; Testosterone; Tunica Media; Ultrasonography

The aim of this study was to determine the associations between vascular endothelial function, intima-media thickness (IMT) of the common carotid artery and anthropometric/metabolic parameters in healthy obese women without obesity-related metabolic complications and age-matched healthy lean controls. Twenty-four obese [body mass index (BMI) > 30 kg/m2; age 31.4 +/- 7.4 yr] and 14 lean (BMI < 24 kg/m2; age 30.5 +/- 7.2 yr) women were studied. All of the subjects had normolipemia. Insulin resistance was calculated according to the homeostasis model assessment (HOMA) formula. Endothelial function was measured by flow-mediated dilation (FMD) of the brachial artery. IMT of the common carotid artery was calculated from high-resolution ultrasound imaging of the two common carotid arteries. Obese and lean women were matched with respect to age, smoking status, blood pressure, glucose, insulin concentrations and HOMA. IMT of common carotid artery was significantly higher (0.56 +/- 0.09 vs 0.45 +/- 0.06 mm, p < 0.001) and FMD (percentage of change from baseline) was significantly lower (13.3 +/- 6.5% vs 25.2 +/- 13.9%,p < 0.001) in the obese subjects. Lipid profile, blood pressure, indirect measurement of insulin resistance, leptin concentrations and anthropometric parameters did not predict the FMD or IMT in the obese and lean groups. It is concluded that even in healthy obese women with a normal metabolic profile, deterioration in endothelial function and early atherosclerotic changes are evident compared with healthy lean counterparts. Some undetermined factors in our study other than obesity-related well-known risk factors could be responsible for this observation.

Topics: Adult; Anthropometry; Biomarkers; Blood Glucose; Blood Pressure; Carotid Artery Diseases; Carotid Artery, Common; Cholesterol, HDL; Cholesterol, LDL; Diastole; Endothelium, Vascular; Female; Homeostasis; Humans; Insulin; Leptin; Obesity; Reference Values; Statistics as Topic; Systole; Time Factors; Triglycerides; Tunica Intima; Vasodilation; Women's Health

To investigate whether intima-media thickness (IMT) of the common carotid artery (CCA), an early marker of asymptomatic atherosclerosis, is significantly and independently associated with plasma concentrations of leptin, an adipose tissue hormone that has recently been proposed as a cardiovascular risk factor in obese patients.. Cross-sectional sample of normal-weight and obese men and women.. One-hundred and twenty healthy subjects (52 men and 68 women), aged 18-45 y and with a wide range of BMI, were recruited for the study.. Fasting plasma leptin concentrations and the IMT of the CCA were measured in all subjects. Leptin concentrations were measured by radioimmunoassay and the IMT of the CCA was quantified by high resolution B-mode ultrasound imaging. Central fat (measured by waist circumference), smoking habits, blood pressure, insulin sensitivity (measured by the insulin tolerance test), and fasting plasma glucose, insulin and lipid pattern (cholesterol, HDL-cholesterol, triglycerides, LDL-cholesterol) were also measured.. IMT of the CCA was positively correlated with log leptin concentrations (P<0.005 in men and P<0.001 in women), body mass index (P<0.001 in men and women), waist circumference (P<0.001 in men and women), age (P<0.001 in men and P<0.05 in women), and negatively associated with insulin sensitivity in both sexes (P<0.05). IMT was also directly correlated with cholesterol (P<0.05), LDL-cholesterol (P<0.01) and systolic blood pressure in men (P<0.05), and with diastolic blood pressure levels in women (P<0.05). When a multiple linear regression model was used without body mass index (BMI), the correlation between leptin and IMT was maintained in both men (P<0.01) and women (P<0.005), independent of age, insulin sensitivity, smoking habits, systolic blood pressure, fasting glucose, triglycerides, cholesterol, LDL-cholesterol and HDL-cholesterol. By contrast, BMI-adjusted leptin concentrations were not significantly associated with IMT (Pc (partial correlation): 0.41 in men and 0.15 in women). Moreover, when BMI was entered into a multiple linear regression model without leptin, the correlation between BMI and IMT was maintained in both men (P<0.005) and women (P<0.01), independent of the same parameters.. Plasma leptin concentrations are independently associated with the IMT of the CCA, suggesting that the increase of adipose tissue mass (or leptin per se) may have an unfavourable influence on the development of atherosclerosis. However, the association between IMT and leptin seems to be dependent and/or confounded by the relationship between IMT and obesity.

Topics: Adipose Tissue; Adolescent; Adult; Age Factors; Blood Pressure; Body Mass Index; Carotid Artery Diseases; Carotid Artery, Common; Cross-Sectional Studies; Female; Humans; Leptin; Lipids; Male; Middle Aged; Obesity; Smoking; Tunica Intima; Ultrasonography