Nikolaos Gouliopoulos

Omega-3 PUFAs improved endothelial function and arterial stiffness with a parallel antiinflammatory effect in adults with metabolic syndrome

OBJECTIVES Metabolic syndrome (MetS) is associated with adverse cardiovascular events, and impaired vascular function. In this study we evaluated the effects of omega-3 polyunsaturated fatty acids (PUFAs) supplementation on vascular function, inflammatory and fibrinolytic process in subjects with MetS. METHODS We studied the effect of a 12 weeks oral treatment with 2 g/day of omega-3 PUFAs in 29 (15 male) subjects (mean age 44 ± 12 years) with MetS on three occasions (day0: baseline, day 28 and day 84). The study was carried out on two separate arms (PUFAs and placebo), according to a randomized, placebo-controlled, double-blind, cross-over design. The diagnosis of MetS was based on the guidelines of Adult Treatment Panel III definition. Endothelial function was evaluated by flow-mediated dilation (FMD) of the brachial artery. Carotid-femoral pulse wave velocity (PWV) was measured as an index of aortic stiffness. Serum levels of interleukin-6(IL-6) and plasminogen activator inhibitor-1(PAI-1) were measured by ELISA. RESULTS Treatment with PUFAs resulted in a significant improvement from day 0 to 28 and 84 in FMD and PWV (p < 0.001 for all). Nevertheless, treatment with placebo resulted in no significant changes in FMD (p = 0.63) and PWV (p = 0.17). Moreover, PUFAs treatment, compared to placebo, decreased IL-6 levels (p = 0.03) and increased PAI-1 levels (p = 0.03). Finally, treatment with PUFAs resulted in a significant decrease in fasting triglyceride levels from day 0 to 28 and 84 (p < 0.001) and in serum total cholesterol levels (p < 0.001). CONCLUSIONS In subjects with MetS, treatment with omega-3 PUFAs improved endothelial function and arterial stiffness with a parallel antiinflammatory effect.

Favorable Effects of Concord Grape Juice on Endothelial Function and Arterial Stiffness in Healthy Smokers

BACKGROUND Smoking is associated with impaired vascular function. Concord grape juice (CGJ), a rich source of flavonoids, can modify cardiovascular risk factors. Endothelial function and arterial stiffness are surrogate markers of arterial health. We examined the impact of CGJ on arterial wall properties in healthy smokers. METHODS We studied the effect of a 2-week oral treatment with CGJ in 26 healthy smokers on 3 occasions (day 0 (baseline), day 7, and day 14) in a randomized, placebo-controlled, double-blind, crossover study. Measurements were taken before (pSm), immediately after (Sm0), and 20 minutes after (Sm20) cigarette smoking. Endothelial function was evaluated by flow-mediated dilation (FMD) of the brachial artery. Carotid-femoral pulse wave velocity (PWV) was measured as an index of aortic stiffness. RESULTS Compared with placebo, treatment with CGJ resulted in a significant improvement in pSm values of FMD (P = 0.02) and PWV (P = 0.04). At baseline, smoking decreased FMD in both the CGJ group (P < 0.001) and the placebo group (P < 0.001). Compared with placebo, CGJ treatment prevented the acute smoking-induced decrease in FMD on day 7 (P = 0.02) and day 14 (P < 0.001). Moreover, at baseline, smoking induced a significant elevation in PWV in both the CGJ group (P = 0.02) and the placebo group (P = 0.04). Treatment with CGJ prevented the smoking-induced elevation in PWV on day 7 (P = 0.003) and day 14 (P < 0.001). CONCLUSIONS CGJ consumption improved endothelial function and vascular elastic properties of the arterial tree in healthy smokers and attenuated acute smoking-induced impairment of arterial wall properties.

Role of Endothelial Dysfunction and Arterial Stiffness in the Development of Diabetic Retinopathy

Diabetic retinopathy (DR) remains one of the most important diabetic microvascular complications and a leading cause of irreversible blindness, highlighting the importance of close monitoring. The atherosclerotic progression in patients with insulin resistance is precipitated by endothelial dysfunction and vascular impairment (1). Therefore, we examined the association of endothelial dysfunction and arterial stiffness with DR and how these measurements can be used for the early identification and monitoring of patients at high risk to develop DR. In this case-control study, we included 100 healthy control (CL) subjects and 200 consecutive subjects with type 2 diabetes recruited from the 1st Department of Ophthalmology of the University of Athens Medical School where they were referred to evaluate for DR. All participants underwent a complete ophthalmological examination by the same experienced ophthalmologist, which included fundoscopy after pupillary dilation, fluorescein angiography, and colorful fundus photographs. The diabetic patients, according to the Early Treatment Diabetic Retinopathy Study (ETDRS) classification, were categorized into three groups: 1 ) no DR (NDR) (108 …

Electrophysiological examination in uveitis: a review of the literature

Purpose Uveitis is the inflammation of the uveal tract, which usually also affects the retina and vitreous humor. The electrophysiological examination is an objective ocular examination that includes the electroretinogram, visual evoked potentials, the electrooculogram, the multifocal electroretinogram, and multifocal visual evoked potentials. Our aim is to review the literature of the use of the electrophysiological examination in cases of uveitis. Methods We performed a systematic search of the literature of published papers until October 2012 using the PubMed search engine. The key terms that were used were “uveitis”, “electrophysiological examination”, “electroretinogram”, “visual evoked potentials”, “electrooculogram”, “multifocal electroretinogram”, and “multifocal visual evoked potentials” in multiple combinations. To the best of our knowledge, this is the first review concerning the assessment of electrophysiology in uveitis. Results Our search of the literature demonstrated that the electrophysiological examination, mainly by means of electroretinogram, multifocal electroretinogram, and visual evoked potentials, is performed in several cases of uveitis for many purposes, including diagnosis and monitoring of disease progression and treatment efficacy. The electrophysiological examination is more useful in patients with multiple evanescent white dot syndrome, acute posterior multifocal placoid pigment epitheliopathy, birdshot chorioretinopathy, Vogt–Koyanagi–Harada disease, Adamantiades–Behçet disease, ocular syphilis, and Fuchs heterochromic cyclitis. Conclusion This review summarizes the use of the electrophysiological examination in uveitic patients and underlines its value as a useful tool in the objective assessment and the monitoring of the disease.

Vascular function and ocular involvement in sarcoidosis.

Ocular involvement occurs in sarcoidosis (Sar) patients mainly in the form of uveitis. This study was designed to determine if uveitis in Sar patients is associated with vascular impairment. We enrolled 82 Sar patients and 77, age and sex matched, control subjects (Cl). Sar patients were divided into those with ocular sarcoidosis (OS) and those without ocular sarcoidosis (WOS). Endothelial function was evaluated by flow-mediated dilation (FMD). Pulse wave velocity (PWV) was measured as an index of aortic stiffness and augmentation index (AIx) as a measure of arterial wave reflections. Although there was no significant difference in sex, age and mean arterial pressure, patients with OS compared to WOS patients and Cl subjects had impaired FMD (p<0.001), increased AIx (p=0.02) and increased PWV (p=0.001). Interestingly, impaired FMD in Sar patients was independently, from possible covariates (age, sex, smoking habits, arterial hypertension, dyslipidemia), associated with increased odds of ocular involvement (odds ratio=1.69, p=0.001). More precisely ROC curve analysis revealed that FMD had a significant diagnostic ability for the detection of OS (AUC=0.77, p<0.001) with a sensitivity of 79% and a specificity of 68% for an FMD value below 6.00%. To conclude in the present study we have shown that ocular involvement in Sar patients is associated with impaired endothelial function and increased arterial stiffness. These results strengthen the vascular theory which considers uveitis a consequence of vascular dysfunction in Sar patients and reveals a possible clinical importance of the use of endothelial function tests.

Novel Biomarkers Assessing Renal Function in Heart Failure: Relation to Inflammatory Status and Cardiac Remodelling

BACKGROUND Patients with heart failure (HF) have a significant decline of renal function. We investigate the association between novel biomarkers of renal dysfunction and indices of inflammatory status and cardiac remodeling in patients with HF. METHODS We enrolled 79 consecutive patients with HF and 79 healthy subjects, adjusted for age and sex. Serum levels of neutrophil gelatinase-associated lipocalin (NGAL), cystatin-C, b-type natriuretic peptide (BNP), tumor necrosis factor alpha (TNFα) and matrix metalloproteinase-9 (MMP-9) were measured by ELISA. Creatinine clearance was estimated using Cockcroft-Gault formula (eCcl). Left ventricular ejection fraction was determined by echocardiography. RESULTS Patients with HF, compared to healthy subjects, had significantly higher NGAL (p=0.007) and cystatin-C levels (p=0.005). In HF patients, NGAL levels were positively correlated with Creatinine levels (r=0.40, p<0.001), TNFa levels (r=0.43, p<0.001), BNP levels (r=0.36, p=0.003), MMP-9 levels (r=0.37, p=0.02) and inversely correlated with left ventricle ejection fraction (r=-0.23, p=0.045). Interestingly, the association between NGAL and MMP-9 levels was independent from confounders such as age, gender, left ventricle ejection fraction, body mass index, TNFα levels, and BNP levels. Moreover, in HF patients, cystatin-C levels were inversely correlated with eCcl (r=-0.21, p=0.04). Cystatin-C levels were not correlated with TNFa, BNP, MMP-9 levels and with left ventricle ejection fraction (p=NS for all). CONCLUSIONS NGAL is associated with left ventricle ejection fraction, and biomarkers of inflammation and cardiac remodeling in patients with HF. These findings highlight a possible common pathogenetic mechanism of renal dysfunction, inflammatory process and cardiac dysfunction in HF.

Novel Risk Factors Related to Stable Angina

Stable angina (SA) pectoris is a common and disabling disorder in patients with coronary artery disease (CAD), with increasing epidemiology and is associated with myocardial infarction and increased mortality. However, within the population of SA patients, an individuals prognosis can vary considerably. Except from conventional risk factors a variety of biomarkers have been evaluated for their prognostic significance in the settings of SA. Novel biomarkers associated with inflammatory status, such as C reactive protein and tumor necrosis factor alpha, with myocardial performance, such as B-type natriuretic peptide, with extracellular matrix remodeling, with vascular calcification such as osteoprotogerin and osteopontin, with myocardial ischemia, such as ischemia modified albumin have been associated with the progression of CAD and with the prognosis of SA patients. Despite the multiplicity of novel biomarkers there is lack of a clinical useful, highly specific for CAD biomarker with the ability to guide treatment decisions. In the context of this evidence in this review article we summarize the so far acquired knowledge of the most promising biomarkers and we discuss the major clinical correlations of novel risk factors with SA physical history, their predictive value for future cardiovascular events and their use in the treatment monitoring of this population.

Arterial Wall Elastic Properties and Endothelial Dysfunction in the Diabetic Foot Syndrome in Patients With Type 2 Diabetes

Diabetic foot (DF) syndrome is the most common lower-extremity complication of poorly controlled type 2 diabetes (T2D) (1). DF affects the quality of life of T2D patients and is associated with increased morbidity (2). T2D-related mechanisms induce endothelial dysfunction and adverse effects on vascular biology (3). We have recently shown that measurements of endothelial function and arterial stiffness are strongly associated with diabetic retinopathy (4), but their association with DF has not been explored yet. To examine this, we enrolled 284 consecutive T2D subjects visiting our outpatient diabetes clinic and 196 age- and sex-matched healthy control subjects without evidence of diabetes or cardiovascular or other disease. Subjects with known malignancy, hepatic impairment, or acute or chronic inflammatory disease were excluded from the study. Study protocol was approved by the institutional ethics committee. Endothelial function was assessed by the flow-mediated dilation (FMD) of the brachial artery and carotid-femoral pulse wave velocity (PWV) and augmentation index (AIx) were assessed by SphygmoCor (AtCor Medical) as …

The impact of T786C and G894T polymorphisms of eNOS on vascular endothelial growth factor serum levels in type 2 diabetes patients.

Endothelial dysfunction (ED) and chemokines such as vascular endothelial growth factor (VEGF) are of vital importance for the development of diabetic vascular complications [1–3]. VEGF is a secreted mitogen which plays a key role in the regulation of angiogenesis, vasculogenesis and vascular permeability to water and proteins [4]. Moreover, the action of VEGF is crucial for themaintenance of the proper endothelial and vascular function. The interaction between VEGF and its receptors is disrupted in diabetes, leading to pathological angiogenesis,which in turn contributes tomicrovascular diseases, such as diabetic retinopathy and diabetic nephropathy [5]. Nitric oxide (NO) is the most important regulator of vascular homeostasis and therefore, a common feature of ED is its diminished bioavailability in the vasculature [6,7]. In the setting of diabetes and insulin resistance, the activity of endothelial nitric oxide synthase (eNOS) is impaired, since insulin-mediated activation of eNOS via PI3kinase/Akt pathway is inhibited [8]. Moreover, diabetes mellitus (DM) enhances the production of reactive oxygen species (ROS), thus resulting in less NO generation and consequent vascular dysfunction [9,10].

Associations between Adiponectin Gene Variability, Pro-inflammatory and Angiogenetic Markers: Implications for Microvascular Disease Development in Type 2 Diabetes Mellitus?

BACKGROUND Adiponectin gene (ADIPOQ) variability may affect the risk for type 2 diabetes mellitus (T2DM) but it remains unclear whether it is involved in microvascular complications. OBJECTIVE To explore the impact of ADIPOQ variability on markers of inflammation and angiogenesis in T2DM. METHODS Overall, 220 consecutive T2DM patients from our outpatient diabetic clinic were genotyped for G276T (rs1501299) and T45G (rs2241766) single nucleotide polymorphisms of ADIPOQ gene. Serum levels of interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1), vascular endothelial growth factor (VEGF) were measured by enzyme-linked immunosorbent assay and high sensitivity Creactive protein (hsCRP) by immunonephelometry. RESULTS Homozygosity for the G allele on rs2241766 was associated with significantly lower serum VEGF and ICAM-1 levels compared with other genotype groups, but had no effect on IL-6. Genetic variability on rs1501299 was not associated with either VEGF or ICAM-1 levels, but T homozygotes for rs1501299 had significantly lower IL-6 concentrations compared with G carriers. Furthermore, the presence of the G allele on rs2241766 was associated with significantly lower HbA1c, whereas no associations were observed for both body mass index and hsCRP with either rs2241766 or rs1501299. CONCLUSION Genetic variability on adiponectin gene was associated with serum levels of inflammatory and angiogenetic markers. Further research is required to elucidate the role of adiponectin in the development and/or progression of microvascular disease in T2DM patients.