Konstantinos Maniatis

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.

Serum osteoprotegerin and osteopontin levels are associated with arterial stiffness and the presence and severity of coronary artery disease

BACKGROUND Osteopontin (OPN) and osteoprotegerin (OPG) have recently emerged as key factors in both vascular remodeling and development of atherosclerosis. Arterial stiffness has an independent predictive value for cardiovascular events. We evaluate the relationship between OPG, OPN serum levels and vascular function in coronary artery disease (CAD) patients. METHODS The study population was consisted of 409 subjects (280 with CAD and 129 without CAD). Carotid-femoral pulse wave velocity (PWV) was measured as an index of aortic stiffness. OPG and OPN levels were measured, as markers of vascular remodeling and calcification, by ELISA. Gensini score was used to evaluate the extent of CAD. RESULTS CAD patients, compared to those without CAD, had higher OPG (3.91 ± 1.87 pmol/l vs. 2.88 ± 1.32 pmol/l, p<0.001) and logOPN levels (1.81 ± 0.18 ng/ml vs. 1.71 ± 0.24 ng/ml, p<0.001) and impaired PWV (8.94 ± 2.21 m/s vs. 8.28 ± 1.91 m/s, p=0.006). Furthermore, PWV was associated with serum OPG levels (r=0.19, p<0.001) and with serum logOPN levels (r=0.10, p=0.049). Multivariate linear regression analysis revealed that increased OPG (p=0.013) and logOPN (p=0.006) levels are associated with 3-vessel CAD and Gensini score (p=0.04 for OPG and p=0.09 for OPN), independently of other known cardiovascular risk factors. CONCLUSION The present study revealed that serum OPG and OPN levels are positively associated with arterial stiffness, and with the extent of CAD. These preliminary results suggest that OPG and OPN levels are significantly correlated with vascular function contributing to the pathogenesis of atherosclerosis in CAD. Further studies are needed to explore the mechanisms of action of OPG and OPN in CAD.

Effects of omega-3 fatty acids on endothelial function, arterial wall properties, inflammatory and fibrinolytic status in smokers: A cross over study

BACKGROUND Smoking is associated with endothelial dysfunction and arterial stiffness. Supplementation of Ω-3 PUFAs is associated with better prognosis. Aim of this study was to evaluate the effects of Ω-3 polyunsaturated fatty acids (PUFAs) supplementation on smoking-induced impairment of arterial function. METHODS We studied the effect of a 12 weeks oral treatment with 2gr/day of Ω-3 PUFAs in 20 healthy smokers on three occasions (day 0:baseline, day 28 and day 84). The study was carried out on two separate arms (Ω-3 fatty acids and placebo), according to a randomized, placebo-controlled, double-blind, cross-over design. Measurements were carried out before (pSm), immediately and 20min after 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 and augmentation index (AIx) as a measure of arterial wave reflections. Circulating levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and plasminogen activator inhibitor-1 (PAI-1) were measured. RESULTS Compared with placebo, Ω-3 PUFAs treatment resulted in a significant improvement in pSm values of FMD (p<0.05), AIx (p<0.001) and PWV (p<0.01). Although, acute cigarette smoking decreased FMD and caused an increase in AIx and PWV, Ω-3 PUFAs treatment blunted the acute smoking-induced impairment of FMD (p<0.001), AIx (p<0.05) and PWV (p<0.05) and significantly decreased levels of TNFα (p<0.05) and IL-6 (p=0.01) and increased levels of PAI-1 (p=0.05). CONCLUSIONS Ω-3 PUFAs improved endothelial function and the elastic properties of the arterial tree in healthy smokers, with a parallel anti-inflammatory effect.

Dose-dependent effects of short term atorvastatin treatment on arterial wall properties and on indices of left ventricular remodeling in ischemic heart failure

OBJECTIVES Statins, beyond their lipid lowering role, exert beneficial effect on endothelial function in patients with atherosclerosis. Aim of the present study was to examine the short term pleiotropic effects of different doses of atorvastatin treatment, on endothelial function, arterial stiffness and indices of left ventricular remodeling in heart failure (HF) patients. METHODS We studied the effect of 4 weeks administration of atorvastatin in 22 patients with ischemic HF. The study was carried out on two separate arms, one with atorvastatin 40 mg/d and one with atorvastatin 10 mg/d (randomized, double-blind, cross-over design). Endothelial function was evaluated by flow mediated dilation (FMD) in the brachial artery and arterial stiffness by augmentation index (AIx). Serum levels of matrix metalloproteinase-9 (MMP-9) and intracellular adhesion molecule-1 (sICAM-1) were measured as biomarkers of left ventricular remodeling and endothelial function, respectively, while, b-type natriuretic peptide (BNP) was measured as a marker of left ventricular function. RESULTS Compared to baseline, atorvastatin 40 mg/d significantly improved FMD values (3.18 ± 3.03% vs. 5.98 ± 2.49%, p = 0.001) and AIx values (25.98 ± 8.55% vs. 23.09 ± 8.87%, p = 0.046). In addition, compared to baseline measurements, treatment with atorvastatin 40 mg/d resulted in significantly decreased levels of serum logMMP-9 levels (2.47 ± 0.23 ng/ml vs. 2.39 ± 0.24 ng/ml, p = 0.04) and of logICAM-1 levels (2.46 ± 0.13 ng/ml vs. 2.37 ± 0.16 ng/ml, p < 0.001). No significant changes were found after treatment with atorvastatin 10 mg/d in the aforementioned parameters. CONCLUSIONS Short term treatment with 40 mg/d of atorvastatin exerts beneficial impact on arterial wall properties and on indices of left ventricle remodeling in heart failure patients.

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.

Vitamin D serum levels are associated with cardiovascular outcome in coronary artery disease

Coronary artery disease (CAD) is a leading cause of death inwestern world. Several cardiovascular risk factors such as age, gender, diabetes mellitus, hyperlipidemia, have been recognized and are associated with atherosclerosis progression and adverse prognosis. Recently, the impact of calcium metabolism in the progression of CAD has emerged [1]. Vitamin D has a pivotal role in regulating calcium homeostasis and vitamin D deficiency is now recognized as a situation highly prevalent worldwide. Moreover, low levels of vitamin D are associated with the presence of classic cardiovascular risk factors such as age, obesity, diabetesmellitus, metabolic syndrome and chronic kidney disease [2,3]. Furthermore, vitamin D deficiency is associated with the presence of subclinical cardiovascular disease, including carotid intima-media thickness, coronary artery calcification and endothelial dysfunction and with overall mortality and cardiovascular risk [4,5]. In the present study we evaluated the diagnostic and prognostic significance of vitamin D status in subjects with established CAD.We consecutively enrolled 252 subjects with CAD. All subjects were treated according to revascularization guidelines with percutaneous coronary intervention and they were followed-up from 3 to 36 months with a median time of 15 months. CAD was defined by coronary angiography as narrowing of more than 50% of at least one major coronary artery. Coronary angiographies were interpreted by at least two experienced cardiologists. On the basis of these coronary angiographies, the number of affected coronary arteries was determined. The severity of CAD was further evaluated by Gensini score and we consider as patients with severe CAD those with a Gensini score more than 80. The baseline characteristics of CAD patients are presented in Table 1. All measurements, in this study were made by the same observer who

The impact of CYP2C19 genotype on cardiovascular events and platelet reactivity in patients with coronary artery disease receiving clopidogrel.

patients with coronary artery disease receiving clopidogrel Dimitris Tousoulis ⁎, Gerasimos Siasos , Marina Zaromitidou , Evangelos Oikonomou , Konstantinos Maniatis , Stamatios Kioufis , Eleni Kokkou , Athanasios G. Papavassiliou , Christodoulos Stefanadis a a 1st Department of Cardiology, ‘Hippokration’ Hospital, University of Athens Medical School, Athens, Greece b Department of Biological Chemistry, University of Athens Medical School, Athens, Greece

C-REACTIVE PROTEIN AS A RISK FACTOR FOR FUTURE CARDIOVASCULAR EVENTS IN PATIENTS WITH STEMI AND NORMAL OR MILDLY IMPAIRED LEFT VENTRICLE SYSTOLIC FUNCTION

Myocardial infarction with ST segment elevation (STEMI) is associated with significant increase in morbidity and mortality. We evaluated the association of C-reactive protein (CRP) and cardiac troponin I (cTnI) with the prognosis of patients presented with STEMI. In this study 235 (36 female)

High platelet reactivity is associated with vascular function in patients after percutaneous coronary intervention receiving clopidogrel

BACKGROUND In the present study, we evaluated the association of platelet reactivity with vascular function in patients after percutaneous coronary intervention receiving clopidogrel treatment. METHODS We enrolled 150 patients with stable CAD receiving clopidogrel regimen (75 mg/d), 1 month after percutaneous coronary intervention. Carotid-femoral pulse wave velocity (PWV) was measured as an index of aortic stiffness and augmentation index (AIx) as an index of arterial wave reflections. High on treatment platelet reactivity (HPR) was evaluated using VerifyNow Assay. VerifyNow reports its results in P2Y12 reaction units (PRU), and the diagnostic cutoff value is 230 PRU. Patients were evaluated prospectively up to 24 months. The primary end point was a composite of death from cardiovascular causes, nonfatal major cardiovascular events and hospitalization for cardiovascular causes. RESULTS There was no difference in the basic clinical and demographic characteristics between subjects with HPR and non-HPR. Subjects with high on treatment platelet reactivity and PRU>230 had significantly increased PWV (8.81 ± 2.25 m/s vs. 7.69 ± 1.95 m/s, p = 0.001) and AIx (25.27 ± 8.67% vs. 20.87 ± 10.57%, p = 0.04) compared to subjects with PRU≤230. PWV was also associated with PRU (r = 0.23, p = 0.02). HPR was associated with significantly increased risk of primary end point [HR = 5.38, 95%CI:(1.15, 26.04), p = 0.03]. CONCLUSIONS Increased platelet reactivity is associated with impaired arterial stiffness in patients after percutaneous coronary intervention receiving clopidogrel treatment, highlighting another clinical factor implicated in individual platelet response to antiplatelet therapy. Moreover, increased platelet reactivity is associated with adverse outcome in these patients.

Vitamin D3, D2 and arterial wall properties in coronary artery disease.

OBJECTIVES There are two major forms of vitamin D, vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol). We studied the effect of the different vitamin D fractions (D3/D2) on arterial wall properties in coronary artery disease (CAD) patients. METHODS We included 252 subjects with CAD. Endothelial function was evaluated by flow mediated dilation (FMD). Carotid femoral pulse wave velocity (PWV) was measured as an index of arterial stiffness and augmentation index (AI) as a measure of reflected waves. Measures for 25(OH)D2 and 25(OH)D3 were performed using Liquid Chromatography Mass Spectrometry technology. RESULTS From the study population, 155(62%), 66(26%) and 31(12%) were categorized as having vitamin D deficiency, insufficiency and sufficiency respectively. There was no difference between subjects with vitamin D deficiency, insufficiency and sufficiency in FMD, AI and PWV (p=NS for all). Subjects with vitamin D insufficiency/deficiency had significantly higher D2 to D ratio compared to subjects with vitamin D sufficiency. Interestingly, FMD was positively associated with D2 to D ratio (rho=0.13, p=0.02) and subjects with D2 levels<0.3ng/ml had impaired FMD compared to those with increased D2 levels (p=0.048). CONCLUSION Vitamin D insufficiency/deficiency is highly prevalent in CAD subjects. Vitamin D2 concentrations are positively associated with endothelial function. These findings may suggest a beneficial role of vitamin D2 levels in vascular health.