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Abstract Background Physical activity has long been associated with reduced risk of coronary heart disease (CHD). In this work we evaluated the effect of physical activity on lipid levels, in a sample of cardiovascular disease free people. Methods The ATTICA study is a population – based cohort that has randomly enrolled 2772 individuals, stratified by age – gender (according to the census 2001), from the greater area of Athens, during 2001–2002. Of them, 1376 were men (45 ± 12 years old, range: 18 – 86) and 1396 women (45 ± 13 years old, range: 18 – 88). We assessed the relationship between physical activity status (measured in kcal/min expended per day) and several lipids, after taking into account the effect of several characteristics of the participants. Results 578 (42%) men and 584 (40%) women were classified as physically active. Compared to sedentary physically active women had significantly lower levels of total serum cholesterol (p < 0.05), LDL (p < 0.05) and oxidized LDL cholesterol (p < 0.05), triglycerides (p < 0.05), apolipoprotein B (p < 0.05), and higher levels of HDL cholesterol (p < 0.05) and apolipoprotein A1 (p < 0.05). Similar associations were observed in men, but the benefits did not reach statistical significance. However, when we adjusted for age, smoking habits and body mass index, physical activity was only significantly associated with higher HDL-cholesterol (p < 0.05) and apolipoprotein A1 (p < 0.05) levels, in women, but not in men. Conclusions Substantial independent increases in HDL-cholesterol and apolipoprotein A1 concentrations were observed in women, but not in men, in a Mediterranean cohort.

Objective: Neoangiogenesis is pathophysiologically related to atherosclerotic plaque growth and vulnerability. We examined the in vivo performance of a computational method using contrast-enhanced intravascular ultrasound (CE-IVUS) to detect and quantify aortic wall neovascularization in rabbits. We also compared these findings with histological data. Methods: Nine rabbits were fed with a hyperlipidemic diet. IVUS image sequences were continuously recorded before and after the injection of a contrast agent. Mean enhancement of intensity of a region of interest (MEIR) was calculated using differential imaging algorithm. The percent difference of MEIR before and after the injection of microbubbles (d_MEIR) was used as an index of the density of plaque or/and adventitial neovascularization. Aortic segments were excised for histological analysis. Results: CE-IVUS and histological analysis were performed in 11 arterial segments. MEIR was significantly increased (~20%) after microbubble injection (from 8.1±0.9 to 9.7±1.8, p=0.016). Segments with increased VV/neovessels in the tunica adventitia (histological scores 2 and 3) had significantly higher d_MEIR compared with segments with low presence of VV/neovessels (score 1); 40.5±22.9 vs. 8±14.6, p=0.024, respectively. Conclusion: It is possible to detect VV or neovessels in vivo using computational analysis of CE-IVUS images, which is in agreement with histological data. These findings may have critical implications on vulnerable plaque assessment and risk stratification. [ABSTRACT FROM AUTHOR]

Abstract: Background: Arterial stiffness and vascular calcification significantly contribute to coronary atherosclerosis progression. The prognostic value of increased arterial stiffness and vascular calcification in subjects with stable coronary artery disease (CAD) after percutaneous coronary intervention(PCI) is currently under question. Materials and Methods: We randomly enrolled 262 patients with stable CAD 1 month after successful PCI. Carotid‐femoral pulse wave velocity (PWV) was measured as a well‐established index of central aortic stiffness. Osteoprotegerin (OPG) plasma levels were measured as a biomarker of vascular calcification. Patients were followed up prospectively up to 52 months. The primary endpoint was the composite of death from cardiovascular causes, myocardial infarction, stroke or hospitalization for cardiovascular causes. Results: During the follow‐up period, 48 patients presented the primary composite endpoint. Subjects who presented the primary endpoint, compared to subjects free of cardiovascular events, had significantly increased PWV (9.45 ± 2.19 m/s vs 8.73 ± 2.07 m/s, P = .04) and OPG levels (4.21 ± 2.19 pmol/L vs 3.18 ± 1.74 pmol/L, P = .003). Survival analysis indicated that PWV predicted adverse cardiac events MACE (Hazard ratio = 1.29 95%CI: 1.07‐1.57, P = .008) independently from confounders such as age, sex, smoking habits, ejection fraction, extent of coronary artery disease, hypertension and diabetes mellitus. Interestingly, for every increase in pulse wave velocity by 1 m/s, there is an anticipated increase in the risk of major adverse cardiovascular event (MACE) by 29%. Conclusions: These findings extend the current knowledge concerning the role of arterial stiffness as powerful biomarkers in cardiovascular disease. Measurement of PWV might have a role in ascertaining prognosis and managing treatment in patients with stable CAD after PCI. [ABSTRACT FROM AUTHOR]

Carotid atherosclerosis (CA) and chronotropic incompetence (CI) during exercise are two independent cardiovascular risk factors. Aim of the current study was to investigate the possible association between them, in apparently healthy individuals, after adjusting for the 10-year cardiovascular disease (CVD) risk score. This cross-sectional study consisted of 139 apparently healthy subjects, 40-65 years old, who underwent treadmill exercise test (Bruce protocol used), which showed no evidence of ischemia. Heart rate reserve (HR reserve) was calculated to assess chronotropic response; a value of ≤0.80 is considered CI. CA was assessed by the presence of carotid plaque(s) in common and internal carotid arteries and carotid bulb bilaterally, using B-mode ultrasound. A calibrated version of SCORE (i.e., HellenicSCORE) was used to estimate the 10-year fatal CVD risk; participants were classified into low-, moderate- or high-risk group. CI was present in 7.9 % and CA in 18.7 % of the participants. After adjusting for 10-year CVD risk and other key confounders, odds of CA were 8.6 times higher in subjects with CI compared to their counterparts with normal chronotropic response to exercise. The results of the study indicate that CI during exercise can lead to high clinical suspicion of CA in apparently healthy individuals. [ABSTRACT FROM AUTHOR]

Background: Erectile dysfunction (ED) is an early manifestation of a generalized arterial disease. The association between penile vascular disease progression and total atherosclerotic burden was investigated using a classification that incorporates ultrasonographic assessments of intima media thickness (IMT) and plaques from both the carotid and femoral arteries. Methods: Sixty-five ED patients (mean age, 56 ± 10 yrs) were evaluated for cavernous vascular disease severity using penile Doppler ultrasound. Ultrasonographic assessments of IMT, lumen diameter, and plaques in the carotid and femoral arteries were evaluated, and patients were classified according to an ultrasound-based morphological system. Results: Based on the results of ultrasonic assessments, patients were divided into two groups-a high-score group and a low-score group. Patients in the high-score group had increased intima-media ( > 1.0 mm) and/or plaque in any of the four arteries. Patients in the low-score group had normal carotid and femoral IMT and an absence of plaques in all four arteries. While the two groups did not differ in blood pressure parameters, metabolic profile, and smoking status, high-score patients (n = 31) had significantly decreased age-adjusted peak systolic velocity (25.2 cm versus 32.3 cm/s, P < 0.01) and a longer duration of ED (3.8 years versus 2 years, P < 0.05), compared with low-score patients (n = 34). In the high-score group, score level was inversely correlated with peak systolic velocity after adjusting for age and systolic blood pressure (b= -0.322, P = 0.025). There also was a positive linear relation of ED duration with prevalence of high score (P < 0.05). Conclusions: In patients with vasculogenic ED, ultrasound findings of penile vasculature damage and longstanding ED correlate significantly with increasing carotid and femoral atherosclerotic burden. These data suggest a close interrelationship between progression of vasculogenic ED and peripheral atherosclerosis. [ABSTRACT FROM AUTHOR]

The article discusses a study which investigated the connection between endothelium function and chronic coffee consumption in elderly inhabitants of Ikaria, Greece. The study evaluated coffee consumption and endothelial function in 142 older people. It noted that chronic coffee consumption was linked with improved endothelial function in the subjects, which provided an association between vascular health and nutrition.

Objectives Both neoangiogenesis and inflammation contribute in atherosclerosis progression. Contrastenhanced ultrasound (CEUS) provides visualisation of plaque neovascularisation. Microwave radiometry (MR) allows in vivo non-invasive measurement of temperature of tissues, reflecting inflammatory activation. We assessed the association of carotid plaque temperature, measured by MR, with plaque neovascularisation assessed by CEUS in intermediate lesions. Methods Consecutive patients with coronary artery disease and carotid atherosclerosis underwent carotid ultrasound imaging, CEUS and MR. Plaque texture, plaque surface and plaque echogenicity were analysed. Contrast enhancement (CE) by CEUS was defined as the % percentage of signal intensity difference, prior and post contrast infusion. Thermal heterogeneity (?T) was assigned as maximal temperature along the carotid artery minus minimum. Results Eighty-six carotid arteries of 48 patients were included. Fatty plaques had higher CE% and ?T compared with mixed and calcified (p<0.01 for all comparisons). Heterogeneous plaques had higher CE% and ?T compared with homogenous (p<0.01 for all comparisons). Plaques with irregular surface had higher CE% and ?T compared with plaques with regular (p<0.01 for all comparisons). There was a good correlation between ?T and CE (R=0.60, p<0.001). Conclusions Carotid plaque neovascularisation on CEUS examination is associated with increased thermal heterogeneity and ultrasound characteristics of plaque vulnerability in intermediate lesions. [ABSTRACT FROM AUTHOR]

Objectives: Soluble tumor necrosis factor-related apoptosis inducing ligand (sTRAIL) has been shown to exert protective action against atherosclerosis. The aim of this study was to investigate potential associations of coronary sTRAIL levels with indices of in-stent neointimal hyperplasia. Methods: 67 patients who underwent percutaneous coronary intervention with drug-eluting stent were followed up at approximately 12 months with determination of coronary sTRAIL concentration, angiography and intravascular ultrasound evaluation of the stent sites. Results: Mean sTRAIL concentration was 72.2 ± 2.8 pg/ml. sTRAIL was negatively correlated to indices of neointimal hyperplasia and positively correlated to in-stent minimum lumen area (p < 0.001). Neointimal obstruction and maximal in-stent cross-sectional neointima burden in patients in the upper sTRAIL quartile were 3.8 ± 1.2 and 12.6 ± 3.3%, respectively, versus 14.0 ± 0.7 and 49.8 ± 2.7% in the lower quartile (p < 0.001 for both). sTRAIL levels were significantly lower in patients with binary restenosis (48.7 ± 3.0 vs. 75.2 ± 2.9 pg/ml; p < 0.001). In the multivariate analysis, sTRAIL was an independent predictor of neointimal hyperplasia. Conclusion: This study demonstrates a negative association of sTRAIL to in-stent neointima formation. The potential pathophysiologic substrate of this effect implicates modulation of apoptosis in various cell types. These observations should prompt further evaluation of the link between sTRAIL and in-stent restenosis. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The prevalence of microalbuminuria (MA) in children and adolescents differs from the one in adults, and it is estimated to be about 5.7-7.3% in boys and 12.7-15.1% in girls. The percentage is greater in smaller age group, whereas a positive association is found between albumin excretion rate and pubertal development stage in nondiabetic subjects. The data so far suggest that impairment of glucose metabolism, obesity-related proatherosclerotic pathways and the impact of haemodynamic load constitute major determinants of albuminuria development in the early years of life. In everyday practice if persistent MA is present at a young age, especially in the setting of diabetes, further investigation of cardiovascular risk factors, a more careful follow-up and dietary/lifestyle interventions are needed. Conclusion: Although the significance of MA in paediatric essential hypertension has yet to be determined, its role in diabetic children and adolescents is established and albuminuria assessment has been utilized as a screening test for the presence of diabetes-related kidney disease. [ABSTRACT FROM AUTHOR]

We explored the role of asymmetrical dimethylarginine (ADMA) as a cause of endothelial dysfunction induced by systemic inflammation. In vitro data suggest that ADMA bioavailability is regulated by proinflammatory stimuli, but it is unclear whether ADMA is a link between inflammation and endothelial dysfunction in humans. In study 1 we recruited 351 patients with coronary artery disease (CAD) and 87 healthy controls. In study 2 we recruited 69 CAD, 69 healthy, and 10 patients with rheumatoid arthritis, whereas in study 3, 22 healthy and 70 CAD subjects were randomly assigned to Salmonella typhii vaccination (n=11 healthy and n=60 CAD) or placebo (n=11 healthy and n=10 CAD). Circulating interleukin 6/ADMA and flow-mediated dilation (FMD) were measured at 0 and 8 hours. In study 1, ADMA was inversely correlated with FMD in healthy individuals and CAD patients (P<0.0001 for both). However, interleukin 6 was inversely correlated with FMD (P<0.0001) in healthy subjects but not in CAD patients. The positive correlation between ADMA and interleukin 6 was stronger in healthy (r=0.515; P<0.0001) compared with CAD (r=0.289; P=0.0001) subjects. In study 2, both patients with rheumatoid arthritis and CAD had higher interleukin 6 (P<0.0001) and ADMA (P=0.004) but lower FMD (P=0.001) versus healthy subjects. In study 3, vaccination increased interleukin 6 in healthy (P<0.001) and CAD (P<0.001) subjects. FMD was reduced in healthy subjects (P<0.05), but its reduction in CAD was borderline. Vaccination increased ADMA only in healthy subjects (P<0.001). Systemic, low-grade inflammation leads to increased ADMA that may induce endothelial dysfunction. This study demonstrated that ADMA may be a link between inflammation and endothelial dysfunction in humans. [ABSTRACT FROM AUTHOR]

Endothelial progenitor cells (EPCs) are under investigation due to their association with vascular injury. In response to chemotactic stimuli they are mobilized from bone-marrow and nonbone marrow sites, they migrate, adhere and home to the injured vessel. Numerous molecular and cellular pathways participate and converge to the EPCs mediated vascular repair. However, the exact phenotypic properties, modes of functions and effects in vascular diseases and particularly in atherosclerosis are under investigation. EPCs represent a heterogeneous group of cells in different stages of differentiation, from hematopoietic bone marrow progenitors to mature endothelial cells that participate in adult vascular repair under ischemic or apoptotic stimuli. This review aims to provide an integrative view of EPC-mediated vascular repair. [ABSTRACT FROM AUTHOR]

BackgroundNonalcoholic fatty liver disease (NAFLD) is the most common liver disease both in the general and pediatric population and has been associated with increased cardiovascular risk. Arterial function and early atherosclerotic changes are markers of cardiovascular disease and independent predictors of the corresponding risk. Through a global approach, we investigated the relationships between NAFLD and functional arterial changes and early atherosclerosis.MethodsA total of 23 consecutive patients (mean age 55 ± 14 years, 11 males) with biopsy evidence of NAFLD and 28 control subjects matched for age, gender, body mass index, and other cardiovascular risk factors participated in the study.ResultsCompared to controls, NAFLD subjects had significantly higher carotid-femoral pulse wave velocity (PWV; 8.2 ± 1.3 m/s vs. 6.9 ± 1.3 m/s, P = 0.001), higher carotid intima-media thickness (IMT; 0.79 ± 0.18 mm vs. 0.67 ± 0.13 mm, P = 0.01), and reduced flow-mediated dilatation (FMD; 1.92 ± 2.11% vs. 4.8 ± 2.43%, P < 0.001). In multivariable analysis, presence of NAFLD was an independent determinant of both PWV and FMD, whereas leptin was an independent determinant of PWV (B = 0.036, P < 0.05), and adiponectin was independently associated with FMD (B = 0.104, P < 0.05). In addition, histological activity of liver disease expressed by the global Brunt Grade was associated independently with FMD (B = -1.054, P < 0.05).ConclusionsNAFLD is associated with arterial stiffness and endothelial dysfunction. Given the important independent prognostic role of these arterial indexes, these findings have important implications for increased cardiovascular risk in patients with NAFLD.American Journal of Hypertension (2010). doi:10.1038/ajh.2010.144 [ABSTRACT FROM AUTHOR]

The article focuses on a study that examined the association between dairy consumption and levels of various inflammatory markers among adults with no evidence of cardiovascular or other chronic disease. The study found that C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) levels of individuals consuming between 11 and 14 weekly servings of dairy products had 29%, 9% and 20% lower levels of CRP, IL-6 and TNF-α, respectively.

Background Asymmetric dimethylarginine (ADMA) and subclinical inflammation are associated with atherosclerosis progression, whereas microalbuminuria is an established index of hypertensive organ damage. Study Design Cross-sectional. Setting & Participants In an outpatient hypertensive unit, 296 nondiabetic and untreated participants with hypertension were studied. Participants with atherosclerotic cardiovascular disease, severe valvulopathy, congestive heart failure, presence of neoplastic or other concurrent systemic disease, atrial fibrillation, serum creatinine level > 1.5 mg/dL in men and > 1.4 mg/dL in women, and urinary albumin excretion > 300 mg/24 h were excluded. Predictors ADMA and high-sensitivity C-reactive protein (hs-CRP) levels. Outcome Variable Albuminuria assessed using albumin-creatinine ratio (ACR). Measurements Participants underwent ambulatory blood pressure monitoring, echocardiography, routine assessment of metabolic profile, ADMA, and hs-CRP, whereas ACR was determined as the mean of 3 values in nonconsecutive morning spot urine samples. Results 64 participants had an ACR of 30-300 mg/g. Stratification based on ADMA level showed that participants with hypertension in quartile [Q] 4 compared with those in Q3, Q2, and Q1 showed the highest ACRs (53.2 vs 31.2 vs 30.4 vs 16.7 mg/g; P < 0.008 for all). Moreover, stratification based on hs-CRP level showed that participants with hypertension in Q4 (69.8% had microalbuminuria) showed the highest ACRs (72.2 vs 25.6, 16.2, and 19.2 mg/g for Q3, Q2, and Q1, respectively; P < 0.008 for all). Stepwise regression analysis showed that age, 24-hour systolic blood pressure, hs-CRP level, ADMA level, and the interaction of hs-CRP with ADMA were independent predictors of ACR (R2 = 0.674; P < 0.001). Limitations Cross-sectional study. Conclusions In patients with untreated essential hypertension, increased hs-CRP and ADMA levels are associated with microalbuminuria, suggesting the involvement of inflammation and endothelial dysfunction in vascular and kidney damage [ABSTRACT FROM AUTHOR]

BackgroundEvidence suggests that resistin, a recently described protein, is associated with subclinical atherosclerosis in different clinical settings. In this study, we investigated the relationship of increased resistin levels with urinary albumin excretion, expressed as the albumin-to-creatinine ratio (ACR), an established index of diffuse vascular damage, in hypertensives.MethodsOur population consisted of 132 untreated nondiabetic subjects with stage I–II essential hypertension (49 males, mean age = 54 years, mean office blood pressure (BP) = 159/100 mm Hg). In all patients, ACR was determined as the average of three nonconsecutive morning spot urine samples, and venous blood sampling was performed for estimation of resistin concentrations. The distribution of resistin was split by the median (4.63 ng/ml), and accordingly, subjects were stratified into those with high and low values.ResultsHypertensive patients with high (n = 66) compared to those with low resistin (n = 66) exhibited higher ACR values (21.8 ± 15.3 vs. 10.3 ± 3.8 mg/g, P < 0.01), even after adjustment for confounders. In the total population, resistin was associated with 24-h systolic BP (r = 0.244, P < 0.05), serum creatinine (r = 0.311, P = 0.007), and ACR (r = 0.499, P < 0.01). Multiple regression analysis revealed that age (b = 0.193, P = 0.02), body mass index (b = 0.237, P = 0.02), 24-h systolic BP (b = 0.338, P < 0.0001), 24-h heart rate (b = 0.169, P = 0.04), and resistin (b = 0.77, P < 0.01) were independently associated with ACR (R2 = 0.471, P < 0.01).ConclusionsHypertensive subjects with augmented resistin levels exhibit higher albuminuria, independently of established risk factors. Moreover, the association of resistin with ACR suggests a link between resistin and microvascular disease in the early stages of essential hypertension.American Journal of Hypertension 2010; doi:10.1038/ajh.2010.34 [ABSTRACT FROM AUTHOR]

BackgroundAngiotensin type 2 receptor (AT2R), plays a crucial role in blood pressure regulation and atherogenesis. AT2R gene is located on chromosome X and the biological effect of polymorphism A1675G in this gene needs to be further specified. We examined the impact of A1675G on the risk and the severity of coronary artery disease (CAD), and the expression of proatherogenic inflammatory molecules in hypertensive patients.MethodsThe study population consisted of 146 with CAD (102 with hypertension) and 266 age-matched individuals without CAD (114 with hypertension). The presence of A1675G polymorphism on AT2R gene was determined by PCR. Serum levels of C-reactive protein (CRP), fibrinogen, interleukin-6 (IL-6) and soluble vascular cell adhesion molecule-1 (sVCAM-1) were measured in all the participants.ResultsThe G allele was associated with decreased risk of CAD among hypertensives (odds ratio (OR) (95% confidence interval (CI))): 0.4 (0.2–0.9), P = 0.01) and less aggressive angiographic CAD (P < 0.001). The G allele was associated with lower IL-6 (median (25–75th percentile): 1.4 (0.6–3.8)), sVCAM-1 (621 (476–799)), CRP (1.2 (0.6–1.7)), and fibrinogen (369 (320–416)) vs. A allele (IL-6: 2.4 (1.1–4.5) P < 0.01, sVCAM-1: 702 (548–925) P < 0.05, CRP: 3.5 (2.0–6.1) P < 0.001, and fibrinogen: 407 (348–514) P < 0.01). The effect of A1675G on serum IL-6, sVCAM-1, and fibrinogen was driven by its effect among hypertensives (IL-6 3.1 (2.1–5.6 in A vs. 1.2 (0.3–3.4) in G P < 0.001, sVCAM-1: 890 (560–1000) in A vs. 556 (377–788) in G P < 0.01, and fibrinogen: 408 (354–510) in A vs. 369 (324–418) in G P < 0.001) whereas it had no effect among nonhypertensives.ConclusionsGenetic polymorphism A1675G on AT2R gene affects cardiovascular risk and the severity of atherosclerosis by modifying systemic inflammation, especially in hypertensive males.American Journal of Hypertension 2010; doi:10.1038/ajh.2009.233 [ABSTRACT FROM AUTHOR]

We investigated the association of apolipoproteins AI and B in relation to the prevalence of metabolic syndrome in a random sample of cardiovascular disease-free adults from the ATTICA study (1,514 men, aged 18-87 y; 1,528 women, aged 18-89 y). Metabolic syndrome was defined according to the National Cholesterol Education Program Adult Treatment Panel III criteria. The prevalence of metabolic syndrome was 25% in men and 15% in women (P < .00 1). Using the area under the Receiver Operation Characteristic curve, apolipoprotein B/AI was the best diagnostic marker of metabolic syndrome, the optimal discriminating cut-off value of this ratio was 0.72 (sensitivity 74%, specificity 67%), and individuals with apolipoprotein B/AI ratio greater than 0.74 had 3.29 times higher odds of having metabolic syndrome (95% confidence interval: 2.56-4.21) after adjusting for potential confounders. [ABSTRACT FROM AUTHOR]

Abstract: Neovascularization is associated with destabilization of atheromatic plaques. Increased expression of vascular endothelial growth factor (VEGF) is important in the process of neovascularization. We assessed the effect of bevacizumab, a monoclonal antibody specific for VEGF, on neovascularization. We used 12 New Zealand rabbits under atherogenic diet for 3 weeks. We immersed a phosphorycholine coated stent into a solution of 4ml bevacizumab according to previous studies. Twelve eluting stents and 12 non-eluting stents were implanted in the middle segment of the rabbit''s iliac arteries. Follow-up angiography was performed at 4 weeks and tissues were obtained for histological analysis. The procedure of stent loading with bevacizumab and stent implantation was successful. There was no difference in angiographic measurements before, after implantation and at follow-up between the two groups. mean neointimal thickness (0.09±0.02 versus 0.12±0.02mm, p <0.01), and mean neointimal area (1.08±0.09 versus 1.20±0.12mm2, p <0.01) were less in the bevacizumab treated segments. bevacizumab-treated arterial segments demonstrated significantly decreased microvessel density compared with the control group (1.69±0.06 CI: 1.65–1.73 versus 15.68±0.56 CI: 15.32–16.04 vessels per mm2, p <0.001) and vegf expression was decreased in the media and adventitia of bevacizumab group. Endothelialization, inflammation and injury scores were similar between the two groups. These results suggest that bevacizumab-eluting stent implantation in rabbit iliac arteries is safe, and inhibits neovascularization without affecting the endothelialization. [Copyright &y& Elsevier]

Background: The α-1 microglobulin (A1M) is considered to be a marker of renal insufficiency, suggesting disturbed tubular function. In the present study we examined the ability of urinary A1M excretion to reflect the overall inflammatory status in patients with newly diagnosed essential hypertension and normal renal function. Methods: The study population consisted of 1445 nondiabetic patients with newly diagnosed arterial hypertension and no evidence of renal insufficiency. Serum levels of C-reactive protein (CRP), serum amyloid α (SAA), and plasma fibrinogen, as well as urinary A1M excretion, were estimated. Multivariate analysis was performed to evaluate the associations between hypertension; A1M urinary excretion; and circulating levels of CRP, SAA, and fibrinogen. Results: Patients with systolic hypertension had higher CRP, SAA, fibrinogen, and A1M compared with patients with isolated diastolic hypertension (P < .0001 for all). In multivariate analysis, systolic (but not diastolic) blood pressure (BP) was independently associated with A1M, CRP, and SAA (P < .0001 for all), whereas urinary A1M was also independently correlated with inflammatory markers such as CRP (P = .0001) and SAA (P = .0001). Conclusions: Urinary A1M is independently associated with circulating acute phase proteins in patients with newly diagnosed hypertension, whereas it is closely associated with systolic but not diastolic BP. Our findings suggest that urinary α-1 microglobulin may reflect the overall inflammatory status in patients with newly diagnosed essential hypertension, beyond its value as a marker of renal function. [Copyright &y& Elsevier]

Abstract: Although previous studies have shown systemic inflammatory activation the relation with the local plaque inflammatory activation has not been extensively studied. The present study investigated the relation between local and systemic inflammatory activation in patients with coronary artery disease and the impact of atorvastatin treatment. We included 215 patients undergoing percutaneous coronary intervention; of them 140 were treated with atorvastatin. Patients with stable angina (SA) and acute coronary syndromes (ACS) were included. Systemic inflammation was assessed by serum C-reactive protein (CRP), soluble adhesion molecules levels and local plaque inflammatory activation by coronary thermography. Temperature difference (ΔT) was assigned as the difference between the proximal vessel wall temperature from the maximal temperature at the culprit plaque. Patients with ACS (n =78) had increased ΔT compared to patients with SA (n =137) (0.16±0.10°C versus 0.08±0.07°C, P <0.001). Patients treated with atorvastatin had lower ΔT compared to untreated patients (0.10±0.07°C versus 0.15±0.10°C, P <0.01). ΔT was less in the treated group compared to the untreated group in patients with SA and ACS (ACS: 0.13±0.08°C versus 0.20±0.11°C, P <0.01, SA: 0.08±0.06°C versus 0.13±0.08°C, P =0.03). Although a correlation was found between CRP levels and ΔT (R =0.29, P <0.01), in certain groups a discrepancy between CRP levels and ΔT was observed. In 25% of patients with low ΔT CRP levels were >1mg/dl and in 35.5% of patients with high ΔT CRP was <2mg/dl. The correlation between soluble adhesion molecules and ΔT did not reach statistical significance. Although there is a correlation between widespread and local inflammatory activation in patients with coronary artery disease, a discrepancy between culprit plaque and systemic inflammatory activation is observed. Atorvastatin has a parallel effect on systemic and local inflammatory process in patients with coronary artery disease. [Copyright &y& Elsevier]

Endothelial dysfunction has been identified as a major mechanism involved in all the stages of atherogenesis. Evaluation of endothelial function seems to have a predictive role in humans, and therapeutic interventions improving nitric oxide bioavailability in the vasculature may improve the long-term outcome in healthy individuals, high-risk subjects, or patients with advanced atherosclerosis. Several therapeutic strategies are now available, targeting both the synthesis and oxidative inactivation of nitric oxide (NO) in human vasculature. Statins seem to be currently the most powerful category of these agents, improving endothelial function and decreasing cardiovascular risk after long-term administration. Other cardiovascular agents improving endothelial function in humans are angiotensin-converting enzyme inhibitors/angiotensin receptors blockers, which increase NO bioavailability by modifying the rennin-angiotensin-aldosterone system. Newer therapeutic approaches targeting endothelial dysfunction in specific disease states include insulin sensitizers, L-arginine (the substrate for endothelial NO synthase [eNOS]) as well as substances that target eNOS “coupling,” such as folates or tetrahydrobiopterin. Although there are a variety of strategies to improve NO bioavailability in human endothelium, it is still unclear whether they have any direct benefit at a clinical level. [ABSTRACT FROM AUTHOR]

Background: Homocystinemia is a metabolic abnormality associated with endothelial dysfunction and increased cardiovascular disease risk. The underlying mechanisms of these effects, however, are obscure. Objective: We examined the effect of asymmetrical dimethylarginine (ADMA) on endothelial dysfunction in methionine-induced and chronic homocystinemia and evaluated the regulatory role of oxidative stress and proinflammatory cytokines on the release of ADMA. Design: In this double-blind, placebo-controlled parallel group study, 30 subjects of both sexes (15 with homocystinemia and 15 healthy controls) underwent methionine loading, with simultaneous administration of a combination of vitaminC(2 g) plus α-tocopherol (800 IU) or placebo. Endothelial function in forearm resistance vessels and concentrations of ADMA, oxidized LDL, and proinflammatory cytokines were determined at baseline and 4 h after methionine loading. Results: Both chronic and methionine-induced homocystinemia were associated with increased oxidized LDL (P < 0.01), higher expression of the proinflammatory cytokine interleukin 6 (P < 0.05), and endothelial dysfunction (P < 0.01). Although ADMA rapidly increased in acute homocystinemia (P < 0.01) and was correlated with forearm hyperemic response at 4 h after methionine loading (r=-0.722, P = 0.0001), it was not higher in subjects with high versus low fasting homocysteine. High-dose antioxidant treatment prevented methionine-induced elevation of oxidized LDL and interleukin 6 but failed to prevent the increase in ADMA or endothelial dysfunction. Conclusions: Both chronic and methionine-induced homocystinemia are characterized by increased oxidative stress and proinflammatory cytokines, which may contribute to the development of endothelial dysfunction. However, the ADMA pathway is activated only in acute homocystinemia by mechanisms not mediated by oxidized LDL or proinflammatory stimuli. [ABSTRACT FROM AUTHOR]

Background: Microalbuminuria (MA) and low-grade inflammation constitute emerging markers of subclinical atherosclerosis. We investigated whether urinary albumin excretion, expressed as the albumin-to-creatinine ratio (ACR), is associated with high sensitivity C-reactive protein (hs-CRP), interleukin (IL)-18, and soluble CD40 ligand (sCD40L), in hypertensive subjects. Methods: The study population consisted of 108 nondiabetic male patients with newly diagnosed untreated stage I to II essential hypertension (aged 44.6 years, office blood pressure [BP] 148/95 mm Hg). According to ACR values determined as the average of two nonconsecutive overnight spot urine samples, subjects were divided into microalbuminurics (n = 28) (mean ACR = 30 to 300 mg/g) and normoalbuminurics (n = 80) (mean ACR <30 mg/g). Results: Although microalbuminurics as compared to normoalbuminuric hypertensives had greater hs-CRP levels (2.55 ± 1.18 v 1.45 ± 0.52 mg/L, P < .0001), independently of confounding factors, these two groups did not differ regarding IL-18 and sCD40L values (P = not significant [NS] for both cases). In the entire population, ACR exhibited a positive correlation with hs-CRP (r = 0.623, P < .0001), whereas there was no association with both IL-18 and sCD40L (P = NS for both cases). When multiple linear regression analysis was performed, it was revealed that age, body mass index, office systolic BP, total cholesterol, and hs-CRP levels were significant independent predictors of the ACR (P < .05). Conclusions: In essential hypertensive subjects, MA is accompanied by elevated hs-CRP levels, but not by augmented IL-18 and sCD40L concentrations, suggesting activation of different inflammatory pathways in the progression of renal and cardiovascular atherosclerotic disease. The pathophysiologic mechanisms of these associations remain to be further elucidated in future studies. [Copyright &y& Elsevier]

In this review article we examine the main mechanisms leading to decreased nitric oxide (NO) bioavailability, and we present the current strategies available to increase NO levels, mainly by using antioxidants in patients with coronary artery disease. Decreased NO bioavailability in the vasculature is a key feature of all the classic risk factors for atherosclerosis, and it can be the result of NO's decreased synthesis and increased oxidative deactivation. Increased NO synthesis can be achieved by improving the intracellular redox state in endothelial cells, stabilizing endothelial NO synthase (eNOS) dimers, and maintaining sufficient intracellular levels of eNOS substrate L-arginine. Antioxidant treatment may have a dual role by increasing NO synthesis and decreasing its oxidative deactivation. However, in patients with coronary artery disease, although intracoronary infusions of vitamins or chronic vitamin treatment improve endothelial function, their effect on clinical outcome is questioned. In conclusion, in coronary artery disease, NO bioavailability can be increased mainly by reversing the causes of endothelial dysfunction via treatment of classic risk factors, while the use of antioxidant vitamins is controversial and the ideal antioxidant strategy is still unknown. [ABSTRACT FROM AUTHOR]

Background: The strong causal role of hypercholesterolaemia on the progression of atherosclerosis and subsequently on the development of cardiovascular disease is well described. Main aim of this study was to evaluate the prevalence of self-reported hypercholesterolaemia and its relation to nutritional habits, in a representative nationwide sample of adult Greek population. Methods: Cross sectional survey. Based on a multistage sampling, 5003 adults (18 - 74 yr) were enrolled (men: 48.8%, women: 51.2%). All participants were interviewed by trained personnel who used a standard questionnaire. The questionnaire included demographic and socioeconomic characteristics, medical history, lifestyle habits and nutritional assessment. Results: The prevalence of self-reported hypercholesterolaemia was 16.4% in men and 21.8% in women (P < 0.001). Hypercholesterolaemic status was positively associated with the prevalence of hypertension, diabetes mellitus, renal failure, obesity and physical inactivity, and inversely with the prevalence of smoking. The analysis of reported food consumption patterns showed that consumption of fish, fruits and juices, cereals, and low fat milk and yogurt was significantly higher among hypercholesterolaemic participants while the opposite was observed for food items as red meat, pork, egg, full fat dairy products and desserts. Conclusion: Hypercholesterolaemia seems to affect a large part of Greek population. It is hopeful that hypercholesterolaemics may have started adopting some more healthy nutritional behaviour compared to normocholesterolaemic ones. [ABSTRACT FROM AUTHOR]

Abstract: Background: Heart failure has been associated with impaired endothelial function, increased inflammatory process and elevated oxidative stress status. Both statins and vitamin E separately improve endothelial function in patients with hypercholesterolemia and/or advanced atherosclerosis. Aim: To evaluate the effect of atorvastatin alone or in combination with vitamin E on endothelial function and serum levels of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α) and vascular cells adhesion molecule (sVCAM-1) in patients with ischemic heart failure. Methods: Thirty-eight male patients with ischemic cardiomyopathy were randomly divided into three groups and received either atorvastatin 10 mg/day (n =14), a combination of atorvastatin 10 mg/day plus vitamin E 400 IU/day (n =12), or no statin or antioxidant treatment (n =12, controls) for 4 weeks. Forearm blood flow (FBF) was measured using venous occlusion strain-gauge plethysmography. Forearm vasodilatory response to reactive hyperemia (RH%) or to nitrate (NTG%) was defined as the percent change of FBF from rest to the maximum flow during reactive hyperemia or after nitrate administration, respectively. Results: RH% was significantly improved in both the atorvastatin-treated (p <0.01) and atorvastatin plus vitamin E groups (p <0.05), but the increase was significantly higher in the atorvastatin-treated group (p <0.05). Serum levels of IL-6, TNF-α and sVCAM-1 were decreased in the atorvastatin-treated group (p <0.05 for all), but remained unaffected in the other two groups (p =NS for all). Conclusions: Low dose atorvastatin treatment improves endothelial function and reduces the expression of proinflammatory cytokines and adhesion molecules in patients with ischemic heart failure, an effect partly depressed by vitamin E. [Copyright &y& Elsevier]

The concept of the “vulnerable” plaque has recently emerged to explain how quiescent atherosclerotic lesions evolve to cause clinical events. The morphologic and immunologic determinants specific for the vulnerable plaque have been reported: a large lipid core (≥40% plaque volume) composed of free cholesterol crystals, cholesterol esters, and oxidized lipids impregnated with tissue factor; a thin fibrous cap depleted of smooth muscle cells and collagen; an outward (positive) remodeling; inflammatory cell infiltration of fibrous cap and adventitia (mostly monocyte-macrophages, some activated T cells, and mast cells); and increased neovascularity. Despite the large amount of information regarding the morphological characteristics of remote lesions, we lack studies with functional assessment of nonculprit lesions. Coronary thermography is a technique for functional assessment of coronary atherosclerotic plaques. Several catheter designs have been proposed. There are catheters with thermistor(s) and wires with thermal sensors at the distal tip. All designs have several advantages and disadvantages. Despite the current limitations of coronary thermography, we gained important pathophysiological and clinical information regarding the vulnerability of atheromatic plaques. It has been documented both experimentally and clinically that increased heat generation is associated with increased macrophage concentration within the plaque. The correlation between local inflammatory involvement and local heat generation has also been observed with the peripheral inflammatory markers such as C-reactive protein. Whether systemic treatment, with agents such as statins or interventional techniques, such as drug-eluting stents, will have an impact on stabilizing vulnerable plaques need to be determined in future studies. In conclusion, although there are several techniques for evaluating morphologically atheromatic plaques, thermography is a promising method for the functional assessment of vulnerable plaque and has been introduced into clinical practice, with a good predictive value for clinical events in patients with increased temperature in the atherosclerotic plaque. [ABSTRACT FROM AUTHOR]

Atherosclerosis is a progressive process with potentially devastating consequences and has been identified as the leading cause of morbidity and mortality, especially in the industrial countries. The underlying mechanisms include endothelial dysfunction, lipid accumulation and enhanced inflammatory involvement resulting in plaque disruption or plaque erosion and subsequent thrombosis. However, it has been made evident, that the majority of rupture prone plaques that produce acute coronary syndromes are not severely stenotic. Conversely, lipid‐rich plaques with thin fibrous cap, heavily infiltrated by inflammatory cells have been shown to predispose to rupture and thrombosis, independently of the degree of stenosis. Therefore, given the importance of plaque composition, a continuously growing interest in the development and improvement of diagnostic modalities will promptly and most importantly, accurately detect and characterize the high‐risk atheromatous plaque. Use of these techniques may help risk stratification and allow the selection of the most appropriate therapeutic approach. [ABSTRACT FROM AUTHOR]

Background: We sought to evaluate the association between prehypertension status and inflammatory markers (C-reactive protein, white blood cells, interleukin-6, tumor necrosis factor-α, amyloid-a, homocysteine, and fibrinogen), in a random sample of cardiovascular disease-free adults.Methods: The ATTICA study is a cross-sectional population-based survey conducted in the Attica region during 2001 to 2002. Based on a multistage and stratified random sampling, 1514 men and 1528 women (18 to 89 years old) were enrolled. The survey included a detailed interview, blood samples collected after 12 h of fasting, and, among other clinical measurements, status of blood pressure levels.Results: The prehypertensive population included 653 men (43%) and 535 women (35%). Compared to normotensives, prehypertensive men and women had 31% higher C-reactive protein (P < .01), 32% higher tumor necrosis factor-α (P < .05), 9% higher amyloid-a (P < .05), 6% higher homocysteine levels (P < .01), and a 10% higher white blood cell counts (P < .05), after correcting for multiple comparisons and adjusting for age, body mass index, blood lipids, glucose, food groups consumed, and other potential confounders.Conclusions: Studying a large sample of cardiovascular disease-free adults, we revealed an association between prehypertension and inflammatory markers linked to the atherosclerotic process, independently of other coexisting risk factors or unhealthy lifestyle behaviors. Our findings may be of clinical importance, as they suggest that prehypertension might be a pro-inflammatory condition. [Copyright &y& Elsevier]

Background Depression is associated with an increase in cardiovascular disease, but the underlying mechanisms are not well understood. The aim of this study was to examine the associations of depressive symptoms with inflammation and coagulation factors related to cardiovascular risk in persons free of cardiovascular disease. [ABSTRACT FROM PUBLISHER]

L-arginine is the substrate for endothelial nitric oxide synthase (eNOS), and the precursor for the synthesis of nitric oxide (NO). This amino acid exerts a number of actions in the cardiovascular system, mainly through the production of NO. However, it also has a number of NO-independent properties, such as the ability to regulate blood and intracellular pH and the effect on the depolarization of endothelial cell membranes. It also has antihypertensive and antioxidant properties, it influences blood viscosity and the coagulation/fibrinolysis system, and it affects the metabolism of glucose, lipids and proteins. L-arginine influences a number of atherosclerosis risk factors such as hypercholesterolemia, hypertension and smoking, improving endothelial function in these patients. However, it does not affect endothelial function in patients with diabetes mellitus. The role of L-arginine in coronary artery disease is still controversial, but it seems that oral or parenteral administration of this amino acid restores endothelial function in the brachial artery and improves coronary microcirculation. The role of L-arginine in heart failure is currently under investigation, and the first results are rather hopeful. In conclusion, L-arginine seems to provide a hopeful prospect for the treatment of cardiovascular diseases. However, more data derived from large-scale prospective studies evaluating the effects of long-term treatment with L-arginine are needed. [ABSTRACT FROM AUTHOR]

We assessed the impact of systematic risk factors on the vasomotor effects of inhibition of nitric oxide synthesis. N[sup G] -monomethyl-L-arginine (LNMMA) was infused intracoronarily at 4, 8 and 16 μmol/min followed by intracoronary bolus administration of 250 μg nitroglycerin. Computerized angiography was used to assess the changes in the diameter of coronary segments. During the LNMMA infusions there was no significant difference in LNMMA response between smokers and non-smokers (–5.5 ± 0.8 and –6.6 ± 0.6%, respectively) or between hypertensives and normotensives (–6.4 ± 1.1 and –6.1 ± 0.6%, respectively), but the response was less in hypercholesterolaemic patients (–4.5 ± 0.7 vs. –8.0 ± 0.6%, p < 0.05). Thus, the reduced nitric oxide activity is related to hypercholesterolaemia but not to smoking and hypertension. [ABSTRACT FROM AUTHOR]

Introduction: The purpose of the present investigation was to study the precise relationship between carotid sinus hypersensitivity (CSH) and both the severity of carotid atherosclerosis and the extent of coronary artery disease in patients who were referred for evaluation for suspected ischemic heart disease. Methods and Results: Duplex echocardiography and coronary angiography were used to assess carotid and coronary artery atherosclerosis in 130 consecutive patients. Carotid sinus stimulation was performed before coronary arteriography with simultaneous recordings of the ECG and aortic pressure. Coronary artery disease was present in 103 patients (79%). Thirty patients (23.08%) had one-vessel disease (1-VD), 31 (23.85%) had 2-VD, 29 (22.31%) had 3-VD. and 13 patients (10%) had left main coronary artery disease. Carotid artery atherosclerosis was present in 100 patients (76.92%) and carotid disease (diameter stenosis ≥ 50%) was present in 24 patients (18.46%). CSH was found in 33 patients (25%). The incidence of CSH was 9% in patients with carotid stenosis 1%-15%, 17% in patients with stenosis 16%-49%, 85% in patients with stenosis 50%-79%, and 100% in patients with stenosis ≥ 80%. The incidence of CSH was 11%, 17%, 23%, 34%, and 62% in patients with no VD, 1-VD, 2-VD, 3-VD, and left main coronary artery disease, respectively. Stepwise multiple logistic regression analysis revealed that carotid disease and left main coronary artery disease were the most significant determinants of CSH (P < 0.001 and P = 0.013, respectively). Conclusion: The incidence of CSH increased in proportion to the severity of carotid and coronary atherosclerosis. These data provide evidence that CSH is closely related to severe carotid atherosclerosis or left main coronary artery disease in patients being evaluated for suspected ischemic heart disease. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Regression of Left Main Coronary Artery Atherosclerotic Stenosis After 12 Years of Follow-up, Despite Bypass Surgery."

Abstract: The long preclinical phase of atherosclerosis involves the interaction of genetic and environmental factors that modulate the progression of disease from early life. Injury to the endothelium is a critical step in atherosclerotic process. Conventional and novel risk factors for coronary artery disease operate from early in life. Noninvasive methods, using mostly ultrasound techniques, have enabled the assessment of early functional and structural arterial disease progression even from the first decade of life. These measures have been shown to be good surrogate markers for atherosclerotic disease progression and future clinical cardiovascular events. Lifestyle and dietary modifications as well as pharmacological interventions have beneficial effects in prevention and restoration of the early arterial changes. [Copyright &y& Elsevier]

Abstract: Smoking is a global risk factor for atherosclerosis, affecting societies all over the world. Smoking exerts its pro-atherogenic effects by triggering the generation of free radicals and by modifying vascular redox signaling. These abnormal vascular responses to cigarette smoking result into impaired endothelial function, decreased nitric oxide bioavailability, increased intima media thickness and finally atherosclerotic plaque formation in human arteries. Importantly, evidence suggests that cigarette smoking may have an effect on vascular smooth muscle cells function, leading to impaired endothelium-independent dilation in response to nitrate, in the brachial artery of healthy smokers. Taken together, it is now well established that smoking induces functional and structural abnormalities in the vascular wall, by mechanisms involving endothelial dysfunction and impairment of vascular smooth muscle cells in human arterial tree. [Copyright &y& Elsevier]

Background and aims Smoking is associated with increased inflammatory process and impairment of fibrinolytic status. Concord grape juice (CGJ), a rich source of flavonoids, can modify cardiovascular risk factors. We aimed to evaluate the impact of CGJ on smoking-induced impairment of inflammatory and fibrinolytic status in healthy smokers. Methods We studied the effect of a 2-week oral treatment with CGJ in 26 healthy smokers on three occasions (day 0: baseline, day 7 and day 14) in a randomized, placebo-controlled, double-blind, cross-over design. Measurements were carried out before (pSm) and 20 min after (Sm20) cigarette smoking. Serum levels of intercellular adhesion molecule-1 (sICAM-1) and plasminogen activator inhibitor 1 (PAI-1) were measured as markers of inflammatory and fibrinolytic status, respectively. Results Treatment with CGJ reduced pSm sICAM-1 levels (p < 0.001), while placebo had no impact on ICAM-1 levels (p = 0.31). Moreover, treatment with CGJ decreased pSm values of PAI-1 (p < 0.001) while placebo had no impact on PAI-1 levels (p = 0.89). Smoking induced an elevation in PAI-1 levels after smoking compared to pro-smoking levels in all study days and in both arms (CGJ and placebo) of the study (p < 0.001 for all). Interestingly, CGJ compared to placebo, attenuated the acute smoking increase in sICAM-1 and PAI-1 levels (p < 0.001 and p = 0.005 respectively). Conclusions CGJ consumption improved inflammatory and fibrinolytic status in healthy smokers and attenuated acute smoking induced increase in ICAM-1 and PAI-1 levels. These findings shed further light on the favorable effects of flavonoids in cardiovascular health. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The vascular endothelium not only is a single monolayer of cells between the vessel lumen and the intimal wall, but also plays an important role by controlling vascular function and structure mainly via the production of nitric oxide (NO). The so called “cardiovascular risk factors” are associated with endothelial dysfunction, that reduces NO bioavailability, increases oxidative stress, and promotes inflammation contributing therefore to the development of atherosclerosis. The significant role of endothelial dysfunction in the development of atherosclerosis emphasizes the need for efficient therapeutic interventions. During the last years statins, angiotensin-converting enzyme inhibitors, angiotensin-receptor antagonists, antioxidants, beta-blockers and insulin sensitizers have been evaluated for their ability to restore endothelial function (Briasoulis et al., 2012). As there is not a straightforward relationship between therapeutic interventions and improvement of endothelial function but rather a complicated interrelationship between multiple cellular and sub-cellular targets, research has been focused on the understanding of the underlying mechanisms. Moreover, the development of novel diagnostic invasive and non-invasive methods has allowed the early detection of endothelial dysfunction expanding the role of therapeutic interventions and our knowledge. In the current review we present the available data concerning the contribution of endothelial dysfunction to atherogenesis and review the methods that assess endothelial function with a view to understand the multiple targets of therapeutic interventions. Finally we focus on the classic and novel therapeutic approaches aiming to improve endothelial dysfunction and the underlying mechanisms. [ABSTRACT FROM AUTHOR]