Plasma Levels of Intact Parathyroid Hormone and Congestion Burden in Heart Failure: Clinical Correlations and Prognostic Role.

Circulating parathyroid hormone (PTH) concentrations increase in heart failure (HF) and are related to disease severity. The relationship between PTH and congestion is still a matter of debate. The objective of this analysis was to evaluate the role of PTH as a marker of congestion and prognosis in HF. We enrolled 228 patients with HF. Intact PTH concentrations and HYDRA score (constituted by: B-type natriuretic peptide, blood urea nitrogen−creatinine ratio, estimated plasma volume status, and hydration status) were evaluated. The study endpoint was all-cause mortality. PTH levels were higher in acute compared with chronic HF and in patients with clinical signs of congestion (i.e., peripheral oedema and orthopnea). PTH concentrations significantly correlated with NYHA class and HYDRA score. At multivariate analysis of HYDRA score, estimated glomerular filtration rate (eGFR), and corrected serum calcium were independently determinants of PTH variability. Fifty patients (22%) died after a median follow-up of 408 days (interquartile range: 283−573). Using univariate Cox regression analysis, PTH concentrations were associated with mortality (hazard ratio [HR]: 1.003, optimal cut-off: >249 pg/mL­area under-the-curve = 0.64). Using multivariate Cox regression analysis, PTH was no longer associated with death, whereas HYDRA score, left ventricular ejection fraction, and eGFR acted as independent predictors for mortality (HR: 1.96, 0.97, and 0.98, respectively). Our study demonstrated that intact PTH was related to clinical and subclinical markers of congestion. However, intact PTH did not act as an independent determinant of all-cause death in HF patients.

Clinical Discussions in Antithrombotic Therapy Management in Patients With Atrial Fibrillation: A Delphi Consensus Panel.

BACKGROUND: In recent years, direct-acting oral anticoagulants (DOACs) have entered clinical practice for stroke prevention in non-valvular atrial fibrillation or prevention and treatment of venous thromboembolism. However, remaining uncertainty regarding DOAC use in some clinical scenarios commonly encountered in the real world has not been fully explored in clinical trials. METHODS: We report on use of a Delphi consensus process on DOAC use in non-valvular atrial fibrillation patients. The consensus process dealt with 9 main topics: (i) DOACs vs vitamin K antagonists in atrial fibrillation (AF) patients; (ii) therapeutic options for patients with stable total time in range treated with vitamin K antagonists; (iii) therapeutic options for patients aged > 85 years; (iv) therapeutic management of hyperfiltering patients; (v) pharmacologic interactions; (vi) therapeutic options in the long-term treatment (prevention) of patients with AF and acute coronary syndrome after the triple therapy; (vii) low doses of DOACs in AF patients; (viii) ischemic stroke in patients inappropriately treated with low doses of DOACs; (ix) management of patients taking DOACs with left atrial appendage thrombosis. RESULTS: A total of 101 physicians (cardiologists, internists, geriatricians, and hematologists) from Italy expressed their level of agreement on each statement by using a 5-point Likert scale (1 = strongly disagree; 2 = disagree; 3 = somewhat agree; 4 = agree; 5 = strongly agree). Votes 1-2 were considered to be disagreement; votes 3-5 were considered to be agreement. Agreement among the respondents of ≥ 66% for each statement was considered consensus. A brief discussion of the results for each topic is also reported. CONCLUSIONS: In clinical practice, there is still uncertainty on DOAC use, especially in elderly, fragile, comorbid, and hyperfiltering patients.

CONTEXTE: Depuis quelques années, les cliniciens prescrivent des anticoagulants oraux directs (AOD) pour prévenir les accidents vasculaires cérébraux (AVC) chez les patients présentant une fibrillation auriculaire (FA) non valvulaire ou pour prévenir et traiter les thromboembolies veineuses. Cependant, les doutes que suscite encore l'emploi des AOD dans certains contextes courants de la pratique clinique n'ont pas encore été bien explorés dans le cadre des études cliniques. MÉTHODOLOGIE: Nous avons utilisé la méthode de Delphes, une démarche visant à dégager un consensus, afin d'évaluer le recours aux AOD chez des patients présentant une FA non valvulaire. L'étude comprenait 9 thèmes principaux : i) utilisation des AOD et des antagonistes de la vitamine K chez les patients présentant une FA; ii) options thérapeutiques pour les patients traités par un antagoniste de la vitamine K dont l'état se maintient depuis un certain temps dans une plage de valeurs normales; iii) options thérapeutiques pour les patients âgés de plus de 85 ans; iv) prise en charge thérapeutique des patients souffrant d'hyperfiltration; v) interactions pharmacologiques; vi) options thérapeutiques pour le traitement prolongé (préventif) des patients présentant une FA et un syndrome coronarien aigu après une trithérapie; vii) utilisation des AOD à faible dose chez les patients présentant une FA; viii) AVC ischémique chez les patients traités de façon inappropriée par un AOD à faible dose; ix) prise en charge des patients prenant un AOD qui présentent une thrombose de l'appendice auriculaire gauche. RÉSULTATS: Au total, 101 médecins (cardiologues, internistes, gériatres et hématologues) italiens ont exprimé leur degré d'accord avec chacun des énoncés proposés sur une échelle de Likert à 5 points (1 = tout à fait en désaccord; 2 = en désaccord; 3 = moyennement d'accord; 4 = d'accord; 5 = tout à fait d'accord). Une note de 1 ou 2 a été considérée comme un désaccord et une note de 3, 4 ou 5, comme un accord. On considérait qu'il y avait un consensus si 66 % ou plus des répondants étaient d'accord avec l'énoncé. Nous présentons également brièvement les résultats obtenus pour chacun des thèmes. CONCLUSIONS: Dans la pratique clinique, l'emploi des AOD soulève encore des doutes, en particulier chez les patients âgés, fragiles ou présentant des affections concomitantes ou une hyperfiltration.

Beneficial effect of ivabradine against cardiovascular diseases.

Coronary artery disease (CAD) and heart failure (HF) are major worldwide threat to health and well-being. Important progress in the treatment of CAD and HF have contributed to a decline in mortality around the world. A considerable number of epidemiological studies reported a strong independent association between elevated heart rate and major cardiovascular risk factors including atherosclerosis, ventricular arrhythmias, and left ventricular dysfunction. Ivabradine (IVA) is a pure heart rate-lowering agent with well-documented anti-anginal and anti-ischemic properties comparable to well-established anti-anginal agents, such as beta-blockers and calcium channel blockers. The heart rate reduction with IVA is beneficial in patients with CAD, chronic stable angina pectoris, and chronic HF, with an acceptable tolerance and safety profile. The pharmacodynamic and pharmacokinetic properties of this drug make it an important agent in the management of patients with CAD and HF. The aim of this short review is to explore recent results with IVA, a new medication that lowers heart rate by selectively inhibiting the If current, and to describe others future potential applications.

Omega-3 Polyunsaturated Fatty Acids: Benefits and Endpoints in Sport.

The influence of nutrition has the potential to substantially affect physical function and body metabolism. Particular attention has been focused on omega-3 polyunsaturated fatty acids (n-3 PUFAs), which can be found both in terrestrial features and in the marine world. They are responsible for numerous cellular functions, such as signaling, cell membrane fluidity, and structural maintenance. They also regulate the nervous system, blood pressure, hematic clotting, glucose tolerance, and inflammatory processes, which may be useful in all inflammatory conditions. Animal models and cell-based models show that n-3 PUFAs can influence skeletal muscle metabolism. Furthermore, recent human studies demonstrate that they can influence not only the exercise and the metabolic response of skeletal muscle, but also the functional response for a period of exercise training. In addition, their potential anti-inflammatory and antioxidant activity may provide health benefits and performance improvement especially in those who practice physical activity, due to their increased reactive oxygen production. This review highlights the importance of n-3 PUFAs in our diet, which focuses on their potential healthy effects in sport.

Effectiveness and Safety of Dietetic Supplementation of a New Nutraceutical on Lipid Profile and Serum Inflammation Biomarkers in Hypercholesterolemic Patients.

Background: To assess the effectiveness and safety of a new nutraceutical (NC) on lipid profile, inflammation biomarkers and creatine phosphokinase (CPK) serum levels in hypercholesterolemic patients. Methods: 40 patients underwent hypolipemic treatment with NC. Initial and final (after 12 weeks) screening included medical history, physical examination, and measurement of serum lipid profile (total cholesterol, HDL-cholesterol, LDL-cholesterol, and triglycerides), hepatic (GOT, GPT, γGT), and renal (serum creatinine and urea) functions, CPK level and many inflammation biomarkers (hs-CRP and fibrinogen). At the screening visit, all patients were instructed to follow a normocaloric and hypolipidic diet during the study period. Results: The treatment with supplementation of NC demonstrated a significant reduction of serum total cholesterol (224 ± 11.2 mg/dL vs. 178 ± 10.7; p < 0.001), LDL-cholesterol (141 ± 10.6 vs. 116 + 10.1; p < 0.001), triglycerides (183 ± 13 vs. 159 ± 11.5; p < 0.01), serum inflammatory biomarkers as hs-CRP (2.24 ± 0.83 vs. 1.76 ± 0.61 mg/dL; p < 0.01), fibrinogen (315 ± 43 vs. 199 ± 41 mg/dL; p < 0.01) and a significantly increase of HDL-cholesterol (44 ± 7 vs. 53 ± 7 mg/dL; p < 0.01). Hepatic and renal function and serum CPK were normal. No adverse events was reported. Conclusions: The treatment with NC has demonstrated a significant reduction of LDL-cholesterol (-17.73%), total cholesterol (-20.53%) and triglycerides (-13.1%), with a significant increase of HDL-cholesterol values (+20.45%). The improvement of lipid profile was associated with a significant reduction of serum inflammation biomarkers as hs-PCR (-27%) and fibrinogen (-36.8%) with good tolerability profile.

Impact of chocolate on the cardiovascular health.

The antioxidants such as polyphenols, especially flavonols, present in large quantitites in cocoa, cause vasodilation, modulate inflammatory markers and cardiovascular health, and possess a range of protective cardiovascular effects. On the other hand, overconsumption of chocolate can lead to tachyarrhythmias, supraventricular tachycardia, atrial fibrillation, ventricular tachycardia and ventricular fibrillation due to its caffeine content. This review describes both the cardioprotective and adverse effects of chocolate and its constituents.

The NF-kB regulates the SHP-1 expression in monocytes in congestive heart failure.

It has been shown that functional recovery of patients with acute congestive heart failure (ACHF) after treatment with conventional drugs (CD) is mediated by suppression of inflammation in peripheral blood mononuclear cells. Here, we analyzed gene expression profiles of monocytes from symptomatic ACHF patients (NYHA Class III-IV) before and after pharmacological treatment with CD. The treatment was associated with selective down-regulation of "TNFR signaling" and pro-inflammatory mediators CCL5, MIP-1α receptor, CD14, ITGAM, and significant up-regulation of "TNFR signaling" as evidenced by increase in anti-inflammatory factors including NF-kBIA, TNFAIP3 and SHP-1. In monocyte TNF-alpha-stimulated there is a down-regulation of the phosphatase SHP-1 which induces a significant activation of TAK-1/IKK/NF-kB signaling. These findings suggest that the therapeutic impact of CD treatment in symptomatic ACHF includes negative regulation of the NF-kB signaling in monocytes and the improvement of the SHP-1 activity.

Coronary artery calcium score and coronary computed tomography angiography for patients with asymptomatic polyvascular (non-coronary) atherosclerosis.

INTRODUCTION: The primary endpoint of this study was to determine the prevalence of coronary artery disease (CAD) and coronary artery calcium score (CACS) using coronary computed tomography angiography (CCTA) among patients with polyvascular atherosclerosis (PVA). Secondary endpoints were to evaluate the prevalence of cardiovascular risk factors and determine the predictors of PVA. METHODS: The presence of atherosclerotic disease was assessed using ultrasonographic vascular examination in 515 asymptomatic patients. All patients with presence of stenosis over 50% and moderate-to-severe cardiovascular risk profile underwent CCTA to identify atherosclerotic coronary disease. RESULTS: Among 515 participants, 143 patients had no evidence of atherosclerotic plaque. Of the 372 patients with atherosclerotic plaque, 184 patients had single-vessel disease, 111 patients had double-vessel disease and 77 patients had triple-vessel disease; among these patients, those who also presented with stenosis > 50% underwent CCTA. Coronary stenosis categories included: normal (6.4%); haemodynamically insignificant (34.6%); intermediate (28.7%); significant (26.6%); and total artery occlusion (3.7%). Based on the coronary vessel involved, the patients were categorised as having single- (41.0%), double- (42.0%) or triple- (17.0%) coronary disease. CACS was significantly higher in patients with double- or triple-vessel disease when compared to those with single-vessel disease. CONCLUSION: Our study confirmed not only the high sensitivity of CCTA for highlighting CAD, but also its negative predictive value for excluding the presence of coronary stenosis or ischaemia. We found good correlation between PVA and CACS, and were able to confirm the risk factors for PVA.

Accuracy of bioimpedance vector analysis and brain natriuretic peptide in detection of peripheral edema in acute and chronic heart failure.

OBJECTIVE: To evaluate the role of bioelectrical impedance vector analysis (BIVA) and brain natriuretic peptide (BNP) in detecting peripheral congestion in heart failure (HF). BACKGROUND: BIVA/BNP are biomarkers for congestion in acute (ADHF) and chronic HF. METHODS: 487 ADHF and 413 chronic HF patients underwent BIVA and BNP tests. RESULTS: BIVA was more accurate than BNP in detecting peripheral congestion both in ADHF (AUC 0.88 vs 0.57 respectively; p < 0.001) and chronic HF patients (AUC 0.89 vs 0.68, respectively; p < 0.001). In ADHF patients, the optimal BNP cut-off for discriminating presence or absence of edema was >870 pg/mL (PPV = 48% and NPV = 58%) whereas in chronic HF it was >216 pg/mL (PPV = 18% and NPV = 95%). The BIVA detected edema when the vector fell into the lower pole of 75th percentile tolerance ellipse (PPV = 84% and NPV = 78%) in ADHF, the lower pole of 50% (PPV = 68% and NPV = 95%) in chronic HF. CONCLUSIONS: In HF patients, BIVA is an easy, fast technique to assess peripheral congestion, and is even more accurate than BNP.

Novel Therapeutic Strategies Against Cancer: Marine-derived Drugs May Be the Answer?

Marine ecosystem represents a wide and untapped reservoir of biologically active metabolites. Most of the sponges, seaweeds, crustaceans, fish species and their associated microorganisms have evolved chemical means in order to defend themselves against predation and to survive in the complex marine environment. Such chemical and biological adaptation produced many bioactive substances with beneficial effects on human health, including potential anticancer agents. With further exploration of sea and ocean environment, several marine bioactives have been identified with promising anticancer activity. More than one hundred novel bioactive compounds with antitumor activity and their synthetic derivative substances displayed in vitro cytotoxic property on neoplastic cell lines and are currently gaining great attention for further evaluations and in vivo applications. This review highlights novel marine molecules and compounds which have been able to inhibit different cancer species in the recent years and aims to describe research on new natural antineoplastic agents obtained from sea world.

Dilated cardiomyopathy following use of xenadrine EFX.

We describe a case of a 35-year-old man presented at the emergency room of our institution with acute onset of dyspnea and dizziness. He was a body builder and had been using Xenadrine EFX for weight loss reduction. The laboratory analyses were normal. A chest radiograph showed an enlarged cardiac silhouette with clear lung fields. Transtoracic two-dimensional color Doppler echocardiography revealed a diffuse hypokinesia with a marked decreased in systolic function and a high teledyastolic diameter. This case document the possible relation to use of Xenadrine EFX for weight loss and the recurrence of dilated cardiomyopathy.

Marine Carotenoids against Oxidative Stress: Effects on Human Health.

Carotenoids are lipid-soluble pigments that are produced in some plants, algae, fungi, and bacterial species, which accounts for their orange and yellow hues. Carotenoids are powerful antioxidants thanks to their ability to quench singlet oxygen, to be oxidized, to be isomerized, and to scavenge free radicals, which plays a crucial role in the etiology of several diseases. Unusual marine environments are associated with a great chemical diversity, resulting in novel bioactive molecules. Thus, marine organisms may represent an important source of novel biologically active substances for the development of therapeutics. In this respect, various novel marine carotenoids have recently been isolated from marine organisms and displayed several utilizations as nutraceuticals and pharmaceuticals. Marine carotenoids (astaxanthin, fucoxanthin, ß-carotene, lutein but also the rare siphonaxanthin, sioxanthin, and myxol) have recently shown antioxidant properties in reducing oxidative stress markers. This review aims to describe the role of marine carotenoids against oxidative stress and their potential applications in preventing and treating inflammatory diseases.

Resveratrol and anti-atherogenic effects.

The role of inflammation and oxidative stress in atherosclerosis development has been increasingly well recognized over the past decade. Inflammation has a significant role at all stages of atherosclerosis, including initiation, progression and plaque formation. Resveratrol is a naturally occurring polyphenolic compound found in grape products, berry fruits and red wine. Its ability to behave therapeutically as a component of red wine has attracted wide attention. Accumulating evidence suggests that it is a highly pleiotropic molecule that modulates numerous targets and molecular functions. Epidemiological studies indicate that the Mediterranean diet, rich in resveratrol, is associated with a reduced risk of atherosclerosis. Resveratrol is believed to decrease circulating low-density lipoprotein cholesterol levels, reduce cardiovascular disease risk; it reduces lipid peroxidation, platelet aggregation and oxidative stress. Resveratrol is considered a safe compound, since no significant toxic effects have been demonstrated after administration of a broad range of concentrations, and an effective anti-atherogenic agent.

Physical exercise reduces synthesis of ADMA, SDMA, and L-Arg.

Increased levels of asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA) and low plasma level of L-arginine (L-ARG) are all conditions likely to decrease nitric oxide (NO) production. Aim of this study is to evaluate ADMA, SDMA, and L-ARG plasmatic levels before and after physical exercise in patients with coronary artery disease (CAD). We studied 30 patient with mean age 52 + 4.5 years. After inclusion in the study, before the execution of physical exercise, heparinized blood sample was drawn from an indwelling arterial line for determination of ADMA, L-ARG and SDMA (baseline values). Subsequently a blood sample was drawn after the physical exercise. The mean plasma concentrations of ADMA (0.68 + 0.06 vs 0.48 + 0.05 µmol/L) and SDMA (0.45 + 0.03 vs 0.30 + 0.03 µmol/L) were significantly lower after physical exercise in comparison to baseline value, while L-ARG mean levels were increased (44.20 + 10.5 vs 74.13 + 11.2 µmol/L). Physical exercise has a beneficial effect by reducing plasmatic ADMA and SDMA levels, and increasing L-ARG substrate for endothelial NO.

Carotenoids: potential allies of cardiovascular health?

Carotenoids are a class of natural, fat-soluble pigments found principally in plants. They have potential antioxidant biological properties because of their chemical structure and interaction with biological membranes. Epidemiologic studies supported the hypothesis that antioxidants could be used as an inexpensive means of both primary and secondary cardiovascular disease (CVD) prevention. In fact, the oxidation of low-density lipoproteins (LDL) in the vessels plays a key role in the development of atherosclerotic lesions. The resistance of LDL to oxidation is increased by high dietary antioxidant intake, so that carotenoids, as part of food patterns such as the Mediterranean diet, may have beneficial effects on cardiovascular health too. Further properties of carotenoids leading to a potential reduction of cardiovascular risk are represented by lowering of blood pressure, reduction of pro-inflammatory cytokines and markers of inflammation (such as C-reactive protein), and improvement of insulin sensitivity in muscle, liver, and adipose tissues. In addition, recent nutrigenomics studies have focused on the exceptional ability of carotenoids in modulating the expression of specific genes involved in cell metabolism. The aim of this review is to focus attention to this effect of some carotenoids to prevent CVD.

Ivabradine, coronary artery disease, and heart failure: beyond rhythm control.

Elevated heart rate could negatively influence cardiovascular risk in the general population. It can induce and promote the atherosclerotic process by means of several mechanisms involving endothelial shear stress and biochemical activities. Furthermore, elevated heart rate can directly increase heart ischemic conditions because of its skill in unbalancing demand/supply of oxygen and decreasing the diastolic period. Thus, many pharmacological treatments have been proposed in order to reduce heart rate and ameliorate the cardiovascular risk profile of individuals, especially those suffering from coronary artery diseases (CAD) and chronic heart failure (CHF). Ivabradine is the first pure heart rate reductive drug approved and currently used in humans, created in order to selectively reduce sinus node function and to overcome the many side effects of similar pharmacological tools (ie, ß-blockers or calcium channel antagonists). The aim of our review is to evaluate the role and the safety of this molecule on CAD and CHF therapeutic strategies.

Marine bioactives and potential application in sports.

An enriched diet with antioxidants, such as vitamin E, vitamin C, ß-carotene and phenolic compounds, has always been suggested to improve oxidative stress, preventing related diseases. In this respect, marine natural product (MNP), such as COX inhibitors, marine steroids, molecules interfering with factors involved in the modulation of gene expression (such as NF-κB), macrolides, many antioxidant agents, thermogenic substances and even substances that could help the immune system and that result in the protection of cartilage, have been recently gaining attention. The marine world represents a reserve of bioactive ingredients, with considerable potential as functional food. Substances, such as chitin, chitosan, n-3 oils, carotenoids, vitamins, minerals and bioactive peptides, can provide several health benefits, such as the reduction of cardiovascular diseases, anti-inflammatory and anticarcinogenic activities. In addition, new marine bioactive substances with potential anti-inflammatory, antioxidant and thermogenic capacity may provide health benefits and performance improvement, especially in those who practice physical activity, because of their increased free radical and Reacting Oxygen Species (ROS) production during exercise, and, particularly, in athletes. The aim of this review is to examine the potential pharmacological properties and application of many marine bioactive substances in sports.

ADMA/SDMA in elderly subjects with asymptomatic carotid atherosclerosis: values and site-specific association.

Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide synthase (NOS) inhibitor known as a mediator of endothelial dysfunction and atherosclerosis. Circulating ADMA levels are correlated with cardiovascular risk factors such as hypercholesterolemia, arterial hypertension, diabetes mellitus, hyperhomocysteinemia, age and smoking. We assessed the relationship between ADMA values and site-specific association of asymptomatic carotid atherosclerosis (intima-media thickness (CIMT) and plaque) in elderly subjects. One hundred and eighty subjects underwent a complete history and physical examination, determination of serum chemistries and ADMA levels, and carotid ultrasound investigation (CUI). All subjects had no acute or chronic symptoms of carotid atherosclerosis. Statistical analyses showed that high plasma levels of ADMA/SDMA were positively correlated to carotid atherosclerosis (CIMT and plaque) (p<0.001), with significant site-specific association. Total cholesterol, low density lipoprotein cholesterol, triglycerides and C-reactive protein plasma concentrations were significantly associated with asymptomatic carotid atherosclerosis (p<0.001). High serum concentrations of ADMA and SDMA were associated with carotid atherosclerotic lesions as measured by CIMT ad plaque and may represent a new marker of asymptomatic carotid atherosclerosis in elderly subjects.

Three-year results of repaired Barlow mitral valves via right minithoracotomy versus median sternotomy in a randomized trial.

OBJECTIVES: To clarify whether the results of repair of a complex mitral lesion (Barlow valve) at the intermediate-term follow-up are independent of the mode of surgical access [minithoracotomy vs. median sternotomy (MS)]. METHODS: In a prospective randomized study of mitral repair for Barlow disease using either a minimally invasive (MI) approach or MS, we achieved an average follow-up of 3 years (echocardiography, physical examination and quality of life). Mitral repair was achieved with polytetrafluoroethylene chordal implantation for both leaflets. RESULTS: Both groups included 80 patients. Mechanical ventilation time and intensive care unit and hospital stay were shorter in the MI group (p = 0.01, p = 0.013 and p = 0.02, respectively). During the follow-up, 5 patients in each group (6.25%) displayed mild mitral regurgitation, while 2 patients in each group (2.5%) developed recurrent regurgitation graded as at least moderate/severe. The rate of mitral reoperation was 2.5% in the MI group and 1.25% in the MS group (p = 0.9). The overall follow-up mortality was 3.75% in both the MI and the MS groups. CONCLUSIONS: The 3-year results of repair of Barlow valves were satisfactory irrespective of the approach used to repair the valve. The advantages of MI surgery can be achieved in patients with mitral Barlow disease without concerns over the durability of repair.

Biological functional relevance of asymmetric dimethylarginine (ADMA) in cardiovascular disease.

There is growing evidence that increased levels of the endogenous NO synthase inhibitor asymmetric dimethylarginine (ADMA) may contribute to endothelial dysfunction. Studies in animal models as well as in humans have suggested that the increase in ADMA occurs at a time when vascular disease has not yet become clinically evident. ADMA competitively inhibits NO elaboration by displacing L-arginine from NO synthase. In a concentration-dependent manner, it thereby interferes not only with endothelium-dependent, NO-mediated vasodilation, but also with other biological functions exerted by NO. The upshot may be a pro-atherogenic state. Recently, several studies have investigated the effect of various therapeutical interventions on ADMA plasma concentrations.