Charalambos Vlachopoulos

Clinical applications of arterial stiffness; definitions and reference values.

Arterial stiffening is the most important cause of increasing systolic and pulse pressure, and for decreasing diastolic pressure beyond 40 years of age. Stiffening affects predominantly the aorta and proximal elastic arteries, and to a lesser degree the peripheral muscular arteries. While conceptually a Windkessel model is the simplest way to visualize the cushioning function of arteries, this is not useful clinically under changing conditions when effects of wave reflection become prominent. Many measures have been applied to quantify stiffness, but all are approximations only, on account of the nonhomogeneous structure of the arterial wall, its variability in different locations, at different levels of distending pressure, and with changes in smooth muscle tone. This article summarizes the methods and indices used to estimate arterial stiffness, and provides values from a survey of the literature, followed by recommendations of an international group of workers in the field who attended the First Consensus Conference on Arterial Stiffness, which was held in Paris during 2000, under the chairmanship of M.E. Safar and E.D. Frohlich.

The role of vascular biomarkers for primary and secondary prevention. A position paper from the European Society of Cardiology Working Group on peripheral circulation: Endorsed by the Association for Research into Arterial Structure and Physiology (ARTERY) Society

While risk scores are invaluable tools for adapted preventive strategies, a significant gap exists between predicted and actual event rates. Additional tools to further stratify the risk of patients at an individual level are biomarkers. A surrogate endpoint is a biomarker that is intended as a substitute for a clinical endpoint. In order to be considered as a surrogate endpoint of cardiovascular events, a biomarker should satisfy several criteria, such as proof of concept, prospective validation, incremental value, clinical utility, clinical outcomes, cost-effectiveness, ease of use, methodological consensus, and reference values. We scrutinized the role of peripheral (i.e. not related to coronary circulation) noninvasive vascular biomarkers for primary and secondary cardiovascular disease prevention. Most of the biomarkers examined fit within the concept of early vascular aging. Biomarkers that fulfill most of the criteria and, therefore, are close to being considered a clinical surrogate endpoint are carotid ultrasonography, ankle-brachial index and carotid-femoral pulse wave velocity; biomarkers that fulfill some, but not all of the criteria are brachial ankle pulse wave velocity, central haemodynamics/wave reflections and C-reactive protein; biomarkers that do no not at present fulfill essential criteria are flow-mediated dilation, endothelial peripheral arterial tonometry, oxidized LDL and dysfunctional HDL. Nevertheless, it is still unclear whether a specific vascular biomarker is overly superior. A prospective study in which all vascular biomarkers are measured is still lacking. In selected cases, the combined assessment of more than one biomarker may be required.

Non-coronary atherosclerosis

During the last decades, the clinical and research interest in atherosclerosis has been mostly focused on coronary arteries. After the publications of the European Society Guidelines and AHA/ACC Guidelines on Peripheral artery diseases, and of the Registry REduction in Atherothrombosis for Continued Health Registry, there has been an increased interest in atherosclerosis of the lower extremity arteries and its presence in multifocal disease. However, awareness in the general population and the medical community of non-coronary artery diseases, and of its major prognostic implications remain relatively low. The aim of this general review stemming out of an ESC Working Group on Peripheral Circulation meeting in 2011 is to enhance awareness of this complex disease highlighting the importance of the involvement of atherosclerosis at different levels with respect to clinical presentation, diagnosis, and co-existence of the disease in the distinct arterial territories. We also emphasize the need of an interdisciplinary approach to face the broad and complex spectrum of multifocal disease, and try to propose a series of tentative recommendations and measures to be implemented in non-coronary atherosclerosis.

The Impact of Oral L-Arginine Supplementation on Acute Smoking–Induced Endothelial Injury and Arterial Performance

BACKGROUNDnSmoking is associated with endothelial dysfunction and increased inflammatory status. The amino acid L-arginine, improves endothelial function in patients with cardiovascular risk factors. We investigated the effect of L-arginine on vascular function and inflammatory process in healthy smokers at rest and after acute smoking.nnnMETHODSnWe studied the effect of L-arginine and/or placebo in 12 healthy young smokers on three occasions (day 0, day 1, and day 3). The study was carried out on two separate arms, one with L-arginine (3 x 7 g/day) and one with placebo, according to a randomized, placebo-controlled, double-blind, cross-over design. Measurements were carried out before, immediately after, and 20 min after cigarette smoking. Endothelial function was evaluated by flow-mediated dilation (FMD). Carotid-femoral pulse wave velocity (PWV) was measured as an index of aortic stiffness and augmentation index (AIx) and as a measure of arterial wave reflections. Serum soluble intercellular adhesion molecule-1 (sICAM-1) was measured.nnnRESULTSnCompared to placebo, L-arginine improved FMD (P < 0.01 at day 1 and P < 0.05 at day 3). L-Arginine reduced PWV and AIx at both days 1 and 3 (P < 0.05 vs. baseline). L-Arginine blunted the acute smoking-induced increase of AIx at both day 1 (P < 0.05) and day 3 (P < 0.01), and prevented the smoking-induced elevation of PWV at day 3 (P < 0.05). Importantly, L-arginine reduced sICAM-1 at days 1 and 3 (P < 0.05 for both vs. baseline).nnnCONCLUSIONSnOral L-arginine improves endothelial function and vascular elastic properties of the arterial tree during the acute phase of smoking, an effect accompanied by reduced sICAM-1 levels in these subjects.

Prostate‐Specific Antigen Levels Are Associated with Arterial Stiffness in Essential Hypertensive Patients

INTRODUCTIONnProstate-specific antigen (PSA) has been recently related to cardiovascular system in a multifactorial way. Arterial stiffness is a independent predictor of cardiovascular events and is involved in the pathogenesis of hypertension. The aim of the present study was to investigate whether PSA values, are associated with arterial stiffness indices in patients with essential arterial hypertension.nnnMETHODSnThe study comprised 150 consecutive male patients (mean age 60 years) with uncomplicated never-treated essential hypertension. All patients underwent a complete clinical and laboratory evaluation, including measurement of PSA levels. Aortic stiffness and arterial wave reflection assessment was made by using carotid-femoral (PWVc-f) pulse wave velocity and aortic augmentation index corrected for heart rate (AIx75). Patients with prostate cancer or benign prostate hyperplasia (PSA > 4 ng/mL) were excluded from the study.nnnRESULTSnPSA was positively associated with waist-to-hip ratio (r = 0.235, P = 0.04), PWVc-f (r = 0.426, P < 0.001), AIx75 (r = 0.264, P = 0.001), and high sensitivity C-reactive protein (hsCRP; r = 0.376, P < 0.001). In categorization to PSA quartiles, patients in the higher quartile presented with higher waist-to hip ratio (P = 0.009), PWVc-f (P < 0.00001), AIx75 (P < 0.001) and hsCRP (P < 0.001) values. In multivariate analysis after adjustment for various confounders PSA remained a significant determinant of PWVc-f values (beta [SE] = 0.477 [0.13], R(2) = 0.405, P < 0.001).nnnCONCLUSIONnThe present study points towards an association between PSA levels and aortic stiffness in untreated essential hypertensive males. Potential causal relationships between PSA and arterial stiffness remain to be further explored.

Ranolazine for the symptomatic treatment of patients with chronic angina pectoris in Greece: a cost-utility study.

BackgroundTo conduct an economic evaluation comparing ranolazine as add-on therapy to standard-of-care (SoC) with SoC alone in patients with stable angina who did not respond adequately to first line therapy, in Greece.MethodsA decision tree model was locally adapted in the Greek setting to evaluate the cost-utility of ranolazine during a 6-month period. The analysis was conducted from a third-party payer perspective. The clinical inputs were extracted from the published literature. The cost inputs considered in the model reflect drug acquisition, hospitalizations, vascular interventions and monitoring of patients. The resource utilization data were obtained from 3 local experts. All costs refer to the year 2014. Cost-effectiveness was assessed by means of the incremental cost per quality adjusted life year (QALY) gained with the ranolazine as add-on therapy relative to SoC alone (ICER). Probabilistic sensitivity analysis (PSA) was performed.ResultsRanolazine as add-on therapy was more costly compared to SoC alone, as the 6-month total cost per patient was €1170 and € 984, respectively. Patients received ranolazine plus SoC and SoC alone gained 0.3155 QALYs and 0.2752 QALYs, respectively. Ranolazine plus SoC resulted in an ICER equal to €4620 per QALY gained, well below the threshold of €34,000 per QALY gained. The PSA showed that the likelihood of ranolazine plus SoC being cost-effective at the threshold of €34,000 per QALY gained was 100xa0%.ConclusionsΤhe results suggest that ranolazine as add–on treatment may be a cost-effective alternative for the symptomatic treatment of patients with chronic stable angina in Greece.

Influence of body composition and physical fitness on arterial stiffness after marathon running

Participation in exhaustive endurance sports competitions continues to be popular. Questions about the cardiovascular side effects of prolonged excessive exercise persist. Our study aimed to elucidate the acute effects of marathon running on arterial stiffness (AST) and to detect the role of body composition, fitness status, and inflammation.

Postmenopausal Hypertension and Coronary Artery Disease Risk

Cardiovascular disease is the leading cause of death in women worldwide [1, 2]. Female hormones, particularly estrogens, exert a protective role on the cardiac and vascular function through many pathophysiological mechanisms. However, this beneficial effect is abolished after menopause; loss of protection is associated with an increase in the incidence of hypertension [3], diabetes mellitus, dyslipidemia and, consequently, cardiovascular disease. Indeed, the large burden of cardiovascular disease in women is noted around the age of 50, coinciding with menopause [4]. However, although endogenous estrogens are cardioprotective, the results concerning the potential beneficial effect of hormone replacement therapy in postmenopausal women are contradictory.

The Effect of Smoking on Inflammation, Prothrombotic State and Endothelial Dysfunction in Patients with Essential Hypertension

AbstractObjective: Smoking is a modifiable cardiovascular risk factor. It has been reported to affect inflammatory, coagulation indices and homocysteine. The purpose of the present study was to evaluate the effect of smoking on inflammatory, coagulation indices and homocysteine as well as on traditional risk factors, in a large cohort of patients with essential hypertension.n Methods: The study comprised 4000 consecutive patients, with uncomplicated essential hypertension (2572 non-smokers and 1428 smokers). Inflammatory indices such as high-sensitivity C-reactive protein (hsCRP), white blood cell count (WBC) and serum amyloid A (SAA) as well as coagulation markers such as serum fibrinogen, plasminogen activator inhibitor (PAI-1) and homocysteine were measured in all patients. Finally, all patients were asked about their smoking habits and, thus, information about smoking intensity and smoking duration was obtained.n Results: All studied markers were significantly higher in smokers compared with non-smokers after adjusting for age and gender (p < 0.001). Furthermore, hsCRP, serum fibrinogen and WBC were positively associated with both increasing smoking intensity and time since smoking initiation, while SAA was positively associated with smoking intensity (p = 0.003) and PAI-1 with smoking duration (p = 0.003). No such association was noticed with homocysteine (p = not significant).n Conclusions: Smoking affects inflammatory, coagulation indices, homocysteine and traditional risk factors in patients with essential hypertension independently of age and gender.

775-2 Deleterious Effect of Smoking on the Elastic Properties of the Aorta

Cigarette smoking alters vascular reactivity and thus may alter the elastic properties of the aorta (Ao). To test this hypothesis, serial pressure-diameter loops (figure A) were obtained from the simultaneous recordings of the thoracic Ao diameter (D) and pressure (P) before and atterthe initiation of smoking of one cigarette (nicotine content 1.3xa0mg) in 20 healthy smokers who underwent diagnostic cardiac catheterization. Ao 0 were measured by a Yshaped catheter, developed in our institution, which incorporates at its distal tips a pair of ultrasonic dimension crystals (Crystal Biotech, MA). This highdefinition diameter gauge was validated in in-vitro and experimental studies. Ao Pwere recorded by a Millar micromanometer. The pressure-diameter relationship changed significantly with smoking (figure A). Ao distensibility (=2Δd/dx ΔP, where Δd and ΔP: changes from systole to diastole of the Ao D and P respectively, and d: diastolic Ao D) was decreased significantly after smoking (figure B). These changes suggest that the Ao became stiffer atter smoking. Download : Download high-res image (63KB) Download : Download full-size image This effect of smoking on the elastic properties of the aorta adds to the multiple other deleterious effects of smoking on human health.