Dimitrios Terentes-Printzios

Prediction of Cardiovascular Events and All-Cause Mortality With Brachial-Ankle Elasticity Index A Systematic Review and Meta-Analysis

Brachial-ankle elasticity index (baEI; also known as brachial-ankle pulse wave velocity) has been proposed as a surrogate end point for cardiovascular disease. We performed a meta-analysis of longitudinal cohort studies for determining the ability of baEI to predict risk of cardiovascular events and all-cause mortality and dissecting factors influencing this predictive ability. Multiple online databases, reference lists from retrieved articles, and abstracts from international cardiovascular conventions were searched until April 2012. Longitudinal cohort studies that reported associations of baEI with clinical risk were included. Of the 18 studies included (8169 participants; mean follow-up, 3.6 years), 15 reported results on total cardiovascular events (5544 individuals), 7 on cardiovascular mortality (2274 individuals), and 9 on all-cause mortality (5097 individuals). The pooled relative risks for total cardiovascular events, cardiovascular mortality, and all-cause mortality were 2.95 (95% CI, 1.63–5.33), 5.36 (95% CI, 2.17–13.27), and 2.45 (95% CI, 1.56–3.86), respectively, for subjects with high versus low baEI (all P<0.001). An increase in baEI by 1 m/s corresponded with an increase of 12%, 13%, and 6% in total cardiovascular events, cardiovascular mortality, and all-cause mortality, respectively. We conclude that baEI is associated with increased risk of total cardiovascular events and all-cause mortality. Issues such as expansion of data to non-Asian populations, validation of path length estimation, determination of reference values, and prospective comparison with carotid-femoral pulse wave velocity remain to be resolved.

Prediction of Cardiovascular Events and All-Cause Mortality With Erectile Dysfunction A Systematic Review and Meta-Analysis of Cohort Studies

Background— Erectile dysfunction (ED) carries an independent risk for cardiovascular (CV) events. We conducted a meta-analysis of all longitudinal studies for determining the ability of ED to predict risk of clinical events and to dissect factors influencing this ability. Methods and Results— We conducted a comprehensive search of electronic databases through July 2012. Longitudinal studies that reported relative risk (RR) estimates with 95% confidence intervals (CIs) were included. Of the 14 studies included (92 757 participants; mean follow-up, 6.1 years; 16 articles), 13 (14 articles) reported results on total CV events (91 831 individuals), 4 on CV mortality (34 761 individuals), 4 on myocardial infarction (35 523 individuals), 6 on cerebrovascular events (27 689 individuals), and 5 on all-cause mortality (17 869 individuals). The pooled RRs for the above-mentioned end points were 1.44 (95% CI, 1.27–1.63), 1.19 (95% CI, 0.97–1.46), 1.62 (95% CI, 1.34–1.96), 1.39 (95% CI, 1.23–1.57), and 1.25 (95% CI, 1.12–1.39), respectively, for men with versus without ED. The RR was higher in intermediate- compared with high- or low-CV-risk populations and with younger age. The RR for studies that diagnosed ED with the use of a questionnaire compared with a single question was higher (RR, 1.61; 95% CI, 1.38–1.86 versus RR, 1.27; 95% CI, 1.18–1.37, respectively; P=0.006). Conclusions— ED is associated with increased risk of CV events and all-cause mortality. RR is higher at younger ages, in intermediate-risk groups, and when a questionnaire is used instead of a single question.

The triad: erectile dysfunction--endothelial dysfunction--cardiovascular disease.

Endothelial dysfunction is an important process in the development of atherosclerotic cardiovascular disease, while it is also a major pathophysiological mechanism underlying vasculogenic erectile dysfunction (ED). Expectedly, these two prevalent disorders are linked also at the clinical level: ED is common in patients with overt and silent coronary artery disease, while ED is increasingly being regarded as the early clinical manifestation of a generalized vascular disease and carries an independent risk for future cardiovascular events. The emerging awareness of ED as a barometer for cardiovascular disease offers a unique opportunity to enhance preventive vascular health in men. Lifestyle and risk factor modification, as well as pharmacologic therapy (both phosphodiesterase type-5 inhibitors and non-ED-targeting drugs), appear to confer additional benefit both in terms of ED treatment and overall cardiovascular risk; this benefit may be related, at least partly, to the improvement of endothelial function and anti-inflammatory effects. The present review identifies pathophysiologic links between endothelial dysfunction, ED and coronary artery disease, presents methodological aspects regarding penile and systemic endothelial function, and discusses the clinical implications in terms of diagnosis of ED, assessment of patient risk, and treatment.

Arterial stiffness and wave reflections in marathon runners.

BACKGROUND Regular aerobic exercise has beneficial effects on the cardiovascular system. Marathon running is an aerobic and extremely vigorous exercise. Arterial stiffness and wave reflections are independent predictors of cardiovascular risk. We investigated the acute effect of marathon race on aortic stiffness and wave reflections, as well as possible chronic alterations of these indexes in marathon runners. METHODS We studied 49 marathon runners (age 38 +/- 9 years) and 46 recreationally active control subjects (age 37 +/- 5 years). To investigate the acute effect of marathon race, a subgroup of 20 runners was evaluated after the race as well. Aortic stiffness was evaluated with carotid-femoral pulse wave velocity (PWV) and wave reflections with augmentation index (AIx). RESULTS Marathon runners had significantly higher systolic, diastolic, pulse (both aortic and brachial), and mean pressures compared to controls (P < 0.05 for all). Marathon runners had significantly higher PWV (6.89 m/s vs. 6.33 m/s, P < 0.01), whereas there was no difference in AIx and AIx corrected for heart rate (AIx@75) compared to controls (13.8% vs. 13.9%, P = 0.985 and 8.2% vs. 10.3%, P = 0.340, respectively). Marathon race caused a significant fall in both AIx (12.2% vs. -5.8%, P < 0.001) and AIx@75 (7.0% vs. 0.0%, P = 0.01), whereas PWV did not change significantly (6.66 m/s vs. 6.74 m/s, P = 0.690). Aortic and brachial systolic, diastolic, and mean pressures were also decreased (P < 0.05). CONCLUSIONS A significant fall in wave reflections was observed after marathon race, whereas aortic stiffness was not altered. Moreover, marathon runners have increased aortic stiffness and pressures, whereas wave reflections indexes do not differ compared to controls.

Tomato paste supplementation improves endothelial dynamics and reduces plasma total oxidative status in healthy subjects

Consumption of tomato products is linked to beneficial outcomes through antioxidant and anti-inflammatory mechanisms. The aim of this study was to determine whether a 14-day period of tomato paste supplementation would improve endothelial function. Nineteen volunteers (mean age, 39 ± 13 years; 8 men/11 women) were studied in a randomized (exposure sequence), single-blind (operator), crossover design. The study consisted of a supplementation arm (70 g tomato paste containing 33.3 mg of lycopene) and a control arm, during which no tomato paste was added to their regular diet. Volunteers maintained their regular diet during study arms. Two-week washout periods preceded each arm. Flow-mediated dilatation (FMD) measured by brachial artery ultrasonography was used as an estimate of endothelial function at day 1 (acute response) and day 15 (midterm response). Plasma lipid peroxides were measured with a photometric enzyme-linked immunosorbent assay as an index of total oxidative status. Tomato supplementation led to an overall FMD increase compared with the control period (P = .047 for repeated-measures 3 × 2 analysis of variance). At day 1, FMD was not significantly increased (P = .329). By day 15, tomato supplementation resulted in an increase in FMD by 3.3% ± 1.4%, whereas at the control arm, FMD declined by -0.5% ± 0.6% (P = .03); magnitudes of change are absolute FMD values. Total oxidative status decreased at the end of the supplementation period compared with baseline values (P = .038). Daily tomato paste consumption exerts a beneficial midterm but not short-term effect on endothelial function. Further studies are warranted to explore the effects of tomato paste on endothelial dilation in different age groups and comorbidities.

Amino-terminal pro-C-type natriuretic peptide is associated with arterial stiffness, endothelial function and early atherosclerosis.

OBJECTIVE C-type natriuretic peptide (CNP) is a paracrine molecule with effects on endothelial integrity, vascular tone and atherosclerotic process. Arterial stiffness, wave reflections, endothelial dysfunction and carotid intima-media thickness (IMT) are predictors of cardiovascular events. We investigated whether CNP is related to arterial structure and function in men. METHODS We evaluated arterial structural and functional characteristics in 117 consecutive men (mean age 57.3 + or - 9.2 years), with and without cardiovascular risk factors, who had no established cardiovascular disease. Arterial elastic properties were evaluated with carotid-femoral pulse wave velocity (PWV), wave reflections with augmentation index (AIx), endothelial function with flow-mediated dilatation of the brachial artery (FMD) and early atherosclerosis with carotid IMT. Amino-terminal proCNP (NT-proCNP) was assessed in venous blood. RESULTS The number of cardiovascular risk factors was inversely related to levels of NT-proCNP (P<0.01) and there was a progressive increase in Framingham risk score according to decreasing tertiles of NT-proCNP (P<0.001). In multivariable regression analysis NT-proCNP exhibited significant negative associations with PWV and IMT and positive association with FMD (all P<0.05) that were independent of age, blood pressure, smoking habits, body mass index, blood glucose, total triglycerides, low-density lipoprotein and endothelin-1 or high-sensitivity C-reactive protein. There was no relation between NT-proCNP and AIx. CONCLUSION The present study is the first to demonstrate in a global arterial approach relationship between CNP and functional and early structural arterial changes. These findings elucidate pathophysiological links and may have important clinical implications for the estimation of cardiovascular risk in men.

Relationship of Asymmetric Dimethylarginine With Penile Doppler Ultrasound Parameters in Men with Vasculogenic Erectile Dysfunction

BACKGROUND Asymmetric dimethylarginine (ADMA), a selective endogenous nitric oxide synthase inhibitor, is elevated in many conditions associated with erectile dysfunction (ED), such as hypertension, diabetes, hyperlipidemia, and renal failure; it is also increased in men with coronary artery disease and ED. The dynamic penile colour Doppler ultrasound is considered the gold standard for the evaluation of penile vascular damage. OBJECTIVE We investigated whether the extent of ultrasonographically documented penile vascular disease is associated with higher ADMA levels. DESIGN, SETTING, AND PARTICIPANTS One hundred four consecutive ED patients (mean age: 56 ± 9 yr) without manifest cardiovascular/atherosclerotic disease and 31 subjects with normal erectile function matched for age and traditional risk factors were studied. MEASUREMENTS We evaluated penile dynamic colour Doppler parameters of arterial insufficiency (peak systolic velocity) and veno-occlusive dysfunction (end diastolic velocity) and measured systemic inflammatory markers/mediators. RESULTS AND LIMITATIONS Compared to men without ED, ED patients had significantly higher ADMA levels (p<0.001). ADMA was significantly increased in patients with severe arterial insufficiency (PSV<25 cm/s) compared to subjects with borderline insufficiency and men with normal penile arterial function (p<0.001, by analysis of variance). Multivariable analysis adjusting for age, mean pressure, other risk factors, high-sensitivity C-reactive protein, testosterone, and treatment showed independent inverse association between ADMA level and peak systolic velocity (p<0.01). The combination of higher ADMA level with arterial insufficiency showed greater impact on 10-yr risk of a cardiovascular event compared to either parameter alone. CONCLUSIONS ADMA level is independently associated with ultrasonographically documented poor penile arterial inflow. This finding underlines the important role of ADMA as a marker of penile arterial damage and implies a contribution of this compound to the pathophysiology of generalised vascular disease associated with ED.

Electronic Cigarette Smoking Increases Aortic Stiffness and Blood Pressure in Young Smokers

Smoking increases aortic stiffness and blood pressure (BP) [(1)][1], which are both important predictors of cardiovascular risk and all-cause mortality [(2,3)][2]. Electronic cigarettes (EC) simulate tobacco cigarettes (TC) and have been advocated as a less harmful alternative [(4)][3]. The effect

PDE5 Inhibitors in Non-Urological Conditions

Phosphodiesterase type-5 (PDE5) inhibitors are widely used as first-line therapy for erectile dysfunction (ED). Their efficacy and safety combined with an increasing understanding of cyclic guanosine monophosphate (cGMP)-regulated mechanisms, have triggered a number of attempts to determine their effects and potential benefits in non-urological conditions. In recent years, extensive and diverse preclinical and clinical evidence has been made available. PDE5 inhibition has shown collateral benefits for a multitude of risk factors or diseases associated with, or accompanying ED. To date, PDE5 inhibition has been shown to be effective for the treatment of idiopathic pulmonary arterial hypertension and both sildenafil and tadalafil are approved for this indication. However, PDE5 inhibitors appear to have the potential of further expanding their indications. Importantly, accumulating data show that the therapeutic potential extends to the cardiovascular, gastrointestinal, cutaneous and nervous system and that these agents may be beneficial in a multitude of conditions such as Raynauds phenomenon, heart failure, essential hypertension and stroke. PDE5 inhibitors are a conceptually attractive therapeutic class of agents with pleiotropic effects. The present review discusses recent findings regarding the effects of PDE5 inhibitors on non-urological conditions and highlights current and future clinical applications beyond ED.

Prediction of Cardiovascular Events With Aortic Stiffness in Patients With Erectile Dysfunction

Erectile dysfunction confers an independent risk for cardiovascular events and total mortality. Aortic pulse wave velocity (PWV) is an important predictor of cardiovascular events and all-cause mortality. We investigated whether PWV predicts major adverse cardiovascular events (MACEs) in patients with erectile dysfunction beyond traditional risk factors. MACEs in relation to PWV were analyzed with proportional hazards models in 344 patients (mean age, 56 years) without established cardiovascular disease. During a mean follow-up of 4.7 years (range, 1–8.5 years), 24 of 344 participants (7.0%) experienced a MACE. Subjects in the highest PWV tertile (>8.8 m/s) had a 4-fold higher risk of MACEs compared with those in the lowest PWV tertile (<7.6 m/s; adjusted hazard ratio, 3.97; P=0.035). A PWV value of 7.81 m/s was associated with a negative predictive value (ability to rule out MACE) of 98.1%. Addition of PWV to standard risk factor model yielded correct patient reclassification to higher or lower risk category by 27.6% (P=0.0332) in the whole cohort. Our results show that higher aortic stiffness is associated with increased risk for a MACE in patients with erectile dysfunction without known cardiovascular disease. Aortic PWV improves risk prediction when added to standard risk factors and may represent a valuable biomarker of prediction of cardiovascular disease risk in these patients.