Divergent associations of tissue inhibitors of metalloproteinases-1 and -2 with the prothrombotic/fibrinolytic state.
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Adult↗
Biomedical subjects
Charalambos Vlachopoulos
Publications and source records attributed to Charalambos Vlachopoulos.
Large recesses associated with left ventricular noncompaction: an unusual presentation of the disease.
Left ventricular noncompaction (LVNC) represents an arrest of myocardial morphogenesis, resulting in persistence of multiple prominent ventricular trabeculations and deep intertrabecular recesses. We report a case of a 30-year-old patient who was referred to our hospital due to familial history of cardiomyopathy. The patient underwent transthoracic echocardiography, cardiac catheterization and contrast ventriculography and cardiac magnetic resonance imaging. All imaging techniques showed the characteristic pattern of noncompaction together with two unusually large recesses in the inferior wall of myocardium. This unusual form of LVNC may have an impact on the clinical course of the disease and may require anticoagulation therapy.
Adult↗
Unfavourable endothelial and inflammatory state in erectile dysfunction patients with or without coronary artery disease.
AIMS: Erectile dysfunction (ED) confers an independent cardiovascular risk. We investigated the role of low-grade inflammation and endothelial dysfunction in ED patients with or without coronary artery disease (CAD). METHODS AND RESULTS: We evaluated 141 men (age 58.8 years) for ED and CAD through a rigourous investigation (including coronary angiography to reveal occult CAD). Blood levels of inflammatory (hsCRP, IL-6, IL-1beta, and TNF-alpha) and endothelial-prothrombotic markers/mediators (vWF, tPA, PAI-1, and fibrinogen) were significantly increased in ED patients and correlated negatively with sexual performance. ED was associated with higher levels of these substances (except for IL-6) on top of CAD alone. For most substances, the unfavourable impact of ED alone was not significantly different than the impact of CAD alone. In multivariable models, these markers/mediators predicted independently ED presence. In our population, the negative predictive value of the combination of fibrinogen <225 mg/dL with IL-6 <1.24 pg/mL for excluding ED was 91.7% (95% CI: 61.5-99.8). CONCLUSION: ED is associated with increased inflammatory and endothelial-prothrombotic activation in men with or without CAD. ED confers an incremental unfavourable impact on the circulating levels of these markers/mediators when combined with CAD. These findings have implications for increased cardiovascular risk in ED patients.
Biomarkers↗
Expert consensus document on arterial stiffness: methodological issues and clinical applications.
In recent years, great emphasis has been placed on the role of arterial stiffness in the development of cardiovascular diseases. Indeed, the assessment of arterial stiffness is increasingly used in the clinical assessment of patients. Although several papers have previously addressed the methodological issues concerning the various indices of arterial stiffness currently available, and their clinical applications, clinicians and researchers still report difficulties in selecting the most appropriate methodology for their specific use. This paper summarizes the proceedings of several meetings of the European Network for Non-invasive Investigation of Large Arteries and is aimed at providing an updated and practical overview of the most relevant methodological aspects and clinical applications in this area.
Adult↗
White blood cell count is a marker of wave reflections and arterial stiffness in healthy individuals.
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Adult↗
Effect of dark chocolate on arterial function in healthy individuals: cocoa instead of ambrosia?
Cocoa has been consumed for at least 2500 years, and for long time it has been regarded as a medicine. Arterial function is of paramount importance for the proper function and integrity of the cardiovascular system. Dark chocolate and flavonoid-rich cocoa have beneficial acute and short-term effects on endothelial function and wave reflections in normal individuals, in adults with cardiovascular risk factors, and in patients with coronary artery disease. Furthermore, dark chocolate and flavonoid-rich cocoa may have a blood pressure-lowering effect. These effects can be attributed to flavonoids and are mainly mediated through increased nitric oxide bioavailability. Further research is needed to demonstrate whether these effects of chocolate on arterial function are translated into clinical benefit.
Ambrosia↗
Acute thoracic aortic thrombosis after intra-aortic balloon pumping.
We present two transesophageal echocardiographic images of a patient with acute myocardial infarction, demonstrating a large thrombus attached to the thoracic aortic wall, considered to be a complication of intra-aortic balloon pumping. The patient had received the device because of hemodynamic instability due to an infarct-related ventricular septal defect. Clinical manifestations which led to the diagnosis of thromboembolism were abdominal pain and deterioration of renal function, without signs of limb ischemia.
Acute Disease↗
Acute effect of black and green tea on aortic stiffness and wave reflections.
OBJECTIVE: While most studies have shown an inverse relation between tea consumption and cardiovascular risk, other studies have shown opposite results. Aortic stiffness and wave reflections are markers of cardiovascular disease and prognosticators of cardiovascular risk. METHODS: The acute effect of black and green tea on aortic stiffness and wave reflections was assessed in 29 healthy volunteers in a randomized, single-blind, sham-procedure controlled, cross-over design. In the black tea sub-study, 16 subjects received 6 gm of tea, caffeine (175 mg), or hot water in 3 different sessions. In the green tea sub-study, 13 subjects received 6 gm of tea, caffeine (125 mg), or hot water. Carotid-femoral pulse wave velocity and wave reflection indices were measured at baseline and for 3 hours after consumption. RESULTS: Black tea increased pulse wave velocity during the first 90 min (increase by 0.49 m/sec, P < 0.05), showing a rapid return towards baseline values thereafter (P = 0.07 for the whole study period); in contrast, green tea had no effect. Both black and green tea increased augmentation index (by 5.0% and by 6.6%, P < 0.01 and P < 0.001, respectively) throughout the study. These changes were less than the respective changes produced by caffeine. Both black and green tea had a significant pressor effect. No change in oxidant status was found with both types of tea. CONCLUSIONS: Both black and green tea increases acutely wave reflections and only black tea increases aortic stiffness. Tea flavonoids may play a role in the attenuation of the effects of caffeine contained in tea.
Adult↗
Relationship between low-grade inflammation and arterial stiffness in patients with essential hypertension.
BACKGROUND: Arterial stiffness is an independent cardiovascular risk factor in hypertensive individuals. Inflammation is associated with increased arterial stiffness and is implicated in the pathogenesis of hypertension. OBJECTIVES: To examine whether low-grade inflammation contributes to arterial stiffness and wave reflections independently of blood pressure, in patients with essential hypertension and in controls. METHODS: We studied 235 consecutive patients with uncomplicated, never-treated essential hypertension and 103 sex- and age-matched controls. The level of inflammation was evaluated with high-sensitivity C-reactive protein (hsCRP) and serum amyloid A (SAA). Arterial stiffness was assessed with carotid-femoral (c-f) and carotid-radial (c-r) pulse wave velocity (PWV), and wave reflections with augmentation index (AIx). RESULTS: In the hypertensive group, in multiple regression analysis, both PWVc-f and PWVc-r were independently correlated with log hsCRP (beta = 0.56, P = 0.006 and beta = 0.45, P = 0.016, respectively), whereas no correlation was found between PWV and log SAA (P = NS). No significant correlation was observed between heart-rate-corrected AIx and log hsCRP (P = NS) and log SAA (P = 0.07) in the same group. Similarly, in the control group, an independent association was observed between PWVc-f and PWVc-r with log hsCRP (beta = 0.68, P = 0.05 and beta = 0.74, P = 0.05 respectively), but not with log SAA (P = NS). Furthermore, no significant association was shown between heart-rate-corrected AIx and log hsCRP or log SAA (P = NS) in the control group. CONCLUSIONS: In hypertensive individuals, hsCRP is related to PWV, a direct marker of arterial stiffness, but not to AIx, a measure of wave reflections. Whether inflammation might act as a pathogenetic or modulating factor in arterial stiffening in chronic hypertension has to be confirmed.
Adult↗
Nonlinear dynamics of blood pressure variability after caffeine consumption.
OBJECTIVES: The occurrence of continuous blood pressure (BP) fluctuations is an intrinsic feature of the cardiovascular system and is related to complex cardiovascular mechanisms and environmental stimulations or daily habits such as coffee drinking. The aim of this study was to investigate the effect of caffeine on indices expressing the complex and "chaotic" nonlinear characteristics of BP variability. DESIGN: Fourteen healthy subjects consumed 240 mg of caffeine or placebo according to a randomized, double-blind, crossover design. Continuous radial pressure waveforms were recorded by applanation tonometry at baseline and at 30, 60, 90 and 120 minutes after ingestion of caffeine or placebo. METHODS: Approximate entropy (ApEn) was determined to assess BP irregularity. Detrended fluctuation analysis was also used to quantify the fractal correlation properties of the BP data by estimating the scaling (self-similarity) exponent alpha. Analysis of variance for repeated measurements was used to detect significant changes in the measured variables at 30, 60, 90 and 120 minutes after ingestion of caffeine or placebo. RESULTS: BP fluctuations demonstrated high regularity and predictability as indicated by the low values of ApEn (0.2 +/- 0.3), and they remained unchanged after caffeine ingestion. In contrast, the long-term scaling exponent alpha of the BP time series was significantly increased from 0.99 to 1.04 (p=0.01) after caffeine ingestion, while the placebo induced no significant change. CONCLUSIONS: Caffeine induced greater "randomness" in BP fluctuations, possibly by triggering cardiovascular mechanisms that could not be directly specified but should be investigated in future studies.
Adult↗
Changes in aortic root function after valve replacement in patients with aortic stenosis.
BACKGROUND: Aortic elastic properties are compromised in various states that induce functional and histological changes in the aortic wall. Aortic stenosis is frequent and often requires replacement of the stenotic valve. The purpose of this study was to examine the effect of aortic valve replacement on the aortic root function. METHODS: 31 patients, mean+/-SD age 67.2+/-9.1 years with severe aortic stenosis, who underwent aortic valve replacement with a bileaflet mechanical prosthesis, were studied. Aortic root function indices such as aortic cross-sectional compliance (CSC), aortic root distensibility (ARD), and aortic stiffness index (ASI) were calculated with the use of M-mode echocardiography in three sessions: one preoperatively (pre-op), one on day 7 postoperatively (early post-op), and one 6 months postoperatively (late post-op). RESULTS: Aortic root function deteriorated early post-op (p<0.001 for all) and returned towards pre-op levels late post-op (p=NS for all). CSC changed from 2.84+/-1.98 to 1.37+/-0.92, and 2.30+/-1.11 cm2/mmHg, ARD from 2.21+/-5.60 to 1.01+/-0.67, and 1.79+/-0.96 cm2/dyne, and ASI from 9.72+/-5.60 to 24.65+/-19.10, and 11.51+/-7.85, respectively. Correlations were found between early changes in some aortic root indices and the degree of aortic stenosis, denoting that aortic function deteriorated less in more severe cases of aortic stenosis. None of the late changes were related to aortic valve or left ventricular indices. CONCLUSIONS: Aortic valve replacement with a mechanical valve results in a significant but transient impairment of aortic distensibility.
Aged↗
Effect of sildenafil on cardiac performance in patients with heart failure.
Sildenafil is rarely used in patients with heart failure despite a high prevalence of erectile dysfunction, and the theoretic possibility that by increasing nitric oxide availability, it may improve left ventricular (LV) load and performance. This study aimed to determine the peak effects of sildenafil on LV load and performance in patients with heart failure caused by systolic LV dysfunction. Twenty patients with controlled LV failure and ejection fractions <35% received sildenafil 50 mg or a matching placebo when not receiving regular medication for > or =12 hours, in a randomized, placebo-controlled, double-blind, 2-way crossover fashion. Cardiac output was measured by Doppler echocardiography. The aortic pressure waveform was determined using generalized transfer function from radial artery applanation tonometry. Aortic and femoral arterial stiffness was determined as carotid-femoral and femoral-pedal pulse-wave velocity (PWV); wave reflection was measured as an augmentation index (AIx). Cardiac index increased significantly (by 0.37 L/min.m(2), p <0.0001), with the peak effect 60 minutes after sildenafil administration. Compared with the baseline value, total systemic resistance showed a reduction of 479 dynes.s.cm(-5) (p <0.0001). Aortic and lower limb PWV decreased significantly (by 0.89 and 1.14 m/s, respectively, p <0.0001 for both), as did AIx (by 3.6% absolute, p <0.0001); these remained significant after adjustment for mean pressure and heart rate changes. In conclusion, sildenafil improves cardiac performance because of a decrease in LV load, which is caused by decreases in peripheral resistance, in aortic and large artery stiffness, and in wave reflection from peripheral sites. This can explain the increase in cardiac output and in exercise capacity with sildenafil in patients with heart failure.
Aged↗
Acute systemic inflammation increases arterial stiffness and decreases wave reflections in healthy individuals.
BACKGROUND: Aortic stiffness is a marker of cardiovascular disease and an independent predictor of cardiovascular risk. Although an association between inflammatory markers and increased arterial stiffness has been suggested, the causative relationship between inflammation and arterial stiffness has not been investigated. METHODS AND RESULTS: One hundred healthy individuals were studied according to a randomized, double-blind, sham procedure-controlled design. Each substudy consisted of 2 treatment arms, 1 with Salmonella typhi vaccination and 1 with sham vaccination. Vaccination produced a significant (P<0.01) increase in pulse wave velocity (at 8 hours by 0.43 m/s), denoting an increase in aortic stiffness. Wave reflections were reduced significantly (P<0.01) by vaccination (decrease in augmentation index of 5.0% at 8 hours and 2.5% at 32 hours) as a result of peripheral vasodilatation. These effects were associated with significant increases in inflammatory markers such as high-sensitivity C-reactive protein (P<0.001), high-sensitivity interleukin-6 (P<0.001), and matrix metalloproteinase-9 (P<0.01). With aspirin pretreatment (1200 mg PO), neither pulse wave velocity nor augmentation index changed significantly after vaccination (increase of 0.11 m/s and 0.4%, respectively; P=NS for both). CONCLUSIONS: This is the first study to show through a cause-and-effect relationship that acute systemic inflammation leads to deterioration of large-artery stiffness and to a decrease in wave reflections. These findings have important implications, given the importance of aortic stiffness for cardiovascular function and risk and the potential of therapeutic interventions with antiinflammatory properties.
Adult↗
Prevalence of asymptomatic coronary artery disease in men with vasculogenic erectile dysfunction: a prospective angiographic study.
OBJECTIVES: Erectile dysfunction (ED) shares common risk factors with coronary artery disease (CAD). It has been suggested that ED may be considered a clinical manifestation of a generalized vascular disease affecting also the penile arteries. The aim of this prospective study was to evaluate angiographically the incidence of asymptomatic CAD in men with ED of vascular origin. METHODS: Fifty consecutive asymptomatic men, aged 41-74 years, with non-psychogenic and non-hormonal ED were comprehensively evaluated using medical history and examination, exercise treadmill test and stress echocardiography. Patients who had positive one or both of the two non-invasive procedures were referred for coronary arteriography in order to document CAD and evaluate the severity of the disease. RESULTS: The mean time interval between the onset of ED and cardiological assessment was 25 months (range 1-66). Smoking (32 patients/64%), hypertension (31 patients/62%) and hyperlipidemia (26 patients/52%) were the most common risk factors. Moreover, 35 men (70%) had two or more risk factors. Twelve patients (24%) with ED had positive one or both of the two non-invasive procedures and one patient presented with acute myocardial infarction before he completed the non-invasive investigation. Coronary arteriography performed in ten patients (in nine with positive one or both of the two non-invasive procedures [while the other three refused], and in the patient with acute myocardial infarction) demonstrated that one patient had three-vessel disease, two patients had two-vessel disease and six patients had single-vessel disease. CONCLUSIONS: A considerable proportion (9/47 or 19%) of patients with ED of vascular origin has angiographically documented silent CAD. These findings support the strategy that patients with ED should undergo further cardiovascular evaluation.
Adult↗
Effect of dark chocolate on arterial function in healthy individuals.
BACKGROUND: Epidemiologic studies suggest that high flavonoid intake confers a benefit on cardiovascular outcome. Endothelial function, arterial stiffness, and wave reflections are important determinants of cardiovascular performance and are predictors of cardiovascular risk. METHODS: The effect of flavonoid-rich dark chocolate (100 g) on endothelial function, aortic stiffness, wave reflections, and oxidant status were studied for 3 h in 17 young healthy volunteers according to a randomized, single-blind, sham procedure-controlled, cross-over protocol. Flow-mediated dilation (FMD) of the brachial artery, aortic augmentation index (AIx), and carotid-femoral pulse wave velocity (PWV) were used as measures of endothelial function, wave reflections, and aortic stiffness, respectively. Plasma oxidant status was evaluated with measurement of plasma malondialdehyde (MDA) and total antioxidant capacity (TAC). RESULTS: Chocolate led to a significant increase in resting and hyperemic brachial artery diameter throughout the study (maximum increase by 0.15 mm and 0.18 mm, respectively, P < .001 for both). The FMD increased significantly at 60 min (absolute increase 1.43%, P < .05). The AIx was significantly decreased with chocolate throughout the study (maximum absolute decrease 7.8%, P < .001), indicating a decrease in wave reflections, whereas PWV did not change to a significant extent. Plasma MDA and TAC did not change after chocolate, indicating no alterations in plasma oxidant status. CONCLUSIONS: Our study shows for the first time that consumption of dark chocolate acutely decreases wave reflections, that it does not affect aortic stiffness, and that it may exert a beneficial effect on endothelial function in healthy adults. Chocolate consumption may exert a protective effect on the cardiovascular system; further studies are warranted to assess any long-term effects.
Adult↗
Effects of atorvastatin on reactive hyperemia and inflammatory process in patients with congestive heart failure.
Purpose of the study was to investigate whether short-term atorvastatin treatment improves endothelial function and affects inflammatory process in patients with heart failure (HF) and normal cholesterol levels. HF is characterized by endothelial dysfunction and increased inflammatory process, while statins restore endothelial function having also anti-inflammatory effects in hypercholesterolemic patients. We investigated the effect of 4-week atorvastatin treatment (10 mg/day) on endothelial function and inflammatory markers in patients with HF and cholesterol levels <220 mg/dl. Patients were randomly allocated into groups and received atorvastatin (n=19) or no statin (n=19). Forearm blood flow was measured using gauge-strain plethysmography. Serum levels of tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), and soluble vascular cell adhesion molecule (sVCAM-1) were determined with ELISA. Data are expressed as median [25th-75th percentile]. Forearm vasodilatory response to reactive hyperemia was significantly improved in atorvastatin-treated patients (from 38.1% [32.0-59.1] to 70.0% [61.1-106.3], P<0.01), while it remained unaffected in the control group. Levels of IL-6, TNF-alpha and sVCAM-1 were decreased in atorvastatin-treated group (from 7.8 pg/ml [4.8-9.5], 3.2 pg/ml [2.7-4.8] and 595 ng/ml [440-810] to 5.6 pg/ml [2.5-9.0], 2.8 pg/ml [2.0-3.6] and 289 ng/ml [169-368], respectively, P<0.05 for all) but not in the control group. These findings indicate that atorvastatin may improve forearm vasodilatory response to reactive hyperemia and depress inflammatory process in patients with heart failure and normal baseline cholesterol levels.
Aged↗
Chronic coffee consumption has a detrimental effect on aortic stiffness and wave reflections.
BACKGROUND: The effect of coffee consumption on the cardiovascular system is still an unresolved issue. Aortic stiffness and wave reflections are important prognosticators of cardiovascular disease risk. We have shown that caffeine acutely increases aortic stiffness and wave reflections. OBJECTIVE: The objective was to investigate the effect of chronic coffee consumption on aortic stiffness and wave reflections. DESIGN: This was a cross-sectional study of 228 healthy subjects: 141 men (x +/- SD: 41 +/- 8 y old) and 87 women (41 +/- 9 y old). Aortic stiffness was evaluated with carotid-femoral pulse wave velocity (PWV). Wave reflections were evaluated with augmentation index (AIx) and augmented pressure (AP) of the aortic pressure waveform with the use of high-fidelity pulse wave analysis. Coffee consumption was ascertained over 1 y with a food-frequency questionnaire. RESULTS: A linear relation between coffee consumption and PWV, AIx, and AP was observed (P for trend < 0.05). Compared with the nonconsumption group, PWV was on average 13% higher, AIx was 2-fold higher, and AP was 2.4-fold higher (P < 0.01 for all) in the high-consumption group (>450 mL/d). The findings remained significant after control for confounders such as age, sex, smoking habits, body mass index, total and LDL cholesterol, triacylglycerols, blood glucose, mean blood pressure, and heart rate. The linear relation (P for trend < 0.05) observed between coffee consumption and arterial pressures was largely explained when the covariates were entered in the model. CONCLUSIONS: Chronic coffee consumption exerts a detrimental effect on aortic stiffness and wave reflections, which may increase the risk of cardiovascular disease.
Adult↗
Benefits from angiotensin-converting enzyme inhibitor 'beyond blood pressure lowering': beyond blood pressure or beyond the brachial artery?
OBJECTIVE: The substantial benefits of ramipril over conventional therapy in high-risk patients are not always associated with clinically significant differences in brachial arterial pressure, and largely remain unexplained. We undertook this acute study to establish the magnitude of and reason for different acute effects of ramipril and atenolol on arterial pressure. METHODS: We enrolled 30 patients, who took 10 mg ramipril, 100 mg atenolol, and placebo at intervals of > or = 7 days, in a randomized, double-blind, placebo-controlled trial. After baseline, measurements were taken at 30-60 min intervals for 5 h, and comprised cuff brachial pressure, radial artery tonometry with generation of central aortic pressure, and pulse wave velocity for aorta, upper limb and lower limb arteries. RESULTS: Both ramipril and atenolol reduced arterial pressure, and the diastolic pressure fall was similar in the aorta and brachial artery, but the systolic pressure fall for ramipril was greater than for atenolol (by 5.2 mmHg, P < 0.0001) in the aorta compared with the brachial artery. The aortic systolic pressure difference with ramipril in comparison with atenolol was accompanied by an absolute difference of 10.7% (P < 0.0001) in the augmentation index, denoting a reduction in peripheral wave reflection by ramipril. The aortic pulse wave velocity fell to a similar degree with ramipril in comparison with atenolol, but fell to a greater degree (1.35 and 0.44 m/s, respectively, P < 0.0001 for both) in muscular arteries of the lower and upper limbs. CONCLUSION: A greater (average, 5.2 mmHg) decrease in aortic systolic pressure caused by ramipril may explain the greater benefit of ramipril over atenolol. The difference is attributable to decreased stiffness of peripheral arteries and a reduction in wave reflection.
Aged↗