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Air pollution is a well-described environmental factor with evidence suggesting a firm association with cardiovascular diseases. The purpose of this study was to determine the association of exposure to gaseous air pollutants on atherosclerosis burden.1955 inhabitants of the Corinthia region, aged 40 years or older, underwent clinical and biochemical assessment as well as carotid ultrasonography to evaluate carotid intima-media thickness (cIMT) and plaque burden. Analyzers recording time series concentration of CO, NOA higher concentration of CO, NO2, and SO2 was observed in Region 4 compared to the other regions. Mean cIMT (Region 1: 0.93 ± 0.24 mm; Region 2: 0.96 ± 0.40 mm; Region 3: 0.94 ± 0.39 mm; Region 4: 1.14 ± 0.55 mm, p 0.001), maximum cIMT (p 0.001) as well as carotid plaque burden (Region 1: 13.3%; Region 2: 18.8%; Region 3: 22.4%; Region 4: 38.6%, p 0.001) were significantly higher in individuals of Region 4. Inhabitants of Region 4 had also higher levels of C reactive protein (Region 1: 4.56 ± 4.85 mg/l; Region 2: 3.49 ± 4.46 mg/l; Region 3: 4.03 ± 3.32 mg/l, Region 4: 5.16 ± 8.26 mg/l, p 0.001). Propensity score analysis revealed higher inter-area differences in mean cIMT of individuals with coronary artery disease (CAD) (high vs low air pollution area: 1.56 ± 0.80 mm; vs. 1.18 ± 0.54 mm, p 0.001) while there was no difference in cIMT of the matched population without CAD (p = 0.52).An increased carotid atherosclerotic and inflammatory burden is observed in inhabitants of areas with the highest concentration of air pollutants.

Introduction Acute exercise and exercise training may confer epigenetic modifications in healthy subjects. Epigenetic effects after exercise have been showed in patients with cardiovascular disease. The aim of this systematic review was to summarize the evidence from available clinical trials that study epigenetic adaptations after exercise in patients with cardiovascular disease. Methods The search strategy was performed in PubMed and CENTRAL databases on articles published until September 2020. Studies with titles and abstracts relevant to exercise epigenetic modification applied to cardiovascular patients were fully examined. Inclusion and exclusion criteria were utilized for studies screening. Quality assessment with PEDro scale and evaluation by two independent reviewers was performed. Results Of the 1714 articles retrieved, 88 articles were assessed for eligibility criteria and 8 articles matched our search criteria and finally included in the systematic analysis. The acute exercise epigenetic (miRNAs) effects were assessed in three studies and the chronic exercise training effects (miRNAs and DNA methylation) in six studies. The results have shown that there is possibly an acute significant exercise effect on epigenetic targets which is more evident after chronic exercise training. Conclusions By the present systematic review, we provide preliminary evidence of beneficial epigenetic adaptations following acute and chronic exercise in patients with cardiovascular disease. More controlled studies are needed to confirm such evidence.

'Cover index' has been proposed to appraise the congruence between the aortic annulus and the device, with the assumption of not taking into account the actual device implantation depth. The aim of this study was to investigate whether the annulus-prosthesis mismatch, as expressed with the new proposed 'true cover index' according to actual implantation depth, can predict aortic regurgitation (AR) after transcatheter aortic valve implantation (TAVI).Patients who had undergone TAVI with the self-expandable CoreValve device, were retrospectively studied. All available prosthesis sizes were ex-vivo scanned and the precise diameter at 0.3mm intervals along each device was measured. The 'true cover index' was evaluated, as a ratio of the following: 100×([prosthesis actual diameter at implantation depth-annulus diameter]/prosthesis actual diameter at implantation depth). AR was echocardiographically evaluated at discharge and 30days and classified as prominent if moderate, or trivial if none or mild.Overall, 120 patients who had undergone TAVI, were considered eligible for the study. 'True cover index' was statistically significantly lower among patients with prominent AR in comparison with trivial AR at discharge (5.7±4.8mm vs 9±5.1, p=0.025), as well as at one month post-TAVI (5.4±5.1mm vs 9.0±5.1, p=0.023), indicating increased AR for smaller index. After adjustment for severe annulus calcification, impaired baseline LVEF and previous valvuloplasty, it remained an independent predictor of one month prominent AR (OR: 0.854, CI: 0.730-0.999; p=0.048). 'True cover index' of4.3 was shown to predict one-month prominent AR with sensitivity =75% and specificity =82.5%.'True cover index' is strongly and independently correlated with the short and mid-term AR after CoreValve implantation.

Background We investigated the effectiveness of perconditioning (Perc) applied at different time points along with the role of RISK, SAFE, STAT5 and eNOS pathways. Methods and results Anesthetized rabbits were subjected to 30-min ischemia/3-hour reperfusion. Perc, consisted of 4cycles of 1-min ischemia/reperfusion, was applied in the carotid artery at different time points. Perc was started and ended during ischemia, started during ischemia and ended at the beginning of reperfusion, started at the end of ischemia and ended at reperfusion and started and ended during reperfusion. The PI3K inhibitor wortmannin, or the JAK-2 inhibitor AG490, was also applied and the infarct size was assessed. In another series assigned to the previous groups, the phosphorylation of Akt, PI3K, ERKs1/2, GSK3β, STAT3, and STAT5 was evaluated. All Perc groups had smaller infarction compared to those without Perc, independently of PI3K or JAK-2 inhibition. STAT5 was the only molecule that was phosphorylated in parallel with cardioprotection. Since Src and angiotensin II mediate the STAT5 pathway, we administered the Scr inhibitor PP1 and the angiotensin II receptor antagonist valsartan. PP1 and valsartan prevented STAT5 phosphorylation, but did not abrogate the effect of Perc. Furthermore, the NOS inhibitor L-NAME was administered and abrogated the infarct size limiting effect of Perc. In parallel, the expression of cleaved caspase-3 was elevated only in the control and Perc-A-L-NAME groups. Conclusion Perc reduces infarction independently of RISK, SAFE and STAT5 pathways. Src kinase and angiotensin II play a predominant role in STAT5 activation. eNOS may protect the myocardium through inhibition of apoptosis.

Background Surrogates of aortic wave reflection and arterial stiffness, such as augmentation index (AIx), augmentation pressure, pulse wave velocity (PWV) and pulse pressure amplification (PPampl) are independent predictors of cardiovascular risk. A novel ambulatory, brachial cuff-based oscillometric device has been recently developed and validated, yielding 24-h assessment of the aforementioned parameters (Mobilo-O-Graph). Aim of this study was to investigate the feasibility and reproducibility of wave reflection and arterial stiffness estimation by pulse wave analysis using this device. Methods Thirty treated or untreated hypertensives (mean age: 53.6±11.6years, 17 men) had test–retest 24-h monitoring one week apart using the test device. Results Mean numbers of valid aortic readings per subject, between test and retest, were comparable. Approximately 12 aortic readings per subject (17%) were not feasible or valid. No differences were observed for any 24-h parameter between the two assessments. Bland–Altman plots showed no systemic difference, while the limits of agreement for each parameter indicated high reproducibility (AIx: −7.2 to 8.2%, AP: −3.7 to 4.1mm Hg, PWV: −0.39 to 0.41m/s, PPampl: −0.08 to 0.06). This was further verified by intraclass correlation coefficients which were >0.8 for each parameter. Conclusions Non-invasive 24-h estimation of wave reflection and arterial stiffness indices, derived by the test device, appear to be highly reproducible. Future studies should investigate whether these measurements have additive prognostic value for cardiovascular risk stratification, beyond common brachial blood pressure measurements or single estimations of wave reflection and PWV at office settings.

Objectives We sought to investigate the differences of pressure waveforms at a distal point of an epicardial coronary artery comparatively to the ostium and to assess the effect of microcirculatory vasodilation on them. Background Pressure waveforms in the systematic circulation and their alterations along the aorta due to wave reflections from the periphery have been extensively studied. However, similar data regarding intracoronary pressure waveforms and the effects of coronary microcirculation on them are limited. Methods In 18 patients who underwent diagnostic coronary angiogram or percutaneous coronary intervention in the left circumflex or the right coronary artery, we studied pressure waveforms recorded by a high-fidelity pressure wire, which was advanced to the ostium and to a distal site of the free of significant lesions left anterior descending coronary artery. Pressure recording was performed both at rest and at hyperemia induced by intravenous infusion of adenosine. Analysis of pressure waveforms at the frequency domain was performed with Fast Fourier Transform. Results At baseline conditions, distal pressure waveforms were characterized by higher pulsatility, higher presystolic wave and higher amplitude of the 11th to the 15th harmonics. Hyperemia increased the pulsatility, compressed the notch and decreased the amplitude of higher than the 10th harmonics of distal waveforms. Conclusions This study identifies differences of pressure waveforms between proximal and distal sites of free of significant lesions coronary arteries, which are affected by the status of coronary microcirculation and may therefore facilitate assessment of microvascular disease.

Despite medical and technical advancements stent thrombosis continued to poses a significant risk in patients after drug eluting stent (DES) implantation and clopidogrel resistance has been recognized as an important determinant of this risk. Novel antiplatelets such as prasugrel and ticagrelor can be used in cases of clopidogrel resistance however bleeding complications remain the Achilles' heel of antiplatelet therapy. Several genetic polymorphisms affect the clopidogrel absorption and bio-activation in the active form of the drug. CYP2C19 is responsible for most of the clopidogrel bio-transformation and loss of function as well as, gain of function polymorphisms of this enzyme has been recognized. Early studies have linked CYP2C19 genetic polymorphisms with clinical events, although, these findings were not confirmed by later studies. However, when the estimated thrombotic risk is high a combination of genetic information and functional platelet tests should be essential for clinicians to access clopidogrel effectiveness and to recommend alternative antiplatelet management.

Background The safe use of selective inhibitors of cyclooxygenase-2 in patients with cardiovascular disease has been questioned because of studies showing an increased risk of cardiac events. We examined the short-term effect of rofecoxib, a selective cyclooxygenase-2 inhibitor, on endothelial function, oxidative damage and inflammation in patients with acute coronary syndromes without ST-segment elevation. Methods Forty-three patients with acute coronary syndromes without ST-segment elevation participated in the study. Flow-mediated dilatation (FMD), nitrate-mediated dilatation (NMD) of the brachial artery, malondialdehyde, a marker of lipid peroxidation, C-reactive protein, an acute phase marker of inflammation, and interleukin-6, a proinflammatory cytokine, were measured within 24 h of admission and a week later. Patients were randomized to receive for a week 100 mg aspirin daily with either 25 mg of rofecoxib ( n =21) or placebo ( n =22) orally once daily. Results Malondialdehyde, C-reactive protein and interleukin-6 levels were reduced in the rofecoxib group ( p =0.04, p =0.003 and p =0.02 respectively) while they remained unchanged in the placebo group after 1 week of treatment. FMD and NMD changes in both groups were not statistically different. Conclusions Co-administration of rofecoxib with low-dose aspirin decreases inflammatory and oxidative indices but does not improve endothelial function. The lack of improvement in FMD despite the improvement in inflammation and oxidative stress could be viewed in association to the recent observations on the adverse effects of COX-2 inhibition on the cardiovascular system.

Mechanical characteristics of circulation and vasculature, such as blood flow in combination with geometrical features, participate in the generation of several pathophysiological processes, such as development of blood vessel structure, chronic vessel tone regulation, atherosclerosis and others. We aim to briefly describe the basic mechanical and haemodynamic phenomena related to the forces applied to arterial walls, especially shear stresses and the shear-induced physiologic and pathophysiologic processes focusing on those related to atherosclerotic disease.

Aortic pressure waveforms are calculated non-invasively by applying generalized transfer functions (GTF) to tonometric radial pressure waveforms. Input errors mainly during acquisition and calibration of tonometric pressures are "transferred" to aortic pressure calculation. The present study aimed to quantify the proportion of specific input errors which is "transferred" by the GTFs in a wide range of hemodynamic conditions and for different error combinations in brachial systolic (SBP) and diastolic (DBP) blood pressure measurements.Aortic pulse wave analysis was performed in 103 subjects (52 normotensive and 51 untreated hypertensive) by the SphygmoCor System. Each pressure waveform was initially calibrated by sphygmomanometrical brachial pressures. Isolated, parallel and reverse errors in brachial SBP/DBP from -10 to +10 mmHg were simulated, by recalibration of the recorded radial pressure waveforms, inducing specific "errors" of GTF-input values. For every recalculated aortic SBP and DBP, the difference from the initial estimated value was considered to represent the "transferred error" to the aortic pressure estimation.Parallel errors by +/-5 mmHg in both SBP and DBP resulted to an identical change in GTF-derived aortic pressures, as expected. When an overestimation in SBP by 5 mmHg and an underestimation in DBP by -5 mmHg occurred (reverse errors), almost 56% of this error (approximately 2.8 mmHg) was transferred. An isolated error in brachial SBP by +/-5 mmHg was transmitted by 76% ( approximately 3.8 mmHg) to GTF-derived aortic SBP. In subjects with mean blood pressure117 mmHg or with heart rates74 bpm, a greater percent of the calibration error was transferred to GTF-derived blood pressures.Input errors in brachial pressure values result in a quantifiable effect on transfer function output (aortic pressures). The percent of the "error transfer" by the GTFs depends on heart rate and BP levels, which should be taken into account when applying GTFs at populations with different hemodynamic conditions.

Background The association between hypothyroidism and increased vascular resistance, arterial wall thickening and endothelial dysfunction is well recognized. The aim of the present study was to examine if hypothyroid subjects have increased arterial stiffness, a risk factor for cardiovascular morbidity and mortality. Methods Sixty-five subjects (59 females and 6 males) with normal thyroid function or hypothyroidism of varying degree were investigated by radial artery applanation tonometry and pulse wave analysis, for evaluation of arterial stiffness. Results Serum TSH values were positively correlated with central systolic blood pressure ( r =0.258, p =0.037), central pulse pressure ( r =0.316, p =0.010), augmentation pressure ( r =0.299, p =0.015) and negatively with reflection time index (RTI), which indicates the pressure wave velocity ( r =−0.311, p =0.012). Hypothyroid patients presented higher central systolic pressure and pulse pressure, higher augmentation pressure and lower RTI, indicating increased arterial stiffness in these subjects. RTI was independently related to age, central systolic pressure and TSH. Mild changes of arterial stiffness were observed even in subjects with TSH range 2.01–4.0 μU/ml suggesting that this group may have an early stage of mild thyroid failure. Conclusions Hypothyroidism, even in the subclinical stage, is associated with changes in arterial stiffness. The observed abnormalities in arterial stiffness may have detrimental effects on left ventricular function and coronary perfusion in hypothyroid subjects.

Background Arterial stiffness is a risk factor for cardiovascular morbidity and mortality and appears to be increased in arterial hypertension. The purpose of the present study was to relate systemic arterial stiffness assessed by pulse wave analysis to variables of 24-h ambulatory blood pressure monitoring (ABPM) in patients with essential hypertension. Methods Seventy-two subjects with untreated mild to moderate arterial hypertension underwent evaluation with 24-h ambulatory blood pressure monitoring. In the same subjects, applanation tonometry and pulse wave analysis was performed for evaluation of systemic arterial stiffness expressed as augmentation index and estimated aortic pulse wave velocity. Results Clinic systolic blood pressure, mean heart rate during 24-h blood pressure monitoring and height were independent predictors of augmentation index and estimated aortic pulse wave velocity. The 41 patients with blunted reduction in nighttime blood pressure (nondippers) showed higher mean systolic blood pressure ( p =0.02), lower systolic and diastolic blood pressure variability ( p p =0.05) and higher estimated aortic pulse wave velocity ( p =0.03), indicating stiffer arteries in this group. Conclusions These results suggest that blood pressure change from day- to nighttime is an important determinant of arterial stiffness assessed by pulse wave analysis; this association could contribute to the higher cardiovascular risk in nondippers.

Background Oxidative stress contributes to endothelial dysfunction, an important step to the pathogenesis of atherosclerosis and coronary events. Latest studies revealed the existence of pleiotropic and especially antioxidant properties of statins. We sought to examine the effects of pravastatin on lipid peroxidation and endothelial function, independently from lipid-lowering, in patients with unstable angina (UA). Methods Thirty-seven patients (males), 64.46±9.09 years, suffering from UA enrolled in the study. Patients were not on statin medication before admission and they received after randomization either 40 mg pravastatin daily (group A, n =20), or placebo (group B, n =17). Malondialdehyde (MDA) concentration, an index of lipid peroxidation and plaque instability, flow-mediated dilatation (FMD) of the brachial artery and blood lipids were measured on the second day of hospitalization and 10 days later. Results MDA decreased significantly in both groups (A, p =0.008; B, p =0.003). FMD increased significantly in group A ( p =0.007), whereas in group B it did not change. Serum lipids remained unaltered in all three groups. Conclusions Pravastatin administration improved FMD within 10 days and this favorable effect occurred before any significant reduction in blood lipids, revealing its pleiotropic effects during the early phase of an acute coronary syndrome. Circulating lipid peroxidation products in patients with UA decreased significantly during the same period independently of endothelial function and pravastatin therapy.

Background: Data concerning blood pressure changes, acutely induced by caffeine consumption, are conflicting. Furthermore, limited data exist regarding central hemodynamic response to caffeine ingestion by healthy young subjects. We investigated the acute effect of coffee (80 mg of caffeine) and decaffeinated coffee on peripheral and central hemodynamics, as well as on wave reflections. Subjects: For this purpose, 16 healthy volunteers (eight females and eight males, mean age 29±3.2 years) were investigated. Methods: Repeated measurements were performed at baseline and 30, 60, 90 and 120 min after oral administration of each beverage in a double-blind crossover design. Aortic blood pressures, augmentation index (AI) and pressure (AP) and timing of reflected waves were evaluated by using applanation tonometry and pulse wave analysis. Results: Regular coffee increased central systolic (SBP) and diastolic pressure (DBP) from 96.2±9.9 to 101.1±10.1 mmHg, p =0.011 and from 72.6±9.4 to 76.5±9.0 mmHg, p =0.027, respectively, but no change was observed following consumption of decaffeinated coffee. Peripheral systolic blood pressure did not change significantly after the administration of either coffee. Augmentation index increased significantly following regular coffee consumption. The change in AI was significantly higher following regular compared to decaffeinated coffee consumption as shown by analysis of variance (ANOVA) for repeated measures ( p =0.001). Conclusions: These caffeine effects reveal an unfavourable effect on wave reflections and therefore on left ventricular (LV) pulsatile afterload. It also revealed a significant acute effect of caffeine consumption on central hemodynamics which is not observed at peripheral pressures.

Background: l -Arginine is a nitric oxide precursor, which augments endothelium-dependent vasodilatation in hypercholesterolemic humans and animals. Endothelium-dependent vasodilation is attenuated in patients with hypertension; however the effects of oral l -arginine on endothelial function of the conduit arteries in patients with essential hypertension have not previously been investigated. Methods: In a prospective randomized double blind trial, 35 patients with essential hypertension received either 6 g l -arginine (18 subjects) or placebo (17 subjects). Patients were examined for flow-mediated endothelium-dependent dilatation of the brachial artery before and 1.5 h after administration of l -arginine or placebo. At the end of the protocol the nitrate-induced, endothelium-independent vasodilatation was evaluated. Results: Two groups of l -arginine and placebo were similar regarding age, sex, blood lipids, smoking, diabetes, coronary artery disease, body mass index, intima-media thickness of the common carotid artery, clinics blood pressure and baseline brachial artery parameters. Administration of l -arginine or placebo did not change significantly heart rate, blood pressure, baseline diameter, blood flow or reactive hyperemia. l -Arginine resulted in a significant improvement of flow-mediated dilatation (1.7±3.4 vs. 5.9±5.4%, P=0.008) while placebo did not significantly change this parameter (3.0±2.7 vs. 3.1±2.2%, P=ns). The effect of l -arginine on flow-mediated dilatation was significantly different from the effect of placebo (P=0.05). l -Arginine did not significantly influence nitrate-induced dilatation (16±6.9 vs. 17.7±6.7%, P=ns). Conclusions: Oral administration of l -arginine acutely improves endothelium-dependent, flow-mediated dilatation of the brachial artery in patients with essential hypertension. The long-term effects of l -arginine in these patients require further investigation.

The elevation of blood pressure levels has been recognised as a determinant of the risk for several common cardiovascular diseases. In this work we examined the effect of Mediterranean type of diet on coronary risk in subjects with hypertension.CARDIO2000 consisted of 848 randomly selected hospitalised patients (695 males, 58 +/- 10 years old; 153 females, 65 +/- 9 years old) for first event of coronary heart disease (CHD) and 1078 paired, by sex-age, hospitalised controls without CHD. The adoption of the Mediterranean diet was assessed through a validated questionnaire developed by the National School of Public Health.418 (49%) of the patients and 303 (28%) of the controls were hypertensive. Of them 21 (5%) patients and 36 (12%) controls were unaware of their condition, 94 (22%) and 34 (11%) were untreated, 148 (35%) and 111 (36%) were uncontrolled and 155 (38%) and 122 (41%) were controlled (P0.01). One hundred and sixty-two (19%) of the patients and 265 (25%) of the controls (P0.01) adopted the Mediterranean type of diet. Our results suggest that the adoption of Mediterranean diet reduces the risk of developing acute coronary syndromes by 17% (odds ratio=0.83, 95% CI 0.73--0.88, P0.01) in controlled hypertensive subjects, by 8% (odds ratio=0.92, 95% CI 0.87-0.95, P0.05) in unaware, by 7% (odds ratio=0.93, 95% CI 0.88-0.95, P0.05) in acknowledged but uncontrolled and by 20% (odds ratio=0.80, 95% CI 0.71-0.89, P0.01) in normotensive subjects.According to our findings the adoption of the Mediterranean diet is associated with the reduction of coronary risk in hypertensive subjects.