The Impact of Omega 3 Fatty Acids in Atherosclerosis and Arterial Stiffness: An Overview of their Actions.

BACKGROUND: Fatty acids are common dietary nutrients particularly in economically developed countries. Research has revealed that omega-3fatty acids exert beneficial effects in the progression of atherosclerosis and cardiovascular disease. Moreover, eicosapentaenoic acid and docosahexaenoic acid possess a number of biological actions which improve cardio-metabolic health. Omega-3 fatty acids display remarkable anti-oxidant, anti-inflammatory, anti-thrombotic and anti-arrhythmogenic actions. Furthermore, they improve the levels of triglycerides, glucose metabolism and endothelial function. METHODS: The aim of this review article is to present physical, biochemical and biological properties of omega-3 fatty acids and summarize the most important mechanisms of action on arterial wall properties and arterial stiffness in atherosclerosis. RESULTS: Omega-3 fatty acids may prevent the progression of atherosclerosis. Endothelial dysfunction and arterial stiffness can be regulated by the supplementation of omega-3 fatty acids. CONCLUSION: The mechanisms of action of omega-3 fatty acids on cardiovascular health and arterial stiffening have been established. However, further research is needed in order to translate the conflicting results among the studies and improve the therapeutic options of cardiovascular disease.

Programmed ventricular stimulation predicts arrhythmic events and survival in hypertrophic cardiomyopathy.

BACKGROUND: Sudden cardiac death (SCD) risk stratification in hypertrophic cardiomyopathy (HCM) in the context of primary prevention remains suboptimal. The purpose of this study was to examine the additional contribution of programmed ventricular stimulation (PVS) on established risk assessment. METHODS: Two-hundred-and-three consecutive patients with diagnosed HCM and ≥1 noninvasive risk factors were prospectively enrolled over 19years. Patients were risk stratified, submitted to PVS and received an implantable cardioverter-defibrillator (ICD) according to then-current American Heart Association (AHA) guidelines and inducibility. Participants were prospectively followed-up for primary endpoint occurrence (appropriate ICD therapy or SCD). Contemporary (2015) AHA and European Society of Cardiology (ESC) guidelines were retrospectively assessed. RESULTS: During a median follow-up period of 60months the primary endpoint occurred in 20 patients, 19 of whom were inducible and received an ICD. Overall, 79 patients (38.9%) were inducible and 92 patients (45.3%) received an ICD (PVS sensitivity=95%, specificity=67.2%, positive predictive value=24%, negative predictive value=99.2%). AHA and ESC guidelines application misclassified 3 and 9 primary endpoint-meeting patients, respectively. Inducibility was the most important determinant of event-free survival in multivariate Cox regression (hazard ratio=33.3). A combined approach of ESC score≥6% or AHA indication for ICD with PVS inducibility yielded absolute sensitivity and negative predictive value, the former at a more cost-effective and specific way. CONCLUSIONS: Inducibility at PVS predicts SCD or appropriate device therapy in HCM. Non-inducibility is associated with prolonged event-free survival, while the procedure was proven safe. Reintegration of PVS into established risk stratification models in HCM may improve patient assessment.

J-shaped relationship between habitual coffee consumption and 10-year (2002-2012) cardiovascular disease incidence: the ATTICA study.

PURPOSE: The purpose of this work was to evaluate the association between coffee consumption and 10-year cardiovascular disease (CVD) incidence in the ATTICA study, and whether this is modified by the presence or absence of metabolic syndrome (MetS) at baseline. METHODS: During 2001-2002, 3042 healthy adults (1514 men and 1528 women) living in the greater area of Athens were voluntarily recruited to the ATTICA study. In 2011-2012, the 10-year follow-up was performed in 2583 participants (15% of the participants were lost to follow-up). Coffee consumption was assessed by a validated food-frequency questionnaire at baseline (abstention, low, moderate, heavy). Incidence of fatal or non-fatal CVD event was recorded using WHO-ICD-10 criteria and MetS was defined by the National Cholesterol Education Program Adult Treatment panel III (revised) criteria. RESULTS: Overall, after controlling for potential CVD risk factors, the multivariate analysis revealed a J-shaped association between daily coffee drinking and the risk for a first CVD event in a 10-year period. Particularly, the odds ratio for low (<150 ml/day), moderate (150-250 ml/day) and heavy coffee consumption (>250 ml/day), compared to abstention, were 0.44 (95% CI 0.29-0.68), 0.49 (95% CI 0.27-0.92) and 2.48 (95% CI 1.56-1.93), respectively. This inverse association was also verified among participants without MetS at baseline, but not among participants with the MetS. CONCLUSIONS: These data support the protective effect of drinking moderate quantities of coffee (equivalent to approximately 1-2 cups daily) against CVD incidents. This protective effect was only significant for participants without MetS at baseline.

The impact of dietary flavonoid supplementation on smoking-induced inflammatory process and fibrinolytic impairment.

BACKGROUND AND AIMS: Smoking is associated with increased inflammatory process and impairment of fibrinolytic status. Concord grape juice (CGJ), a rich source of flavonoids, can modify cardiovascular risk factors. We aimed to evaluate the impact of CGJ on smoking-induced impairment of inflammatory and fibrinolytic status in healthy smokers. METHODS: We studied the effect of a 2-week oral treatment with CGJ in 26 healthy smokers on three occasions (day 0: baseline, day 7 and day 14) in a randomized, placebo-controlled, double-blind, cross-over design. Measurements were carried out before (pSm) and 20 min after (Sm20) cigarette smoking. Serum levels of intercellular adhesion molecule-1 (sICAM-1) and plasminogen activator inhibitor 1 (PAI-1) were measured as markers of inflammatory and fibrinolytic status, respectively. RESULTS: Treatment with CGJ reduced pSm sICAM-1 levels (p < 0.001), while placebo had no impact on ICAM-1 levels (p = 0.31). Moreover, treatment with CGJ decreased pSm values of PAI-1 (p < 0.001) while placebo had no impact on PAI-1 levels (p = 0.89). Smoking induced an elevation in PAI-1 levels after smoking compared to pro-smoking levels in all study days and in both arms (CGJ and placebo) of the study (p < 0.001 for all). Interestingly, CGJ compared to placebo, attenuated the acute smoking increase in sICAM-1 and PAI-1 levels (p < 0.001 and p = 0.005 respectively). CONCLUSIONS: CGJ consumption improved inflammatory and fibrinolytic status in healthy smokers and attenuated acute smoking induced increase in ICAM-1 and PAI-1 levels. These findings shed further light on the favorable effects of flavonoids in cardiovascular health.

Short term omega-3 polyunsaturated fatty acid supplementation induces favorable changes in right ventricle function and diastolic filling pressure in patients with chronic heart failure; A randomized clinical trial.

INTRODUCTION: Omega-3 polyunsaturated fatty acids (omega 3-PUFAs) seem to favorably affect cardiac hemodynamics and may benefit the clinical course of heart failure patients. The role of omega 3-PUFAs supplementation on the left and right ventricular function of patients with chronic compensated systolic heart failure, under optimal treatment, was studied. METHODS: 205 consecutive patients with chronic compensated heart failure, due to ischemic (IHF) or dilated cardiomyopathy (DCM)-NYHA classification I-III, under optimal medical treatment, were enrolled. Participants were 1-to-1 randomized on 1000 mg omega 3-PUFA supplementation or no supplementation, in a non-blinded fashion. Echocardiographic assessment was performed at first visit and 6 months after. Plasma BNP and serum creatinine levels were also measured. RESULTS: As compared with the control group, BNP levels in omega 3-PUFA intervention group were 34.6% lower (p=0.001); end-diastolic and end-systolic left ventricle dimensions were decreased by 2.5% (p=0.047) and 3.7% (p=0.01), maximum diameter of left atrium was decreased by 8.4% (p=0.004), left atrium ejection fraction was ameliorated by 6.03% (p=0.021) and as regards tissue Doppler parameters, TDI_Etv/Atv was decreased in omega 3-PUFA intervention group by 6.3% (p=0.038). Moreover, improvement in diastolic indices was more prominent in subjects with DCM as compared to IHF patients. CONCLUSION: Omega 3-PUFA supplementation was associated with improved left diastolic function and decreased BNP levels in patients with chronic heart failure. These findings suggest a beneficial role of omega 3-PUFAs on the hemodynamic course of patients with systolic heart failure.

Diagnosis and management of phantom tachycardias based on an electrophysiologically guided approach.

BACKGROUND: Non-documented palpitations, or phantom tachycardias, are palpitations deemed to be of unknown origin after evaluation with conventional diagnostic tools, such as 12-lead electrocardiogram and Holter recordings. Our aim was to determine the diagnostic value of an electrophysiologic study (EPS) and its role in the management of patients presenting with non-documented palpitations. METHODS: We performed EPS in 78 consecutive patients with repeatable, poorly tolerated symptoms of paroxysmal, non-documented tachycardia, the absence of structural heart disease and at least one 24-h Holter recording. The duration and frequency of palpitations was registered in each patient. RESULTS: Long-lasting palpitations (>1 hour) were present in 15.4% of patients. Half of patients reported symptoms less often than once per week. Only 13/78 patients (16.6%) had normal EPS findings, while dual pathways at the AV node ± echo beats were identified in another 13 patients without inducible tachycardia. At least one tachycardia event was induced in 52 patients (66.6%). AVNRT was provoked in 32 patients (41.2%). Ablation was performed in 14/52 patients with inducible tachycardia (26.9%). Slow pathway ablation was also performed in three patients with dual AV pathways and atrial echo-beats but without provoked tachycardia. Follow-up data were available in 52 patients, and 84.6% had fewer or no clinical recurrences. CONCLUSIONS: EPS is safe and of enhanced diagnostic value in patients with unexplained palpitations because only 1/6 had negative results. EPS also provided an explanation about the mechanism of arrhythmia and successfully guided the management of these patients, as well as enhanced improvement in the quality of life.

Omega-3 PUFAs improved endothelial function and arterial stiffness with a parallel antiinflammatory effect in adults with metabolic syndrome.

OBJECTIVES: Metabolic syndrome (MetS) is associated with adverse cardiovascular events, and impaired vascular function. In this study we evaluated the effects of omega-3 polyunsaturated fatty acids (PUFAs) supplementation on vascular function, inflammatory and fibrinolytic process in subjects with MetS. METHODS: We studied the effect of a 12 weeks oral treatment with 2 g/day of omega-3 PUFAs in 29 (15 male) subjects (mean age 44 ± 12 years) with MetS on three occasions (day0: baseline, day 28 and day 84). The study was carried out on two separate arms (PUFAs and placebo), according to a randomized, placebo-controlled, double-blind, cross-over design. The diagnosis of MetS was based on the guidelines of Adult Treatment Panel III definition. Endothelial function was evaluated by flow-mediated dilation (FMD) of the brachial artery. Carotid-femoral pulse wave velocity (PWV) was measured as an index of aortic stiffness. Serum levels of interleukin-6(IL-6) and plasminogen activator inhibitor-1(PAI-1) were measured by ELISA. RESULTS: Treatment with PUFAs resulted in a significant improvement from day 0 to 28 and 84 in FMD and PWV (p < 0.001 for all). Nevertheless, treatment with placebo resulted in no significant changes in FMD (p = 0.63) and PWV (p = 0.17). Moreover, PUFAs treatment, compared to placebo, decreased IL-6 levels (p = 0.03) and increased PAI-1 levels (p = 0.03). Finally, treatment with PUFAs resulted in a significant decrease in fasting triglyceride levels from day 0 to 28 and 84 (p < 0.001) and in serum total cholesterol levels (p < 0.001). CONCLUSIONS: In subjects with MetS, treatment with omega-3 PUFAs improved endothelial function and arterial stiffness with a parallel antiinflammatory effect.

Renal and cardiac effects of renal sympathetic denervation and carotid baroreceptor stimulation.

Cumulative evidence nowadays supports the dominant role of sympathetic nervous system (SNS) activation in patients with hypertension, congestive heart failure, and renal dysfunction. During the last years innovative interventional treatments [renal sympathetic denervation (RSD) and baroreflex activation therapy (BAT)] have emerged and accompanied by sustained reductions of blood pressure (BP) levels. Moreover, these promising therapies are favorable not only on BP regulation but also on the SNS overdrive-related organ damage. The present review focuses on the association of SNS activation with renal and cardiac diseases and presents the cardiorenal effects of RSD and BAT in experimental and clinical settings.

Cognitive impairment and dietary habits among elders: the Velestino Study.

To investigate the association of dietary habits with cognitive function among elders (>65 years). Complete sociodemographic, dietary information, serum measurements, and Mini-Mental State Examination (MMSE) assessments were available for 237 elderly men and 320 women residing in Velestino, Greece (a rural Greek town). All models were adjusted for age, education, social activity, smoking, depression symptomatology (using the Geriatric Depression Scale), MedDietScore (range 0-55), and metabolic syndrome. About 49.8% men and 66.6% women had MMSE scores <24, with a mean MMSE score of 22.7±4.43 and 21.1±4.73, respectively. Adherence to the Mediterranean diet was moderate (mean MedDietScore of 34.1±3.25 in men and 35.1±2.48 in women). Indicative cognitive impairment (MMSE score <24) was positively associated with age and low education in women and with depressive symptoms, low education status, and low social activity in men. Adherence to the Mediterranean diet was positively associated with MMSE score in men (P=.02), but inversely associated in women (P=.04). Concerning the food groups studied, intake of pulses, nuts, and seeds was associated with lower likelihood of having MMSE score<24 in men (P=.04). Only the Mediterranean dietary pattern showed a significant association with MMSE score positive for cognitive impairment (i.e., protective in men, but not in women), while individual food groups or nutrients did not achieve significance. The latter findings support the role of whole diet in the prevention of mental disorders, and state a research hypothesis for a sex-diet interaction on cognitive function among elders.

Consumption of a boiled Greek type of coffee is associated with improved endothelial function: the Ikaria study.

OBJECTIVE: The association of coffee consumption with cardiovascular disease remains controversial. Endothelial function is associated with cardiovascular risk. We examined the association between chronic coffee consumption and endothelium function in elderly inhabitants of the island of Ikaria. METHODS: The analysis was conducted on 142 elderly subjects (aged 66-91 years) of the Ikaria Study. Endothelial function was evaluated by ultrasound measurement of flow-mediated dilation (FMD). Coffee consumption was evaluated based on a food frequency questionnaire and was categorized as 'low' (< 200 ml/day), 'moderate' (200-450 ml/day), or 'high' (> 450 ml/day). RESULTS: From the subjects included in the study, 87% consumed a boiled Greek type of coffee. Moreover, 40% had a 'low', 48% a 'moderate' and 13% a 'high' daily coffee consumption. There was a linear increase in FMD according to coffee consumption ('low': 4.33 ± 2.51% vs 'moderate': 5.39 ± 3.09% vs 'high': 6.47 ± 2.72%; p = 0.032). Moreover, subjects consuming mainly a boiled Greek type of coffee had a significantly higher FMD compared with those consuming other types of coffee beverages (p = 0.035). CONCLUSIONS: Chronic coffee consumption is associated with improved endothelial function in elderly subjects, providing a new connection between nutrition and vascular health.

Extreme but not life-threatening QT interval prolongation? Take a closer look at the neck!

We present the case of a 82-year-old woman with a history of total thyroidectomy who was admitted in hospital with severe hypocalcemia. A 12-lead surface ECG revealed atrial fibrillation along with an extremely prolonged QT interval of approximately 730ms. In the absence of any other possible cause of QT interval prolongation, hypocalcemia was attributed to surgical hypoparathyroidism and undue discontinuation of calcium supplementation. Surprisingly, no ventricular arrhythmias were recorded and calcium repletion was followed by normalization of QT interval.

Effects of Ω-3 fatty acids on endothelial function, arterial wall properties, inflammatory and fibrinolytic status in smokers: a cross over study.

BACKGROUND: Smoking is associated with endothelial dysfunction and arterial stiffness. Supplementation of Ω-3 PUFAs is associated with better prognosis. Aim of this study was to evaluate the effects of Ω-3 polyunsaturated fatty acids (PUFAs) supplementation on smoking-induced impairment of arterial function. METHODS: We studied the effect of a 12 weeks oral treatment with 2gr/day of Ω-3 PUFAs in 20 healthy smokers on three occasions (day 0:baseline, day 28 and day 84). The study was carried out on two separate arms (Ω-3 fatty acids and placebo), according to a randomized, placebo-controlled, double-blind, cross-over design. Measurements were carried out before (pSm), immediately and 20min after cigarette smoking. Endothelial function was evaluated by flow-mediated dilation (FMD) of the brachial artery. Carotid-femoral pulse wave velocity (PWV) was measured as an index of aortic stiffness and augmentation index (AIx) as a measure of arterial wave reflections. Circulating levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and plasminogen activator inhibitor-1 (PAI-1) were measured. RESULTS: Compared with placebo, Ω-3 PUFAs treatment resulted in a significant improvement in pSm values of FMD (p<0.05), AIx (p<0.001) and PWV (p<0.01). Although, acute cigarette smoking decreased FMD and caused an increase in AIx and PWV, Ω-3 PUFAs treatment blunted the acute smoking-induced impairment of FMD (p<0.001), AIx (p<0.05) and PWV (p<0.05) and significantly decreased levels of TNFα (p<0.05) and IL-6 (p=0.01) and increased levels of PAI-1 (p=0.05). CONCLUSIONS: Ω-3 PUFAs improved endothelial function and the elastic properties of the arterial tree in healthy smokers, with a parallel anti-inflammatory effect.

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.

Novel oral anticoagulants in the treatment of acute coronary syndromes: is there any room for new anticoagulants?

Thrombosis plays a key role in the pathophysiology of acute coronary syndromes (ACS). The management of patients with ACS includes interventional procedures and use of antithrombotic agents acutely, and dual antiplatelet therapy (aspirin and a P2Y12 receptor antagonist) for secondary prevention. However, patients with recent ACS remain at a substantial residual risk for recurrent ischemic events or death. The idea of follow-up treatment with an oral anticoagulant on top of standard therapy seems promising. Warfarin was the first oral anticoagulant thoroughly investigated in this direction, but the widespread long-term use of warfarin in ACS has been limited by challenges associated with pharmacodynamic/pharmacokinetic deficiencies of the drug and the risk of bleeding. Novel oral anticoagulants, such as direct thrombin inhibitors (DTIs) and FXa inhibitors overcome the downsides of VKAs. Ximelagatran was the first DTI, investigated and proven to be effective in prevention of recurrent ischemic events in ACS patients, but the drug association with hepatotoxicity prompted its withdrawal. Dabigatran etexilate, apixaban, darexaban (YM150) and TAK-442 were studied in phase II dose-escalation trials in order to determine the balance between clinical effectiveness and bleeding risk in daily use with dual antiplatelet therapy, with both positive and negative results. Rivaroxaban is the only agent that completed a phase III trial, showing reduction in recurrent ischemic events rate and death from cardiovascular causes as well as all-cause death. This review summarizes the data from completed and ongoing clinical trials of the new oral anticoagulants in patients with ACS.

Novel direct factor IIa and Xa inhibitors: mechanisms of action and preclinical studies.

The need to overcome certain limitations of the existing anticoagulant agents (heparin, LMWH and VKAs) and to achieve more convenient long-term anticoagulation has fueled the quest for the "ideal anticoagulant", an agent that would exert at least similar antithrombotic effects with a substantially improved pharmacologic profile and significantly less bleeding complications. The major disadvantages of the traditional agents were the narrow therapeutic window with serious drug and food interactions and the need for regular blood monitoring. Coagulation factors IIa and Xa have proved the most attractive pharmacologic targets due to their key role in the coagulation process and the opportunity of blocking thrombin generation before the level of thrombin production that results in amplification of the anticoagulant effect while preserving some of thrombin hemostatic effect. This review summarizes the mechanism of action of some of the most promising novel oral direct factor IIa and Xa inhibitors with a focus on published preclinical trials that led to their clinical development.

Novel therapeutic strategies in the management of arterial hypertension.

Essential hypertension is a disease with a major impact on health worldwide, thus control of blood pressure seems to be a key component of cardiovascular disease prevention. Despite considerable advances in the treatment of hypertension, effective management remains poor and new strategies to control high blood pressure and cardiovascular risk reduction are required. These seem to be divided into two major categories: those seeking to advance blood pressure-lowering efficacy of already existing agents, and others related to novel approaches, both pharmacological and non-pharmacological. Moreover, numerous clinical trials have evaluated the use of nutritional supplements in the prevention of cardiovascular diseases and in achievement of optimal blood pressure control. Additionally, the advent of interventional techniques, such as carotid baroreceptor stimulation and renal ablation of sympathetic nerve activity, seems to be proved effective in cases where medical management and lifestyle modifications are insufficient. Genetic technology, which has advanced tremendously over the past few years, could assist novel treatment options in hypertensive patients, such as RNA interference targeting hypertension-related genes. However, continued efforts must progress in these areas and the effects of therapeutic strategies in hypertensive patients need to be further explored in larger trials over a longer period of time.