Atrial Fibrillation and Myocardial Infarction: A Systematic Review and Appraisal of Pathophysiologic Mechanisms

A growing body of evidence suggests that atrial fibrillation (AF) is associated with myocardial infarction (MI). However, incidence and management of MI in AF is still undefined. METHODS AND RESULTS: We searched MEDLINE via PubMed and Cochrane database between 1965 and 2015. All observational clinical studies and interventional trials reporting 1-year incidence of MI in AF were included. We also discussed pathophysiological mechanisms, predictors, and therapeutic approaches to reduce the risk of MI in AF. Twenty-one observational studies and 10 clinical trials were included. The annual rate of MI in observational studies including AF patients ranged from 0.4% to 2.5%. Higher rates of MI were reported in AF patients with stable coronary artery disease (11.5%/year), vascular disease (4.47%/year), heart failure (2.9%/year), and in those undergoing coronary artery interventions (6.3%/year). However, lower annual rates have been described in AF patients from Eastern countries (0.2-0.3%/year), and in those enrolled in clinical trials (from 0.4 to 1.3%/year). CONCLUSIONS: AF patients had a significant residual risk of MI despite anticoagulant treatment. Coexistence of atherosclerotic risk factors and platelet activation account for the increased risk of MI in AF. Identification of high-risk AF patients is a needed first step to develop cost-effective approaches for prevention. A new score, the 2MACE score, has been recently developed to stratify MI risk in AF, and may help not only in allocating resources to high-risk groups, but also in design of studies examining novel therapies for prevention of MI in AF

A review of picotamide in the reduction of cardiovascular events in diabetic patients

Picotamide is an antiplatelet drug with a dual inhibitory action. Thus, picotamide inhibits both thromboxane A2 (TxA2) receptors and TxA2 synthase and, at variance with aspirin, does not interfere with endothelial prostacyclin (PGI2) production. Two large randomized trials have been performed to assess the clinical efficacy of picotamide in patients at risk of atherothrombosis. The ADEP study compared peripheral artery disease (PAD) patients randomized to picotamide or placebo. This study did not show a significant reduction of cardiovascular events by picotamide but a subgroup analysis showed its potential usefulness in patients with diabetes. To investigate this issue further, the DAVID study recently enrolled diabetic patients with PAD randomized to picotamide versus aspirin; the results showed a significant reduction of overall mortality in the picotamide group. Moreover long-term picotamide treatment in diabetes promotes the reduction of microalbuminuria and the inhibition of growth of carotid plaques. These data suggest that picotamide may represent an interesting drug to be further investigated in future trials in the atherothrombotic setting

Oxidative stress: new insights on the association of nonalcoholic fatty liver disease and atherosclerosis

Non-alcoholic fatty liver disease (NAFLD) represents the most common and emerging chronic liver disease worldwide. It includes a wide spectrum of liver diseases ranging from simple fatty liver to non-alcoholic steatohepatitis (NASH), which may progress to fibrosis and more severe liver complications such as cirrhosis, hepatocellular carcinoma and liver mortality. NAFLD is strongly associated with obesity, insulin resistance, hypertension, and dyslipidaemia, and is now regarded as the liver manifestation of the metabolic syndrome. The increased mortality of patients with NAFLD is primarily a result of cardiovascular disease and, to a lesser extent, to liver related diseases. Increased oxidative stress has been reported in both patients with NAFLD and patient with cardiovascular risk factors. Thus, oxidative stress represents a shared pathophysiological disorder between the two conditions. Several therapeutic strategies targeting oxidative stress reduction in patients with NAFLD have been proposed, with conflicting results. In particular, vitamin E supplementation has been suggested for the treatment of non-diabetic, non-cirrhotic adults with active NASH, although this recommendation is based only on the results of a single randomized controlled trial. Other antioxidant treatments suggested are resveratrol, silybin, L-carnitine and pentoxiphylline. No trial so far, has evaluated the cardiovascular effects of antioxidant treatment in patients with NAFLD. New, large-scale studies including as end-point also the assessment of the atherosclerosis markers are needed

The Remains of the Day: The International Economic Order in the Era of Disintegration

The last two decades of the XX century have been marked by a vigorous acceleration of international economic integration both at a global and regional level. States accepted pervasive constraints on their national decision-making in the hope that stability and predictability would favor economic growth. This model of international economic integration, however, has recently shown worrying signs of ‘disintegration’. Disintegration manifests itself both as disintegration of the international legal regimes which compose the international economic order; and disintegration through law, namely the social, economic and environmental disintegration phenomena,triggered or at leastfacilitated by these regimes. Relying on the paradox integration/disintegration as an analytical framework, this article draws a blueprint of the various disintegration phenomena, which are further analyzed in the individual contributions to this Special Issue. It seeks to identify a relationship betweenthetwo dimensions of disintegration and detect possible correlation patterns. Last, after engaging with the different normative alternatives put forward by the contributors, it concludes by calling for a rethinking of the traditional approach to international economic integration. This reconceptualization should be premised on the full realization that the current model entails a great deal of environmental and social ‘hidden costs’

Aging-Related Decline of Glutathione Peroxidase 3 and Risk of Cardiovascular Events in Patients With Atrial Fibrillation

BACKGROUND: Experimental studies demonstrated that glutathione peroxidase 3 (GPx3), an antioxidant enzyme that catabolizes hydrogen peroxide, protects against thrombosis. Little is known about its role in cardiovascular disease. METHODS AND RESULTS: A prospective cohort study was conducted in 909 atrial fibrillation patients. Serum activities of GPx3, superoxide dismutase (SOD), and catalase were measured at baseline to assess the risk of cardiovascular events during a mean follow-up of 43.4 months (3291 person-years). Serum Nox2 and urinary excretion of 11-deydro-thromboxane B2 were also measured. During follow-up 160 cardiovascular events occurred (4.9%/year). Significantly lower values of GPx3 (P<0.001) and SOD (P=0.037) were detected in patients with, compared to those without, cardiovascular events. A lower survival rate was observed in patients with GPx3 (P<0.001) and SOD (P=0.010) activities below the median, as compared to those above. In a fully adjusted Cox regression model, GPx3 was the only antioxidant enzyme predictor of cardiovascular events (hazard ratio 0.647, 95% confidence interval 0.524-0.798, P<0.001). GPx3 was inversely associated with urinary 11-dehydro-thromboxane B2 (B -0.337, P<0.001) and serum Nox2 (B: -0.423, P<0.001). GPx3 activity progressively decreased with decades of age (P<0.001), with a progressive reduction in people aged ≥70 years. CONCLUSIONS: This study provides evidence that a low antioxidant status, as depicted by reduced levels of GPx3, increases the risk of cardiovascular events in patients with atrial fibrillation. The age-related decline of GPx3 may represent a mechanism for the enhanced cardiovascular risk in the elderly population

HIV-1 induces in vivo platelet activation by enhancing platelet NOX2 activity.

OBJECTIVES: HIV-1 patients show increased platelet activation, but the mechanisms involved are not completely clarified. We speculated that HIV-1 might induce in vivo platelet activation by enhancing platelet NOX2-related oxidative stress. METHODS: We measured soluble CD40 Ligand (sCD40L), a systemic marker of platelet activation, in 36 HIV-1 patients under effective combined antiretroviral therapy (cART) and in 10 naïve HIV-1 subjects. As control, 20 healthy subjects (HS) were included. Platelet oxidative stress was measured by platelet NOX2-derived peptide (sNOX2-dp), p47(phox) translocation to platelet membrane and platelet prostaglandin F2α (8-iso-PGF2α). RESULTS: sCD40L was increased both in HIV-1 naïve and cART patients compared to HS (p &lt; 0.001). Platelet sNOX2-dp and 8-iso-PGF2α were significantly higher in HIV-1 naïve subjects compared to those on cART and to HS, and both were mutually correlated (R = 0.734, p &lt; 0.001). A stepwise multivariable linear regression analysis showed that platelet sNOX2-dp (β: 0.803, p &lt; 0.001), HIV-1 infection (β: 0.146, p = 0.014) and age (β: 0.166, p = 0.001) were independently associated to sCD40L levels. CONCLUSIONS: HIV-1 infection is associated with increased platelet oxidative stress, which was related to the activation of NOX2. The independent association between platelet NOX2 activation and plasma levels of sCD40L suggest that in vivo platelet activation may be dependent upon platelet oxidative stress

Extra virgin olive oil use is associated with improved post-prandial blood glucose and LDL cholesterol in healthy subjects

Extra virgin olive oil (EVOO) is a key component of the Mediterranean diet and seems to account for the protective effect against cardiovascular disease. However, the underlying mechanism is still elusive