The new in anticoagulation: factor XI inhibitors.

Haemostasis and thrombosis are closely linked, so that any anticoagulant strategy available today that reduces the thrombotic risk inevitably increases the bleeding risk. However, epidemiological and experimental evidence suggests that inhibiting the contact pathway-the first phase of the intrinsic coagulation pathway-and especially factor XI (FXI) achieves the objective of preventing thrombosis with minimal interference on the haemostatic process. Several pharmacological strategies that act by inhibiting FXI are being studied in clinical trials. Specifically, Phase 2 clinical trials in patients undergoing major orthopaedic surgery, end-stage renal disease, atrial fibrillation (AF), and acute coronary syndrome have shown promising results, allowing clinical research to advance into Phase 3 clinical trials. FXI inhibitors will not necessarily replace currently available direct oral anticoagulants: this would appear too ambitious as of today. However, it is possible to hypothesize that FXI inhibitors are a useful addition to our therapeutic armamentarium in contexts where current anticoagulants have failed or have not been adequately tested, as well as in categories of patients who are at a high risk of bleeding even with current direct oral anticoagulants.

Pollution and coronary risk: how much does it matter?

Air pollutants are a complex mixture of gaseous substances and particulate matter (PM). Each component potentially has specific harmful effects on human health, but several experimental and clinical studies have shown a strong impact of fine particles on major adverse cardiovascular events. Most of the available evidence concerns the effects of exposure to PM with a diameter of <2.5 µm (PM2.5) and the risk of developing coronary heart disease through inflammation and oxidative stress. While prolonged exposure to PM2.5 has been shown to be associated with the development of atherosclerosis and cardio-metabolic risk factors, short-term exposure has instead proved to be a trigger for acute coronary events, and especially in subjects with pre-existing coronary artery disease. As such, environmental PM2.5 is a major risk element for global public health. This underlines on the one hand not only the need to adopt and encourage preventive measures especially for individuals with a higher risk profile but also to practice environmental policies that are effective in promoting the reduction of exposure to pollutants.

New insights from the MESA study: increased high-sensitivity troponins as a cardiovascular risk factor.

The most recent high-sensitivity assays for troponins I and T (hs-TnI and hs-TnT) have made it possible to detect blood concentrations up to 10 times lower than previous assays, making troponins detectable even in asymptomatic subjects without manifest cardiovascular disease. For this reason, hs-Tn, initially introduced as markers of myocardial damage in an acute setting, have also become possible markers of subclinical myocardial damage in baseline conditions. In fact, recent evidence suggests that hs-TnT and hs-TnI predict the risk of future cardiovascular events also in the context of primary prevention, and offer incremental information when added to current risk stratification models. The different association highlighted with different outcome measures, such as coronary heart disease, atherosclerotic cardiovascular disease, heart failure, and death from all causes, seems to indicate that the risk observed in asymptomatic subjects with high levels of hs-Tn is an expression of subclinical damage secondary to multiple pathophysiological mechanisms, and not only to atherothrombosis. However, the ability of hs-TnT and hs-TnI (until now used interchangeably), to provide differential predictive information, and not redundant with respect to more traditional factors, remains to be definitively clarified, both for the purpose of predicting specific outcomes and for the implementation of specific preventive strategies. To date, evidences available allow us to hypothesize their role more as markers than as risk factors.

Causal relationship between influenza infection and risk of acute myocardial infarction: pathophysiological hypothesis and clinical implications.

Presently several evidences support an association between acute myocardial infarction and influenza infection. The pathophysiology rationale rests on the release of inflammation cytokines, rupture of atherosclerotic plaque, and triggering of prothrombotic events leading to coronary artery occlusion. Several observational evidences support a potential role of influenza vaccine in cardiovascular prevention. It is estimated that the efficacy of influenza vaccine in preventing myocardial infarction could range between 15% and 45%. Notwithstanding the clear recommendation of numerous guidelines concerning patients with cardiovascular diseases, vaccination rates are still low in the high-risk groups. Influenza vaccine as preventive measure of cardiovascular disease still awaits support from randomized clinical trials. Nonetheless, considering the favourable cost-efficacy and safety profile of influenza vaccination, its use should be encouraged in everyday clinical practice.

Challenges in ischaemic heart disease: not sleeping enough, not brushing your teeth, and skipping breakfast-three ways of increasing your risk of myocardial infarction?

Despite optimal medical therapies, there is currently a persistent residual cardiovascular risk. The most likely pathway responsible for this residual risk has been identified in the inflammatory state. Recent studies have confirmed that inflammation increases cardiovascular risk independently from LDL cholesterol levels. Addressing traditional risk factors, such as obesity, cigarette smoking, diabetes, arterial hypertension, and dyslipidaemia, also provides an important reduction of the levels of inflammation. Nonetheless, inflammation is also a target for specific and focused therapeutic interventions. Recent studies have outlined an association between oral hygiene, sleep deprivation, and nutritional patterns on the one hand, with the development of multi-districts atherosclerosis and/or adverse cardiovascular events on the other. These lifestyle patterns appear to be involved in fostering inflammation associated with atherosclerosis. There is, however, a persistent need for further studies to clarify whether such associations with cardiovascular disease are direct and causal, and if they are all channelled through vascular inflammation.

A Ruptured Mitral Valve Aneurysm as Complication of a Bicuspid Aortic Valve Endocarditis.

We present a case of a ruptured mitral valve (MV) aneurysm as a complication of a bicuspid aortic valve (BAV) endocarditis. It is about a young 35-year-old man, admitted to Cardiology Unit because of unexpected heart failure picture. We found a BAV endocarditis complicated by anterior MV-anterior leaflet aneurysm formation and subsequent severe MV regurgitation caused by aneurysm perforation. It was a particular and rare situation characterized by an infection of anterior mitral leaflet secondary to an infected regurgitant jet of a primary aortic infective endocarditis due to a BAV. A resulting aneurysm formation on the atrial side of the mitral anterior leaflet leads later to mitral perforation. In this article, we review the more relevant medical literature on this topic.

[Biomarkers in primary cardiovascular prevention: rationale, premises, and promises]. / Biomarcatori e prevenzione cardiovascolare primaria: razionale, premesse e promesse.

Cardiovascular disease remains the leading cause of death worldwide, and this underscores the importance of primary prevention before the occurrence of its clinical manifestations. Actually, there is an important need for new ways to improve upon traditional risk assessment. Efforts to address the problem of better identifying persons at risk of developing a first cardiovascular event have largely focused on the use of new measurements - biomarkers - which could add to traditional risk scores to improve prediction. Hundreds of candidate biomarkers, mostly deriving from measurement of plasma levels of certain substances, have been proposed, and some of them have shown solid statistical associations with the incidence of future events in addition to traditional markers. However, in general they offer only a modest increase in the predictive value of current scores. On the contrary, assessment of subclinical atherosclerosis by multiple means clearly shows a substantial incremental return. Here we critically review the available literature for studies assessing the added value of new biomarkers, especially in multiple combinations, with a particular focus on non-invasive imaging markers of subclinical atherosclerosis, on top of traditional risk algorithms in primary prevention of cardiovascular disease.

[Primary cardiac lymphoma: a case report]. / Linfoma primitivo cardiaco: un caso clinico.

Primary cardiac lymphomas are rare entities (1.3% of all primary cardiac tumors) of difficult clinical identification. We report a case of a primitive cardiac lymphoma in a 35-year-old immunocompetent patient, presenting with signs and symptoms of cardiac tamponade. Echocardiography revealed a lateral atrioventricular mass associated with large pericardial effusion. After pericardiocentesis, surgical excision was performed. Chemotherapy regimens were administered according to established protocols and were effective in inducing complete remission at 6 months.

Polypill: quo vadis?

Cardiovascular disease (CVD) is still the leading cause of death worldwide. The overall growth of this epidemic during the last decade is largely because of the increasing incidence of CVD in low and middle-income countries, where inadequate health policies, poor availability, and lack of affordable medications, as well as poor patient adherence to treatment all limit the efficacy of cardiovascular prevention strategies. Complementary to a promotion of healthy lifestyles, a fixed dose combination or a 'polypill,' containing two or more drugs addressed at controlling various risk factors, might reduce costs and improve patient accessibility and adherence to treatment. As of now, several clinical trials have shown that combination pills are well tolerated and decrease risk factors for CVD, with a projected improvement of end points by as much as 60-70% by reducing blood pressure and low-density lipoprotein cholesterol. However, uncertainty remains about changes of hard end points, long-term adherence, cost-effectiveness and the 'medicalization' of asymptomatic individuals who account for a large percentage of the world population. Because cardiovascular risk increases significantly for patients aged more than 50 years, it has been proposed to use a polypill to treat specifically all such patients. However, approach to be neither practical nor cost-effective, because it involves a large number of patients at low risk. Some investigators have suggested to incorporate the Coronary Artery Calcium Score with the Framingham Risk Score to identify a suitable target population of patients benefitting most from the polypill. Trials in progress will shed light on several issues currently debated and unresolved.

Nitrates and other nitric oxide donors in cardiology: current positioning and perspectives.

Nitric oxide donors have been commonly used in the therapy of cardiovascular disease for more than 150 years. In spite of this longevity and the popularity of their use, it appears somewhat paradoxical that there is no current consistent use among cardiologists, as to both their indications and their optimal mode of administration. In part this results from their contradictory pharmacodynamics: when given acutely, their effectiveness is undisputable; however, their long-term efficacy is potentially limited by the development of tolerance and the induction of endothelial dysfunction, which may have negative prognostic implications. This review reports recent biochemical and pathophysiological acquisitions, re-examines the role of nitrates and other nitric oxide donors in cardiovascular medicine, comparing and commenting on international guidelines; and highlights areas of uncertainty, where more clinical research with these drugs would still be warranted.

[Nitrates in cardiology: current role and areas of uncertainty]. / I nitroderivati in cardiologia: attualità e incertezze.

Nitrates have been commonly used in the therapy of cardiovascular disease for more than 150 years. In spite of this longevity and the popularity of their use, it appears somewhat paradoxical that their use is not consistent among cardiologists, both as to their indications and as to their mode of administration. In part this results from their contradictory pharmacodynamics: when given acutely, their effectiveness is indisputable; however, their long-term efficacy is substantially limited by the development of tolerance and the induction of endothelial dysfunction, which may have negative prognostic implications. This review, reporting the most recent biochemical and pathophysiological acquisitions, re-examines the role of nitrates in cardiovascular medicine, reporting, comparing and commenting international guidelines.