Acute coronary syndromes (ACS) are frequently reported in patients with coronavirus disease 2019 (COVID-19) and may impact patient clinical course and mortality. Although the underlying pathogenesis remains unclear, several potential mechanisms have been hypothesized, including oxygen supply/demand imbalance, direct viral cellular damage, systemic inflammatory response with cytokine-mediated injury, microvascular thrombosis, and endothelial dysfunction. The severe hypoxic state, combined with other conditions frequently reported in COVID-19, namely sepsis, tachyarrhythmias, anemia, hypotension, and shock, can induce a myocardial damage due to the mismatch between oxygen supply and demand and results in type 2 myocardial infarction (MI). In addition, COVID-19 promotes atherosclerotic plaque instability and thrombus formation and may precipitate type 1 MI. Patients with severe disease often show decrease in platelets count, higher levels of d-dimer, ultralarge von Willebrand factor multimers, tissue factor, and prolongation of prothrombin time, which reflects a prothrombotic state. An endothelial dysfunction has been described as a consequence of the direct viral effects and of the hyperinflammatory environment. The expression of tissue factor, von Willebrand factor, thromboxane, and plasminogen activator inhibitor-1 promotes the prothrombotic status. In addition, endothelial cells generate superoxide anions, with enhanced local oxidative stress, and endothelin-1, which affects the vasodilator/vasoconstrictor balance and platelet aggregation. The optimal management of COVID-19 patients is a challenge both for logistic and clinical reasons. A deeper understanding of ACS pathophysiology may yield novel research insights and therapeutic perspectives in higher cardiovascular risk subjects with COVID-19.

Coronary artery ectasia (CAE) is defined as a diffuse or focal dilation of an epicardial coronary artery, which diameter exceeds by at least 1. 5 times the normal adjacent segment. The term ectasia refers to a diffuse dilation, involving more than 50% of the length of the vessel, while the term aneurysm defines a focal vessel dilation. CAE is a relatively uncommon angiographic finding and its prevalence ranges between 0.3 and 5% of patients undergoing coronary angiography. Although its pathophysiology is still unclear, atherosclerosis seems to be the underlying mechanism in most cases. The prognostic role of CAE is also controversial, but previous studies reported a high risk of cardiovascular events and mortality in these patients after percutaneous coronary intervention. Despite the availability of different options for the interventional management of patients with CAE, including covered stent implantation and stent-assisted coil embolization, there is no one standard approach, as therapy is tailored to the individual patient. The abnormal coronary dilation, often associated with high thrombus burden in the setting of acute coronary syndromes, makes the interventional treatment of CAE patients challenging and often complicated by distal thrombus embolization and stent malapposition. Moreover, the optimal antithrombotic therapy is debated and includes dual antiplatelet therapy, anticoagulation, or a combination of them. In this review we aimed to provide an overview of the pathophysiology, classification, clinical presentation, natural history, and management of patients with CAE, with a focus on the challenges for both clinical and interventional cardiologists in daily clinical practice.

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Introduction: The aim of this study was to evaluate the association of lipoprotein(a) [Lp(a)] levels with long-term outcome in patients with recent history of myocardial infarction (MI), and to investigate if diabetes may influence this association.Methods: Consecutive MI patients who underwent urgent/emergent coronary angiography from February 2013 to June 2019 were prospectively collected. The primary outcome was the composite of MI recurrence and all-cause death. The propensity score weighting technique was used to account for covariates potentially influencing the relationship between Lp(a) levels and the study outcomes.Results: The study population consisted of 1018 post-MI patients (median age 63 years). Diabetes was reported in 280 patients (27.5%), who showed lower Lp(a) levels than patients without diabetes (p = 0.026). At a median follow-up of 1121 days, the primary outcome was reported in 182 patients (17.9%). At univariable Cox regression analysis, Lp(a) was associated with the risk of the primary outcome in the overall population and in non-diabetic patients, but not in diabetics. The adjusted Cox regression analysis confirmed the independent association between Lp(a) values and the primary outcome in non-diabetic patients, but not in diabetics.Lp(a) levels > 70 mg/dL were independently associated with the risk of the primary outcome in non-diabetic patients (adjusted HR: 2.839; 95% CI, 1.382–5.832), but not in diabetics.Conclusions: In this real-world post-MI population, increasing Lp(a) levels were significantly associated with the risk of recurrent MI and all-cause death, and very high Lp(a) serum concentration independently predicted long-term outcome in non-diabetic patients, but not in diabetics.

The control of cardiovascular risk factors, the promotion of a healthy lifestyle, and antithrombotic therapy are the cornerstones of secondary prevention after acute coronary syndrome (ACS). However, many patients have recurrent ischemic events despite the optimal control of traditional modifiable risk factors and the use of tailored pharmacological therapy, including new-generation antiplatelet and lipid-lowering agents. This evidence emphasizes the importance of identifying novel risk factors and targets to optimize secondary preventive strategies. Lipoprotein(a) (Lp(a)) has emerged as an independent predictor of adverse events after ACS. New molecules such as anti-PCSK9 monoclonal antibodies, small interfering RNAs, and antisense oligonucleotides can reduce plasma Lp(a) levels and are associated with a long-term outcome benefit after the index event. The inflammatory stimulus and the inflammasome, pivotal elements in the development and progression of atherosclerosis, have been widely investigated in patients with coronary artery disease. More recently, randomized clinical trials including post-ACS patients treated with colchicine and monoclonal antibodies targeting cytokines yielded promising results in the reduction in major cardiovascular events after an ACS. Gut dysbiosis has also raised great interest for its potential pathophysiological role in cardiovascular disease. This evidence, albeit preliminary and needing confirmation by larger population-based studies, suggests the possibility of targeting the gut microbiome in particularly high-risk populations. The risk of recurrent ischemic events after ACS is related to the complex interaction between intrinsic predisposing factors and environmental triggers. The identification of novel risk factors and targets is fundamental to customizing patient clinical management with a precision medicine perspective.

Current research on cardiovascular prevention predominantly focuses on risk-stratification and management of patients with coronary artery disease (CAD) to optimize their prognosis. Several basic, translational and clinical research efforts aim to determine the etiological mechanisms underlying CAD pathogenesis and to identify lifestyle-dependent metabolic risk factors or genetic and epigenetic parameters responsible for CAD occurrence and/or progression. A log-linear association between the absolute exposure of LDL cholesterol (LDL-C) and the risk of atherosclerotic cardio-vascular disease (ASCVD) was well documented over the year. LDL-C was identified as the principal enemy to fight against, and soluble proprotein convertase subtilisin kexin type 9 (PCSK9) was attributed the role of a powerful regulator of blood LDL-C levels. The two currently available antibodies (alirocumab and evolocumab) against PCSK9 are fully human engineered IgG that bind to soluble PCSK9 and avoid its interaction with the LDLR. As documented by modern and dedicated “game-changer” trials, antibodies against soluble PCSK9 reduce LDL-C levels by at least 60 percent when used alone and up to 85 percent when used in combination with high-intensity statins and/or other hypolipidemic therapies, including ezetimibe. Their clinical indications are well established, but new areas of use are advocated. Several clues suggest that regulation of PCSK9 represents a cornerstone of cardiovascular prevention, partly because of some pleiotropic effects attributed to these newly developed drugs. New mechanisms of PCSK9 regulation are being explored, and further efforts need to be put in place to reach patients with these new therapies. The aim of this manuscript is to perform a narrative review of the literature on soluble PCSK9 inhibitor drugs, with a focus on their indications and clinical impact.

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Aims The Academic Research Consortium for High Bleeding Risk (ARC-HBR) has recently proposed, by consensus, 20 clinical criteria for the assessment of the bleeding risk after percutaneous coronary intervention (PCI). A major criterion was defined as any individual clinical condition conferring in isolation a risk for major bleeding ≥4% up to 1 year after PCI; instead, a minor criterion was considered to confer a bleeding risk of < 4%. The aim of this meta-analysis was to assess the performance of the ARC-HBR criteria in stratifying the risk of bleeding and ischaemic events after PCI. Methods and results MEDLINE, COCHRANE, Web of Sciences, and SCOPUS were searched for studies aimed at validating the ARC-HBR criteria in patients treated with PCI. The primary outcome measure of this meta-analysis was major bleeding. The analysis included 10 studies encompassing 67 862 patients undergoing PCI; the HBR definition was fulfilled in 44.7% of the cases. The risk of major bleeding was significantly higher in HBR vs. Non-HBR group (RR: 2.56, 95% CI: 2.28–2.89). The average C-statistic was 0.64 (95% CI: 0.60–0.68), indicating modest discrimination. The risk of intracranial haemorrhage, gastrointestinal bleeding, fatal bleeding, ischaemic stroke, cardiac death and all-cause death was higher in HBR vs. Non-HBR group. Despite a higher incidence of myocardial infarction and stent thrombosis in patients deemed at HBR, the rate of target lesion revascularization was comparable between groups (RR, 1.01, 95% CI: 0.88–1.16). When assessed in isolation, the mean cumulative incidence of major bleeding at 1 year exceeded the cut-off value of 4% for all the major criteria and for two out of six minor criteria, including age ≥75 years and moderate chronic kidney disease (CKD) (Figure). Conclusions The ARC-HBR definition identifies patients at higher risk of major bleeding and other adverse cardiovascular events after PCI. Almost all major criteria, but also two of the minor criteria, were individually associated with rates of major bleeding above 4% thus fulfilling the definition of major HBR criteria. These findings corroborate the ability of ARC-HBR major criteria in identifying PCI patients who are more likely to develop adverse events, but also suggest caution in the decision making of patients with isolated minor criteria, including age ≥ 75 years and moderate CKD.