Eliminate LDL cholesterol after heart attack but only for a while.

There is a clear demonstration of the inverse linear correlation between LDL cholesterol levels and clinical benefit. However, the timing of the action of lipid-lowering drugs is not clear. According to animal studies with recombinant lipoprotein A-1, the composition of atherosclerosis changes within 40 h (with variations in lipid and inflammatory contents). Progression-regression studies of atherosclerosis in humans confirm the data, highlighting a rapid change in the plaque over 5 weeks. The data are also in line with what emerges from the survival curves of the old study comparing atorvastatin 80 mg vs. placebo (Myocardial Ischaemia Reduction with Aggressive Cholesterol Lowering). The spacing of the curves occurs after only 4 weeks, indicating the precociousness of the favourable effects of powerful statins. Finally, a recent Odyssey post hoc analysis compared the risk of cardiac death and coronary revascularization between a group in which alirocumab lowered LDL cholesterol to below 15 mg (Group 1 and in which the drug was therefore stopped) against the subjects in the placebo group (Group 2), applying a propensity score matching. The primary endpoint occurred in a lower percentage of patients in Group 1 (6.4 vs. 8.4%). Furthermore, patients in Group 1 had a significantly lower hazard ratio (HR) for major adverse cardiovascular events [0.72; 95% confidence interval (CI) 0.51-0.997; P = 0.047] compared with the entire alirocumab group vs. placebo (HR 0.85; 95% CI 0.78-0.93; P < 0.001). According to these preliminary observations, aggressive and early treatment of hypercholesterolaemia in subjects with acute coronary syndrome translates into improved clinical results compared with a strategy that provides for more gradual control. These data will need to be confirmed through further prospective clinical studies and ideally with early conducted atherosclerosis regression studies.

Controversy in cardiology: clopidogrel or acetylsalicylic acid in the treatment of chronic coronary syndromes?

Secondary prevention of patients with chronic coronary syndrome is based on the long-term use of a single anti-aggregating drug which is traditionally represented by acetylsalicylic acid (ASA) in light of the results of studies and meta-analyses which have demonstrated a clear anti-ischaemic efficacy against of an acceptable increase in the risk of bleeding, especially intracranial and gastrointestinal bleeding. The availability of drugs such as clopidogrel, which inhibits platelet activity through the P2Y12 receptor pathway, has called into question this paradigm, also in consideration of the fact that the scientific evidence that supports the use of ASA in secondary prevention is based on dated studies with some limitations. Over the last few years, randomized trials have demonstrated how clopidogrel has an efficacy profile comparable to that of ASA and a safety profile that is sometimes even better. In light of the new evidence, it is therefore legitimate to ask whether in this clinical scenario, ASA should still be considered the drug of choice or whether clopidogrel could represent the preferable alternative.

Intracoronary imaging to guide percutaneous coronary intervention: from evidence to guidelines.

Despite notable advances in devices and techniques, percutaneous coronary intervention (PCI) is still affected by a substantial number of complications and failure rates. Over the years, the use of intracoronary imaging (ICI) has dramatically improved the understanding of mechanical and technical factors related to successful and failed PCI, becoming a mainstay in complex trans-catheter interventions. However, ICI modalities are invasive, time-consuming, and costly, and a net clinical benefit needs to be shown in order to recommend their routine use in clinical practice. In the past, the lack of evidence from randomized trials has been reflected in the scepticism shown by international guidelines. The recent publication of large randomized clinical trials conducted worldwide has provided new evidence regarding the clinical usefulness of ICI guidance in PCI. The consistent reduction of adverse events achieved in these trials, also demonstrated in an updated meta-analysis, suggested that the use of ICI in PCI is compelling to achieve optimal technical results and better outcomes, especially in complex high-risk interventions. Also considering the burden of information provided by ICI on coronary artery disease, looking from the inside seems today an opportunity that modern cardiology cannot ignore anymore.

The double injection technique to improve visualization of severe coronary lesions with optical coherence tomography.

BACKGROUND: Optical coherence tomography (OCT) is a high-resolution imaging modality that provides a precise evaluation of coronary anatomy. However, the presence of severe coronary lesions can prevent the required adequate distal contrast flushing resultting in inadequate blood clearance and poor image quality or complete blood shadowing of the underlying vessel wall. OBJECTIVES: The aim of this prospective study was to evaluate the feasibility and safety of a novel "double injection technique" (DIT) to overcome the limitations of the conventional technique (CT) in patients with severely stenotic lesions. METHODS: Twenty-three patients with severe angiographic lesions were sequentially imaged before intervention with OCT with the CT and then with DIT. A total of 5125 OCT frames were carefully matched and analyzed by an independent central core lab. A semiquantitative image quality score was used to grade the number of quadrants (0-4) with vessel wall visualization. RESULTS: Optimal OCT visualization (Grades 3-4) significantly improved by the DIT (68% vs. 38% of frames, p < 0.001). The DIT also improved the mean score (3.1 ± 0.6 vs. 2.0 ± 0.8; p < 0.05; mean improvement of 1.1 ± 0.5 per patient). There were no complications associated with the DIT. CONCLUSION: The DIT significantly improved preintervention image quality of OCT in severe coronary lesions.

Bleeding and mortality risk in patients implanted with mechanical prosthetic heart valves with and without thrombocytopenia. Insights from the nationwide PLECTRUM registry.

Previous studies showed that mechanical prosthetic heart valve (MPHV) patients may develop thrombocytopenia, but its association with clinical outcomes has not been investigated. We enrolled 1,663 patients with available platelet count from the multicenter nationwide retrospective PLECTRUM registry to investigate the association of thrombocytopenia with all-cause mortality and major bleeding (MB) in patients implanted with MPHV. Thrombocytopenia was defined by platelet count <150 × 109/L. Overall, 44.9% of patients were women and the mean age was 56.7 years. At baseline, 184 (11.1%) patients had thrombocytopenia. Patients with thrombocytopenia were more frequently men and elderly. Platelet count showed an age-dependent decline in men but not in women. We found an increased risk of death in patients with age ≥ 65 years, with a low anticoagulation quality, concomitant arterial hypertension, heart failure, a higher INR range, or with thrombocytopenia (OR 1.739, 95%CI 1.048-2.886, p = .032). At multivariable logistic regression, patients with age ≥65 years, concomitant AF and thrombocytopenia (OR 1.907, 95%CI 1.219-2.983, p = .005) had an increased risk of MBs. In MPHV patients, thrombocytopenia is associated with an increased risk of death and MB. There is a growing need for a sex- and age-specific threshold to define platelet count in adult patients.

The risk of acute coronary events in microvascular disease.

The microvascular disease represents a widespread clinical entity in the general population, especially among women. The dysfunction of the microcirculation is often responsible for myocardial ischaemia and angina in the absence of significant stenosis of the epicardial district, while in other cases it can represent a contributing cause of angina even in the presence of coronary artery disease, cardiomyopathies or heart failure. The cardiovascular risk factors of people with microvascular disease are similar to those who develop epicardial atherosclerotic disease. However, the prognostic significance of microvascular disease remains a matter of debate. An element to be clarified, in fact, is whether subjects with dysfunction of the microcirculation and coronary tree without significant stenoses present an increased risk of myocardial infarction and sudden death. In recent years, several studies seem to confirm an association between microvascular disease and progression of coronary epicardial atherosclerosis. The prognosis of microvascular disease would therefore not be benign as was previously believed, but associated with an increased risk of cardiovascular events including revascularization, heart attack, and cardiac death.

D-dimer for risk stratification and antithrombotic treatment management in acute coronary syndrome patients: asystematic review and metanalysis.

BACKGROUND: Data on the prognostic role of D-dimer in patients with acute coronary syndrome (ACS) are controversial. Our aim was to summarize current evidence on the association between D-dimer levels and short/long-term poor prognosis of ACS patients. We also investigated the association between D-dimer and no-reflow phenomenon. METHODS: Systematic review and metanalysis of observational studies including ACS patients and reporting data on D-dimer levels. PubMed and SCOPUS databases were searched. Data were combined with hazard ratio (HR) and metanalysed. The principal endpoint was a composite of cardiovascular events (CVEs) including myocardial infarction, all-cause and cardiovascular mortality. RESULTS: Overall, 32 studies included in the systematic review with 28,869 patients. Of them, 6 studies investigated in-hospital and 26 studies long-term outcomes. Overall, 23 studies showed positive association of high D-dimer levels with CVEs. D-dimer levels predicted poor prognosis in all studies reporting in-hospital outcomes. Five studies satisfied inclusion criteria and were included in the metanalysis, with a total of 8616 patients. Median follow-up was 13.2 months with 626 CVEs. The pooled HR for D-dimer levels and CVEs was 1.264 (95% CI 1.134-1.409). Five out of 7 studies (4195 STEMI patients) investigating the association between D-dimer levels and no-reflow showed a positive correlation of D-dimer levels with no-reflow. CONCLUSIONS: In patients with ACS, D-dimer was associated with higher in-hospital and short/long-term complications. D-dimer was also higher in patients with no-reflow phenomenon. The use of D-dimer may help to identify patients with residual thrombotic risk after ACS. TRIAL REGISTRATION: The review protocol was registered in PROSPERO International Prospective Register of Systematic Reviews: CRD42021267233 .

Low serum albumin levels and in-hospital outcomes in patients with ST segment elevation myocardial infarction.

BACKGROUND AND AIMS: Low serum albumin (SA) is associated with an increased risk of long-term adverse events (AEs) among patients with chronic coronary syndromes. Its prognostic role in patients with ST-elevation myocardial infarction (STEMI) is less clear. To investigate the association between low SA and in-hospital AEs in STEMI patients. METHODS AND RESULTS: Multicenter retrospective cohort study of 220 STEMI patients undergoing primary percutaneous coronary intervention within 12 h from the onset of symptoms. Hypoalbuminemia was defined by serum SA <35 g/L. SA. In-hospital AEs were defined as cardiogenic shock, resuscitated cardiac arrest and death. Median SA was 38 (IQR 35.4-41.0) g/L and 37 (16.8%) patients showed hypoalbuminemia (<35 g/L) on admission. Patients with hypoalbuminemia were older, more frequently women and diabetics, prior CAD and HF. Furthermore, they showed lower hemoglobin levels and impaired renal function. At multivariable logistic regression analysis, diabetes (odds ratio [OR]:4.59, 95% confidence interval [CI] 1.71-12.28, p = 0.002) and haemoglobin (OR:0.52, 95%CI 0.37-0.72, p < 0.001) were associated with low SA. In a subgroup of 132 patients, SA inversely correlated with D-Dimer (rS -0.308, p < 0.001). Globally, twenty-eight (14.6%) AEs were recorded. Hypoalbuminemia (OR:3.43, 95%CI 1.30-9.07, p = 0.013), high-sensitive (HS)-Troponin peak above median (OR:5.41, 95%CI 1.99-14.7, p = 0.001), C-reactive protein (CRP) peak above median (OR:6.03, 95%CI 2.02-18.00, p = 0.001), and in-hospital infection (OR:3.61, 95%CI 1.21-10.80, p = 0.022) were associated with AEs. CONCLUSION: Low SA levels are associated with worse in-hospital AEs in STEMI patients, irrespective of HS-troponin and CRP plasma levels. Our findings suggest that low SA may contribute to the pro-thrombotic phenotype of these patients.

Present and future of coronary risk assessment.

The search for subclinical atherosclerosis is carried out in several arterial districts using ultrasonography and computed tomography (CT). Coronary calcium assessed by computerized tomography (calcium score) is a well-validated marker of atherosclerosis and able to correlate with the extent of coronary artery disease and the risk of cardiovascular events. The evaluation of carotid atherosclerosis by ultrasonography is a technically simple and low-cost solution. However, the literature does not provide a sufficient number of evidence to clarify the clinical impact of carotid atherosclerosis and in particular the risk of developing cardiac events. According to the researchers of the Progression of Early Subclinical Atherosclerosis (PESA) study, subclinical atherosclerosis research should preferably be carried out in the femoral district, which is more easily affected by atherosclerosis. Pending the data from the PESA study, which will better clarify the role of ultrasound applied in non-coronary districts, the coronary calcifications seems to be a reasonable solution. It is possible that in the future imaging techniques (CT-PET) capable of studying the extent and functional status of coronary atherosclerosis will further improve the identification of the risk of cardiovascular events.

Automatic assessment of atherosclerotic plaque features by intracoronary imaging: a scoping review.

Background: The diagnostic performance and clinical validity of automatic intracoronary imaging (ICI) tools for atherosclerotic plaque assessment have not been systematically investigated so far. Methods: We performed a scoping review including studies on automatic tools for automatic plaque components assessment by means of optical coherence tomography (OCT) or intravascular imaging (IVUS). We summarized study characteristics and reported the specifics and diagnostic performance of developed tools. Results: Overall, 42 OCT and 26 IVUS studies fulfilling the eligibility criteria were found, with the majority published in the last 5 years (86% of the OCT and 73% of the IVUS studies). A convolutional neural network deep-learning method was applied in 71% of OCT- and 34% of IVUS-studies. Calcium was the most frequent plaque feature analyzed (26/42 of OCT and 12/26 of IVUS studies), and both modalities showed high discriminatory performance in testing sets [range of area under the curve (AUC): 0.91-0.99 for OCT and 0.89-0.98 for IVUS]. Lipid component was investigated only in OCT studies (n = 26, AUC: 0.82-0.86). Fibrous cap thickness or thin-cap fibroatheroma were mainly investigated in OCT studies (n = 8, AUC: 0.82-0.94). Plaque burden was mainly assessed in IVUS studies (n = 15, testing set AUC reported in one study: 0.70). Conclusion: A limited number of automatic machine learning-derived tools for ICI analysis is currently available. The majority have been developed for calcium detection for either OCT or IVUS images. The reporting of the development and validation process of automated intracoronary imaging analyses is heterogeneous and lacks critical information. Systematic Review Registration: Open Science Framework (OSF), https://osf.io/nps2b/.Graphical AbstractCentral Illustration.

Efficacy and Safety of Combination Therapy with Low-Dose Rivaroxaban in Patients with Cardiovascular Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Objectives: To review the evidence on the effectiveness and safety of low-dose-rivaroxaban 2.5 mg twice daily (LDR) in patients with coronary artery disease (CAD) and/or peripheral artery disease (PAD) taking antiplatelets. Methods: We performed a systematic review and meta-analysis of randomized controlled trials (RCTs). Efficacy endpoints were cardiovascular events (CVEs), myocardial infarction, stroke, all-cause, and cardiovascular death. Any, major, fatal bleeding, and intracranial hemorrhage (ICH) were safety endpoints. Numbers needed to treat (NNT), and numbers needed to harm (NNH) were also calculated. Results: Seven RCTs were included with 45,836 patients: 34,276 with CAD and 11,560 with PAD. Overall, 4247 CVEs and 3082 bleedings were registered. LDR in association with either any antiplatelet drug or aspirin (ASA) alone reduced the risk of CVEs (hazard ratio [HR] 0.86, 95% confidence interval [95%CI] 0.78-0.94) and ischemic stroke (HR 0.68, 95%CI 0.55-0.84). LDR + ASA increased the risk of major bleeding (HR 1.71, 95%CI 1.38-2.11) but no excess of fatal bleeding or ICH was found. The NNT to prevent one CVE for LDR + ASA was 63 (43-103) and the NNH to cause major bleeding was 107 (77-193). Conclusions: The combination of LDR with either antiplatelet drugs or low-dose aspirin reduces CVEs and ischemic stroke in patients with CAD/PAD. There was an increased risk of major bleeding but no excess of fatal or ICH was found. LDR seems to have a favorable net clinical benefit compared to ASA treatment alone.

Relationship between non-invasively detected liver fibrosis and in-hospital outcomes in patients with acute coronary syndrome undergoing PCI.

BACKGROUND: Patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) still experience a high rate of in-hospital complications. Liver fibrosis (LF) is a risk factor for mortality in the general population. We investigated whether the presence of LF detected by the validated fibrosis 4 (FIB-4) score may indicate ACS patients at higher risk of poor outcome. METHODS: In the prospective ongoing REAl-world observationaL rEgistry of Acute Coronary Syndrome (REALE-ACS), LF was defined by a FIB-4 score > 3.25. We repeated the analysis using an APRI score > 0.7. The primary endpoint was in-hospital adverse events (AEs) including a composite of in-hospital cardiogenic shock, PEA/asystole, acute pulmonary edema and death. RESULTS: A total of 469 consecutive ACS consecutive patients were enrolled. Overall, 21.1% of patients had a FIB-4 score > 3.25. Patients with LF were older, less frequently on P2Y12 inhibitors (p = 0.021) and admitted with higher serum levels of white blood cells (p < 0.001), neutrophils to lymphocytes ratio (p < 0.001), C-reactive protein (p = 0.013), hs-TnT (p < 0.001), creatine-kinase MB (p < 0.001), D-Dimer levels (p < 0.001). STEMI presentation and higher Killip class/GRACE score were more common in the LF group (p < 0.001). 71 patients experienced 110 AEs. At the multivariate analysis including clinical and laboratory risk factors, FIB-4 > 3.25 (OR 3.1, 95%CI 1.4-6.9), admission left ventricular ejection fraction% below median (OR 9.2, 95%CI 3.9-21.7) and Killip class ≥ II (OR 6.3, 95%CI 2.2-18.4) were the strongest independent predictors of in-hospital AEs. Similar results were obtained using the APRI score. CONCLUSION: LF detected by FIB-4 score > 3.25 was associated with more severe ACS presentation and worse in-hospital AEs irrespective of clinical and laboratory variables.

Effects of Lipid Lowering Therapies on Vulnerable Plaque Features: An Updated Narrative Review of the Literature.

The clinical evidence on the efficacy of lipid lowering therapy in patients with coronary artery disease (CAD) is unequivocally established. However, the effects of these therapies on plaque composition and stability are less clear. The use of intracoronary imaging (ICI) technologies has emerged as a complement to conventional angiography to further characterize plaque morphology and detect high-risk plaque features related to cardiovascular events. Along with clinical outcomes studies, parallel imaging trials employing serial evaluations with intravascular ultrasound (IVUS) have shown that pharmacological treatment has the capacity to either slow disease progression or promote plaque regression, depending on the degree of lipid lowering achieved. Subsequently, the introduction of high-intensity lipid lowering therapy led to much lower levels of low-density lipoprotein cholesterol (LDL-C) levels than achieved in the past, resulting in greater clinical benefit. However, the degree of atheroma regression showed in concomitant imaging trials appeared more modest as compared to the magnitude of clinical benefit accrued from high-intensity statin therapy. Recently, new randomized trials have investigated the additional effects of achieving very low levels of LDL-C on high-risk plaque features-such as fibrous cap thickness and large lipid accumulation-beyond its size. This paper provides an overview of the currently available evidence of the effects of moderate to high-intensity lipid lowering therapy on high-risk plaque features as assessed by different ICI modalities, reviews data supporting the use of these trials, and analyse the future perspectives in this field.

Prediction of new onset atrial fibrillation in patients with acute coronary syndrome undergoing percutaneous coronary intervention using the C2HEST and mC2HEST scores: A report from the multicenter REALE-ACS registry.

BACKGROUND: New onset atrial fibrillation (NOAF) is associated with worse clinical outcomes after acute coronary syndrome (ACS). Identification of ACS patients at risk of NOAF remains challenging. To test the value of the simple C2HEST score for predicting NOAF in patients with ACS. METHODS: We studied patients from the prospective ongoing multicenter REALE-ACS registry of patients with ACS. NOAF was the primary endpoint of the study. The C2HEST score was calculated as coronary artery disease or chronic obstructive pulmonary disease (1 point each), hypertension (1 point), elderly (age ≥ 75 years, 2 points), systolic heart failure (2 points), thyroid disease (1 point). We also tested the mC2HEST score. RESULTS: We enrolled 555 patients (mean age 65.6 ± 13.3 years; 22.9% women), of which 45 (8.1%) developed NOAF. Patients with NOAF were older (p < 0.001) and had more prevalent hypertension (p = 0.012), chronic obstructive pulmonary disease (p < 0.001) and hyperthyroidism (p = 0.018). Patients with NOAF were more frequently admitted with STEMI (p < 0.001), cardiogenic shock (p = 0.008), Killip class ≥2 (p < 0.001) and had higher mean GRACE score (p < 0.001). Patients with NOAF had a higher C2HEST score compared with those without (4.2 ± 1.7 vs 3.0 ± 1.5, p < 0.001). A C2HEST score > 3 was associated with NOAF occurrence (odds ratio 4.33, 95% confidence interval 2.19-8.59, p < 0.001). ROC curve analysis showed good accuracy of the C2HEST score (AUC 0.71, 95%CI 0.67-0.74) and mC2HEST score (AUC 0.69, 95%CI 065-0.73) in predicting NOAF. CONCLUSIONS: The simple C2HEST score may be a useful tool to identify patients at higher risk of developing NOAF after presentation with ACS.

Sex-specific features of optical coherence tomography detected plaque vulnerability related to clinical outcomes: insights from the CLIMA study.

PURPOSE: To investigate the different impact of optical coherence tomography (OCT)-derived vulnerable plaque features on future adverse events (AEs) according to the biological sex. METHODS: The prospective multicenter CLIMA study (ClinicalTrials.gov: NCT02883088) enrolled 1003 patients with OCT plaque analysis of non-treated coronary plaques located in the proximal left anterior descending artery. Sex-specific differences in plaque composition and vulnerable features were described. We investigated the incidence of AEs, including cardiac death, any myocardial infarction and target vessel revascularization at 1-year. RESULTS: Among 1003 patients, 24.6% were women. Women were older and more frequently affected by chronic kidney disease. Dyslipidemia, prior MI and smoking habit were more common in men. At OCT analysis, women had shorter plaque length (p < 0.001), ticker fibrous cap (p = 0.001), smaller maximum lipid arc (p = 0.019), lower macrophage infiltration (p < 0.001) and intra-plaque layered tissue (p = 0.007). During follow-up, 65 AEs were registered. The presence of a thin fibrous cap and a large macrophage infiltration (> 67°) predicted AEs in both sexes. The presence of macrophages (HR 3.38, p = 0.018) and a small minimum lumen area (HR 4.97, p = 0.002) were associated with AEs in women but not in men, while a large lipid arc (> 180°) was associated with AEs in men (HR 2.56, p = 0.003) but not in women. CONCLUSION: This subanalysis of the CLIMA study investigated for the first-time sex-specific OCT features of plaque vulnerability associated with AEs. Local inflammation was associated with AEs in women and a large lipid arc was predictive in men. OCT may help develop sex-specific risk stratification strategies.

Optical coherence tomography-derived lipid core burden index and clinical outcomes: results from the CLIMA registry.

AIMS: The aim of this study was to assess the morphological characteristics and prognostic implications of the optical coherence tomography (OCT)-derived lipid core burden index (LCBI). METHODS AND RESULTS: OCT-LCBI was assessed in 1003 patients with 1-year follow-up from the CLIMA multicentre registry using a validated software able to automatically obtain a maximum OCT-LCBI in 4 mm (maxOCT-LCBI4mm). Primary composite clinical endpoint included cardiac death, myocardial infarction, and target-vessel revascularization. A secondary analysis using clinical outcomes of CLIMA study was performed. Patients with a maxOCT-LCBI4mm ≥ 400 showed higher prevalence of fibrous cap thickness (FCT) <75 µm [odds ratio (OR) 1.43, 95% confidence interval (CI) 1.03-1.99; P = 0.034], lipid pool arc >180° (OR 3.93, 95%CI 2.97-5.21; P < 0.001), minimum lumen area <3.5 mm2 (OR 1.5, 95%CI 1.16-1.94; P = 0.002), macrophage infiltration (OR 2.38, 95%CI 1.81-3.13; P < 0.001), and intra-plaque intimal vasculature (OR 1.34, 95%CI 1.05-1.72; P = 0.021). A maxOCT-LCBI4mm ≥400 predicted the primary endpoint [adjusted hazard ratio (HR) 1.86, 95%CI 1.1-3.2; P = 0.019] as well as the CLIMA endpoint (HR 2.56, 95%CI 1.24-5.29; P = 0.011). Patients with high lipid content and thin FCT < 75 µm were at higher risk for adverse events (HR 4.88, 95%CI 2.44-9.72; P < 0.001). CONCLUSIONS: A high maxOCT-LCBI4mm was related to poor outcome and vulnerable plaque features. This study represents a step further in the automated assessment of the coronary plaque risk profile.

Mediterranean Diet: A Tool to Break the Relationship of Atrial Fibrillation with the Metabolic Syndrome and Non-Alcoholic Fatty Liver Disease.

Atrial fibrillation (AF) is the most common supraventricular arrhythmia associated with increased cardiovascular and non-cardiovascular morbidity and mortality. As multiple factors may predispose the onset of AF, the prevention of the occurrence, recurrence and complications of this arrhythmia is still challenging. In particular, a high prevalence of cardio-metabolic comorbidities such as the metabolic syndrome (MetS) and in its hepatic manifestation, the non-alcoholic fatty liver disease (NAFLD), have been described in the AF population. A common pathogenetic mechanism linking AF, MetS and NAFLD is represented by oxidative stress. For this reason, in the past decades, numerous studies have investigated the effect of different foods/nutrients with antioxidant properties for the prevention of, and their therapeutic role is still unclear. In this narrative comprehensive review, we will summarize current evidence on (1) the association between AF, MetS and NAFLD (2) the antioxidant role of Mediterranean Diet and its components for the prevention of AF and (3) the effects of Mediterranean Diet on MetS components and NAFLD.

[From regression to stabilization: new insights into the evolution of coronary atherosclerotic plaque]. / Dalla regressione alla stabilizzazione: l'evoluzione della placca aterosclerotica coronarica secondo le nuove evidenze.

Coronary artery atherosclerosis is a constantly evolving disease. Over the years, new drug therapies have been shown to reduce adverse cardiovascular events and improve the survival of patients with coronary artery disease. New intracoronary imaging modalities, including intravascular ultrasound, optical coherence tomography, and near-infrared spectroscopy, have been introduced to detect the anatomic changes which follow an effective lipid-lowering therapy in human coronary plaques. Particularly, the use of optical coherence tomography made it possible to evaluate plaque composition and showed how an intensive lipid-lowering therapy can stabilize atherosclerosis by improving vulnerable plaque features. Future non-invasive applications are required for large-scale use of these findings.

The Role of the Association Between Serum C-Reactive Protein Levels and Coronary Plaque Macrophage Accumulation in Predicting Clinical Events - Results from the CLIMA Registry.

The present investigation aims to study the interaction between systemic and intra-plaque inflammation in predicting cardiac events. We investigated C-reactive protein (CRP) levels as well as plaque inflammation with optical coherence tomography (OCT)-detected macrophages in the CLIMA study. 689 patients had admission CRP serum values reported, and high CRP values were defined as ≥ 2 mg/dl. The main study endpoint was a composite of cardiac death, myocardial infarction, and/or target vessel revascularization at 1-year follow-up. At multivariate Cox regression analysis, a large (hazard ratio [HR] 2.27, 95% confidence interval [CI] 1.2-4.3; p = 0.013) and superficial (HR 2.78, 95%CI 1.5-5.1; p = 0.001) macrophage arc was predicted of the main composite endpoint in patients with high CRP levels. Patients with large/superficial macrophage accumulation and low CRP levels were not at higher risk of adverse events. The presence of high CRP levels and large/superficial macrophage accumulation at OCT analysis identified patients at higher risk of clinical events.