[ANMCO/SIC Consensus statement on pulmonary arterial hypertension]. / Documento di consenso ANMCO/SIC sull'ipertensione arteriosa polmonare.

Pulmonary hypertension (PH) is a frequent pathological condition worldwide, mainly secondary to cardiovascular and respiratory diseases, with a poor prognosis. Pulmonary arterial hypertension (PAH) is a rare form that affects the arterial pulmonary vasculature. PH and PAH are characterized by non-specific symptoms and a progressive increase of pulmonary vascular resistance that results in progressive, sometimes irreversible, right ventricular dysfunction. In recent years, a growing medical and social commitment on this disease allowed more accurate diagnosis in shorter times. However, the gap between guidelines and clinical practice remains a challenge for all medical doctors involved in the disease management. Considering the needs to share and describe diagnostic and therapeutic pathways, to measure the results obtained and to address the economical and organizational problems of this disease, all involved figures should collaborate to improve its prognostic impact and health expenses. In this consensus document, the PH experts of the Italian Association of Hospital Cardiologists (ANMCO) together with those of the Italian Society of Cardiology (SIC), address 1) definition, classification and unmet needs of PH and PAH; 2) classification and characteristics of centers involved in the diagnosis and treatment of the disease; 3) proposal of organization of a diagnostic-therapeutic pathway, based on robust and recent scientific evidence.

[Pulmonary hypertension associated with left heart diseases: pathophysiology, diagnosis, treatment]. / Ipertensione polmonare associata ad insufficienza cardiaca: fisiopatologia, diagnosi, terapia.

Pulmonary hypertension (PH) is a common complication of diseases affecting the left heart, mostly found in patients suffering from heart failure. Left atrial hypertension is the initial driver of post-capillary PH. However, several mechanisms may lead in a subset of patients to structural changes in the pulmonary vessels with development of a pre-capillary component. The right ventricle may be frequently affected, leading to right ventricular failure and a worse outcome. The differential diagnosis of PH associated with left heart disease vs pulmonary arterial hypertension (PAH) is challenging in patients with cardiovascular comorbidities, risk factors for PAH and/or a preserved left ventricular ejection fraction. Multidimensional clinical phenotyping is needed to identify patients in whom hemodynamic confirmation is deemed necessary, that may be completed by provocative testing in the cath lab. In contrast with PAH, management of PH associated with left heart disease should focus on the treatment of the underlying condition. There is currently no approved therapy for PH associated with left heart disease: some PAH-specific treatments have led to an increase in adverse events in these patients.

[Anticoagulation therapy during pulmonary embolism follow-up in clinical practice]. / Gestione della terapia anticoagulante nel follow-up dell'embolia polmonare nella pratica clinica.

Patients with pulmonary embolism are a heterogeneous population and, after the acute phase and the first 3-6 months, the main issue is whether to continue, and hence how long and at what dose, or to stop anticoagulation therapy. In patients with venous thromboembolism (VTE), direct oral anticoagulants (DOACs) are the recommended treatment (class I, level of evidence B in the latest European guidelines), and in most cases, an "extended" or "long-term" low-dose therapy is warranted. This paper aims to provide a practical management tool to the clinician dealing with pulmonary embolism follow-up: from the evidence behind the most used exams (D-dimer, ultrasound Doppler of the lower limbs, imaging tests, recurrence and bleeding risk scores), and the use of DOACs in the extended phase, to six real clinical scenarios with the relative management in the acute phase and at follow-up. Lastly, a practical algorithm is shown to deal with anticoagulation therapy in the follow-up of VTE patients in a simple, schematic, and pragmatic way.

[Pulmonary hypertension: pre- or post-capillary? The role of provocative tests in the cath lab]. / Ipertensione polmonare pre-capillare o post-capillare? Il ruolo dei test provocativi in sala di emodinamica.

The discrimination between heart failure with preserved ejection fraction (HFpEF) and pulmonary arterial hypertension (PAH) requires a multiparametric approach, eventually culminating in right heart catheterization. Solving this differential diagnosis is crucial in order to properly tailor patient treatment, with relevant clinical implications. However, it is not uncommon to be confronted with patients at intermediate or high risk of having HFpEF whose pulmonary artery wedge pressure (PAWP) falls in a grey zone in between 13 and 15 mmHg. In these patients, a provocative test in the cath lab might be considered, with the aim of unmasking an occult form of HFpEF with non-overt hemodynamic manifestations, or to definitely exclude it.Saline load and physical exercise can be viewed as the most suitable provocative tests seeking to help for the differential diagnosis in this specific patient population. Although normative values for the hemodynamic response to these maneuvers have been proposed, supporting evidence is still preliminary or equivocal. In this paper, we will review the pathophysiological background for the application of provocative tests in the cath lab, as well as methodological and interpretative aspects to discriminate between HFpEF and PAH, highlighting strengths and weaknesses of fluid load and physical exercise.

[Incidence of acute pulmonary embolism in hospitalized COVID-19 Italian patients. A pooled meta-analysis]. / Tasso di embolia polmonare acuta nei pazienti ospedalizzati per COVID-19 in Italia. Metanalisi aggregata.

BACKGROUND: Acute pulmonary embolism (PE) represents a frequent and prognostically relevant complication of COVID-19. METHODS: We performed a systematic review and meta-analysis, according to the PRISMA guidelines to determine the in-hospital incidence of acute PE, based on Italian studies published on this issue. We searched PubMed and Scopus to locate all articles published between February 2020 to October 15, 2021, reporting the incidence of acute PE in Italian COVID-19 patients. The pooled in-hospital incidence of acute PE was calculated using a random-effect model and presented with relative 95% confidence interval (CI). RESULTS: We analysed data from 3287 Italian COVID-19 patients (mean age 65.7 years) included in 20 studies. The pooled in-hospital incidence of acute PE was 20% (95% CI 13.4-28.7%; I2 = 95.1%); the incidence was lower among patients hospitalized in intensive care unit (ICU) (32.3%; 95% CI 20.2-44.0%; I2 = 77.2%) compared to those admitted in general wards (47.6%; 95% CI 18.7-78.2%; I2 = 94.4%). Meta-regression showed a significant direct correlation of acute PE incidence using age, male gender and previous coronary artery disease as moderating variables. Conversely, an inverse correlation was observed in relation to the use of anticoagulation at therapeutic dose. Prophylactic and therapeutic anticoagulation was administered in 80.2% of patients (95% CI 72.5-86.2%; I2 = 91.0%); the former regimen was more frequently used compared to the latter (63.5% vs 14.3%; p<0.001). Computed tomography angiography (CTPA) was used only in 10.7% of infected patients across 7 studies. CONCLUSIONS: One in five COVID-19 patients experienced acute PE as complication of the infection during hospitalization. The in-hospital incidence of acute PE was lower in ICU compared to general wards. CTPA was scantly used. Early prophylactic anticoagulation was associated with a lower incidence of acute PE.

The paradox of pulmonary arterial hypertension in Italy in the COVID-19 era: is risk of disease progression around the corner?

OBJECTIVE: The coronavirus disease 2019 (COVID-19) outbreak has led to significant restrictions on routine medical care. We conducted a multicentre nationwide survey of patients with pulmonary arterial hypertension (PAH) to determine the consequences of governance measures on PAH management and risk of poor outcome in patients with COVID-19. MATERIALS AND METHODS: The present study, which included 25 Italian centres, considered demographic data, the number of in-person visits, 6-min walk and echocardiographic test results, brain natriuretic peptide/N-terminal pro-brain natriuretic peptide test results, World Health Organization functional class assessment, presence of elective and non-elective hospitalisation, need for treatment escalation/initiation, newly diagnosed PAH, incidence of COVID-19 and mortality rates. Data were collected, double-checked and tracked by institutional records between March 1 and May 1, 2020, to coincide with the first peak of COVID-19 and compared with the same time period in 2019. RESULTS: Among 1922 PAH patients, the incidences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 were 1.0% and 0.46%, respectively, with the latter comparable to that in the overall Italian population (0.34%) but associated with 100% mortality. Less systematic activities were converted into more effective remote interfacing between clinicians and PAH patients, resulting in lower rates of hospitalisation (1.2% versus 1.9%) and related death (0.3% versus 0.5%) compared with 2019 (p<0.001). A high level of attention is needed to avoid the potential risk of disease progression related to less aggressive escalation of treatment and the reduction in new PAH diagnoses compared with 2019. CONCLUSION: A cohesive partnership between healthcare providers and regional public health officials is needed to prioritise PAH patients for remote monitoring by dedicated tools.

Sex-Specific Impact of Different Obesity/Metabolic Phenotypes on Long-Term Cardiovascular Outcomes in Acute Coronary Syndrome Patients.

Obesity, a major risk factor for acute coronary syndrome (ACS), is a multifaceted disease with different metabolic phenotypes and sex-specific features. Here, we evaluated the long-term cardiovascular risk by different obesity/metabolic phenotypes and by sex in ACS patients. The occurrence of the composite outcome of death, nonfatal reinfarction with or without PCI and/or stroke was evaluated in 674 patients (504 men; 170 women), consecutively hospitalized for ACS and followed-up for 7 years, who were stratified in metabolically healthy (MHNW) and unhealthy normal weight (MUNW), and in metabolically healthy (MHO) and unhealthy obese (MUO) groups. At baseline, 54.6% of patients were included in the MHNW group, 26.4% in the MUNW, 5.9% in the MHO and 13.1% in the MUO, with no sex-differences in the distribution of phenotypes. The overall rate of major outcome (100 person-years) in the reference group (MHNW) was higher in men than in women (RR: 1.19 vs. 0.6). The Kaplan-Meier curves for cumulative survival free from cardiovascular events according to obesity/metabolic status diverged significantly according to sex (log rank test, p = 0.006), this effect being more prominent in men (log 11.20; p = 0.011), than in women (log 7.98; p = 0.047). Compared to MHNW, the risk increased in obese men (RR: 2.2; 95% 1.11-1.54 in MUO group), whereas in women the risk was confined to metabolically unhealthy subjects (RR: 3.2; 95% CI 1.23-9.98, MUNW group). Our data show a sex-specific impact of obesity phenotypes on long-term cardiovascular risk in patients hospitalized for ACS.

Prevalence of Pulmonary Hypertension in an Unselected Community-Based Population: A Retrospective Echocardiographic Study-RES-PH Study.

INTRODUCTION: The actual prevalence of pulmonary hypertension (PH) in Italy is unknown. Echocardiography is useful in the screening of patients with suspected PH by estimation of the pulmonary artery systolic pressure (PASP) from the regurgitant tricuspid flow velocity evaluation, according to the simplified Bernoulli equation. OBJECTIVES: We aimed to evaluate the frequency of suspected PH among unselected patients. METHODS: We conducted a retrospective cross-sectional database search of 7005 patients, who underwent echocardiography, to estimate the prevalence of PH, between January 2013 and December 2014. Medical and echocardiographic data were collected from a stratified etiological group of PH, using criteria of the European Society of Cardiology classifications. RESULTS: The mean age of the study population was 57.1 ± 20.5 years, of which 55.3% were male. The prevalence of intermediate probability of PH was 8.6%, with nearly equal distribution between men and women (51.3 vs. 48.7%; p = 0.873). The prevalence of high probability of PH was 4.3%, with slightly but not significant higher prevalence in female patients (43.2 vs. 56.8%; p = 0.671). PH is predominant in patients with chronic obstructive pulmonary disease (COPD) or left ventricle (LV) systolic dysfunction and related with age. PASP was significantly linked with left atrial increase and left ventricular ejection fraction. In addition, an increased PASP was related to an enlargement of the right heart chamber. CONCLUSIONS: PH has a frequency of 4.3% in our unselected population, but the prevalence may be more relevant in specific subgroups. A larger epidemiological registry could be an adequate strategy to increase quality control and identify weak points in the evaluation and treatment of these patients.

Pharmacological therapy for the prevention of cardiovascular events in patients with myocardial infarction with non-obstructed coronary arteries (MINOCA): Insights from a multicentre national registry.

AIMS: To assess the effect of pharmacological therapy on long-term prognosis of patients with MINOCA. METHODS AND RESULTS: In this retrospective multicentre cohort study involving 9 Hub Hospitals across Italy we enrolled consecutive patients 18 years and older with diagnosis of MINOCA discharged from 1st March 2012 to 31st March 2018. Data on baseline characteristics and pharmacological therapy at discharge (ACEI/ARB, angiotensin-converting enzyme inhibitors/angiotensin receptor antagonists; ASA, acetylsalicylic acid; beta-blockers; CCB, calcium-channel blockers; DAPT, dual anti-platelet therapy; statins), were collected systematically. The primary endpoint (PE) of the study was a composite of all cause death or acute myocardial infarction or acute coronary syndrome or heart failure leading to hospitalization or stroke. A total of 621 patients were included (mean [SD] age 65.1 [13.9] years; 344 [55.4%] female), of whom 106 (17.1%) experienced PE, including 27 patients (4.3%) who died. Multivariable analysis, after correction for all baseline differences, showed a significant association between pharmacological therapy at discharge and an increased risk of PE for aspirin (HR[95%CI] = 2.47[1.05-5.78], adjusted p = 0.04), whereas beta-blockers were associated with a significant benefit (HR[95%CI] = 0.49 [0.31-0.79], adjusted p = 0.02). CONCLUSION: The use of beta-blockers was significantly associated to a less frequent occurrence of adverse outcomes at long-term follow-up among patients with MINOCA, whereas ASA displayed a potentially harmful impact on prognosis. The findings in the study may be relevant for the design of future studies which should take into account possible heterogeneity among MINOCA patients.

Machine Learning to Calculate Heparin Dose in COVID-19 Patients with Active Cancer.

To realize a machine learning (ML) model to estimate the dose of low molecular weight heparin to be administered, preventing thromboembolism events in COVID-19 patients with active cancer. Methods: We used a dataset comprising 131 patients with active cancer and COVID-19. We considered five ML models: logistic regression, decision tree, random forest, support vector machine and Gaussian naive Bayes. We decided to implement the logistic regression model for our study. A model with 19 variables was analyzed. Data were randomly split into training (70%) and testing (30%) sets. Model performance was assessed by confusion matrix metrics on the testing data for each model as positive predictive value, sensitivity and F1-score. Results: We showed that the five selected models outperformed classical statistical methods of predictive validity and logistic regression was the most effective, being able to classify with an accuracy of 81%. The most relevant result was finding a patient-proof where python function was able to obtain the exact dose of low weight molecular heparin to be administered and thereby to prevent the occurrence of VTE. Conclusions: The world of machine learning and artificial intelligence is constantly developing. The identification of a specific LMWH dose for preventing VTE in very high-risk populations, such as the COVID-19 and active cancer population, might improve with the use of new training ML-based algorithms. Larger studies are needed to confirm our exploratory results.

[ANMCO Position paper: Pulmonary circulation diseases and COVID-19]. / Position paper ANMCO: Malattie del circolo polmonare e COVID-19.

The new coronavirus disease 2019 (COVID-19), which is causing hundreds of thousands of deaths worldwide, is complex and can present with a multi-organ localization. One of its worst complications is an interstitial pneumonia with acute respiratory failure also known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which requires non-invasive or invasive ventilation. A severe coagulopathy with poor prognosis is found in 5-10% of cases. SARS-CoV-2 is manifesting as a multi-dimensional disease and, recently, unique co-existing pathophysiological and clinical aspects are being defined: (i) an increased immune and inflammatory response with the activation of a cytokine storm and consequent coagulopathy, which promote both venous thromboembolic events and in situ thrombosis localized in small arterioles and pulmonary alveolar capillaries; (ii) a high intrapulmonary shunt, which often accounts for the severity of respiratory failure, due to reduced hypoxic pulmonary vasoconstriction with pulmonary neo-angiogenetic phenomena. Furthermore, the high incidence of venous thromboembolism in COVID-19 patients admitted to the intensive care unit and the autoptic findings of in situ micro-thrombosis at the pulmonary vascular level, suggest that in this disease coagulopathy, unlike septic disseminated intravascular coagulation, is driven towards a hyper-thrombogenic state, giving rise to a debate (with ongoing studies) about the preventive use of anticoagulant doses of heparin to reduce mortality. The aim of this position paper from the Italian Association of Hospital Cardiologists (ANMCO) is to highlight the main implications that COVID-19 infection has on the pulmonary circulation from a pathophysiological, clinical and management point of view.

[Proposal for a standardized discharge letter after hospital stay for acute pulmonary embolism]. / Proposta di una lettera di dimissione standardizzata dopo ospedalizzazione per embolia polmonare acuta.

Pulmonary embolism represents the third leading cause of cardiovascular mortality in developed countries. It requires, in most cases, hospital treatment and always a structured follow-up program. Therefore, at the time of discharge, the communication and the transfer of information from the specialist to the general practitioner, through the discharge letter, represents a crucial opportunity. The aim is to improve the quality of the transmitted content, including information regarding initial assessment, procedures during hospitalization, residual risks, discharge treatments, therapeutic goals and follow-up plan in accordance with the latest guidelines. The discharge letter after hospitalization for pulmonary embolism must include personalized information, especially regarding the anticoagulant regimen in the specific onset setting. Finally, the follow-up program should be accurately described. A standardized discharge letter template, accompanied by some final notes addressed to the general practitioner and patient, could represent a useful tool to improve the quality and time of transmission of information between health professionals after pulmonary embolism.

[Diagnostic and therapeutic models for the management of acute pulmonary embolism: an issue of local available resources]. / Modelli diagnostici e terapeutici nel trattamento dell'embolia polmonare acuta: una questione di risorse locali.

Acute pulmonary embolism (PE) still represents the third leading cause of cardiovascular mortality in developed countries. In this regard, the last European guidelines offer important suggestions on the management of the disease in daily clinical practice but, at the same time, they do not take into account the feasibility of the recommendations according to the local available resources, including the presence or lack of adequate healthcare facilities (cardiological intensive care unit, cath-lab) or specialists (cardiologist available on a 24 h basis, interventional cardiologist, cardiac surgeon, etc.) all over the day. In the real clinical practice, those recommendations should be adapted to the local available resources. The aim of this document is to provide some suggestions regarding the diagnosis and treatment of acute PE, according to the possible available resources in different local circumstances.

[ANMCO statement: Arterial and venous thromboembolism: what implications for clinical practice?] / Statement ANMCO: Tromboembolismo arterioso e venoso: quali implicazioni per la pratica clinica?

Acute myocardial infarction, stroke, peripheral arterial disease and pulmonary embolism share thrombosis as a common mechanism. Some well-known risk factors for arterial thromboembolism are recognized as "weak risk factors" of venous one, too. Arterial and venous thrombosis share also some pathophysiological mechanisms, including inflammation, endothelial damage, and hypercoagulability. It is likely, thus, that any disease related to arterial and venous thrombosis belong to the same "pan-vascular syndrome", that constitutes itself a chronic, recurrent inflammatory disease. According to the available data, there are elements for implementing an omni-comprehensive cardiovascular evaluation after an episode of venous thromboembolism, requiring the investigations, in addition to the known unrecognized prothrombotic conditions, also of indirect signs and risk factors for a possible arterial thromboembolic event. Large, prospective studies are needed to establish the more appropriate therapeutic strategies in this context.The aim of the present statement is to make aware all the physicians involved in the management of arterial and venous diseases and to provide some tools for evaluating the implications of related major risk factors. Thus, it could be possible to lay the foundation for a reduction of total cardiovascular risk, in terms of primary and secondary prevention of arterial and venous thromboembolism.

Arterial stiffness and mitral regurgitation in arterial hypertension: an intriguing pathophysiological link.

BACKGROUND: We examined the relative impact of arterial stiffness on the presence and/or severity of chronic mitral regurgitation (MR) in hypertensive patients. METHODS: We prospectively enrolled 141 untreated hypertensive patients (mean age 56.6 ±â€¯11.5 years): 94 with MR, 47 without MR. As a measure of arterial stiffness, pulse wave velocity (PWV) was assessed by applanation tonometry. Assessment of MR severity was obtained through calculation of effective regurgitant orifice area (EROA) and vena contracta by standard two-dimensional transthoracic echocardiography. RESULTS: PWV appears to progressively increase according to the presence and severity of MR (no MR = 7.3 ±â€¯1.1 m/s, mild MR = 7.9 ±â€¯1.3 m/s, moderate MR = 9.0 ±â€¯1.7 m/s, severe MR = 13.3 ±â€¯4.1 m/s; P < 0.001 for all comparisons). EROA was positively correlated with age (P = 0.011), left atrial volume index (P = 0.023), PWV (P < 0.001) and augmentation index (P < 0.001), and negatively correlated with left ventricular ejection fraction (P = 0.002) and heart rate (HR) (P = 0.018). On stepwise multivariate logistic regression analysis, only PWV (OR = 2.87, 95% CI 1.750-4.738, P < 0.001) and HR (OR = 0.94, 95% CI 0.895-0.994, P = 0.02) appeared to be independent predictors of severe MR. Receiver operating characteristic curves showed that a cutoff of 9 m/s for PWV provided the best sensitivity/specificity for predicting both the presence of any degree of MR (sensitivity 73%, specificity 87%, AUC = 0.863; P < 0.001) and MR severity (sensitivity 100%, specificity 81%, AUC = 0.954; P < 0.001). CONCLUSION: Reduced arterial elasticity because of increased stiffness may be an important marker for the presence and severity of MR in hypertensive patients.

Effect of type D personality on smoking status and their combined impact on outcome after acute myocardial infarction.

BACKGROUND: Smoking cessation is correlated with several psychological, social, biological, and pharmacological aspects. The combined tendency to experience negative emotions and to inhibit the expression of these emotions is indicated as "type D personality," an independent risk marker for clinical outcome in cardiac disease. Despite this effect of type D personality on cardiovascular disease, it is still unclear whether this personality trait may influence smoking cessation after a myocardial infarction. HYPOTHESIS: we hypothesized that there is a relationship between type D personality and smoking persistence in acute coronary syndrome patients, and this association may predict a worse long-term prognosis. METHODS: The study enrolled 231 patients with ST-segment elevation myocardial infarction, treated with primary percutaneous coronary intervention. Type D scale 14 (ds 14) was administered upon admission to the hospital. RESULTS: After controlling for demographic and clinical confounders, non-type D patients reported statistically significant higher frequencies of smoking cessation when compared with the type D group. In addition, the presence of this psychological factor anticipates significantly the onset of smoking during adolescence. Furthermore, current type D smokers had a higher incidence of cardiovascular events during long-term follow-up. CONCLUSIONS: Type D personality and smoking status increase the risk of cardiac events. An emotionally stressed personality and persistence of smoking after the first cardiac event, and mostly their mutual influence, indicate a population at high cardiovascular risk.

ANMCO Position Paper: the use of non-vitamin K dependent new oral anticoagulant(s) in pulmonary embolism therapy and prevention.

The new oral anticoagulants (NOACs) have radically changed the approach to the treatment and prevention of thromboembolic pulmonary embolism. The authors of this position paper face, in succession, issues concerning NOACs, including (i) their mechanism of action, pharmacodynamics, and pharmacokinetics; (ii) the use in the acute phase with the 'double drug single dose' approach or with 'single drug double dose'; (iii) the use in the extended phase with demonstrated efficacy and with low incidence of bleeding events; (iv) the encouraging use of NOACs in particular subgroups of patients such as those with cancer, the ones under- or overweight, with renal insufficiency (creatinine clearance > 30 mL/min), the elderly (>75 years); (v) they propose a possible laboratory clinical pathway for follow-up; and (vi) carry out an examination on the main drug interactions, their potential bleeding risk, and the way to deal with some bleeding complications. The authors conclude that the use of NOACs both in the acute phase and in the extended phase is equally effective to conventional therapy and associated with fewer major bleeding events, which make their use in patients at higher risk of recurrences safer.

Clinical impact of angiotensin I converting enzyme polymorphisms in subjects with resistant hypertension.

Angiotensin I converting enzyme (ACE) insertion/deletion (I/D) polymorphism is thought to affect renin-angiotensin system (RAS) activity and development of cardiovascular disease; significant associations between I/D polymorphism and atherosclerosis, stroke, nephropathy, and early mortality were already found. We investigated whether Southern Italy resistant hypertensives presented an association between the presence of I and/or D alleles and early vascular damage, inflammation, and insulin resistance. One-hundred-fifty resistant hypertensives were enrolled, studied, and genotyped; carotid intima-media thickness (cIMT), arterial stiffness (AS), and HOMA indices were also evaluated. D allele was more prevalent, and 74 patients presented DD homozygosis. Sixty-eight patients had metabolic syndrome (MetS), without significant differences between DD and I allele carriers. DD genotype appeared strongly associated with higher HOMA values (p < 0.001), and also with both Augmentation Index (AIx, p = 0.003) and Pulse Wave Velocity (PWV, p = 0.023). A significant association was found between DD genotype and cIMT (p < 0.005), while no association between ACE genotype and the presence of carotid plaques. HOMA was correlated with AS (PWV: p < 0.001; AIx: p < 0.01). DD genotype appeared to be associated with AS and HOMA index, but not with inflammation, independently from blood pressure values and the presence of other MetS factors, confirming D allele as an independent risk marker. Vascular damage may develop and progress independently from other risk factors in resistant hypertensives, likely through the interplay between ACE gene, RAS activity, and insulin resistance.

[ANMCO position paper: Use of new oral anticoagulants for the treatment and prevention of pulmonary thromboembolism]. / Position paper ANMCO: Uso dei nuovi anticoagulanti orali nella terapia e nella prevenzione della tromboembolia polmonare.

The new oral anticoagulants (NOACs) have radically changed the approach to the treatment and prevention of thromboembolic pulmonary embolism. The authors of this position paper face, in succession, issues concerning NOACs, including 1) their mechanism of action, pharmacodynamics and pharmacokinetics; 2) the use in the acute phase with the "double drug single dose" approach or with "single drug double dose"; 3) the use in the extended phase with demonstrated efficacy and with low incidence of bleeding events; 4) the encouraging use of NOACs in particular subgroups of patients such as those with cancer, the ones under- or overweight, with renal insufficiency (creatinine clearance >30 ml/min), the elderly (>75 years); 5) they propose a possible laboratory clinical pathway for follow-up; 6) carry out an examination on the main drug interactions, their potential bleeding risk, and the way to deal with some bleeding complications. The authors conclude that the use of NOACs both in the acute phase and in the extended phase is equally effective to conventional therapy and associated with fewer major bleeding events, which make their use in patients at higher risk of recurrences safer.