Rita Pavasini

Chronic obstructive pulmonary disease and ischemic heart disease comorbidity: overview of mechanisms and clinical management.

In the last few years, many studies focused their attention on the relationship between chronic obstructive pulmonary disease (COPD) and ischemic heart disease (IHD), showing that these diseases are mutually influenced. Many different biological processes such as hypoxia, systemic inflammation, endothelial dysfunction, heightened platelet reactivity, arterial stiffness and right ventricle modification interact in the development of the COPD-IHD comorbidity, which therefore deserves special attention in early diagnosis and treatment. Patients with COPD-IHD comorbidity have a worst outcome, when compared to patients with only COPD or only IHD. These patients showed a significant increase on risk of adverse events and of hospital readmissions for recurrent myocardial infarction, heart failure, coronary revascularization, and acute exacerbation of COPD. Taken together, these complications determine a significant increase in mortality. In most cases death occurs for cardiovascular cause, soon after an acute exacerbation of COPD or a cardiovascular adverse event. Recent data regarding incidence, mechanisms and prognosis of this comorbidity, along with the development of new drugs and interventional approaches may improve the management and long-term outcome of COPD-IHD patients. The aim of this review is to describe the current knowledge on COPD-IHD comorbidity. Particularly, we focused our attention on underlying pathological mechanisms and on all treatment and strategies that may improve and optimize the clinical management of COPD-IHD patients.

Cardiac troponin elevation predicts all-cause mortality in patients with acute exacerbation of chronic obstructive pulmonary disease: Systematic review and meta-analysis

BACKGROUND Cardiovascular disease, especially ischemic heart disease, is a major comorbidity in chronic obstructive pulmonary disease (COPD) patients. Several studies suggested that after acute exacerbation of COPD (AECOPD), there is a significant increase of mortality (cardiac and all-cause) and of myocardial infarction. Whether cardiac troponin (Tn) elevation during AECOPD could be considered a prognostic marker of all-cause mortality is still debated. METHODS To assess the prognostic role of cardiac Tn elevation during AECOPD, we performed a systematic review and meta-analysis. We included studies with patients admitted to the hospital for AECOPD, with at least one Tn assessment and reporting the relationship (after multivariable analysis) between Tn elevation and all-cause mortality. Secondarily, studies were stratified according to: i) type of troponin (Tn I or Tn T), and ii) follow-up length (≤6 months vs. >6 months). RESULTS Ten studies were included in the systematic review and 8 in the meta-analysis. Cardiac Tn elevation ranges from 18% to 73%. We found that cardiac Tn elevation was significantly related to an increased risk for all-cause mortality (OR 1.69; 95% CI 1.25-2.29; I(2) 40%). This finding was independent to the follow-up length of studies (≤6 months: OR 3.22; 95% CI 1.31-7.91; >6 months: OR 1.38; 95% CI 1.02-1.86). Finally, Tn T seems to be more helpful in predicting all-cause mortality as compared to Tn I (OR 1.54; 95% CI 1.2-1.96 vs. OR 3.39, 95% CI 0.86-13.36, respectively). CONCLUSIONS In patients admitted to the hospital for AECOPD, cardiac Tn elevation emerged as an independent predictor of increased risk of all-cause mortality.

Uric acid and coronary artery disease: An elusive link deserving further attention

Uric acid is the final product of purine metabolism. Classically it is recognized as the cause of gouty arthritis and kidney stones. Western civilization has increased serum levels of uric acid which is no longer considered a benign plasma solute. It has been postulated and recently demonstrated that it can penetrate cell membrane and exerts damaging intracellular actions such as oxidation and inflammation. These observations have stimulated several epidemiological researches suggesting that hyperuricemia is linked or even provokes hypertension and coronary artery disease. In this review we summarize the current evidences regarding uric acid which contribute in the pathophysiology of coronary artery disease.

Relationship between Troponin Elevation, Cardiovascular History and Adverse Events in Patients with acute exacerbation of COPD

ABSTRACT Evidence suggests that troponin (Tn) elevation during acute exacerbation of chronic obstructive pulmonary disease (AECOPD) may predict an increase in mortality risk. We performed an observational study of 935 patients admitted to hospital for AECOPD from January 2010 to December 2012. Principal clinical and laboratory data were recorded, especially ischemic heart disease (IHD) history, Tn T values and cardiovascular drug prescription. The occurrence of all-cause death, cardiac death (CD), nonfatal myocardial infarction (MI), heart failure and cerebrovascular accident (CVA) was assessed on December 2013. Overall, 694 patients respected inclusion and exclusion criteria. We identified 210 (30%) patients without Tn elevation (negative Tn T group) and 484 (70%) patients with Tn elevation (positive Tn T group). With the exception of CVA, all adverse events were significantly higher in positive Tn T group as compared to negative Tn T group. At multivariable analysis, positive Tn T failed to predict all-cause death. Contrarily, positive Tn T emerged as independent predictors of CD (HR 1.61, 95%CI 1.2–2.2, p = 0.04), nonfatal MI (HR 3.12, 95%CI 1.4–8.1, p = 0.03) and composite endpoint including CD and nonfatal MI (HR 1.73, 95%CI 1.2–2.7, p = 0.03). Of note, positive Tn T stratified prognosis in patients without IHD history, but not in those with IHD history. In conclusion, after hospital admission for AECOPD, we observed a significant increase in the risk of cardiac adverse events in patients with Tn T elevation, especially in those without IHD history.

On-treatment platelet reactivity in patients with chronic obstructive pulmonary disease undergoing percutaneous coronary intervention

Patients with chronic obstructive pulmonary disease (COPD) show a poor prognosis after myocardial infarction (MI) and percutaneous coronary intervention (PCI). We evaluated on-treatment platelet reactivity (PR) and several gene polymorphisms related to PR in 130 patients undergoing PCI with and without COPD. Those with concomitant COPD showed higher on-treatment PR values both at the time of PCI and 1 month after. This finding may contribute to explain the poor prognosis of COPD patients after MI and PCI.

Thrombin generation assay: a new tool to predict and optimize clinical outcome in cardiovascular patients?

Antithrombotic therapy (including antiplatelet and anticoagulant drugs) is the cornerstone of the current medical treatment of patients with acute coronary syndromes (ACS). This therapy and particularly the new antiplatelet and anticoagulant drugs have significantly reduced the ischemic risk, but have increased bleeding complications. Recently, several studies have emphasized the negative prognostic impact on long-term mortality of these bleeding adverse events. Thus, new assays to estimate the bleeding risk and the efficacy of these antithrombotic drugs are clearly in demand. Regarding the anticoagulant drugs, new promising data have emerged about the thrombin generation assay (TGA). TGA measures the ability of plasma to generate thrombin. TGA may be used to check coagulation function, to value risk of thrombosis and to compare the efficacy of different anticoagulants employed in clinical management of patients with ACS. The TGA result is a curve which describes the variation of thrombins amount during the activation of the coagulation cascade. All available anticoagulant drugs influence the principal parameters generated by TGA and so it is possible to evaluate the effects of the medical treatment. In this review we provide a brief description of the assay and we summarize the principals of previous studies by analyzing the relationship between anticoagulant drugs and TGA. Moreover, a brief summary of its ability to predict ischemic and bleeding risks has been provided.

Occurrence, causes, and outcome after switching from ticagrelor to clopidogrel in a real-life scenario: data from a prospective registry

Abstract In randomized clinical trials, ticagrelor has been substituted in roughly one-third of the patients during follow-up. To date, there are no studies addressing safety and modalities of switching from ticagrelor to clopidogrel. The aim of our study is to describe the occurrence, causes, and outcome of the switch from ticagrelor to clopidogrel in a real-life scenario. From June 2013 to March 2015, 586 patients were treated with ticagrelor in our centre. Overall, 101 (17%) patients were switched to clopidogrel through a standardized protocol, and they were followed-up for 12 months. Ischemic and bleeding events were prospectively recorded. The switch from ticagrelor to clopidogrel occurred mostly after discharge (69 ± 40 days), and the most frequent cause was the need of oral anticoagulation treatment, followed by bleeding events. Patients requiring ticagrelor discontinuation were older, more frequently female, with lower body mass index and creatinine clearance if compared to the “non-switched” group. In the 10 days after the switch, we did not observe ischemic adverse events. No definite/probable stent thrombosis was recorded. Before the switch, there was a significant higher occurrence of BARC bleedings in the “switched” group, particularly BARC 1 and 2. Our data confirm that the switch from ticagrelor to clopidogrel is common, and it occurs for several reasons. Our analysis did not demonstrate a significant increase in adverse cardiovascular events in the days following the switch from ticagrelor to clopidogrel, although larger studies are needed to validate our findings.

Overview of the pharmacological challenges facing physicians in the management of patients with concomitant cardiovascular disease and chronic obstructive pulmonary disease

Cardiovascular disease (CVD), including ischaemic heart disease (IHD) and heart failure (HF), and chronic obstructive pulmonary disease (COPD) are often concomitant because they share both risk factors (smoke) and pathological pathways (systemic inflammation). Cardiovascular disease and COPD association is increasing overtime. Several registries clearly showed a negative impact on the clinical outcome of the concomitant presence of CVD and COPD. Patients with CVD and COPD present an increased risk for myocardial infarction, HF, and hospital admission for acute exacerbation of COPD, with a negative impact on prognosis. To reduce the effect of this negative association, it is of paramount importance the pharmacological treatment with both cardiovascular and respiratory drugs, according to current guidelines. Nevertheless, several registries and studies showed that evidence-based drugs (both cardiovascular and respiratory) are often under administered in this subset of patients. In this overview, we summarize the available data regarding the use of cardiovascular drugs (antiplatelet agents, angiotensin converting enzyme inhibitors, β-blockers, and statins) in COPD patients, with or without concomitant IHD. Furthermore, we report advantages and disadvantages of respiratory drugs (β2 agonists, anti-cholinergics, and corticosteroids) administration in COPD patients with CVD.

Biological effects of ticagrelor over clopidogrel in patients with stable coronary artery disease and chronic obstructive pulmonary disease

Summary Patients with SCAD and concomitant COPD are at high risk of cardiovascular adverse events, due to chronic inflammation, responsible of endothelial dysfunction, oxidative stress and heightened platelet reactivity (PR). The objective of this randomised clinical trial was to test if ticagrelor is superior to clopidogrel in improving endothelial function in patients with stable coronary artery disease (SCAD) and concomitant chronic obstructive pulmonary disease (COPD). Forty-six patients with SCAD and COPD undergoing percutaneous coronary intervention (PCI) were randomly assigned to receive clopidogrel (n=23) or ticagrelor (n=23) on top of standard therapy with aspirin. The following parameters were assessed at baseline and after 1 month: i) rate of apoptosis and ii) nitric oxide (NO) levels in human umbilical vein endothelial cells (HUVECs), iii) levels of reactive oxygen species (ROS) in peripheral blood mononuclear cell, iv) 29 cytokines/chemokines, v) on-treatment PR. The primary endpoint of the study was the 1-month rate of HUVECs apoptosis. The rate of apoptosis after 1 month was significantly lower in patients treated with ticagrelor (7.4 ± 1.3% vs 9.3 ± 1.5%, p<0.001), satisfying the pre-specified primary endpoint. In the ticagrelor arm, levels of NO were higher (10.1 ± 2.2 AU vs 8.5 ± 2.6 AU, p=0.03) while those of ROS (4 ± 1.8 AU vs 5.7 ± 2.8 AU, p=0.02) and P2Y 12 reactivity units (52 ± 70 PRU vs 155 ± 62 PRU, p<0.001) were lower. There were no differences in cytokines/chemokines levels and aspirin reactivity units between groups. In patients with SCAD and COPD undergoing PCI, ticagrelor, as compared to clopidogrel is superior in improving surrogate markers of endothelial function and on-treatment PR (ClinicalTrials.gov, NCT02519608). Supplementary Material to this article is available online at www.thrombosis-online.com.

Fo ATP synthase C subunit serum levels in patients with ST-segment Elevation Myocardial Infarction: Preliminary findings

BACKGROUND Recent studies in cell cultures hypothesized that the long-sought molecular pore of the mitochondrial permeability transition pore could be the Fo ATP synthase C subunit (Csub). We assessed Csub in patients with ST-segment elevation myocardial infarction (STEMI) and if it is associated with surrogate endpoints of myocardial reperfusion. METHODS We enrolled 158 first-time acute anterior STEMI treated with successful percutaneous coronary intervention (PCI). Csub was measured, after the procedure, in serum by ELISA. Csub values were related to thrombolysis in myocardial infarction (TIMI) myocardial perfusion grade (TMPG), TIMI frame count (TFC), ST-segment resolution and cardiac marker release. Echocardiography and clinical outcome were recorded at 6months. RESULTS Csub was detectable in serum and it was not normally distributed (6.3% [4-9.3%]). Csub values were higher in patients with poor values of TMPG and TFC (p=0.002 and p=0.001, respectively). Csub values were higher in patients with absent or partial ST-segment resolution as compared to those with complete ST-segment resolution (p<0.0001 and p=0.003, respectively). After adjustment for potential confounding factors, Csub emerged as an independent determinant of absent ST-segment resolution (HR 1.8, 95% CI 1.5-2.3, p=0.007), TMPG 0-1 (HR 1.7, 95% CI 1.3-2.5, p=0.01) and TFC above the median value (HR 1.5, 95% CI 1.3-2.1, p=0.03). Left ventricle ejection fraction, wall motion score index and cumulative incidence of death and heart failure were worse in patients with elevated Csub. CONCLUSIONS Our study is the first evidence that Csub is detectable in STEMI patients and that it is significantly related to several surrogate markers of myocardial reperfusion.