Manuela Fiuza

Cystatin C as Prognostic Biomarker in ST-Segment Elevation Acute Myocardial Infarction

Cystatin C is a marker of renal dysfunction, and preliminary studies have suggested it might have a role as a prognostic marker in patients with coronary artery disease. The aim of the present study was to evaluate the usefulness of cystatin C for risk stratification of patients with ST-segment elevation myocardial infarction, regarding in-hospital and long-term outcomes. We included 153 consecutive patients with ST-segment elevation myocardial infarction treated by primary angioplasty. The baseline cystatin C level was measured at coronary angiography. The in-hospital outcome was determined as progression to cardiogenic shock or in-hospital death, and the long-term outcome was assessed, considering the following end points: (1) death and (2) death or reinfarction. Of the 153 patients evaluated (age 61 ± 12 years; 75.6% men), 15 (14.4%) progressed to cardiogenic shock and 4 (2.7%) died during hospitalization. The patients who progressed to cardiogenic shock or died during hospitalization had significantly greater cystatin C levels (1.02 ± 0.44 vs 0.69 ± 0.24 mg/L; p = 0.001). Long-term follow-up was available for 130 patients (583 ± 163 days). Among them, 11 patients died and 7 had reinfarction. A high baseline cystatin C level was associated with an increased risk of death (hazard ratio 8.5; p = 0.009) and death or reinfarction (hazard ratio 3.89; p = 0.021). Furthermore, only high baseline cystatin C levels and left ventricular ejection fraction ≤40% were independent predictors of the long-term risk of death, with synergistic interaction between the 2. In conclusion, cystatin C is a new biomarker with significant added prognostic value for patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention, predicting both short- and long-term outcomes.

Circulating miR-122-5p/miR-133b Ratio Is a Specific Early Prognostic Biomarker in Acute Myocardial Infarction

BACKGROUND MicroRNAs (miRNAs) are key players in cardiovascular development and disease. However, not only miRNAs of a cardiac origin have a critical role in heart function. Recent studies have demonstrated that miR-122-5p, a hepatic miRNA, increases in the bloodstream during ischemic cardiogenic shock and it is upregulated in the infarcted myocardium. The aim of the present study was to determine the potential of circulating miR-122-5p as a biomarker for early prognostic stratification of ST-segment elevation acute myocardial infarction (STEMI) patients. METHODSANDRESULTS One hundred and forty-two consecutive STEMI patients treated with primary angioplasty were included in the study. Serum levels of miR-1-3p, -122-5p, -133a-3p, -133b, -208b-3p and -499a-5p were measured at the time of cardiac catheterization by quantitative polymerase chain reaction and related to in-hospital and long-term outcome. During a follow up of 20.8 months, 9 patients died, 6 had recurrence of myocardial infarction, and 26 patients suffered an adverse cardiovascular event. Event-free survival was significantly worse in patients with a higher miR-122-5p/133b ratio (3rd tertile distribution, above 1.42 Log(10)), having almost a 9-fold higher risk of death or myocardial infarction and a 4-fold higher risk of adverse cardiovascular events. CONCLUSIONS This study showed that the miR-122-5p/133b ratio is a new prognostic biomarker for the early identification of STEMI patients at a higher risk of developing major adverse events after undergoing primary percutaneous coronary intervention. (Circ J 2016; 80: 2183-2191).

Association of metabolic risk factors with uncontrolled hypertension: comparison of the several definitions of metabolic syndrome

Aims: To evaluate the influence of metabolic syndrome in the effectiveness of antihypertensive treatment and to compare it using the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) (2001 and 2004), International Diabetes Federation (IDF) and American Heart Association/National Heart, Lung and Blood Institute (AHA-NHLBI) definitions. Methods: The VALSIM (Estudo de Prevalência da Síndrome Metabólica) survey was designed as an observational cross-sectional study performed in a primary healthcare setting in Portugal. The first two adult patients scheduled for an appointment on a given day were invited to participate. The treatment effectiveness was evaluated by the occurrence of uncontrolled hypertension (≥140/90 mmHg) in patients taking antihypertensive drugs. Logistic regression analysis was used to determine the association between uncontrolled hypertension and metabolic risk factors, with adjustments for age, sex, and pattern of antihypertensive treatment. Results: Among the 16 856 individuals evaluated, 8925-treated hypertensive patients were identified. Only 35.8% of them had controlled hypertension. The risk of poor blood pressure control increased with age, waist circumference, serum levels of triglycerides and HDL-cholesterol. Among treatable risk factors, metabolic syndrome as defined by NCEP-ATP III 2001 diagnostic criteria was the strongest independent predictor of uncontrolled hypertension (odds ratio: 1.23; 95% CI: 1.08–1.41; P = 0.002). In opposition, the IDF or AHA-NHLBI definitions of metabolic syndrome failed to identify patients at risk of poor blood pressure control. Conclusion: Metabolic syndrome is associated with lower effectiveness of antihypertensive therapy and the NCEP-ATP III 2001 definition of metabolic syndrome is the one that better identifies patients at risk of poor blood pressure control.

Expanding the functional role of miRNAs in the establishment of permanent atrial fibrillation.

a University Hospital Santa Maria, Department of Cardiology, Lisbon Academic Medical Centre, CCUL, Lisbon University, Lisbon, Portugal b Programme for Advanced Medical Education, Fundação Calouste Gulbenkian, Ministry of Health and Foundation for Science and Technology, Lisbon, Portugal c Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal d University Hospital Santa Maria, Department of Cardiothoracic Surgery, Lisbon Academic Medical Centre, CCUL, Lisbon University, Lisbon, Portugal

Caracterização do perfil lipídico nos utentes dos cuidados de saúde primários em Portugal

AIM To characterize the distribution of total cholesterol (TC), LDL cholesterol (LDL-C), HDL cholesterol (HDL-C) and triglycerides in primary health care users. METHODS We performed a cross-sectional study in a primary care setting, involving 719 general practitioners based on stratified distribution proportional to the population density of each region of Portugal. The first two adult patients scheduled for an appointment on a given day were invited to participate. A questionnaire was applied to assess sociodemographic, clinical and laboratory data including lipid profile. RESULTS The study included 16 856 individuals (mean age 58.1±15.1 years; 61.6% women). Data on TC, LDL-C, HDL-C and triglycerides were available for 95.9% (n=16 159), 59.1% (n=9956), 95.4% (n=16 074) and 97.9% (n=16 494) of the population, respectively. Hypercholesterolemia (TC ≥200 mg/dl) was detected in 47%, and 38.4% had high levels of LDL-C (≥130 mg/dl). Hypertriglyceridemia (≥200 mg/dl) and low HDL-C (<40 mg/dl) were less prevalent, affecting roughly 13% of the population. Dyslipidemia was more common in middle-aged men and in post-menopausal women. Of the population aged over 40, 54.1% met eligibility criteria for lipid-lowering therapy and 44.7% were medicated with statins, but only 16.0% of these had TC ≤175 mg/dl. CONCLUSIONS Dyslipidemia is highly prevalent in primary health care users in Portugal. It is particularly common in middle-aged men and post-menopausal women, who should be considered target groups for preventive public health measures.

Síndrome metabólica e doença coronária

Atherosclerotic cardiovascular disease (CVD) is the leading cause of death in the western world. In recent years there have been significant reductions in associated mortality, but these gains are at risk of being reversed in the future by the increasing incidence of obesity, metabolic syndrome (MS) and diabetes. MS is defined as a cluster of metabolic risk factors that are associated with a high risk for CVD and diabetes. Its prevalence is rising worldwide, although different epidemiological studies give widely varying estimates, which may be explained by variations between geographical areas and ethnic groups, as well as differences in the definition of MS used. Based on the NCEP-ATP III criteria, the prevalence in the USA is 23.7% and in Portugal it is 27.5%.1 The cardiovascular risk arising from different combinations of the components of MS is not uniform; each component is an independent risk factor for CVD, and they all interact synergistically, further increasing risk. This highlights the epidemiological importance of the concept of MS, which can help identify a subgroup of individuals with increased cardiovascular risk among the overall population at low absolute risk of coronary events. Atherosclerosis, the main predisposing factor for CVD, is a process that begins in childhood and remains silent for decades. This presents the opportunity for early detection and individualized preventive measures. Despite their importance in the etiology of atherosclerosis, there are significant limitations to the use of conventional cardiovascular risk factors for identifying asymptomatic individuals

COMPARISON OF DEFINITIONS OF METABOLIC SYNDROME IN RELATION TO THE RISK OF CORONARY HEART DISEASE AND STROKE: PP.34.360

Aims: To compare definitions of metabolic syndrome (MS) with regard to their association with coronary artery disease (CAD) and stroke. Methods: Cross-sectional study performed in a primary care setting, involving 719 general practitioners pursuant to stratified distribution proportional to the population density. The first 2 adult patients scheduled for an appointment on a given day were invited to participate, irrespective of the reason for the consultation. A questionnaire for social-demographic, clinical and laboratory data was applied. MS diagnosis was defined according to NCEP-ATP III 2001, NCEP-ATP III 2004, IDF and AHA/NHLBI criteria. Multivariate logistic regression analysis was used to assess the risk of CAD and stroke according to sex, age, body mass index, waist circumference, HDL-cholesterol, triglycerides, hypertension (HT), diabetes and MS according to each definition. Results: The study included 16,856 individuals (58.1 ± 15.1 years). The prevalence of MS adjusted to sex, age and size of the regions by NCEP-ATP III 2001, 2004, IDF and AHA/NHLBI definitions was 28.4%, 32.8%, 65.5% and 69.4%, respectively. The degrees of agreement according to the k statistics were modest and only 60.3% simultaneously fulfilled the criteria of all definitions. HT was the treatable risk factor most strongly associated to CAD and stroke. Only the IDF and AHA/NHLBI definitions of MS were independently associated to CAD (OR: 1.74 and 2.26, respectively). Regarding to stroke, only AHA/NHLBI criteria provided statistically significant association (OR: 1.85). Conclusions: The definition of MS according to the AHA/NHLBI criteria appears to be a better predictor of CAD and stroke in the Portuguese population. MS as defined by AHA/NHLBI criteria remains an independent risk factor for CAD and stroke after adjustment to its individual components. Figure 1. No caption available.

Cardiovascular Damage Induced by Anti-VEGF Therapy

Vascular endothelial growth factor (VEGF) plays an important role in maintaining the regular homeostasis of vascular walls. VEGF binds its receptor (VEGFR) promoting the regular survival and function of endothelial cells. Anti-VEGF and anti-VEGFR drugs inhibit the action of VEGF and VEGFR. These drugs can cause cardiovascular toxic effects such as arterial hypertension, thromboembolism, myocardial ischemia and heart failure. The monoclonal antibody bevacizumab and tyrosine kinase inhibitors (sorafenib, sunitinib, pazopanib, regorafenib, axitinib, cabozantinib, ponatinib) are the main inhibitors of VEGF, VEGFR and other tyrosine kinases. In this chapter we will illustrate the cardiovascular toxic effects of these drugs, their mechanism of action, strategy to early diagnose and treat these complications. We will also illustrate strategy to prevent cardiovascular toxicity. It is important to know cardiovascular toxic effect of these drugs widely used in oncological field, to avoid the development of severe future complications.

Cardiovascular Damage Induced by Anti-BCR-ABL TKIs

Anti-BCR-ABL TKIs (tyrosine kinase inhibitors) are drugs that inhibit BCR ABL tyrosine. They are used especially in the treatment of hematological cancer and gastrointestinal stromal tumors (GIST). Anti-BCR-ABL TKIs include first (imatinib), second (nilotinib, dasatinib, bosutinib) and third-generation drugs (ponatinib). Especially second- and third-generation drugs can cause cardiovascular complications such as arterial thrombosis, myocardial ischemia, peripheral arterial diseases, QTc prolongation, and pulmonary hypertension. Nilotinib and ponatinib can cause thrombotic arterial events with various mechanisms. Particularly dasatinib can cause pulmonary hypertension. Compared to conventional chemotherapy, myocardial dysfunction was found in a smaller number of cases. In this chapter, we will illustrate cardiovascular adverse effects induced by anti-BCR-ABL TKIs, the main mechanisms that could explain such effects, and the influence played by cardiovascular risk factors. It is essential for both cardiologists and oncologists to know these issues in order to develop appropriate monitoring and apply preventive strategies to avoid the occurrence of toxicity and the need of any premature interruption of the antineoplastic treatment.

Organização e implementação de uma consulta de cardio‐oncologia

Considerable advances in cancer therapies in recent decades have reshaped the prognosis of cancer patients. There are now estimated to be over 20 million cancer survivors in the USA and Europe, numbers unimaginable a few years ago. However, this increase in survival, along with the aging of the patient population, has been accompanied by a rise in adverse cardiovascular effects, particularly when there is a previous history of heart disease. The incidence of cardiotoxicity continues to grow, which can compromise the effectiveness of cancer therapy. Cardiotoxicity associated with conventional therapies, especially anthracyclines and radiation, is well known, and usually leads to left ventricular dysfunction. However, heart failure represents only a fraction of the cardiotoxicity associated with newer therapies, which have diverse cardiovascular effects. There are few guidelines for early detection, prevention and treatment of cardiotoxicity of cancer treatments, and no well-established tools for screening these patients. Echocardiography is the method of choice for assessment of patients before, during and after cancer treatment. It therefore makes sense to adopt a multidisciplinary approach to these patients, involving cardiologists, oncologists and radiotherapists, collaborating in the development of new training modules, and performing clinical and translational research in a cardio-oncology program. Cardio-oncology is a new frontier in medicine and has emerged as a new medical subspecialty that concentrates knowledge, understanding, training and treatment of cardiovascular comorbidities, risks and complications in patients with cancer in a comprehensive approach to the patient rather than to the disease.