Prognostic stratification in pulmonary hypertension: A multi-biomarker approach. / Estratificação prognóstica na hipertensão pulmonar: valor acrescido da abordagem multibiomarcadores.

INTRODUCTION: Pulmonary hypertension (PH) covers a group of conditions characterized by an increase in pulmonary vascular resistance leading to right ventricular failure. Risk stratification is crucial for adequate prognostic and therapeutic assessment. However, the accuracy of conventional parameters is limited, especially biomarkers. OBJECTIVES: To determine the prognostic value of new biomarkers and their combination in a multi-biomarker approach to predict outcome in patients with PH. METHODS: In this prospective cohort study, PH patients underwent clinical, echocardiographic and laboratory assessment, including quantification of serum N-terminal pro-brain natriuretic peptide (NT-proBNP) and of the following new biomarkers: mid-regional pro-adrenomedullin (MR-proADM), copeptin, endothelin-1, mid-regional pro-atrial natriuretic peptide (MR-proANP) and soluble ST2 (sST2), the interleukin-33 receptor. The accuracy of the different parameters for predicting all-cause mortality and death or hospitalization of cardiac causes was determined. The prognostic value of a multi-biomarker score based on the tertile distribution of serum NT-proBNP, MR-proANP, renin and sST2 was compared to conventional markers. RESULTS: Forty-three patients (72.1% female, age 59±15 years) were included, most of whom (65.1%) had group 1 PH. During a median follow-up of 34 months, 26% of the patients died and 35% were hospitalized for cardiac causes. Atrial and ventricular dimensions and right ventricular fractional area change were prognostic predictors. Log NT-proBNP (HR: 31.14; 95% CI: 3.12-310.7; p=0.003) and renin (HR: 1.02; 95% CI: 1.005-1.038; p=0.009) were independent predictors of mortality. MR-proANP (HR: 1.008; 95% CI 1.004-1.011; p<0.001) and sST2 (HR: 1.005; 95% CI 1.001-1.009; p=0.04) were predictors of death or hospitalization. The prognostic value of the multi-biomarker score was higher than any of the conventional parameters, and enabled identification of risk groups (the high-risk group had three-year mortality of 77.8%). CONCLUSION: A multi-biomarker approach was superior for risk stratification to any single marker. A score that incorporates NT-proBNP, MR-proANP, renin and sST2 accurately identifies patients at low, intermediate and high risk.

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. METHODS AND RESULTS: 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).

Takotsubo Syndrome: A Pathway through the Pituitary Disease.

Takotsubo cardiomyopathy (TTC) is characterized by reversible left ventricular apical and/or midventricular hypokinesia with unknown etiology. The clinical presentation is similar to acute myocardial infarction in the absence of significant obstructive coronary artery disease. Various predisposing factors have been related to TTC, such as acute neurological illnesses, endocrine diseases, pain, and emotional stress. We present the first description of an association between TTC cardiomyopathy and panhypopituitarism. This case reinforces the connection between the hormonal and cardiovascular systems. Furthermore, it supports the importance of a comprehensive and integrated medical history in the approach of a patient with cardiac disease, towards clinical decision-making.

[Characterization of lipid profile in primary health care users in 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.

Pulmonary hypertension in Portugal: first data from a nationwide registry.

INTRODUCTION: Pulmonary arterial hypertension (PAH) is a rare disease that must be managed in specialized centers; therefore, the availability of epidemiological national data is critical. METHODS: We conducted a prospective, observational, and multicenter registry with a joint collaboration from five centers from Portugal and included adult incident patients with PAH or chronic thromboembolic pulmonary hypertension (CTEPH). RESULTS: Of the 79 patients enrolled in this study, 46 (58.2%) were classified as PAH and 33 patients (41.8%) as CTEPH. PAH patients had a mean age of 43.4 ± 16.4 years. Idiopathic PAH was the most common etiology (37%). At presentation, PAH patients had elevated right atrial pressure (RAP) (7.7 ± 5.9 mmHg) and mean pulmonary vascular resistance (11.4 ± 6.5 Wood units), with a low cardiac index (2.7 ± 1.1 L·min(-1)·m(-2)); no patient was under selective pulmonary vasodilators; however, at follow-up, most patients were on single (50%), double (28%), or triple (9%) combination vasodilator therapy. One-year survival was 93.5%, similar to CTEPH patients (93.9%), that were older (60.0 ± 12.5 years) and had higher RAP (11.0 ± 5.2 mmHg, P = 0.015). CONCLUSIONS: We describe for the first time nationwide data on the diagnosis, management, and prognosis of PAH and CTEPH patients in Portugal. Clinical presentation and outcomes are comparable with those reported on other national registries.