Portuguese Heart Failure Prevalence Observational Study (PORTHOS) rationale and design - A population-based study.

INTRODUCTION AND OBJECTIVES: Current epidemiological data on heart failure (HF) in Portugal derives from studies conducted two decades ago. The main aim of this study is to determine HF prevalence in the Portuguese population. Using current standards, this manuscript aims to describe the methodology and research protocol applied. METHODS: The Portuguese Heart Failure Prevalence Observational Study (PORTHOS) is a large, three-stage, population-based, nationwide, cross-sectional study. Community-dwelling citizens aged 50 years and older will be randomly selected via stratified multistage sampling. Eligible participants will be invited to attend a screening visit at a mobile clinic for HF symptom assessment, anthropomorphic assessment, N-terminal pro-B-type natriuretic peptide (NT-proBNP) testing, one-lead electrocardiogram (ECG) and a sociodemographic and health-related quality of life questionnaire (EQ-5D). All subjects with NT-proBNP ≥125 pg/mL or with a prior history of HF will undergo a diagnostic confirmatory assessment at the mobile clinic composed of a 12-lead ECG, comprehensive echocardiography, HF questionnaire (KCCQ) and blood sampling. To validate the screening procedure, a control group will undergo the same diagnostic assessment. Echocardiography results will be centrally validated, and HF diagnosis will be established according to the European Society of Cardiology HF guidelines. A random subsample of patients with an equivocal HF with preserved ejection fraction diagnosis based on the application of the Heart Failure Association preserved ejection fraction diagnostic algorithm will be invited to undergo an exercise echocardiography. CONCLUSIONS: Through the application of current standards, appropriate methodologies, and a strong research protocol, the PORTHOS study will determine the prevalence of HF in mainland Portugal and enable a comprehensive characterization of HF patients, leading to a better understanding of their clinical profile and health-related quality of life.

Missed opportunities in the diagnosis of heart failure: a real-world assessment.

AIMS: Heart failure (HF) is a leading cause of hospitalization worldwide. An early HF diagnosis is key to reducing hospitalizations. We used electronic health records (EHRs) to characterize HF pathways at the primary care physician (PCP) level prior to a first HF hospitalization (hHF). This study aimed to identify missed opportunities for HF diagnosis and management at the PCP level before a first hHF. METHODS AND RESULTS: This cohort study used EHRs of a large health care organization in Portugal. Patients with incident hHF between 2017 and 2020 were identified. Missed opportunities were defined by the absence of any of the following work-up in the 6 months after signs or symptoms had been recorded: lab results and electrocardiogram, natriuretic peptides, echocardiogram, referral to HF specialist, or HF medication initiation. A total of 2436 patients with a first hHF were identified. The median (interquartile range) age at the time of hospitalization was 81 (14) years, and 1361 (56%) were women. Most patients were treated with cardiovascular drugs prior or at index event. A total of 720 (30%) patients had records of HF signs or symptoms, 94% (n = 674) within 6 months prior to hHF. Among patients with recorded HF signs or symptoms, 410 (57%) had clinical management considered adequate before signs and symptoms were recorded. Of the 310 remaining patients, 155 (50%) had a follow-up that was considered inadequate. CONCLUSIONS: Relatively few patients with a first hHF had primary care records of signs or symptoms prior to admission. Of these, nearly half had inadequate management considering diagnosis and treatment. These data suggest the need to improve PCP HF awareness.

Twenty years of real-world data to estimate chronic kidney disease prevalence and staging in an unselected population.

Chronic kidney disease (CKD) represents a global public health burden, but its true prevalence is not fully characterized in the majority of countries. We studied the CKD prevalence in adult users of the primary, secondary and tertiary healthcare units of an integrated health region in northern Portugal (n = 136 993; representing ∼90% of the region's adult population). Of these, 45 983 (33.6%) had at least two estimated glomerular filtration rate (eGFR) assessments and 30 534 (22.2%) had at least two urinary albumin:creatinine ratio (UACR) assessments separated by at least 3 months. CKD was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines as a persistent decrease in eGFR (<60 ml/min/1.73 m2) and/or an increase in UACR (≥30 mg/g). The estimated overall prevalence of CKD was 9.8% and was higher in females (5.5%) than males (4.2%). From these, it was possible to stratify 4.7% according to KDIGO guidelines. The prevalence of CKD was higher in older patients (especially in patients >70 years old) and in patients with comorbidities. This is the first real-world-based study to characterize CKD prevalence in a large, unselected Portuguese population. It probably provides the nearest estimate of the true CKD prevalence and may help healthcare providers to guide CKD-related policies and strategies focused on prevention and on the improvement of cardiovascular disease and other outcomes.

Characteristics of Oral Corticosteroid Users Among Persons with Asthma on GINA Step 3 Therapy and Above: A Cross-Sectional Study in Portuguese Community Pharmacies.

Purpose: Oral corticosteroids (OCS) are frequently used in asthma management but have an important risk-profile. The aim of the study is to characterize and compare the sociodemographic and clinical characteristics, treatment regimen and asthma control between OCS users and non-users among the population of asthma patients (≥18 years) at GINA step 3 and above treated with a fixed combination of an inhaled corticosteroid and a long-acting beta-agonist (ICS/LABA). Methods: Cross-sectional study in Portuguese community pharmacies. Data was collected via paper-based interview delivered at the pharmacy (sociodemographic characteristics and asthma treatment regimen, namely ICS/LABA and OCS utilization), followed by a telephonic interview collecting smoking history, comorbidities, body mass index (BMI), history of exacerbations and asthma-related healthcare resource utilization (HCRU) in the previous 12 months, as well as asthma control using the Control of Allergic Rhinitis and Asthma Test (CARAT®). Results: A total of 347 patients recruited in 98 pharmacies were included in the analysis. Of those, 328 had completed both questionnaires. A quarter of the individuals reported OCS use in the previous 12 months (OCS users), either as add-on therapy (6%) or exacerbation treatment (19%). Patients were mostly females (72%), with an average age of 59.5 years (SD=15.4). OCS users were significantly older and reported more frequently having conjunctivitis (25.9% vs 15.0%), osteoporosis (25.9% vs 13.4%), arthritis (14.6% vs 6.9%), and gastrointestinal disease (16.1% vs 8.1%). OCS users also reported greater urgent HCRU: unscheduled consultations (33.3% vs 9.3%) and emergency department (ED) visits (32.1% vs 12.1%). Both groups presented poor disease control (85.2% of OCS users vs 72.9% of non-OCS users). Conclusion: These results highlight the burden of OCS therapy to asthma patients and the need to improve asthma management, by adopting OCS sparing strategies in this subgroup of patients.

Prevalence and Characterisation of Patients with Asthma According to Disease Severity in Portugal: Findings from the EPI-ASTHMA Pilot Study.

Objective: To assess the feasibility of the procedures of EPI-ASTHMA. EPI-ASTHMA is a population-based multicentre stepwise study about the prevalence and characterisation of patients with asthma based on disease severity in Portugal. Methods: A pilot study of EPI-ASTHMA was conducted with adults from three primary care centres. We followed a stepwise approach comprising 4 stages: stage 0-invitation phone call (n ~1316); stage 1-telephone interview (n ~658); stage 2-clinical assessment with physical examination, diagnostic tests, and patient-reported outcome measures, to confirm the diagnosis of those with possible asthma at stage 1 (n ~160); stage 3-characterization of a subgroup of asthma patients by collecting data through a telephone interview, patient file review and CARATm app (n ~40), after 3-months. The frequency of asthma was calculated in relation to the entire study population (stage 1) and the frequency of difficult-to-treat/severe asthma in relation to the number of asthma patients (stage 3). Results: From 1305 adults invited, 892 (68%) accepted to participate (stage 0) and 574 (64%; 53[42-67] y; 43% male) were interviewed (stage 1). From those, 148 (26%; 60[46-68] y; 43% male) were assessed at stage 2, and 46 (31%; 51[39-67] y; 44% male) were diagnosed with asthma. Half of these patients (n = 23) accepted to install the app. Stage 3 was completed by 41 (93%) patients, of whom 31 (83%) had asthma confirmed by their file review. A total of 8% of participants had asthma, of those 17% had difficult-to-treat and 5% severe asthma. Conclusion: Attained recruitment rates and the quality of the results confirmed the feasibility of the EPI-ASTHMA stepwise approach. This pilot study provided insight into the improvement of the procedures to be generalized across the country.

EPI-ASTHMA study protocol: a population-based multicentre stepwise study on the prevalence and characterisation of patients with asthma according to disease severity in Portugal.

INTRODUCTION: In Portugal as in other countries, data on the epidemiology of asthma are mainly grounded in questionnaire studies. Additionally, the detailed characterisation of asthma in terms of disease severity, control and phenotypes remain scarce. Studies assessing the prevalence of asthma and its subgroups using accurate methods are needed. This study aims to determine the prevalence of asthma, difficult-to-treat asthma and severe asthma, and to evaluate sociodemographic and clinical characteristics of those patients, in mainland Portugal. METHODS AND ANALYSIS: A population-based nationwide study with a multicentre stepwise approach will be conducted between 2021 and 2023 in 38 primary care centres of the Portuguese National Health Service. The stepwise approach will comprise four stages: Stage 0-telephone call invitation to adult subjects (≥18 years) randomly selected (n~15 000); stage 1-telephone screening interview assessing the participants' respiratory symptoms (n~7500); stage 2-diagnostic visit, including physical examination, diagnostic tests (eg, spirometry, fraction of exhaled nitric oxide, blood eosinophil count) and patient-reported outcome measures for diagnostic confirmation of those identified with possible asthma at stage 1 (n~1800); stage 3-further evaluation of patients with asthma and of patients with difficult-to-treat asthma and severe asthma, after 3 months (n~460). At stage 3, data will be collected from a review of the patient's electronic health records, a follow-up telephone call and the CARATm (Caracteristicas Auto-reportadas de Asma em Tecnologias Móveis) app database. The prevalence of asthma, difficult-to-treat asthma and severe asthma will be determined as the percentage of patients with asthma confirmed from the overall population (stage 1). For the analysis of factors associated with asthma, difficult-to-treat asthma and severe asthma, logistic regression models will be explored. ETHICS AND DISSEMINATION: Ethical approvals for the study were obtained from the ethics committee of the local health unit of Matosinhos, Porto (38/CES/JAS), Alto Minho (38/2021/CES) and the regional health administration of Lisbon-Vale do Tejo (035/CES/INV/2021). Results will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05169619.

20 Years of Real-World Data to Estimate the Prevalence of Heart Failure and Its Subtypes in an Unselected Population of Integrated Care Units.

Introduction: Heart failure (HF) is a clinical syndrome caused by structural and functional cardiac abnormalities resulting in the impairment of cardiac function, entailing significant mortality. The prevalence of HF has reached epidemic proportions in the last few decades, mainly in the elderly, but recent evidence suggests that its epidemiology may be changing. Objective: Our objective was to estimate the prevalence of HF and its subtypes, and to characterize HF in a population of integrated care users. Material and Methods: A non-interventional cross-sectional study was performed in a healthcare center that provides primary, secondary and tertiary health cares. Echocardiographic parameters (left ventricle ejection fraction (LVEF) and evidence of structural heart disease) and elevated levels of natriuretic peptides were used to define two HF phenotypes: (i) HF with a reduced ejection fraction (HFrEF, LVEF ≤ 40% and either NT-proBNP ≥ 400 pg/mL (≥600 pg/mL if atrial fibrillation (AF)/flutter) or BNP ≥ 100 pg/mL (≥125 pg/mL if AF/flutter)) and (ii) HF with a non-reduced ejection fraction (HFnrEF), which encompasses both HFpEF (LVEF ≥ 50% and either NT-proBNP ≥ 200 pg/mL (≥600 pg/mL if AF/flutter) or BNP ≥ 100 pg/mL (≥125 pg/mL if AF/flutter) in the presence of at least one structural cardiac abnormality) and HF with a mildly reduced fraction (HFmrEF, LVEF within 40−50% and either NT-proBNP ≥ 200 pg/mL (≥600 pg/mL if AF/flutter) or BNP ≥ 100 pg/mL (≥125 pg/mL if AF/flutter) in the presence of at least one structural cardiac abnormality). The significance threshold was set at p ≤ 0.001. Results: We analyzed 126,636 patients with a mean age of 52.2 (SD = 18.3) years, with 57% (n = 72,290) being female. The prevalence of HF was 2.1% (n = 2700). The HF patients' mean age was 74.0 (SD = 12.1) years, and 51.6% (n = 1394) were female. Regarding HF subtypes, HFpEF accounted for 65.4% (n = 1765); 16.1% (n = 434) had HFmrEF and 16.3% (n = 439) had HFrEF. The patients with HFrEF were younger (p < 0.001) and had a history of myocardial infarction more frequently (p < 0.001) compared to HFnrEF, with no other significant differences between the HF groups. The HFrEF patients were more frequently prescribed CV medications than HFnrEF patients. Type 2 Diabetes Mellitus (T2D) was present in 44.7% (n = 1207) of the HF patients. CKD was more frequently present in T2D vs. non-T2D HF patients at every stage (p < 0.001), as well as stroke, peripheral artery disease, and microvascular disease (p < 0.001). Conclusions: In this cohort, considering a contemporary definition, the prevalence of HF was 2.1%. HFrEF accounted for 16.3% of the cases, with a similar clinical−epidemiological profile having been previously reported in the literature. Our study revealed a high prevalence of patients with HFpEF (65.4%), raising awareness for the increasing prevalence of this entity in cardiology practice. These results may guide local and national health policies and strategies for HF diagnosis and management.

Premature Mortality in Type 2 Diabetes Mellitus Associated with Heart Failure and Chronic Kidney Disease: 20 Years of Real-World Data.

INTRODUCTION: Type 2 diabetes mellitus (T2D) increases the risk of heart failure (HF) and chronic kidney disease (CKD). Nonetheless, evidence of cardiovascular (CV) prognosis is relatively scarce in young T2D patients. PURPOSE: To estimate the risk of all-cause death, CV death, and non-fatal major CV events (MACEs) in T2D patients younger than 65 years old. METHODS: We designed a retrospective cohort study using incident cases of either T2D, HF, or CKD in the population aged 40-65 years, from 1st January 2000 to 31st December 2019. Each individual was followed for up to one year. The primary analysis consisted of survival analysis with Cox proportional hazards to compare one-year risk of all-cause death, CV death, and MACEs between T2D without HF or CKD (T2D), T2D with HF (T2D-HF), and T2D with CKD (T2D-CKD) groups. RESULTS: A total of 14,986 incident adult diabetic patients from the last two decades in our institution were included with an average age at cohort inclusion of 55-58 years old. Glycemic control was similar among groups. The adjusted hazard ratio (HR) of one-year all-cause death was 2.77 (95% CI: 2.26-3.40) for T2D-HF and 3.09 (2.77-3.45) for T2D-CKD compared with the baseline T2D risk. The highest event rate (T2D-CKD) was 0.15 per person-year. The adjusted HR of one-year CV death was 2.75 (95% CI: 2.19-3.46) for T2D-CKD and 2.59 (1.72-3.91) for T2D-HF. The non-fatal MACE risk was significantly increased in T2D-HF or T2D-CKD compared with T2D (2.82 (CI95%: 2.34-3.41) for T2D-CKD vs. 1.90 (CI95%: 1.66-2.17) for T2D-CKD) with a 32% event rate in non-fatal MACEs. CONCLUSIONS: Coexistence of HF or CKD is associated with increased premature mortality as well as non-fatal CV events in T2D patients under 65 years old.

Characteristics of Reliever Inhaler Users and Asthma Control: A Cross-Sectional Multicenter Study in Portuguese Community Pharmacies.

PURPOSE: SABA overuse might indicate poorly managed or uncontrolled asthma and be responsible for poor health outcomes. The aim of this study integrated in new fourth multi-design SABINA+ pillar was to characterize the population using short-acting ß2-agonists for asthma and examine the patterns of its use among community pharmacy customers in Portugal, as well as identify characteristics associated with disease control and explore potential differences between GINA treatment steps. PATIENTS AND METHODS: This cross-sectional multicenter study was conducted in Portuguese community pharmacies between 29 May 2018 and 15 August 2018. Participants were adults (age ≥18 years) self-reporting asthma diagnosis recruited in the context of a short-acting ß2-agonist dispense. A two-part questionnaire (pharmacist interview and self-administered) was used to collect information about sociodemographic characteristics, comorbidities, reliever inhaler use, healthcare resource consumption and self-reported disease control (assessed by the Control of Allergic Rhinitis and Asthma Test - CARAT®). Descriptive statistics was done to characterize the study sample. After categorizing patients according to GINA steps, based on their therapeutic regimen, we performed an exploratory subgroup analysis to evaluate if there were any differences between such groups in terms of the variables collected. A logistic regression was used to identify the potential determinants of overall disease control. RESULTS: Around 50.8% of patients were male, and the average age was 52 years old. Half of the patients never smoked, and 51.9% were employed. More than half of the patients report inhaler overreliance - purchasing more than 1 pack in 3 months (65.0%) or using the inhaler on more than 8 days over the previous 4 weeks (50.2%). Of the total number of patients in the study, 79.1% had poorly controlled asthma symptoms, and 78.7% had overall poorly controlled respiratory symptoms. We found statistically significant differences between GINA treatment steps in all sociodemographic characteristics (sex, mean age, education level, employment status); maximum number of SABA uses in 24h, CARAT score (total an asthma sub-score); history of exacerbations requiring ED visits or treatment with OCS for at least 3 days in the previous 12 months. Logistic regression revealed that patients reporting SABA use in more than 8 days in the previous 4 weeks and patients with at least 1 exacerbation requiring treatment with OCS for at least 3 days in the previous 12 months have greater odds of poor disease control [adjusted OR (95% CI): 2.6 (1.3-5.2) and 3.0 (1.3-6.6)]. CONCLUSION: Based on the results of this study, it can be inferred that the asthma population using SABA is largely uncontrolled and uses reliever inhalers excessively.