Perceptions of cardiology, professional preferences and impact on career choices among Portuguese cardiologists: Results from the Portuguese Society of Cardiology's Women and Cardiology Task Force survey.

INTRODUCTION AND OBJECTIVES: Cardiology has not been seen as an attractive specialty, and women have avoided it for many years. Some surveys have been performed in other countries, but in Portugal, the situation is largely unknown. METHODS: An online survey on perceptions of cardiology and professional preferences was sent to 1371 members of the Portuguese Society of Cardiology, of whom 18.2% completed the survey. RESULTS: We included 219 cardiologists or cardiology trainees, of whom 50.2% were female, with decreasing proportions from younger to older age groups, in which males still predominate. Women are less often married and more frequently childless, particularly those working in an invasive subspecialty, where they represent only 16% of all respondents working in these areas. Men's perception is that women do not choose these areas due to family reasons, radiation concerns and difficult working conditions, but from the female perspective, male dominance, lack of female role models and restricted access are the main barriers. Women consider it is difficult for them to obtain a leadership role, but men do not think the same (75.5% vs. 27.5%). CONCLUSION: In Portugal, females predominate in younger age groups, suggesting a paradigm change. Women are less frequently married and more frequently childless, particularly women working in invasive subspecialties. Women consider that it is more difficult for them to obtain a leadership role. Moreover, the barriers reported by women are substantially different from men regarding the reasons for not choosing an invasive subspecialty.

Characterization and LDL-C management in a cohort of high and very high cardiovascular risk patients: The PORTRAIT-DYS study.

AIM: This study aims to characterize sociodemographic and clinical characteristics, use of lipid-lowering therapies (LLTs), and low-density lipoprotein cholesterol (LDL-C) control in a population with increased cardiovascular (CV) risk. METHODS: A cross-sectional observational study that uses electronic health records of patients from one hospital and across 14 primary care health centers in the North of Portugal, spanning from 2000 to 2020 (index date). Patients presented at least (i) 1 year of clinical data before inclusion, (ii) one primary care appointment 3 years before the index date, and (iii) sufficient data for CV risk classification. Patients were divided into three cohorts: high CV risk; atherosclerotic cardiovascular disease (ASCVD) risk equivalents without established ASCVD; evidence of ASCVD. CV risk and LDL-C control were defined by the 2019 and 2016 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) dyslipidemia guidelines. RESULTS: A total of 51 609 patients were included, with 23 457 patients classified as high CV risk, 19 864 with ASCVD equivalents, and 8288 with evidence of ASCVD. LDL-C control with 2016 ESC/EAS guidelines was 32%, 10%, and 18% for each group, respectively. Considering the ESC/EAS 2019 guidelines control level was even lower: 7%, 3%, and 7% for the same cohorts, respectively. Patients without any LLT prescribed ranged from 37% in the high CV risk group to 15% in patients with evidence of ASCVD. CONCLUSION: We found that LDL-C control was very low in patients at higher risk of CV events. An alarming gap between guidelines on dyslipidemia management and clinical implementation persists, even in those at very high risk or with established ASCVD.

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.

Sex differences in LDL-C control in a primary care population: The PORTRAIT-DYS study.

BACKGROUND AND AIMS: Cardiovascular (CV) diseases show clear differences in clinical manifestation and treatment outcomes between men and women. To reduce sex disparities in achieving lipid-lowering therapy (LLT) goals, a sex-focused assessment is essential and more studies are needed to bring new evidence to clinicians. This study aims to assess the role of sex in attaining low-density lipoprotein cholesterol (LDL-C) goals, after correction for age, CV risk category, LLT intensity, and presence of mental health disorder and social deprivation. METHODS: A retrospective cohort analysis of patients aged 40-85, followed in 1 hospital and 14 primary care centers in Portugal, using electronic health records from 1/1/2012 to 31/12/2020, was performed. The analysis considered an episode-based design, where exposure consists of any time when LLT was started or intensity changed. The likelihood of reaching the LDL-C goal according to contemporary ESC/EAS guidelines was modeled using multivariate Cox regression. LDL-C goal achievement at 180 days was defined as the outcome. The analysis was repeated at 30-day follow-up intervals up to 360 days, and also stratified by CV risk category. RESULTS: We identified 40,032 exposure episodes (LLT initiation or intensity change) in 30,323 distinct patients. Male sex, older age, lower CV risk and increasing LLT intensity were associated with improved LDL-C control. Women were 22% less likely to reach the LDL-C goal than men (HR = 0.78, 95% CI:0.73, 0.82) independently of covariates. CONCLUSIONS: Women have a lower likelihood of attaining LDL-C goals than men after adjustment for LLT intensity, age, CV risk category, presence of mental health disorder and social deprivation. This finding underscores the need for further investigation and tailoring of LLT management strategies in women.

Polypill use for the prevention of cardiovascular disease: A position paper.

Cardiovascular (CV) guidelines stress the need for global intervention to manage risk factors and reduce the risk of major vascular events. Growing evidence supports the use of polypill as a strategy to prevent cerebral and cardiovascular disease, however it is still underused in clinical practice. This paper presents an expert consensus aimed to summarize the data regarding polypill use. The authors consider the benefits of polypill and the significant claims for clinical applicability. Potential advantages and disadvantages, data regarding several populations in primary and secondary prevention, and pharmacoeconomic data are also addressed.

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.

Cardiovascular diseases in women - Consensus document of the Sociedade Portuguesa de Cardiologia, Sociedade Portuguesa de Ginecologia, Sociedade Portuguesa de Obstetrícia e Medicina Materno-Fetal, Sociedade Portuguesa de Contraceção e Associação Portuguesa de Medicina Geral e Familiar. / Saúde cardiovascular da mulher ­ Documento de Consenso da Sociedade Portuguesa de Cardiologia, Sociedade Portuguesa de Ginecologia, Sociedade Portuguesa de Obstetrícia e Medicina Materno­Fetal, Sociedade Portuguesa de Contraceção e Associação Portuguesa de Medicina Geral e Familiar.

The main objective of this consensus statement from the Portuguese Society of Cardiology, the Portuguese Society of Gynecology, the Portuguese Society of Obstetrics and Maternal-Fetal Medicine, Portuguese Society of Contraception, Portuguese Association of General Practice and Family Medicine is to improve cardiovascular care for women. It includes a brief review of the state-of-the-art of cardiovascular diseases in women and of the links to other fields such as Gynaecology, Obstetrics and Endocrinology. It also provides final recommendations to help clinicians working in care of women's health.

Cardiovascular Risk Profile and Lipid Management in the Population-Based Cohort Study LATINO: 20 Years of Real-World Data.

The rising prevalence of cardiovascular (CV) risk factors in Portugal has translated into more than 35,000 annual deaths due to CV diseases. We performed a multicenter observational cohort study encompassing clinical activities performed between 2000 and 2019 to characterize the CV risk profile and LDL-C management of patients in every CV risk category using electronic health records of a regional population in Portugal. We analyzed data from 14 health centers and 1 central hospital in the north of Portugal of patients between 40 and 80 years that had at least 1 family medicine appointment at these institutions. Living patients were characterized on 31 December 2019. CV risk assessment was computed according to the 2019 ESC/EAS Guidelines. Lipid-lowering therapy (LLT) and achievement of LDL-C targets were assessed. In total, the analysis included 78,459 patients. Patient proportions were 33%, 29%, 22%, and 17% for low, intermediate, high, and very high CV risk, respectively. Moderate-intensity statins were the most frequently used medication across all CV risk categories. High-intensity statins were used in 5% and 10% of high and very high CV risk patients, respectively. Ezetimibe was used in 6% and 10% of high and very high CV risk patients, respectively. LDL-C targets were achieved in 44%, 27%, 7%, and 3% of low, intermediate, high, and very high CV risk patients, respectively. For uncontrolled patients in the high and very high CV risk categories, a median LDL-C reduction of 44% and 53%, respectively, would be required to meet LDL-C targets. There are clear opportunities to optimize LDL-C management in routine clinical practice. The prescription of LLT according to CV risk represents an important missed treatment opportunity.

Prognostic implications of fibrosis in low risk aortic stenosis patients.

INTRODUCTION AND OBJECTIVES: Among patients with aortic stenosis (AS), interstitial fibrosis has been associated with progression to heart failure and is a marker of poorer prognosis. We aimed to assess the impact of myocardial fibrosis on clinical events after aortic valve replacement (AVR) in low risk, severe AS. METHODS: We prospectively followed 56 severe AS patients with ejection fraction >40%, who underwent AVR with simultaneous myocardial biopsies and collagen volume fraction (CVF) determination. Baseline and follow-up echocardiographic parameters were assessed. Outcomes were all-cause death and the combined endpoint of all-cause death or non-fatal cardiovascular hospitalization. RESULTS: Patients were predominantly women (67.9%) and mean age was 66±12 years. At follow-up, there was a significant decrease in transaortic gradients and wall stress, as well as regression in indexed LV mass. Patients who suffered a fatal event or the combined endpoint had a higher degree of fibrosis (27.1±20.7% vs. 15.4±11.8%, p=0.035; 24.0±18.2% vs. 15.3±12.0%, p=0.038, respectively). Patients with CVF≥15.4% had higher rates of all-cause death (37.5% vs. 97.0%, p=0.001) and lower survival free of the combined endpoint of all-cause death or non-fatal cardiovascular hospitalization (0% vs. 91.2%, p<0.001). CVF was the only independent predictor of all-cause death (hazard ratio (HR) 1.88; 95% confidence interval (CI): 1.08-3.29 for each 10% increase; p=0.026) and all-cause death or cardiovascular hospitalization (HR 1.73; 95% CI: 1.03-2.911 for each 10% increase; p=0.038). CONCLUSIONS: In low risk AS patients, higher levels of fibrosis are independent predictors of all-cause death and the composite of all-cause death or non-fatal cardiovascular hospitalization. Further advances in anti-fibrotic therapies in AS are needed.

Optimization of a Protocol for Protein Extraction from Calcified Aortic Valves for Proteomics Applications: Development of a Standard Operating Procedure.

The comprehension of the pathophysiological mechanisms, the identification of druggable targets, and putative biomarkers for aortic valve stenosis can be pursued through holistic approaches such as proteomics. However, tissue homogenization and protein extraction are made difficult by tissue calcification. The reproducibility of proteome studies is key in clinical translation of the findings. Thus, we aimed to optimize a protocol for aortic valve homogenization and protein extraction and to develop a standard operating procedure (SOP), which researchers can use to maximize protein yield while reducing inter-laboratory variability. We have compared the protein yield between conventional tissue grinding in nitrogen followed by homogenization with a Potter apparatus with a more advanced bead-beating system. Once we confirmed the superiority of the latter, we further optimized it by testing the effect of beads size, the number of homogenization cycles, tube capacity, lysis buffer/tissue mass ratio, and two different lysis buffers. Optimal protein extraction was achieved with 2.8 mm zirconium dioxide beads, in two homogenization cycles, in the presence of 20 µL RIPA buffer/mg tissue, using 2 mL O-ring cryotubes. As a proof of concept of the usefulness of this SOP for proteomics, the AV proteome of men and women with aortic stenosis was characterized, resulting in the quantification of proteins across six orders of magnitude and uncovering some putative proteins dysregulated by sex.

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.

Heterogeneity amongst GLP-1 RA cardiovascular outcome trials results: can definition of established cardiovascular disease be the missing link?

Atherosclerotic cardiovascular diseases are the leading cause of adverse outcomes in patients with type 2 diabetes, and all new anti-diabetic agents are mandated to undergo cardiovascular outcome trials (CVOTs). Glucagon-like peptide-1 receptor agonists (GLP-1 RA) are incretin mimetics that reduce blood glucose levels with a low associated risk of hypoglycaemia. CVOTs with different GLP-1 RAs yielded different results in terms of major cardiovascular composite outcome (MACE), with some trials showing superiority in the treatment arm, whereas other simply displayed non-inferiority. More importantly, the significance of each component of MACE varied between drugs. This begs the question of whether these differences are due to dissimilarities between drugs or other factors, namely trial design, are at the root of these differences. We analyse the trial designs for all CVOTs with GLP-1 RAs and highlight important differences between them, namely in terms of definition of established cardiovascular disease, and discuss how these differences might explain the disparate results of the trials and preclude direct comparisons between them. We conclude that a fair comparison between GLP-1 RA CVOTs would involve post-hoc analysis re-grouping the patients into different cardiovascular risk categories based upon their baseline clinical parameters, in order to even out the criteria used to classify patients.