Recommendations for the care of patients with cardiovascular disease in health emergency situations: a call to action.

COVID-19 has had a negative impact on the health care of patients with cardiovascular disease and patients at high risk of cardiovascular disease. The restrictions affecting access to the health care system have conditioned the care received, resulting in poorer control and a higher risk of events. Taking action to improve the care provided during health emergencies is mandatory. It is important to promote the development of telemedicine and patient empowerment by fostering health literacy and a higher degree of self-care. In addition, primary care and coordination between health care levels should be improved. Moreover, the simplification and optimization of treatment, for example, using the cardiovascular polypill, have led to an improvement in adherence, better control of vascular risk factors, and a reduced risk of events. The present document provides specific recommendations for improving the care provided to patients under a health emergency.

Alirocumab and Coronary Atherosclerosis in Asymptomatic Patients with Familial Hypercholesterolemia: The ARCHITECT Study.

BACKGROUND: The effect of alirocumab, a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor, on coronary plaque burden in patients with familial hypercholesterolemia has not been addressed. Our aim was to assess changes in coronary plaque burden and its characteristics after treatment with alirocumab by quantification and characterization of atherosclerotic plaque throughout the coronary tree on the basis of a noninvasive analysis of coronary computed tomographic angiography in asymptomatic subjects with familial hypercholesterolemia receiving optimized and stable treatment with maximum tolerated statin dose with or without ezetimibe. METHODS: This study is a phase IV, open-label, multicenter, single-arm clinical trial to assess changes in coronary plaque burden and its characteristics after 78 weeks of treatment with alirocumab in patients with familial hypercholesterolemia without clinical atherosclerotic cardiovascular disease. Participants underwent an initial coronary computed tomographic angiography at baseline and another at 78 weeks. Every patient received 150 mg of alirocumab subcutaneiously every 14 days in addition to high-intensity statin therapy. The main outcome was the change on coronary plaque burden and its characteristics by quantification and characterization of atherosclerotic plaque throughout the coronary tree on the basis of analysis of coronary computed tomographic angiography. RESULTS: The study was completed by 104 patients. The median age was 53.3 (46.2-59.4) years. Of these patients, 54 were women (51.9%). Median low-density lipoprotein cholesterol was 138.9 (117.5-175.3) mg/dL at entry and 45.0 (36.0-65.0) mg/dL at follow-up (P<0.001). Coronary plaque burden changed from 34.6% (32.5%-36.8%) at entry to 30.4% (27.4%-33.4%) at follow-up (P<0.001). A significant change in the characteristics of the coronary atherosclerosis was also found: an increase in the proportion of calcified (+0.3%; P<0.001) and mainly fibrous (+6.2%; P<0.001) plaque, accompanied by a decrease in the percentage of fibro-fatty (-3.9%; P<0.001) and necrotic plaque (-0.6%; P<0.001). CONCLUSIONS: Treatment with alirocumab in addition to high-intensity statin therapy resulted in significant regression of coronary plaque burden and plaque stabilization on coronary computed tomographic angiography over 78 weeks in these groups of patients with familial hypercholesterolemia without clinical atherosclerotic cardiovascular disease. ARCHITECT (Effect of Alirocumab on Atherosclerotic Plaque Volume, Architecture and Composition) could link and explain ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) results. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT05465278.

Persistence with long-term PCSK9 inhibitor treatment and its effectiveness in familial hypercholesterolaemia: data from the SAFEHEART study.

AIMS: Most heterozygous familial hypercholesterolaemia (FH) patients require intensive lipid-lowering therapy (LLT) including PCSK9 inhibitors (PCSK9is) to reach current low-density lipoprotein cholesterol (LDL-C) goals. Persistence with chronic treatment is important to reduce the burden of atherosclerotic cardiovascular disease. We analysed persistence, efficacy, and impact on quality of life (QoL) of PCSK9i in FH patients in clinical practice setting. METHODS AND RESULTS: Spanish Familial Hypercholesterolaemia Cohort Study (SAFEHEART) is an open, prospective study in genetically defined FH patients in Spain. Patients ≥18 years of age (n = 696, 46% females) on stable LLT treated with PCSK9i were analysed. Median LDL-C at starting PCSK9i was 145 mg/dL [interquartile range (IQR), 123-177], 3.8 mmol/L (IQR 3.2-4.6). After a median follow up of 3.7 years (IQR 2.3-4.8), 27 patients (4%) discontinued PCSK9i treatment: 5 temporarily (0.7%) and 22 permanently (3.2%). Persistence with PCSK9i was 96.1% in the whole period. Median LDL-C levels and % LDL-C reduction attained after 1 year of treatment and in the last follow-up visit were 63 mg/dL (IQR 43-88), 1.6 mmol/L (IQR 1.1-2.23); 61 mg/dL (IQR 44-82), 1.6 mmol/L (IQR 1.1-2.1); 57.6% (IQR 39.5-69); and 58% (IQR 44-68), respectively. 2016 and 2019 ESC/EAS LDL-C goals were attained by 77 and 48% of patients, respectively, at the last follow-up visit (P < 0.001). Mean QoL score increased slightly in the first year and remained stable. CONCLUSION: Long-term persistence with PCSK9i in FH patients is very high, with a good QoL. Effectiveness in LDL-C reduction and LDL-C goal achievement dramatically improved with PCSK9i in this high-risk population in clinical practice setting. TRIAL REGISTRATION: ClinicalTrials.gov number NCT02693548.

Efficacy of PCSK9 inhibitors in the treatment of heterozygous familial hypercholesterolemia: A clinical practice experience.

BACKGROUND: PCSK9 inhibitors are a treatment option for patients with familial hypercholesterolemia not on low-density lipoprotein cholesterol goals despite the use of maximally tolerated high intensity-statins dose. OBJECTIVE: To evaluate the efficacy of alirocumab and evolocumab in LDL-C reduction and targets attainment in patients with heterozygous familial hypercholesterolemia in clinical practice setting. METHODS: SAFEHEART is an open, long-term prospective study of a cohort of subjects with molecular diagnosis of familial hypercholesterolemia. This study analyze subjects ≥ 20 years of age on stable lipid-lowering therapy, who received PCSK9 inhibitors during the period 2016 to January 2020. RESULTS: 433 patients (mean age 55 years, 53% male, 39% with cardiovascular disease) were included and followed-up for a median of 2.5 years (IQR 1.6-3.0). Median LDL-C level prior to PCSK9 inhibitors was 145 mg/dL (IQR 125-173). The addition of PCSK9 inhibitors (211 alirocumab, 222 evolocumab) reduced LDL-C by 58% (IQR 41-70) p<0.001, in men and women, achieving a median LDL-C level of 62 mg/dL (IQR 44-87) without differences between both PCSK9 inhibitors. Out of them 67% with and 80% without cardiovascular disease reached 2016 ESC/EAS LDL-C targets, and 46% very high risk and 50% high risk patients achieved 2019 ESC/EAS LDL-C goals. Independent predictor factors for attainment of 2019 ESC/EAS LDL-C goals were to be male, smoking and the use of statins with ezetimibe. Both inhibitors were well tolerated. CONCLUSIONS: PCSK9 inhibitors on top of maximum lipid-lowering treatment significantly reduced LDL-C levels in patients with familial hypercholesterolemia and improved the achievement of LDL-C targets.

Budget impact of ferric carboxymaltose treatment in patients with chronic heart failure and iron deficiency in Spain.

OBJECTIVE: The treatment of iron deficiency (ID) with ferric carboxymaltose (FCM) improves the functional class and quality of life of chronic heart failure (CHF) patients with reduced left ventricular ejection fraction (LVEF), and reduces the rate of hospitalization due to worsening CHF. This study aims to evaluate the budget impact for the Spanish National Health System (SNHS) of treating ID in reduced LVEF CHF with FCM compared to non-iron treatment. METHODS: We simulated a hypothetical cohort of 1000 CHF patients with ID and reduced LVEF based on the Spanish population characteristics. A decision-analytic model was also built using the data from the largest FCM clinical trial (CONFIRM-HF) that lasted for a year. We considered the use of healthcare resources from a national prospective study. A deterministic sensitivity analysis was carried out varying the corresponding baseline data by ±25%. RESULTS: The cost of treating the simulated population with FCM was €2,570,914, while that of the non-iron treatment was €3,105,711, which corresponds to a cost saving of €534,797 per 1,000 patients in one year. Cost savings were mainly due to a decrease in the number of hospitalizations. All sensitivity analysis showed cost savings for the SNHS. CONCLUSIONS: FCM results in an annual cost saving of €534.80 per patient, and would thus be expected to reduce the economic burden of CHF in Spain.

Descripción morfológica e histológica del tejido hepático de Gambusia holbrooki (Pisce: Poeciliidae) que habita en la Provincia de Arica - Chile / Morphological and histological description of the liver tissue of Gambusia holbrooki (Pisce: Poeciliidae) inhabiting the Province of Arica - Chile

Gambusia holbrooki es el pez de agua dulce con mayor distribución en Chile y el mundo, pero los estudios que abordan la morfología e histología hepática del pez son escasos. El hígado es utilizado para evidenciar efectos subletales de contaminantes ambientales y es preciso contar con una descripción histomorfológica del hígado para futuros estudios comparativos. El presente estudio tiene como objetivo describir patrones histomorfológicos del hígado de Gambusia holbrooki, para ello se colectaron 97 individuos adultos de los sistemas límnicos de los valles de Lluta y Azapa (Extremo norte de Chile), para observar patrones morfológicos comunes en ambas poblaciones, se utilizó técnicas histológicas de rutina e histoquímica. Las evidencias demostraron que el hígado contiene tejido pancreático y su arquitectura tisular es trabecular con mayor presencia de capilares sinusoides.

Gambusia holbrooki is the freshwater fish with the greatest distribution in Chile and the world. However, studies dealing with morphology and liver histology of fish are scarce. The liver commonly shows the sublethal effects of environmental pollutants and there should be a histomorphological description of the liver for further comparative studies. The present study aims to describe histomorphological patterns of the liver of Gambusia holbrooki. A total of 97 adult individual specimens were collected from the ecosystems in the valleys of Lluta and Azapa (Region of Arica and Parinacota), to observe patterns morphologically common in both populations. Routine histological and histochemical techniques were used for analysis. The evidence showed that the liver contains pancreatic tissue, and that tissue architecture is trabecular with greater presence of capillary sinusoids.

Incidence of cardiovascular events and changes in the estimated risk and treatment of familial hypercholesterolemia: the SAFEHEART registry.

INTRODUCTION AND OBJECTIVES: The SAFEHEART study was designed to analyze the situation of familial heterozygous hypercholesterolemia (FHH) and improve knowledge of this disease in Spain. Our objective was to determine the incidence rate of cardiovascular events, the estimated risk of developing an event and its modification, the use of lipid-lowering treatment, and the achievement of low-density lipoprotein cholesterol targets in patients with FHH. METHODS: SAFEHEART is a prospective, open, multicenter, nationwide cohort study, with long-term protocol-based follow-up in a population of individuals with molecularly-characterized FHH. We analyzed patients older than 18 years with complete follow-up. RESULTS: We included 2648 patients with FHH. The median follow-up was 6.6 (4.8-9.7) years. The overall incidence rate of cardiovascular events was 1.3 events/100 patient-years. After the follow-up, the 10-year estimated risk of developing a cardiovascular event was reduced from 1.6% to 1.3% (P <.001). In the last follow-up, 20.6% and 22.2% of the patients in primary and secondary prevention achieved low-density lipoprotein cholesterol values <100mg/dL and <70mg/dL, respectively. CONCLUSIONS: This study was performed in the largest population of patients with FHH in Spain. We identified the incidence rate of cardiovascular events, the estimated risk of developing a cardiovascular event and its modification, the achievement of low-density lipoprotein cholesterol targets, and the therapeutic management in this population. Although the cardiovascular risk of FHH is high, appropriate treatment reduces the likelihood of an event. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Identifier: NCT02693548.

Long-term effect of 2 intensive statin regimens on treatment and incidence of cardiovascular events in familial hypercholesterolemia: The SAFEHEART study.

BACKGROUND: Maximal doses of potent statins are the basement of treatment of familial hypercholesterolemia (FH). Little is known about the use of different statin regimens in FH. OBJECTIVES: The objectives of the study were to describe the treatment changes and low-density lipoprotein cholesterol (LDL-C) goal achievement with atorvastatin (ATV) and rosuvastatin (RV) in the SAFEHEART cohort, as well as to analyze the incidence of atherosclerotic cardiovascular events (ACVEs) and changes in the cardiovascular risk. METHODS: SAFEHEART is a prospective follow-up nationwide cohort study in a molecularly defined FH population. The patients were contacted on a yearly basis to obtain relevant changes in life habits, medication, and ACVEs. RESULTS: A total of 1939 patients were analyzed. Median follow-up was 6.6 years (5-10). The estimated 10-year risk according the SAFEHEART risk equation was 1.61 (0.67-3.39) and 1.22 (0.54-2.93) at enrollment for ATV and RV, respectively (P < .001). There were no significant differences at the follow-up: 1.29 (0.54-2.82) and 1.22 (0.54-2.76) in the ATV and RV groups, respectively (P = .51). Sixteen percent of patients in primary prevention with ATV and 18% with RV achieved an LDL-C <100 mg/dL and 4% in secondary prevention with ATV and 5% with RV achieved an LDL-C <70 mg/dL. The use of ezetimibe was marginally greater in the RV group. One hundred sixty ACVEs occurred during follow-up, being its incidence rate 1.1 events/100 patient-years in the ATV group and 1.2 in the RV group (P = .58). CONCLUSION: ATV and RV are 2 high-potency statins widely used in FH. Although the reduction in LDL-C levels was greater with RV than with ATV, the superiority of RV for reducing ACVEs was not demonstrated.

miR-505-3p controls chemokine receptor up-regulation in macrophages: role in familial hypercholesterolemia.

Familial hypercholesterolemia (FH) conveys a high risk of premature atherosclerosis as a result of lifelong exposure to high LDL cholesterol levels that are not fully reduced by standard-of-care lipid-lowering treatment. Inflammatory mediators have played a role in the progression of atherosclerotic lesions. Here, we investigated whether innate immunity cells in patients with FH have a specific proinflammatory phenotype that is distinct from that of cells in normal participants. To this end, miR-505-3p-a microRNA related to chronic inflammation-and its target genes were investigated in monocyte-derived macrophages (MACs) of patients with FH (FH-MACs) and non-FH controls (co-MACs). On the basis of the profiler PCR array analysis of agomiR-505-3p-transfected MACs, we identified the chemokine receptors, CCR3, CCR4, and CXCR1, as genes that are regulated by miR-505-3p via the transcription factor, RUNX1. miR-505-3p was significantly down-regulated, whereas CCR3, CCR4, CXCR, and RUNX1 were increased in FH-MAC compared with co-MAC, with the increase being more evident in the proinflammatory M1-like FH-MAC. Chemokine receptor levels were unrelated to LDL plasma levels at entry, but correlated with age in patients with FH, not in controls. In summary, we demonstrate for first time to our knowledge that MACs from FH-MACs have an inflammatory phenotype that is characterized by the up-regulation of CCR3, CCR4, and CXCR1 under the control of miR-505-3p. These results suggest a chronic inflammatory condition in FH innate immunity cells that is not reverted by standard lipid-lowering treatment.-Escate, R., Mata, P., Cepeda, J. M., Padró, T., Badimon, L. miR-505-3p controls chemokine receptor up-regulation in macrophages: role in familial hypercholesterolemia.

Predicting Cardiovascular Events in Familial Hypercholesterolemia: The SAFEHEART Registry (Spanish Familial Hypercholesterolemia Cohort Study).

BACKGROUND: Although risk factors for atherosclerotic cardiovascular disease (ASCVD) in familial hypercholesterolemia (FH) have been described, models for predicting incident ASCVD have not been reported. Our aim was to use the SAFEHEART registry (Spanish Familial Hypercholesterolemia Cohort Study) to define key risk factors for predicting incident ASCVD in patients with FH. METHODS: SAFEHEART is a multicenter, nationwide, long-term prospective cohort study of a molecularly defined population with FH with or without previous ASCVD. Analyses to define risk factors and to build a risk prediction equation were developed, and the risk prediction equation was tested for its ability to discriminate patients who experience incident ASCVD from those who did not over time. RESULTS: We recruited 2404 adult patients with FH who were followed up for a mean of 5.5 years (SD, 3.2 years), during which 12 (0.5%) and 122 (5.1%) suffered fatal and nonfatal incident ASCVD, respectively. Age, male sex, history of previous ASCVD, high blood pressure, increased body mass index, active smoking, and low-density lipoprotein cholesterol and lipoprotein(a) levels were independent predictors of incident ASCVD from which a risk equation with a Harrell C index of 0.85 was derived. The bootstrap resampling (100 randomized samples) of the original set for internal validation showed a degree of overoptimism of 0.003. Individual risk was estimated for each person without an established diagnosis of ASCVD before enrollment in the registry by use of the SAFEHEART risk equation, the modified Framingham risk equation, and the American College of Cardiology/American Heart Association ASCVD Pooled Cohort Risk Equations. The Harrell C index for these models was 0.81, 0.78, and 0.8, respectively, and differences between the SAFEHEART risk equation and the other 2 were significant (P=0.023 and P=0.045). CONCLUSIONS: The risk of incident ASCVD may be estimated in patients with FH with simple clinical predictors. This finding may improve risk stratification and could be used to guide therapy in patients with FH. CLINICAL TRIAL REGISTRATION: URL: http://clinicaltrials.gov. Unique identifier: NCT02693548.

Statins do not increase the risk of developing type 2 diabetes in familial hypercholesterolemia: The SAFEHEART study.

BACKGROUND: Familial Hypercholesterolemia (FH) is the most common monogenic disorder that causes premature coronary artery disease (CAD). Our objective was to examine the risk of new onset type 2 diabetes mellitus (T2DM) among FH patients and unaffected relatives in relation to treatment with different statins in the SAFEHEART cohort study. METHODS: This is a cross-sectional and prospective cohort study in 2558 FH and 1265 unaffected relatives with a mean follow-up of 5.9 years. Several pertinent data, such as age, gender, metabolic syndrome, lipid profile, body mass index (BMI), waist circumference, HOMA-IR, dose, duration and type of statins, were obtained and examined as predictors of incident diabetes. RESULTS: The new onset diabetes was 1.7% in FH and 0.2% in non FH patients (p=0.001). In multivariate logistic regression, age (OR 1.02, CI 95%: 1.02-1.08), HOMA-IR (OR 1.17, CI 95%: 1.03-1.33), metabolic syndrome (OR 3.3, CI 95%: 1.32-8.28) and specifically plasma glucose, as a component of metabolic syndrome (OR 15.7, CI 95%: 4.70-52.53) were significant predictors of new onset T2DM in the FH group alone. In the adjusted Cox regression model in FH group, age (HR 1.03, CI 95% 1.00-1.06, p=0.031) and metabolic syndrome (HR 4.16, CI 95% 1.58-10.92, p=0.004) remained significant predictors of new onset T2DM. CONCLUSIONS: Our data do not support the postulated diabetogenic effect associated with high-dose statins use in our cohort of FH patients.

De estar "toda Teletubbie" a ser Verónica: utilidad de las sesiones de observación (sesiones diagnósticas) para trazar el proceso evolutivo de un sufrimiento mental / From Being "Completely Teletubbie" to Being Veronica: Usefulness of Observation Sessions (Diagnostic Sessions) in Tracing the Evolutionary Process of a Mental Suffering

Introducción: En este estudio se usa un modelo evolutivo de los trastornos y del desarrollo del psiquismo que permite tener una visión global del paciente, en el cual concurre no sólo lo que podría aportar la genética, sino todas las distorsiones producto de las experiencias con el ambiente. Las teorías sobre el desarrollo psíquico han mostrado que el nacimiento, la construcción y la organización del psiquismo de un individuo deben comprenderse como una progresión evolutiva. Objetivo: Mostrar a través de una sesión de observación cómo se comprende la organización psíquica de una paciente y el origen y posterior evolución de sus trastornos. Método: Observación de un caso particular de interacción de una paciente con su madre, su abuela y un equipo de trabajo y, luego, este último reflexionó sobre diversas hipótesis, que surgieron de la comprensión de las relaciones entre la psicopatología de la paciente y las teorías del desarrollo psíquico. Resultados: En el caso ilustrado se descartó el diagnóstico de autismo con el cual venía remitida la paciente, pues los síntomas de esta paciente podrían verse desde la perspectiva de las primeras relaciones interpersonales. Las teorías actuales sobre el desarrollo psíquico permiten comprender que no se trata de algo "que le dio", sino que se fue gestando desde muy temprano en la vida emocional de este ser. Conclusión: En esta sesión de observación se ve cómo estas citas, que inicialmente fueron establecidas para diagnosticar, conducen a una profunda comprensión del paciente, que al ser compartida con sus padres, tiene también un efecto terapéutico y se constituyen así en "consultas terapéuticas", como las propuestas por D. W. Winnicott.

Introduction: In this study an evolutionary model of the disorders and the development of psychism is used, that allows achiving an overall vision of the patient and which combines not only what could contribute to genetics, but all the distortions resulting from experiences with the environment. The theories about psychic development have shown that the birth, building and organization of the psychism of an individual must be understood as an evolutionary progression. Objective: To show, by means of an observation session, how the psychic organization of a female patient and the subsequent evolution of her disorders may be understood. Method: Observing an individual case of interaction between a female patient and her mother, grandmother and a work team. Subsequently this team discussed different hypothesis that emerged from the understanding of the relationships between the patient’s psicopathology and the psychic development theories. Results: In this case the diagnosis of autism, with which the patient was remitted, was ruled out because the symptoms of this patient could be seen from the perspective of first interpersonal relationships. Current theories on psychic development allow understanding that it is not "just something that she got", but that it started developing very early in the emotional life of this being. Conclusion: In this observation session it is apparent how these visits, which initially were established to reach a diagnosis, lead to a deep understanding of the patient that, when shared with her parents, have a therapeutic effect and become "therapeutic consultations" as those proposed by D.W. Winnicott.

Value of the congenital hypertrophy of the retinal pigment epithelium in the diagnosis of familial adenomatous polyposis.

BACKGROUND: Several kinds of congenital hypertrophy of the retinal pigment epithelium (CHRPE) have been described in patients with familial adenomatous polyposis (FAP). This study aims to assess which properties of CHRPE better predict FAP and investigate whether a relationship exists between specific CHRPE characteristics and FAP variants. METHODS: We examined 286 subjects, Group I--patients with FAP plus individuals "at risk"; n = 173; Group II--controls n = 113. Retinal lesions were classified in five types (A-E) and different characteristics (distribution, number, shape, size, pigmentation and site) were evaluated. RESULTS: The most common lesions in affected subjects were types A-D (83.4%) whilst in the "at risk" and control groups were type E. Greater numbers of lesions and bilateral distribution occurred more frequently among affected subjects than in other participants (p < 0.001). Large lesions with mixed pigmentation were associated with polyposis (p > 0.5). Controls had solitary CHRPE lesions (3.5%) and types C and E lesions (23%). The cumulative sensitivities and specificities of CHRPE were 42 and 97%, respectively. CHRPE was most common among those with classical FAP, but no specific characteristic was associated with any particular FAP variant. CONCLUSIONS: Pigmented fundal lesions are highly pleomorphic and represent the variable expression of a common genetic defect of growth regulation. No association was found between CHRPE characteristics and specific FAP variants.