Predictors of cardiovascular risk in familial hypercholesterolemia.

PURPOSE OF REVIEW: Familial hypercholesterolemia is associated with an increased risk of cardiovascular disease. The current international guidelines of the main scientific societies consider that, all people with Familial Hypercholesterolemia have a high or very high cardiovascular risk. However, the occurrence of atherosclerotic cardiovascular disease is very heterogeneous in this population. Stratifying risk within people with familial hypercholesterolemia is essential to identify individuals who require intensive cholesterol-lowering therapies. RECENT FINDINGS: In the last year, several studies have been published focusing on the contribution of diabetes to Familial Hypercholesterolemia, the role of stroke, as a manifestation of atherosclerotic disease, and the external validation of the SAFEHEART risk equation in the English population diagnosed with Familial Hypercholesterolemia. SUMMARY: It is necessary the development of a tool that allows us to identify, in a simple, reproducible, and universal way, patients who may have a high risk of suffering a cardiovascular event and who are susceptible to more intensive treatments to reduce cholesterol levels.

Risk factors for cardiovascular events in patients with heterozygous familial hypercholesterolaemia: protocol for a systematic review.

INTRODUCTION: Heterozygous familial hypercholesterolaemia (heFH) is the most common monogenic cause of premature atherosclerotic cardiovascular disease. The precise diagnosis of heFH is established by genetic testing. This systematic review will investigate the risk factors that predict cardiovascular events in patients with a genetic diagnosis of heFH. METHODS AND ANALYSIS: Our literature search will cover publications from database inception until June 2023. We will undertake a search of CINAHL (trial), clinicalKey, Cochrane Library, DynaMed, Embase, Espacenet, Experiments (trial), Fisterra, ÍnDICEs CSIC, LILACS, LISTA, Medline, Micromedex, NEJM Resident 360, OpenDissertations, PEDro, Trip Database, PubPsych, Scopus, TESEO, UpToDate, Web of Science and the grey literature for eligible studies. We will screen the title, abstract and full-text papers for potential inclusion and assess the risk of bias. We will employ the Cochrane tool for randomised controlled trials and non-randomised clinical studies and the Newcastle-Ottawa Scale for assessing the risk of bias in observational studies. We will include full-text peer-reviewed publications, reports of a cohort/registry, case-control and cross-sectional studies, case report/series and surveys related to adults (≥18 years of age) with a genetic diagnostic heFH. The language of the searched studies will be restricted to English or Spanish. The Grading of Recommendations, Assessment, Development and Evaluation approach will be used to assess the quality of the evidence. Based on the data available, the authors will determine whether the data can be pooled in meta-analyses. ETHICS AND DISSEMINATION: All data will be extracted from published literature. Hence, ethical approval and patient informed consent are not required. The findings of the systematic review will be submitted for publication in a peer-reviewed journal and presentation at international conferences. PROSPERO REGISTRATION NUMBER: CRD42022304273.

Predictors of subclinical atherosclerosis in HIV.

BACKGROUND: Cardiovascular disease is a major cause of morbidity and mortality in people with HIV. The detection of subclinical atherosclerosis through vascular ultrasound allows us to identify patients at an increased risk of cardiovascular disease as a primary prevention strategy; this test is not routine. Our objective is to identify predictors of subclinical atherosclerosis in a population with HIV. METHODS: People with HIV infection were selected for primary prevention and underwent carotid and femoral ultrasound to detect atheromatous plaques. Logistic regression analysis including vascular risk factors was performed to predict the presence of atherosclerosis. RESULTS: One hundred eighty-three patients were included, 54% of whom were smokers; the mean duration of HIV infection was 9.52 years, and all patients were undergoing antiretroviral treatment. Subclinical atherosclerosis was present in 62.29% of the patients; 83.32% had plaque in the carotid territory, 57.93% in the femoral territory and 25.6% in both vascular territories. Compared to those without atherosclerosis, patients with atherosclerosis were on average 5.35 years older (53.86 vs. 48.51, p < 0.001) and had a higher prevalence of smoking (63.23% vs. 39.12%, p = 0.020) and a CD4/CD8 ratio below 0.7 (44.23% vs. 29.02%, p = 0.043). A CD4/CD8 ratio lower than 0.3 was always associated with subclinical atherosclerosis (95% confidence interval (CI): 83.9-100%). The inclusion of smoking, the CD4/CD8 ratio and age in the logistic regression analysis led to a diagnostic yield of 72% measured by the area under the receiving operator characteristic (ROC) curve (95% CI: 64-80%). CONCLUSIONS: Tobacco use, age and a CD4/CD8 ratio below 0.7 allow prediction of the presence of subclinical atherosclerosis in primary prevention. A CD4/CD8 ratio below 0.3 was a diagnostic indicator of atherosclerosis in HIV patients undergoing primary prevention in our sample.

A resilient type of familial hypercholesterolaemia: case-control follow-up of genetically characterized older patients in the SAFEHEART cohort.

AIMS: Knowledge of the features of patients with familial hypercholesterolaemia (FH) who are protected from atherosclerotic cardiovascular disease (ASCVD) is important for the clinical and prognostic care of this apparently high-risk condition. Our aim was to investigate the determinant and characteristics of patients with FH who are protected from ASCVD and have normal life expectancy, so-called 'resilient' FH (R-FH). METHODS AND RESULTS: Spanish Familial Hypercholesterolaemia cohort study (SAFEHEART) is an open, multicentre, nation-wide, long-term prospective cohort study in genetically defined patients with heterozygous FH in Spain. Patients in the registry who at the time of analysis were at least 65 years or those who would have reached that age had they not died from an ASCVD event were analysed as a case-control study. Resilient FH was defined as the presence of a pathogenic mutation causative of FH in a patient aged ≥65 years without clinical ASCVD. Nine hundred and thirty registrants with FH met the study criteria. A defective low-density lipoprotein (LDL)-receptor mutation, higher plasma level of high-density lipoprotein cholesterol (HDL-C), younger age, female gender, absence of hypertension, and lower plasma lipoprotein (a) [Lp(a)] concentration were independently predictive of R-FH. In a second model, higher levels of HDL-C and lower 10-year score in SAFEHEART-RE were also independently predictive of R-FH. CONCLUSION: Resilient FH may be typified as being female and having a defective LDL-receptor mutation, higher levels of plasma HDL-C, lower levels of Lp(a), and an absence of hypertension. The implications of this type of FH for clinical practice guidelines and the value for service design and optional care of FH remains to be established. TRIAL REGISTRATION: ClinicalTrials.gov number NCT02693548.

Detection of Familial Hypercholesterolemia through centralized analytical data. HF HUELVA DETECTA Program.

BACKGROUND: Familial Hypercholesterolemia is the most frequent genetic cause of premature coronary heart disease. The delay in the diagnosis prevents the correct early treatment. There are no effective screening strategies at the national level that ensure a correct diagnosis. OBJECTIVE: To determine the capacity of a centralized laboratory for the diagnosis of Familial Hypercholesterolemia through the creation of a health program for population screening in the province of Huelva. METHOD: Active search of patients with primary hypercholesterolemia through the blood tests carried out in the reference laboratories with results of low-density lipoprotein cholesterol greater than 200 mg/dl and assessment in the Lipid Unit of Huelva to identify index cases, with subsequent family cascade screening. RESULTS: 37,440 laboratory tests with lipid profile were examined. After screening, 846 individuals were seen in the Lipid Unit, of which they were diagnosed according to criteria of the Dutch Lipid Clinic Network as possible 654 and probable/definitive 192 individuals, representing 1.74% and 0.51% of the general population examined respectively. CONCLUSIONS: The point prevalence of Familial Hypercholesterolemia in patients submitted to laboratory lipid profile tests was 1:195, higher compared to the prevalence of Familial Hypercholesterolemia in the general population (based on 1 in 200-300). The opportunistic search strategy of the index case through a laboratory alert and centralized screening is an efficient strategy to implement a national screening for the diagnosis of Familial Hypercholesterolemia.

Incorporación de parámetros bioquímicos y algoritmos diagnósticos en el sistema informático de laboratorio para la detección precoz de alteraciones lipídicas desde las unidades de lípidos / Incorporation of biochemical parameters and diagnostic algorithms in the laboratory computer system for the early detection of lipid abnormalities from the lipid units

Introducción: La combinación de marcadores bioquímicos y el diseño e implementación de algoritmos diagnósticos en el sistema informático de los laboratorios podrían convertirse en herramientas muy potentes en la estratificación del riesgo cardiovascular. Objetivos: Implementar nuevos marcadores bioquímicos y algoritmos diagnósticos hasta ahora no disponibles para facilitar la estimación del riesgo cardiovascular y la orientación diagnóstica de las alteraciones lipídicas. Material y métodos: Estudio para la implementación de apolipoproteína B y de lipoproteína (a), así como la inclusión de diferentes algoritmos diagnósticos. Se ha realizado conjuntamente entre las diferentes unidades de lípidos de la Sociedad Española de Arteriosclerosis, Hospital Virgen Macarena de Sevilla, Hospital Juan Ramón Jiménez, Hospital Infanta Elena y Hospital de Río Tinto durante los años 2018 y 2019. Resultados: Se han aplicado 4 algoritmos diagnósticos en el sistema de información del laboratorio, que mostraron 9.985 pacientes totales con c-LDL>200mg/dl. Según el algoritmo diagnóstico, que se amplió para que incluyera ApoB, 8.182 determinaciones presentaban una apolipoproteína B>100mg/dl. Se determinaron 747 casos de lipoproteína (a), de las cuales un 30,65% fueron superiores a 50mg/dl. El 71,80% presentaban resultados compatibles con partículas de LDL pequeñas y densas. Conclusiones: La implementación de nuevos parámetros analíticos y el uso de algoritmos en los laboratorios en atención primaria permite identificar un número considerable de pacientes con diferentes alteraciones en el metabolismo lipídico que, junto con los factores de riesgo clásicos, podría contribuir a una correcta estratificación de riesgo y a evitar la progresión de la enfermedad cardiovascular.(AU)

Introduction: The combination of biochemical markers, together with the design and implementation of diagnostic algorithms in laboratory computer systems could become very powerful tools in the stratification of cardiovascular risk. Objectives: To implement new biochemical markers and diagnostic algorithms not yet available, in order to provide an estimation of cardiovascular risk and the diagnostic orientation of lipid alterations. Material and methods: Study of the implementation of apolipoprotein B and lipoprotein (a), as well as the inclusion of different diagnostic algorithms. This was carried out jointly by the different Lipid Units of the Spanish Society of Atherosclerosis, Hospital Virgen Macarena in Seville, Hospital Juan Ramón Jiménez, Hospital Infanta Elena, and Hospital de Río Tinto during 2018 and 2019. Results: The 4diagnostic algorithms entered into the Laboratory Information System, showed a total of 9,985 patients with c-LDL>200mg/dl. The diagnostic algorithm was extended to include Apo B, with 8,182 determinations showing an apolipoprotein B>100mg/dl). A total of 747 lipoprotein (a) were determined, of which 30.65% were> 50mg/dl. More than 2/3 (71.80%) showed results compatible with small and dense LDL particles. Conclusions: The implementation of new analytical parameters and algorithms in Primary Care laboratory results can identify a considerable number of patients with different alterations in lipid metabolism. This, together with the classic risk factors, could contribute to a correct risk stratification in preventing the progression of cardiovascular disease.(AU)

Incorporation of biochemical parameters and diagnostic algorithms in the laboratory computer system for the early detection of lipid abnormalities from the lipid units. / Incorporación de parámetros bioquímicos y algoritmos diagnósticos en el sistema informático de laboratorio para la detección precoz de alteraciones lipídicas desde las unidades de lípidos.

INTRODUCTION: The combination of biochemical markers, together with the design and implementation of diagnostic algorithms in laboratory computer systems could become very powerful tools in the stratification of cardiovascular risk. OBJECTIVES: To implement new biochemical markers and diagnostic algorithms not yet available, in order to provide an estimation of cardiovascular risk and the diagnostic orientation of lipid alterations. MATERIAL AND METHODS: Study of the implementation of apolipoprotein B and lipoprotein (a), as well as the inclusion of different diagnostic algorithms. This was carried out jointly by the different Lipid Units of the Spanish Society of Atherosclerosis, Hospital Virgen Macarena in Seville, Hospital Juan Ramón Jiménez, Hospital Infanta Elena, and Hospital de Río Tinto during 2018 and 2019. RESULTS: The 4diagnostic algorithms entered into the Laboratory Information System, showed a total of 9,985 patients with c-LDL>200mg/dl. The diagnostic algorithm was extended to include Apo B, with 8,182 determinations showing an apolipoprotein B>100mg/dl). A total of 747 lipoprotein (a) were determined, of which 30.65% were> 50mg/dl. More than 2/3 (71.80%) showed results compatible with small and dense LDL particles. CONCLUSIONS: The implementation of new analytical parameters and algorithms in Primary Care laboratory results can identify a considerable number of patients with different alterations in lipid metabolism. This, together with the classic risk factors, could contribute to a correct risk stratification in preventing the progression of cardiovascular disease.

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.

Presentación de un caso de derrame pleurocárdico en un paciente diagnosticado de polimialgia reumática / Pleural and pericardial effusion in a patient with polymyalgia rheumatica: a case presentation

La polimialgia reumática es una enfermedad inflamatoria reumática que se caracteriza por dolor y rigidez bilateral que afecta principalmente a la musculatura proximal. Aparece sobre todo en personas por encima de los 50 años y se asocia a una velocidad de sedimentación globular elevada en la analítica. La enfermedad generalmente responde muy bien a dosis bajas de corticoides. A continuación, presentamos el caso de un varón de 80años que presentó un cuadro compatible con polimialgia reumática asociado a derrame pleuropericárdico que respondió rápidamente a corticoides, con rápida mejoría en la sintomatología y en los hallazgos de laboratorio. La polimialgia reumática es una enfermedad que se presenta con relativa frecuencia pero que raramente se asocia a derrame pleuropericárdico. Es importante tenerla en cuenta en el diagnóstico diferencial del derrame pericárdico en personas mayores de 50años por su buena respuesta a tratamiento (AU)

Polymyalgia rheumatica is an inflammatory rheumatic disease that presents with bilateral pain and stiffness affecting mainly proximal muscles. It affects individuals over 50 years of age and it is usually associated with a raised erythrocyte sedimentation rate. Classically, treatment with low-dose corticosteroids results in a dramatic improvement in both symptoms and laboratory findings. We report the case of an 80 years old patient presenting polymyalgia rheumatica coinciding with pleuropericardial effusion. The patient had a very good response to treatment with rapid improvement in the symptomatology and laboratory findings. Polymyalgia Rheumatica is a common disease but it is rarely associated to pleuropericardial effusion. It should be considered in the differential diagnostic in patients presenting with pericardial effusion over 50 of age years due to the good response to treatment (AU)

Pleural and pericardial effusion in a patient with polymyalgia rheumatica: a case presentation.

Polymyalgia rheumatica is an inflammatory rheumatic disease that presents with bilateral pain and stiffness affecting mainly proximal muscles. It affects individuals over 50 years of age and it is usually associated with a raised erythrocyte sedimentation rate. Classically, treatment with low-dose corticosteroids results in a dramatic improvement in both symptoms and laboratory findings. We report the case of an 80 years old patient presenting polymyalgia rheumatica coinciding with pleuropericardial effusion. The patient had a very good response to treatment with rapid improvement in the symptomatology and laboratory findings. Polymyalgia Rheumatica is a common disease but it is rarely associated to pleuropericardial effusion. It should be considered in the differential diagnostic in patients presenting with pericardial effusion over 50 of age years due to the good response to treatment.

[Hepatitis as unique manifestation of Q fever: clinical and epidemiologic characteristics in 109 patients]. / Hepatitis aislada como forma de presentación de la fiebre Q: características clínicas y epidemiológicas en 109 pacientes.

INTRODUCTION: To describe the clinical and epidemiologic characteristics of hepatic involvement in a cohort of 109 patients with Q fever. RESULTS: Involvement of the liver alone was documented in 55% of cases. In 96% it was manifested as a febrile process without focal symptoms and hepatic cytolysis. There were no differences in epidemiologic characteristics between patients with hepatitis and those and without. CONCLUSION: Q fever should be included in the differential diagnosis of community-acquired febrile syndromes.

Hepatitis aislada como forma de presentación de la fiebre Q: características clínicas y epidemiológicasen 109 pacientes / Hepatitis as unique manifestation of Q fever: Clinical and epidemiologic characteristics in 109 patients

INTRODUCCIÓN. Describir las características clínicas y epidemiológicas de la hepatitis aislada en una cohorte de 109 pacientes con fiebre Q.RESULTADOS. La hepatitis aislada representó el 55 por ciento. En el 96 por ciento de los casos se manifestó como un cuadro febril sin síntomas focales y cistólisis hepática. No se ha encontrado ninguna diferencia en las características epidemiológicas entre los pacientes con y sin hepatitis. CONCLUSIÓN. Debería considerarse la fiebre Q en del diagnóstico diferencial de los síndromes febriles adquiridos en la comunidad (AU)