Differential expression of m5C RNA methyltransferase genes NSUN6 and NSUN7 in Alzheimer's disease and traumatic brain injury.

Epigenetic processes have become increasingly relevant in understanding disease-modifying mechanisms. 5-Methylcytosine methylations of DNA (5mC) and RNA (m5C) have functional transcriptional and RNA translational consequences and are tightly regulated by writer, reader and eraser effector proteins. To investigate the involvement of 5mC/5hmC and m5C effector proteins contributing to the development of dementia neuropathology, RNA sequencing data of 31 effector proteins across four brain regions was examined in 56 aged non-affected and 51 Alzheimer's disease (AD) individuals obtained from the Aging, Dementia and Traumatic Brain Injury Study. Gene expression profiles were compared between AD and controls, between neuropathological Braak and CERAD scores and in individuals with a history of traumatic brain injury (TBI). We found an increase in the DNA methylation writers DNMT1, DNMT3A and DNMT3B messenger RNA (mRNA) and a decrease in the reader UHRF1 mRNA in AD samples across three brain regions whilst the DNA erasers GADD45B and AICDA showed changes in mRNA abundance within neuropathological load groupings. RNA methylation writers NSUN6 and NSUN7 showed significant expression differences with AD and, along with the reader ALYREF, differences in expression for neuropathologic ranking. A history of TBI was associated with a significant increase in the DNA readers ZBTB4 and MeCP2 (p < 0.05) and a decrease in NSUN6 (p < 0.001) mRNA. These findings implicate regulation of protein pathways disrupted in AD and TBI via multiple pre- and post-transcriptional mechanisms including potentially acting upon transfer RNAs, enhancer RNAs as well as nuclear-cytoplasmic shuttling and cytoplasmic translational control. The targeting of such processes provides new therapeutic avenues for neurodegenerative brain conditions.

Unraveling the role of relative telomere length and CAG expansion on initial symptoms of juvenile Huntington disease.

BACKGROUND AND PURPOSE: Juvenile-onset Huntington disease (JHD) is defined when symptoms initiate before 20 years of age. Mechanisms explaining differences between juvenile and adult onset are not fully understood. Our aim was to analyze the distribution of initial symptoms in a cohort of JHD patients and to explore its relationship with CAG expansion and relative telomere length (RTL). METHODS: A total of 84 JHD patients and 54 neurologically healthy age and sex matched individuals were recruited. CAG length was measured by southern blot or triplet repeat primed polymerase chain reaction. RTL was measured using the Cawthon method. RESULTS: Psychiatric symptoms were most frequent when considering the entire cohort. When divided into onset before or after 10 years, cognitive symptoms were more frequent in the youngest, whilst in the older group psychiatric symptoms prevailed. Motor symptoms were rare in the youngest and epilepsy was observed only in this group as well as a larger CAG expansion. RTL analysis revealed shorter telomeres in JHD patients compared to controls. This difference is not influenced by age, initial symptoms, time of disease or CAG expansion. CONCLUSIONS: To the best of our knowledge this is the largest cohort of JHD patients reported. Psychiatric manifestations deserve special attention when JHD is suspected and epilepsy is especially important in the youngest patients. Initial symptoms seem to be influenced by CAG expansion and therefore age of onset. RTL is significantly reduced in JHD patients which can influence the characteristic neurodegeneration of JHD and contribute to the clinical discrepancy between adult and juvenile forms of Huntington disease.

Documento internacional de consenso sobre apnea obstructiva del sueño / International Consensus Document on Obstructive Sleep Apnea

El objetivo principal de este documento internacional de consenso sobre apnea obstructiva del sueño es proporcionar unas directrices que permitan a los profesionales sanitarios tomar las mejores decisiones en la asistencia de los pacientes adultos con esta enfermedad según un resumen crítico de la literatura más actualizada. El grupo de trabajo de expertos se ha constituido principalmente por 17 sociedades científicas y 56 especialistas con amplia representación geográfica (con la participación de 4 sociedades internacionales), además de un metodólogo experto y un documentalista del Centro Cochrane Iberoamericano. El documento consta de un manuscrito principal, con las novedades más relevantes, y una serie de manuscritos online que recogen las búsquedas bibliográficas sistemáticas de cada uno de los apartados del documento internacional de consenso. Este documento no cubre la edad pediátrica ni el manejo del paciente en ventilación mecánica crónica no invasiva (que se publicarán en sendos documentos de consenso aparte). Palabras clave: Apnea obstructiva del sueño Diagnóstico Tratamiento

The main aim of this international consensus document on obstructive sleep apnea is to provide guidelines based on a critical analysis of the latest literature to help health professionals make the best decisions in the care of adult patients with this disease. The expert working group was formed primarily of 17 scientific societies and 56 specialists from a wide geographical area (including the participation of 4 international societies), an expert in methodology, and a documentalist from the Iberoamerican Cochrane Center. The document consists of a main section containing the most significant innovations and a series of online manuscripts that report the systematic literature searches performed for each section of the international consensus document. This document does not discuss pediatric patients or the management of patients receiving chronic non-invasive mechanical ventilation (these topics will be addressed in separate consensus documents). Keywords: Obstructive sleep apnea Diagnosis Treatment

International Consensus Document on Obstructive Sleep Apnea. / Documento internacional de consenso sobre apnea obstructiva del sueño.

The main aim of this international consensus document on obstructive sleep apnea is to provide guidelines based on a critical analysis of the latest literature to help health professionals make the best decisions in the care of adult patients with this disease. The expert working group was formed primarily of 17 scientific societies and 56 specialists from a wide geographical area (including the participation of 4 international societies), an expert in methodology, and a documentalist from the Iberoamerican Cochrane Center. The document consists of a main section containing the most significant innovations and a series of online manuscripts that report the systematic literature searches performed for each section of the international consensus document. This document does not discuss pediatric patients or the management of patients receiving chronic non-invasive mechanical ventilation (these topics will be addressed in separate consensus documents).

circRNA Regulates Dopaminergic Synapse, MAPK, and Long-term Depression Pathways in Huntington Disease.

Huntington disease (HD) is the most common neurogenetic disorder caused by expansion of the CAG repeat in the HTT gene; nevertheless, the molecular bases of the disease are not fully understood. Non-coding RNAs have demonstrated to be involved in the physiopathology of HD. However, the role of circRNAs has not been investigated. The aim of this study was to identify the circRNAs with differential expression in a murine cell line model of HD and to identify the biological pathways regulated by the differentially expressed circRNAs. CircRNA expression was analyzed through a microarray, which specifically detects circular species of RNA. The expression patterns between a murine cell line expressing mutant Huntingtin and cells expressing wild-type Huntingtin were compared. We predicted the miRNAs with binding sites for the differentially expressed circRNAs and the corresponding target genes for those miRNAs. Using the target genes, we performed a function enrichment analysis. We identified 23 circRNAs differentially expressed, 19 downregulated and four upregulated. Most of the downregulated circRNAs derive from the Rere gene. The dopaminergic synapse, MAPK, and long-term depression pathways were significantly enriched. The three identified pathways have been previously associated with the physiopathology of HD. The understanding of the circRNA-miRNA-mRNA network involved in the molecular mechanisms driving HD can lead us to identify novel biomarkers and potential therapeutic targets. To the best of our knowledge, this is the first study analyzing circRNAs in a model of Huntington disease.

Coronary plaque burden, plaque characterization and their prognostic implications in familial hypercholesterolemia: A computed tomographic angiography study.

BACKGROUND AND AIMS: Heterozygous familial hypercholesterolemia (FH) is associated with premature atherosclerotic cardiovascular disease. Semi-automated plaque characterization (SAPC) by coronary computed tomographic angiography (CTA) provides information regarding coronary plaque burden and plaque characterization. Our aim was to quantify and characterize the coronary plaque burden of patients with FH using SAPC analysis and to identify which factors are related to plaque burden and plaque characteristics. A second aim was to analyse the prognostic implications of these parameters. METHODS: Two hundred and fifty-nine asymptomatic individuals with molecularly determined FH were enrolled in this follow-up cohort study and underwent a coronary CTA analysed with SAPC. RESULTS: Mean follow-up time after coronary CTA was 3.9 ± 2 years. Mean age was 46.9 (10.7) years (130 women, 50.2%). Median plaque burden was 25.0% (19.0-29.0), non-calcified plaque burden 22.83% (17.94-26.88), calcified plaque-burden 1.12% (0.31-2.86) and CCS 8.9 (0-93). Five-year risk was independently related to plaque burden, non-calcified plaque burden, calcified plaque burden and coronary calcium score (B:3.75, 95%CI:2.92-4.58; p < 0.001, B:2.9, 95%CI:2.15-3.66; p < 0.001, B:0.75, 95%CI 0.4-1.1; p < 0.001 and B:82.2, 95%CI:49.28-115.16; p < 0.001 respectively). During follow-up, there were 15 (5.81%) nonfatal events and 1 (0.4%) fatal event. Plaque burden was significantly related to event-free survival during follow-up (HR:1.11; 95%CI:1.05-1.18; p < 0.001). CONCLUSIONS: Coronary atherosclerosis and its qualitative components may be quantified by means of SAPC in patients with FH. Plaque burden, calcified plaque burden and non-calcified plaque burden were independently related to the estimated cardiovascular risk. Plaque burden was also related to prognosis.

Telomere length analysis on leukocytes derived from patients with Huntington Disease.

INTRODUCTION: Huntington´s disease (HD) is a neurodegenerative disorder characterized by neuropsychiatric, motor and cognitive manifestations. It is caused by expansion of the trinucleotide CAG on HTT. The molecular bases are not completely understood, DNA damage, such as double and single strand breaks and oxidative stress (OS) have been implicated. At telomeres, DNA breaks are less efficiently repaired. Double strand breaks evoke the break induced replication (BIR) mechanism. BIR, plus inefficient repair can produce telomere shortening and cellular senescence. Our aim was to investigate the correlation between leukocyte relative telomeric length (RTL) and HD. METHODS: 206 samples were analyzed, 71 patients with molecular diagnosis and symptomatology (HD), 29 individuals with positive molecular test but asymptomatic (PP) and 106 healthy individuals (NP). RESULTS: We found a significant difference in RTL between HD patients compared with both, PP and NP, independently of subjects' age. DISCUSSION: Here we present evidence supporting an association between telomere shortening and HD. Telomere shortening could be related to DNA damage caused by ROS and defective DNA repair mechanism. Both events have been probed to occur in the presence of a mutant Huntingtin. This study contributes with current evidence suggesting a potential role of telomere shortening as HD biomarker.

Mitral valve navigator. A new diagnostic tool for effective regurgitant orifice quantification in mitral regurgitation.

INTRODUCTION: Mitral regurgitation severity assessment is usually carried out using qualitative, semiquantitative, and quantitative parameters. The mitral valve navigation (MVN) tool allows to measure the mitral effective regurgitant orifice (MERO) from 3D echo datasets. Our aim was to validate the MVN as a new tool to quantify MERO. A secondary aim was to assess the intra- and interobserver variability. METHODS: This is a retrospective study in which consecutive subjects undergoing a transoesophageal echocardiogram for more than mild mitral regurgitation evaluation were included. MERO measurement obtained by means of 3D color Doppler was used as the gold standard method for comparison. In every patient, MERO was also obtained using the MVN tool. RESULTS: Fifty-nine consecutive patients were analyzed (47.5% female; mean age 50.8 years). Mitral regurgitation was moderate in 23 (39%) and severe in 36 (61%) patients. Forty patients (67.8%) had a primary and 19 (32.2%) a secondary mitral regurgitation. The intraclass correlation coefficient (ICC) between 3D color Doppler and MVN was excellent (ICC: 0.95; 95% CI: 0.82 to 0.98; P < 0.001) in the total group and for patients with primary and secondary mitral regurgitation. Intra- and interobserver agreements were also good. CONCLUSIONS: Mitral valve navigator shows an excellent accuracy for measuring MERO when the transoesophageal 3D color Doppler is used as the reference method, either primary or secondary mitral regurgitation. Intraobserver reproducibility and interobserver reproducibility are also excellent. These findings make this software a good alternative method to measure mitral regurgitation severity.

Coronary computed tomographic angiography findings and their therapeutic implications in asymptomatic patients with familial hypercholesterolemia. Lessons from the SAFEHEART study.

BACKGROUND: Familial hypercholesterolemia (FH) confers an increased risk of premature atherosclerotic disease. Coronary computed tomographic angiography (CTA) can assess preclinical coronary atherosclerosis. OBJECTIVES: To describe coronary CTA findings in asymptomatic molecularly defined FH individuals, to identify those factors related to its presence and extension, and to assess the impact of these results in patients' care and estimated risk. METHODS: Four hundred and forty individuals with FH, without clinical cardiovascular disease, were consecutively enrolled and underwent a coronary CTA that was used to analyze coronary atherosclerosis based on coronary calcium score (CCS), sum of stenosis severity, and plaque composition sum (PCS). For FH patients, cardiovascular risk was estimated using the specific SAFEHEART risk equation. Follow-up was performed using a standardized protocol. RESULTS: Mean age was 46.4 years (231 women, 52%). Coronary calcium was present in 55%, mean CCS was 130.9, 46% had a plaque with lumen involvement, and mean PCS was 1.1. During follow-up, there were 17 (4%) nonfatal events and 2 (1%) fatal events. CCS was independently associated to the estimated risk and low-density lipoprotein-cholesterol life-years, sum of stenosis severity to the estimated risk, and PCS to the estimated risk and low-density lipoprotein-cholesterol life-years. CTA findings induced a positive change in patients' care and in their estimated risk. CONCLUSION: Coronary artery atherosclerosis is highly prevalent in asymptomatic patients with FH and it is independently associated to cardiovascular risk. More advanced disease on CTA was associated with subsequent intensification of therapy and reduction of estimated risk. Further longitudinal studies are required to know if these findings might improve the risk stratification in patients with FH.

Curva de aprendizaje en ecocardioscopia. Utilidad de un programa docente interespecialidad / Echocardioscopy learning curve. Usefulness of an inter-speciality training program

OBJETIVO: Comprobar los resultados de un entrenamiento en habilidad para realizar ecocardioscopias para oncólogos por parte de cardiólogos y estudiar la variabilidad en las mediciones y la significación clínica de esa variabilidad. MÉTODOS: Se incluyeron pacientes consecutivos que habían sido atendidos en las consultas de oncología previamente. Un oncólogo les realizó una ecocardioscopia con un equipo portátil. Por otro lado, un cardiólogo realizó un ecocardiograma reglado con un equipo de gama alta. Todos los oncólogos participantes recibieron un entrenamiento básico en ecocardioscopia por parte de cardiólogos especializados en imagen cardiovascular. RESULTADOS: Se incluyeron 101 pacientes (31,7% varones; edad media 56,03±16,88 años). Los resultados mostraron una clara curva de aprendizaje durante el periodo de reclutamiento, alcanzando a los dos meses una buena similitud entre oncólogo y cardiólogo para las medidas de los diámetros ventriculares, pero sin alcanzar la misma similitud hasta pasados 4 meses las medidas de la fracción de eyección del ventrículo izquierdo. De la misma manera, se produjo una importante reducción de las diferencias clínicamente significativas de la fracción de eyección del ventrículo izquierdo a partir del cuarto mes. CONCLUSIONES: Un entrenamiento breve dirigido a Facultativos Especialistas en Oncología en ecocardioscopia dirigido por cardiólogos expertos en imagen cardiovascular permite al oncólogo obtener las habilidades necesarias para evaluar las dimensiones del ventrículo izquierdo y la fracción de eyección del ventrículo izquierdo de una forma precisa. El tiempo de entrenamiento se estima en una semana de formación teórico-práctica intensa, y adicionalmente cuatro meses de realización de ecocardioscopias supervisadas estrechamente por los cardiólogos

OBJECTIVE: To assess the results of a training to perform echocardioscopic studies to oncologists by cardiologists, and to study the variability in measurements, as well as the clinical significance of this variability. METHODS: Participant oncologists received basic training in echocardioscopy by cardiologists specialised in cardiovascular imaging. Consecutive patients attending the oncology outpatient clinic were included in the study. Every patient underwent an echocardioscopic study performed by an oncologist with a portable device and an echocardiogram performed by a cardiologist using high-end equipment. RESULTS: The study included 101 patients, with a mean age of 56.03±16.88 years, and 31.7% were males. The results showed a clear learning curve over time, with a good similarity in ventricular diameters measurements between oncologists and cardiologist being reached in two months, but it took 4 months to reach the same similarity for left ventricular ejection fraction (LVEF) measurements. Likewise, there was a significant reduction in clinically significant differences in LVEF after the fourth month. CONCLUSIONS: A brief training in echocardioscopy for oncologists, led by cardiology experts in cardiovascular imaging, allows the oncologist to obtain the necessary skills to accurately assess left ventricular ejection fraction and diameters. The training time proposed is a week of intensive theoretical and practical training, followed by four months of completion of echocardioscopic examinations closely monitored by the cardiologist

Selección de lo mejor del año 2017 en cardiología clínica. Continuidad asistencial entre cardiología y atención primaria / Selection of the best of 2017 in clinical cardiology. continuum healthcare between cardiology and primary care

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Selección de lo mejor del año 2017 en cardiología clínica. Novedades terapéuticas / Selection of the best of 2017 in clinical cardiology. Therapeutic novelties

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Consecución de objetivos terapéuticos de colesterol LDL en niños y adolescentes con hipercolesterolemia familiar. Registro longitudinal SAFEHEART / Attainment of LDL cholesterol treatment goals in children and adolescents with familial hypercholesterolemia. The SAFEHEART Follow-up registry

Introducción y objetivos: Poco se conoce acerca de las características de los sujetos con hipercolesterolemia familiar (HF) menores de 18 años, así como del tratamiento hipolipemiante empleado en estos pacientes y la consecución de objetivos lipídicos en la vida real. Nuestro objetivo es valorar la consecución de objetivos de colesterol unido a lipoproteínas de baja densidad (cLDL) en pacientes con HF menores de 18 años incluidos en un gran registro nacional. Métodos: Se analizó a los pacientes menores de 18 años incluidos en un gran registro en marcha de pacientes con diagnóstico genético de HF en España. Se analizó la consecución de los objetivos recomendados de cLDL en plasma a la inclusión y en el seguimiento en relación con el uso de terapia hipolipemiante. Resultados: Se incluyó a 392 individuos menores de 18 años, de los que 217 obtuvieron diagnóstico genético de HF y seguimiento completo. El tiempo de seguimiento medio fue 4,69 [intervalo intercuartílico, 2,48-6,38] años; el 68,2% de los casos con HF tomaban estatinas y el 41,5% de los pacientes tenían el cLDL < 130 mg/dl. El uso de estatinas fue el único predictor de consecución de objetivos de cLDL. Conclusiones: Este estudio demostró que una alta proporción de pacientes con HF menores de 18 años tenía altas concentraciones de cLDL y no lograron alcanzar los objetivos de cLDL recomendados. El uso de estatinas fue el único predictor independiente asociado a conseguir el objetivo de cLDL recomendado. No se detectó ningún problema de seguridad durante el seguimiento. Estos resultados enfatizan que muchos pacientes con HF no están suficientemente controlados y aún es posible mejorar del tratamiento (AU)

Introduction and objectives: Little is known about the characteristics of persons with familial hypercholesterolemia (FH) younger than 18 years, the lipid-lowering therapy used in these patients, and the lipid goals reached in real life. Our aim was to evaluate the achievement of low-density lipoprotein cholesterol (LDL-C) treatment goals in FH patients younger than 18 years enrolled in a large national registry. Methods: We analyzed patients younger than 18 years enrolled in a large ongoing registry of molecularly-defined patients with FH in Spain. The attainment of guideline-recommended plasma LDL-C goals at entry and follow-up was analyzed in relation to the use of lipid-lowering therapy. Results: We enrolled 392 individuals younger than 18 years. Of these, 217 were molecularly-diagnosed FH patients and had a complete follow-up. The median follow-up time was 4.69 years (interquartile range, 2.48-6.38 years), 68.2% of FH patients were on statins, and 41.5% patients had LDL-C < 130 mg/dL. Statin use was the only predictor of LDL-C goal attainment. Conclusions: This study shows that a high proportion of FH patients younger than 18 years have high LDL-C levels and fail to achieve recommended LDL-C targets. Statin use was the only independent predictor of LDL-C goal achievement. No safety concerns were detected during follow-up. These results indicate that many FH patients are not adequately controlled and that there is still room for treatment improvement (AU)

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.

Attainment of LDL Cholesterol Treatment Goals in Children and Adolescents With Familial Hypercholesterolemia. The SAFEHEART Follow-up Registry.

INTRODUCTION AND OBJECTIVES: Little is known about the characteristics of persons with familial hypercholesterolemia (FH) younger than 18 years, the lipid-lowering therapy used in these patients, and the lipid goals reached in real life. Our aim was to evaluate the achievement of low-density lipoprotein cholesterol (LDL-C) treatment goals in FH patients younger than 18 years enrolled in a large national registry. METHODS: We analyzed patients younger than 18 years enrolled in a large ongoing registry of molecularly-defined patients with FH in Spain. The attainment of guideline-recommended plasma LDL-C goals at entry and follow-up was analyzed in relation to the use of lipid-lowering therapy. RESULTS: We enrolled 392 individuals younger than 18 years. Of these, 217 were molecularly-diagnosed FH patients and had a complete follow-up. The median follow-up time was 4.69 years (interquartile range, 2.48-6.38 years), 68.2% of FH patients were on statins, and 41.5% patients had LDL-C < 130mg/dL. Statin use was the only predictor of LDL-C goal attainment. CONCLUSIONS: This study shows that a high proportion of FH patients younger than 18 years have high LDL-C levels and fail to achieve recommended LDL-C targets. Statin use was the only independent predictor of LDL-C goal achievement. No safety concerns were detected during follow-up. These results indicate that many FH patients are not adequately controlled and that there is still room for treatment improvement.

Vascular age calculation and equivalent risk factors in HIV-infected patients obtained from the D:A:D risk equation.

BACKGROUND: Vascular age is a concept that represents the hypothetical age of the cardiovascular system and might be an alternative way of expressing the cardiovascular risk of a patient. The Data Collection on Adverse Effects of Anti-HIV Drugs Study (D:A:D) developed a cardiovascular risk equation from a population of HIV-infected patients, incorporating exposure to individual antiretroviral therapy drugs and traditional classic cardiovascular risk factors. OBJECTIVES: The aim of this study was to determine the vascular age calculated from the D:A:D equation, for HIV infected patients. METHODS: Vascular age was calculated according to its definition by using the D:A:D equation. The Poisson regression model used in the D:A:D equation is an exponential model to calculate the vascular age to match the exponent of the equation with the factors of a patient with the exponent of a subject with controlled risk factors. RESULTS: We obtained an equation that allows calculating the vascular age of a patient considering cardiovascular risk factors listed in the same D:A:D equation. From the equation, we have built a table for easy calculation of the vascular age and a table of cardiovascular risk equivalents. CONCLUSIONS: Vascular age is a new concept derived from Framingham risk tables that can be calculated with other risk scales, such as D:A:D for HIV patients. The calculation of vascular age in HIV patients could be a useful tool for communicating cardiovascular risk and to improve the control of modifiable risk factors.

Coronary Heart Disease, Peripheral Arterial Disease, and Stroke in Familial Hypercholesterolaemia: Insights From the SAFEHEART Registry (Spanish Familial Hypercholesterolaemia Cohort Study).

OBJECTIVE: Heterozygous familial hypercholesterolemia (FH) is the most common premature atherosclerotic cardiovascular disease (ASCVD)-related monogenic disorder, and it is associated with ischemic heart disease. There is limited information whether FH increases the risk of peripheral arterial and cerebrovascular disease. Our aim was to analyze ASCVD prevalence and characteristics in different arterial territories in a large FH population, to compare them with an unaffected control population and to determine which factors are associated to ASCVD. APPROACH AND RESULTS: SAFEHEART (Spanish Familial Hypercholesterolaemia Cohort Study) is an ongoing registry of molecularly defined patients with heterozygous FH in Spain. ASCVD in the different arterial territories was analyzed, as well as individual characteristics, genetic variables, and lipid-lowering therapies. The study recruited 4132 subjects (3745 ≥18 years); 2,752 of those enrolled were molecularly diagnosed FH cases. Median age was 44.0 years (45.9% men) and 40 years (46.6% men) in FH patients and unaffected relatives (P<0.001). ASCVD was present in 358 (13.0%) and 47 (4.7%) FH patients and unaffected relatives, respectively (P<0.001). History of premature ASCVD was more prevalent in FH patients (9.4% and 2.4% in FH patients and unaffected relatives, respectively; P<0.001). Coronary artery-related manifestations and peripheral artery disease were more prevalent in FH patients than in controls, but no significant differences were found for cerebrovascular events. Age, body mass index, type 2 diabetes mellitus, high blood pressure, previous use of tobacco, and lipoprotein(a) >50 mg/dL were independently associated with ASCVD. CONCLUSIONS: The prevalence of ASCVD is higher, and the involvement of the arterial territories is different in FH patients when compared with their unaffected relatives. Age, male sex, increased body mass index, hypertension, type 2 diabetes mellitus, smoking habit, and lipoprotein(a) >50 mg/dL were independently associated to ASCVD. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02693548.