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.

Prevalence of musculoskeletal disorders and rheumatic diseases in Cuenca, Ecuador: a WHO-ILAR COPCORD study.

The aim of this study was to determine the prevalence of musculoskeletal pain and rheumatic diseases in subjects over 18 years of age from the canton of Cuenca, Ecuador. Cross-sectional analytical community-based study was conducted in subjects over 18 years of age using the validated Community-Oriented Program for the Control of Rheumatic Diseases (COPCORD) questionnaire. Random sampling was used. The questionnaire was administered by standardized health workers. Subjects were visited house by house. Subjects positive for musculoskeletal (MSK) pain in the last 7 days and at some point in life were assessed by rheumatologists to confirm the diagnosis. A total of 4877 subjects participated, with an average age of 42.8 (SD 18.8) years of age; 59.7 % were women; 69.7 % lived in urban areas. 32.5 % reported MSK pain in the last 7 days and 45.7 % at some point in life. The prevalence of knee osteoarthritis was 7.4 %, hand osteoarthritis 5.3 %, low back pain 9.3 %, rheumatoid arthritis 0.8 %, fibromyalgia 2 %, gout 0.4 %, and lupus 0.06 %. Subjects from rural areas reported experiencing more MSK pain in the last 7 days and at some point in life, lower income, poorer health-care coverage, and increased physical activity involving repetitive tasks such as lifting weights or cooking with firewood. MSK pain prevalence was high. Osteoarthritis and low back pain were the most common diseases. Age, sex, physical activity, repetitive tasks, living in a rural area, and lack of health-care coverage were found to be associated with MSK pain.

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.

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.

Molecular basis of the familial chylomicronemia syndrome in patients from the National Dyslipidemia Registry of the Spanish Atherosclerosis Society.

BACKGROUND: Familial chylomicronemia syndrome (FCS) is an extremely rare lipoprotein disorder caused by mutations in at least 5 genes of the lipoprotein lipase (LPL) complex. OBJECTIVE: This work shows the molecular analysis of patients diagnosed with FCS, who attended the Spanish Arteriosclerosis Society lipid units and were included in the National Dyslipidemia Registry. METHODS: Among the 238 patients registered with severe hypertriglyceridemia (fasting triglycerides >1000 mg/dL), 26 were diagnosed with FCS as they had confirmed postheparin plasma LPL activity deficiency and/or homozygosity for loss-of-function mutations in LPL, GPIHBP1, APOC2, LMF1, or Apolipoprotein A5 (APOA5). RESULTS: Among the 26 FCS cases, 23 had mutations in the homozygous state: 19 in LPL and 4 in the GPIHBP1 gene. The molecular analysis revealed 3 novel mutations: 2 in LPL, in 2 unrelated patients (c.312delA; p.Asp105Thrfs*66 and c.629A>G; p.His210Arg), and 1 in GPHIBP1 in a third patient (c.502delC; p.Leu168Serfs*83). These 3 patients had confirmed lack of LPL activity. Three additional patients with confirmed LPL activity deficiency were heterozygous carriers of mutations in the genes analyzed. Among these, we found 2 novel mutations in APOA5 (c.50-1G>A and c.326_327insC; p.Tyr110Leufs*158). CONCLUSION: We have identified 5 novel pathogenic mutations: 2 in LPL, 1 in GPIHBP1, and 2 in the APOA5 gene. The genetic defaults accounting for the LPL activity deficiency of 23 of them have been clearly identified and 3 patients, who harbored mutations in heterozygosity, were diagnosed based on LPL activity deficiency, which raises the question of the involvement of new genes in the manifestation of FCS.

Nonalcoholic fatty liver disease is associated with carotid atherosclerosis: a case-control study.

OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) frequently coexists with obesity, diabetes, and dyslipidemia. We examined whether NAFLD was associated with atherosclerosis, as measured by ultrasound in the carotid arteries. METHODS AND RESULTS: Carotid atherosclerosis and cardiovascular risk factors were assessed in 40 patients with an ultrasound diagnosis of primary NAFLD and 40 matched population controls. The metabolic syndrome and all its individual traits, including elevated C-reactive protein, were significantly (P<0.005) more frequent in NAFLD patients than in control subjects. Patients with NAFLD showed more carotid atherosclerosis than controls, with mean intima-media thickness (IMT) of 0.70+/-0.20 mm and 0.54+/-0.13 mm (P<0.0001) and plaque prevalence of 50% and 25% (P=0.021), respectively. By multivariate analysis, older age (odds ratio [OR], 2.5 per 10 years; 95% CI, 1.4 to 4.4; P=0.002), the presence of NAFLD (OR, 8.4; 95% CI, 2.49 to 29.4; P=0.001), and elevated serum ferritin (OR, 3.1; 95% CI, 1.2 to 7.9; P=0.016) were independent predictors of an increased IMT. CONCLUSIONS: Patients with NAFLD show a cluster of risk factors of the metabolic syndrome and advanced carotid atherosclerosis. NAFLD appears to be a feature of the metabolic syndrome, and its detection on abdominal ultrasound should alert to the existence of an increased cardiovascular risk.

Homozygous Familial Hypercholesterolemia in Spain: Prevalence and Phenotype-Genotype Relationship.

BACKGROUND: Homozygous familial hypercholesterolemia (HoFH) is a rare disease characterized by elevated plasma levels of low-density lipoprotein cholesterol (LDL-C) and extremely high risk of premature atherosclerotic cardiovascular disease. HoFH is caused by mutations in several genes, including LDL receptor (LDLR), apolipoprotein B (APOB), proprotein convertase subtilisin/kexin type 9 (PCSK9), and LDL protein receptor adaptor 1 (LDLRAP1). No epidemiological studies have assessed HoFH prevalence or the clinical and molecular characteristics of this condition. Here, we aimed to characterize HoFH in Spain. METHODS AND RESULTS: Data were collected from the Spanish Dyslipidemia Registry of the Spanish Atherosclerosis Society and from all molecular diagnoses performed for familial hypercholesterolemia in Spain between 1996 and 2015 (n=16 751). Clinical data included baseline lipid levels and atherosclerotic cardiovascular disease events. A total of 97 subjects were identified as having HoFH-of whom, 47 were true homozygous (1 for APOB, 5 for LDLRAP1, and 41 for LDLR), 45 compound heterozygous for LDLR, 3 double heterozygous for LDLR and PSCK9, and 2 double heterozygous for LDLR and APOB. No PSCK9 homozygous cases were identified. Two variants in LDLR were identified in 4.8% of the molecular studies. Over 50% of patients did not meet the classical HoFH diagnosis criteria. The estimated HoFH prevalence was 1:450 000. Compared with compound heterozygous cases, true homozygous cases showed more aggressive phenotypes with higher LDL-C and more atherosclerotic cardiovascular disease events. CONCLUSIONS: HoFH frequency in Spain was higher than expected. Clinical criteria would underestimate the actual prevalence of individuals with genetic HoFH, highlighting the importance of genetic analysis to improve familial hypercholesterolemia diagnosis accuracy.

Características socio-demográficas asociadas a la presencia de dolor músculo-esquelético, en Cuenca-Ecuador / Socio - demographic characteristics associated with the presence of skeletal muscle pain, in Cuenca - Ecuador

RESUMENOBJETIVO: Determinar las características socio-demo-gráficas asociadas a la presencia de dolor músculo-esquelético (MSQ) en personas mayores de 18 años que viven en el Cantón Cuenca.PACIENTES Y MÉTODOS: Estudio transversal analítico, realizado en su-jetos del área rural y urbana, mayores de 18 años, utilizando la metodología COPCORD (Community Oriented Program for the Con-trol of Rheumatic Diseases), adaptada para Ecuador. Se identificaron a los individuos con síntomas reumáticos, casa por casa. La revisión para confirmar el diagnóstico realizó un médico Reumatólogo.El análisis estadístico fue univariado y multi-variado. RESULTADOS:Participaron 2500 personas encuestadas, el 59,6% correspondió al sexo femenino, con una edad promedio de 42,8 años, el 25,5% de los participantes realizaban actividades domésticas. El dolor MSQ se presentó en el 32,2% de las personas, el cual se asoció sig-nificativamente a vivir en el área rural, tener menor escolaridad, ingresos económicos por debajo de 340 dólares, carga física ma-yor de 8 libras, mayor discapacidad funcional y el cocinar con leña en el sector rural. CONCLUSIÓN: El dolor MSQ tiene un alta prevalencia en la población de Cuenca, Ecuador; producien-do discapacidad especialmente en el área rural. se asocia con menor nivel de escola-ridad, ingresos económicos bajos y mayor carga física.

OBJECTIVE: To determine the socio-demographic cha-racteristics associated with the presence of musculoskeletal pain (MSK) in people over 18 years who are living in Cuenca.PATIENTS AND METHODSAn analytical cross-sectional study was con-ducted in subjects of rural and urban areas, who are over 18 years, using the metho-dology COPCORD (Community Oriented Program for the Control of Rheumatic Di-seases) adapted to Ecuador. We identified individuals with rheumatic symptoms, house by house. The revision to confirm the diagnosis was made by a rheumatologist. The statistical analysis was univariate and multivariate. RESULTSA total of 2500 people were surveyed. The 59.6% were female, with an average age of 42.8 years, the 25.5% of participants perfor-med domestic activities. The MSK pain oc-curred in 32.2% of people, which was signi-ficantly associated with living in rural areas, have lower education, lower income to $ 340, increased physical load of 8 pounds, more functional disability, and cooking with firewood in the rural area. CONCLUSIONThe MSK pain has a high prevalence in the population of Cuenca, Ecuador; producing disability especially in rural areas. It is asso-ciated with lower levels of education, lower income and increased physical load

Pautas para el manejo anestésico del paciente con trauma abdominal / Guidelines for the antestetic handling of the patient with abdominal trauma

Expone que el trauma constituye una importante causa de muerte, en los EE.UU., cada año se producen 50 millones de accidentes, 10 millones de los cuales determinan una incapacidad permanente. En el mundo de las lesiones traumáticas constituyen la cuarta parte del total de las causas de muerte, cifra que va en aumento, mientras que la mortalidad por carcinomas y otras enfermedades disminuyen, y lo más grave es que las lesiones traumáticas ocurren en las tres primeras décadas de la vida es decir en la edad productiva. En el Ecuador del deceso por trauma constituye la primera causa de muerte, de incapacidad o discapacidad y de lesiones temporales o permanentes en la edad económicamente activa. Muchas lesiones traumáticas requieren cirugía emergente, generalmente en las noches, los fines de semana o durante las vacaciones. Para planificar una técnica anestésica y elaborar un protocolo de seguimiento del paciente con trauma es necesario comprender los principales del paciente politraumatizado...

Leiomiosarcoma en diverticulo de Meckel: a propósito de un caso / Leiomiosarcoma in divertículo of Meckel: with regard to a case

Presenta el caso de una paciente de 75 años de edad, sin antecedentes de importancia quién acude con sintomatología de sangrado digestivo bajo recidivante. Se realizan endoscopía para descartar sangrado alto, Rx de abdomen, colonoscopía, gamagrafía, sin llegar a un diagnóstico etiológico definitivo por lo que se somete a paciente a laparotomía exploradora encontrándose divertículo de Meckel perforado, examen histopatológico revela leiomiosarcoma de bajo grado, inflamación aguda y necrosis tumoral. El diagnóstico preoperatorio de este tipo de tumores es siempre difícil debido a la rareza de esta patología, la mayor parte son hallazgos incidentales durante la exploración quirúrgica de un sangrado digestivo de origen no detectado. Se discuten los aspectos de diagnóstico y tratamiento...

Intoxicación por fósforo blanco

This is a descriptive and retrospective stadistical study too realize in Pablo Artuto Suares Hospital in Quito Ecuador. Make the ingestion withe phosphorus prevalence in the period to 01-01-1996 to 31-12-1996. Complete 39 patients, men 19, women 20, year average 20.35, time ingestion average 11.10 days, morbility 84.6 por ciento and mortality 15.37 por ciento.

Cosmovisión de la patogenesis infecciosa

Las enfermedades infecciosas no deberían considerarse un capítulo más de patología formal sino el resultado de la relación ecológica entre tres eslabones de un crículo dinámico; el medio, el huésped y el agente infeccioso. La relación de los dos primeros, de carácter mecro-ecológico tiene un canal de comunicación que es la situación social de sujeto, implicitamente anexa a su condición orgánica integral (conocimiento y función) que será poco o suficientemente competente para neutralizar los factores de riesgo ambintales (naturales y artificiales) que favorecen la prsentación de la enfermedades infecciosas, especialmente en el territorio tropical (5 al 7). En él se encuentra la mayor área de nuestro país. (8). Estos factores naturales con: topografía (bajo 1.00snm), humedad (superior al 70 por ciento y fluviosidad sobre los 1.000 mn. anuales), fauna (presencia de vectores, de huéspedes intermdiarios, definitivos, reservorios) y flora (especies forestales que favorecen la vida de la fauna) que en el ecosistema tropical son exhuberantes, provocando la lucha por la supervivencia entre el huésped y los gérmenes patógenos. El huésped trata de neutralizar este medio ambiente natural creando condiciones (artificiales) que son: explotación apropiada de los recursos naturales sin agresión ecológica, educación, saneamiento ambiental y distribución de la riqueza que en forma directa influirá en la conformación de grupos sociales protegidos y desprotegidos. Si la relación macro-ecológica es armónica el medio ambiente natural y social (artificial) brindará al huésped un nivel adecuado de protección y éste lo revertirá con un nivel de productividad directamente proporcional.

Infecciones necrosantes de tejidos blandos

Las infecciones necrotizantes de tejidos blandos conocidas también con fascitis necrotisantes o mal llamadas gangrena gaseosa, son actualmente un reto para el personal médico ya sea porque no existe una terminología estandarizada, lo que dificulta el diagnóstico y en si el tratamiento, como tambíen por el alto índice de mortalidad que presenta, así del 38 por ciento puede ascender a un 71 por ciento inclusive al 100 por ciento si no se realiza una buena intervención en el primero y en el segundo acto operatorio. El cuadro clínico, diagnóstico y la mortalidad en sí depende de la capacidad de huésped para defenderse ante una infección, la localización de la misma, grado de afectación tisular, transtornos predisponentes y de la virulencia como de la cantidad de microorganismos presentes, entre otros, estreptococos hemolíticos, asociación sinérgica entre estafilococos anaerobios, costridios, bacteroides etc. Los signos y síntomas que conllevan al diagnóstico se los califican como locales y generales aunque la mejor maniobra diagnóstica es: presentación clínica, sospecha de infección necrosante de tejidos blandos y exploración quirúrgica. Al ser consideradas estas infecciones como variaciones del mismo proceso patológico los pasos a seguir serán: reanimación del enfermo, motorización de signos vitales, corrección de transtornos metabólicos, tratamiento antibiótico de amplio espectro, revisión o actualización de la vacuna antitetánica y por último una buena limpieza quirúrgica, por lo ya descrito el paciente debe ser tratado en una unidad de terapia intensiva. En nuestro medio en el Anuario de 1995 del Instituto Nacional de Estadísticas y Censos (INEC) en el capítulo XII que corresponde a enfermedades de la piel y tejido celular subcutáneo desde el número 680 hasta el 709 no constan como tales, de ahí la importancia de realizar este trabajo: el mismo que consta de; clínica, diagnóstico y tratamiento, para sí tener una idea global acerca de esta patología.

Abcesos intra-abdominales post-apendicectomia en el Hospital Pablo Arturo Suárez 1990-1995

Se trata de un estudio retrospectivo, en el que se analiza los pacientes que fueron diagnosticados de absceso intra-abdominal postapendicectomía (AIPA), en el Hospital Pablo Arturo Suárez, entre enero de 1990 a diciembre de 1995. El 2.25 por ciento de los pacientes apendicectomizados, tuvieron AIPA. La perforación y la gangrena apendicular fueron observadas en el 91.7 por ciento de los casos con AIPA. El promedio de horas transcurridas entre el ingreso del paciente a emergencia y la cirugía fue de 14,25 horas, rango 3-45 horas. La fosa ilíaca derecha fue la localización más frecuente de AIPA (50 por ciento). El 66.7 por ciento de los pacientes con AIPA se sometieron a drenaje quirúrgico del absceso más antibiotico-terapia. Nos se observó mortalidad en este grupo de estudio. El cirujano debe desarrollar su criterio diagnóstico, para identificar pacientes en riesgo de AIPA y dar celeridad en el tratamiento quirúrgico d este tipo de paciente...

Infecciones necrosantes de tejidos blandos

Las infecciones necrosantes de tejidos blandos conocidas tambièn como fascitis necrosantes o mal llamadas gangrena gaseosa, son actualmente un reto para el personal mèdico ya sea porque no existe una terminologìa estandarizada, lo que dificulta el diagnòstico y en sì el tratamiento, como tambièn por el alto ìndice de mortalidad que presenta, asì del 38 por ciento puede ascender a un 71 por ciento inclusive al 100 por ciento si no se realiza una buena intervenciòn en el primero y en el segundo acto operatorio. El cuadro clìnico, diagnòstico y la mortalidad en sì depende de la capacidad del huèsped para defenderse ante una infecciòn, la localizaciòn de la misma, grado de afectaciòn tisular, trastornos predisponentes y de la virulencia como de la cantidad de microorganismos presentes...