RESUMEN
BACKGROUND: Sex differences in atherosclerotic cardiovascular disease (ASCVD) in familial hypercholesterolaemia have been reported but are not fully established. We aimed to assess sex differences in the risk of ASCVD and life-time burden of ASCVD in patients with heterozygous familial hypercholesterolaemia. METHODS: SAFEHEART is a nationwide, multicentre, long-term prospective cohort study conducted in 25 tertiary care hospitals and one regional hospital in Spain. Participants in the SAFEHEART study aged 18 years or older with genetically confirmed familial hypercholesterolaemia were included in our analysis. Data were obtained between Jan 26, 2004, and Nov 30, 2022. ASCVD and age at onset were documented at enrolment and at follow-up. Our aim was to investigate the differences by sex in the risk and burden of ASCVD in patients with heterozygous familial hypercholesterolaemia, over the study follow-up and over the life course. The SAFEHEART study is registered with ClinicalTrials.gov, NCT02693548. FINDINGS: Of the 5262 participants in SAFEHEART at the time of analysis, 3506 (1898 [54·1%] female and 1608 [45·9%] male participants) met the inclusion criteria and were included in the current study. Mean age was 46·1 years (SD 15·5) and median follow-up was 10·3 years (IQR 6·4-13·0). Mean on-treatment LDL-cholesterol at follow-up was 3·1 mmol/L (SD 1·4) in females and 3·0 mmol/L (1·5) in males. LDL-cholesterol reductions over time were similar in both sexes (1·39 mmol/L [95% CI 1·30-1·47] absolute reduction in females vs 1·39 mmol/L [1·29-1·48] in males; p=0·98). At enrolment, 130 (6·8%) females and 304 (18·9%) males (p<0·0001) had cardiovascular disease. During follow-up, 134 (7·1%) females and 222 (13·8%) males (p<0·0001) had incident cardiovascular events. Median age at first ASCVD event (mostly due to coronary artery disease) was 61·6 years (IQR 50·0-71·4) in females and 50·6 years (42·0-58·6) in males (p<0·0001). The adjusted hazard ratio for ASCVD in males compared with females during follow-up was 1·90 (95% CI 1·49-2·42) and for cardiovascular death was 1·74 (1·11-2·73). Major adverse cardiovascular disease event (MACE)-free survival from birth was lower in males than females (hazard ratio 3·52 [95% CI 2·98-4·16]; p<0·0001). Median MACE-free survival time was 90·1 years (95% CI 86·5-not estimable) in females and 71·0 years (69·2-74·6) in males. The age at which 25% of female participants have had a MACE event was 74·9 years, this figure was 55·5 years in male participants. INTERPRETATION: Our findings suggest that the burden and risk of ASCVD are markedly lower in females than males with familial hypercholesterolaemia. The impact of sex needs to be considered to improve risk stratification and personalised management in patients with heterozygous familial hypercholesterolaemia. FUNDING: Fundación Hipercolesterolemia Familiar, the Instituto de Salud Carlos III, and Next Generation EU funds from the Recovery and Resilience Mechanism Program. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.
Asunto(s)
Aterosclerosis , Hiperlipoproteinemia Tipo II , Humanos , Masculino , Femenino , Hiperlipoproteinemia Tipo II/epidemiología , España/epidemiología , Persona de Mediana Edad , Estudios Prospectivos , Adulto , Aterosclerosis/epidemiología , Anciano , Factores Sexuales , Heterocigoto , Factores de Riesgo , Enfermedades Cardiovasculares/epidemiología , Estudios de SeguimientoRESUMEN
BACKGROUND: Intensive lipid-lowering therapy may induce coronary atherosclerosis regression. Nevertheless, the factors underlying the effect of lipid-lowering therapy on disease regression remain poorly characterized. Our aim was to determine which characteristics of atherosclerotic plaque are associated with a greater reduction in coronary plaque burden (PB) after treatment with alirocumab in patients with familial hypercholesterolemia. METHODS: The ARCHITECT study (Effect of Alirocumab on Atherosclerotic Plaque Volume, Architecture and Composition) is a phase IV, open-label, multicenter, single-arm clinical trial to assess the effect of the treatment with alirocumab for 78 weeks on the coronary atherosclerotic PB and its characteristics in subjects with familial hypercholesterolemia without clinical atherosclerotic cardiovascular disease. Participants underwent a coronary computed tomographic angiography at baseline and a final one at 78 weeks. Every patient received alirocumab 150 mg subcutaneously every 14 days in addition to high-intensity statin therapy. RESULTS: One hundred and four patients were enrolled. Median age was 53.3 (46.2-59.4) years and 54 were women (51.9%). The global coronary PB changed from 34.6% (32.5%-36.8%) at entry to 30.4% (27.4%-33.4%) at follow-up, which is -4.6% (-7.7% to -1.9%; P<0.001) reduction. A decrease in the percentage of unstable core (fibro-fatty+necrotic plaque; from 14.1 [7.9-22.3] to 8.0 [6.4-10.6]; -6.6%; P<0.001) was found. A greater PB (ß, 0.36 [0.13-0.59]; P=0.002) and a higher proportion of unstable core (ß, 0.15 [0.08-0.22]; P<0.001) were significantly related to PB regression. CONCLUSIONS: Treatment with alirocumab in addition to high-intensity statin therapy might produce a greater PB regression in patients with familial hypercholesterolemia with higher baseline PB and in those with larger unstable core. Further studies are needed to corroborate the hypothesis raised by these results. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05465278.
Asunto(s)
Anticuerpos Monoclonales Humanizados , Enfermedad de la Arteria Coronaria , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Hipercolesterolemia , Hiperlipoproteinemia Tipo II , Placa Aterosclerótica , Humanos , Femenino , Persona de Mediana Edad , Masculino , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Enfermedad de la Arteria Coronaria/inducido químicamente , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Placa Aterosclerótica/tratamiento farmacológico , Placa Aterosclerótica/complicaciones , Hipercolesterolemia/inducido químicamente , Hipercolesterolemia/complicaciones , Hipercolesterolemia/tratamiento farmacológico , LDL-Colesterol/uso terapéutico , Hiperlipoproteinemia Tipo II/complicaciones , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/tratamiento farmacológico , Resultado del TratamientoRESUMEN
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.
Asunto(s)
Síndrome Coronario Agudo , Aterosclerosis , Enfermedad de la Arteria Coronaria , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Hipercolesterolemia , Hiperlipoproteinemia Tipo II , Placa Aterosclerótica , Humanos , Femenino , Persona de Mediana Edad , Masculino , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Proproteína Convertasa 9 , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Hipercolesterolemia/tratamiento farmacológico , Placa Aterosclerótica/tratamiento farmacológico , Hiperlipoproteinemia Tipo II/complicaciones , Hiperlipoproteinemia Tipo II/tratamiento farmacológico , Aterosclerosis/tratamiento farmacológico , Síndrome Coronario Agudo/tratamiento farmacológico , Resultado del TratamientoRESUMEN
Background: Insulin-like growth factor 1 (IGF-1) seems to be involved in the neural circuits associated with social cognition and brain structure. Objectives: To investigate the association of IGF-1 levels with social cognition and brain structure in Huntington's disease (HD). Methods: We evaluated social cognition using the Ekman test in 22 HD patients and 19 matched controls. Brain structure was assessed using standard volume-based voxel-based morphometry and surface-based cortical thickness pipeline. We analyzed the association of IGF-1 levels with social cognition and brain structure using adjusted regression analysis. Results: Social cognition was worse in HD patients (P < 0.001), on antidopaminergic drugs (P = 0.02), and with lower IGF-1 levels (P = 0.04). In neuroimaging analyses, lower IGF-1 levels were associated with social cognition impairment and atrophy mainly in frontotemporal regions (P < 0.05 corrected). Conclusions: In HD, abnormal IGF-1 function seems to be associated with brain atrophy leading to clinical deficits in social cognition.
RESUMEN
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.
Asunto(s)
Anticolesterolemiantes , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Hiperlipoproteinemia Tipo II , Femenino , Humanos , Masculino , Inhibidores de PCSK9 , LDL-Colesterol , Anticolesterolemiantes/uso terapéutico , Proproteína Convertasa 9 , Calidad de Vida , Estudios de Cohortes , Estudios Prospectivos , Hiperlipoproteinemia Tipo II/tratamiento farmacológico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéuticoRESUMEN
Defining patients with familial hypercholesterolemia (FH) destined not to develop clinical atherosclerotic cardiovascular disease (ASCVD) has significant implications for precision and discovery medicine. We investigated the predictors of resilience to ASCVD in a cohort of 248 octogenarian patients with FH enrolled in the SAFEHEART study. Median age at the time of analysis was 84.7 years (82.3-88.1) and 83.6 years (81.9-86.4) in the octogenarian resilient FH (OR-FH) and octogenarian controls non-resilient FH (OCNoR-FH) groups, respectively (p=0.073); 92 (80.0%) and 68 (51.1%) patients were female in the first compared with the second group (p<0.001). Multivariate logistic regression showed that a low 10-year score in SAFEHEART-Risk Equation was the only independent predictor of OR-FH. Application of this simple and validated risk equation may potentially be useful for predicting patients ultra-resilient to the ASCVD sequelae of FH who may require less intensive use of healthcare resources.
Asunto(s)
Aterosclerosis , Hiperlipoproteinemia Tipo II , Humanos , Femenino , Anciano de 80 o más Años , Masculino , Estudios de Cohortes , Octogenarios , Hiperlipoproteinemia Tipo II/epidemiología , Hiperlipoproteinemia Tipo II/genética , Hiperlipoproteinemia Tipo II/complicaciones , Aterosclerosis/complicaciones , Factores de RiesgoRESUMEN
PURPOSE OF REVIEW: Familial hypercholesterolemia is a high cardiovascular risk disorder. We will review the role of lipoprotein(a) in cardiovascular risk and in aortic valve stenosis in familial hypercholesterolemia, as well as its association with their phenotype, and strategies to identify this high-risk population. RECENT FINDINGS: Patients with familial hypercholesterolemia have higher lipoprotein(a) levels mainly due to an increased frequency of LPA variants, and the cardiovascular risk is increased twofolds when both conditions coexist. Also, an increased risk for aortic valve stenosis and valve replacement has been observed with high lipoprotein(a) levels. Assessment of lipoprotein(a) during the cascade screening for familial hypercholesterolemia is a good opportunity to identify this high-risk population. High cardiovascular risk in familial hypercholesterolemia is increased even more when lipoprotein(a) is also elevated. Measurement of lipoprotein(a) in these patients is crucial to identify those subjects who need to intensify LDL-cholesterol reduction pending availability of lipoprotein(a)-specific treatments.
Asunto(s)
Estenosis de la Válvula Aórtica , Hiperlipoproteinemia Tipo II , Lipoproteína(a)/sangre , Estenosis de la Válvula Aórtica/complicaciones , LDL-Colesterol , Crimen , Humanos , Hiperlipoproteinemia Tipo II/complicaciones , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/genéticaRESUMEN
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.
Asunto(s)
Anticuerpos Monoclonales Humanizados/administración & dosificación , Hiperlipoproteinemia Tipo II/sangre , Hiperlipoproteinemia Tipo II/tratamiento farmacológico , Inhibidores de PCSK9/administración & dosificación , Anciano , LDL-Colesterol/antagonistas & inhibidores , LDL-Colesterol/sangre , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Hiperlipoproteinemia Tipo II/diagnóstico , Inyecciones Subcutáneas , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del TratamientoRESUMEN
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.
Asunto(s)
Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Hiperlipoproteinemia Tipo II/tratamiento farmacológico , Adulto , Anciano , Atorvastatina/uso terapéutico , LDL-Colesterol/sangre , Estudios de Cohortes , Quimioterapia Combinada , Ezetimiba/uso terapéutico , Femenino , Humanos , Hiperlipoproteinemia Tipo II/sangre , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Rosuvastatina Cálcica/uso terapéutico , Resultado del TratamientoRESUMEN
We assessed the real-life use of direct oral anticoagulants (DOACs) in patients with venous thromboembolism (VTE) and exclusion criteria for randomized trials. From 2013 to 2016, 3,578 of 18,853 patients (19%) had exclusion criteria. Irrespective of which anticoagulant was chosen, they had more VTE recurrences (hazard ratio (HR): 3.10; 95% confidence interval (CI): 2.47-3.88), major bleeds (HR: 4.10; 95% CI: 3.38-4.96), and deaths (HR: 9.47; 95% CI: 8.46-10.6) than those without exclusion criteria. During initial therapy, no patient with exclusion criteria on DOACs (n = 115) recurred, but those on rivaroxaban bled less often (adjusted HR: 0.18; 95% CI: 0.04-0.79) than those on unfractionated heparin (n = 224) and similar to those (n = 3,172) on low-molecular-weight (LMWH) heparin. For long-term therapy, patients on rivaroxaban (n = 151) had nonsignificantly fewer VTE recurrences (adjusted HR: 0.74; 95% CI: 0.08-1.32) and major bleeds (adjusted HR: 0.41; 95% CI: 0.15-1.15) than those on LMWH (n = 2,071). The efficacy and safety of DOACs were similar to standard therapy.
Asunto(s)
Hemorragia/diagnóstico , Selección de Paciente , Rivaroxabán , Tromboembolia Venosa/tratamiento farmacológico , Anciano , Anticoagulantes/administración & dosificación , Anticoagulantes/efectos adversos , Anticoagulantes/clasificación , Inhibidores del Factor Xa/administración & dosificación , Inhibidores del Factor Xa/efectos adversos , Inhibidores del Factor Xa/farmacocinética , Femenino , Hemorragia/inducido químicamente , Heparina/administración & dosificación , Heparina/efectos adversos , Heparina de Bajo-Peso-Molecular/administración & dosificación , Heparina de Bajo-Peso-Molecular/efectos adversos , Humanos , Efectos Adversos a Largo Plazo/inducido químicamente , Efectos Adversos a Largo Plazo/diagnóstico , Masculino , Persona de Mediana Edad , Ensayos Clínicos Controlados Aleatorios como Asunto , Recurrencia , Rivaroxabán/administración & dosificación , Rivaroxabán/efectos adversos , Rivaroxabán/farmacocinética , Resultado del Tratamiento , Tromboembolia Venosa/mortalidadRESUMEN
Objetivo. Conocer las causas de la mortalidad en la hemorragia cerebral de los pacientes con malformaciones arteriovenosas (MAV) tratadas en un hospital terciario. Pacientes y métodos. De un registro prospectivo de malformaciones vasculares se han seleccionado los pacientes que fallecieron con MAV en el período 1990-2014. Se han revisado aspectos demográficos, localización de la MAV, aneurismas asociados y tratamientos previos. Se han establecido tres causas principales de muerte: sangrado inicial/resangrado, relacionadas con el tratamiento de la MAV y otras causas no relacionadas con la MAV. Resultados. Se trató a 400 pacientes de MAV, 216 (54%) con MAV rotas, de los que fallecieron 26 (12,1%) por hemorragia cerebral. La media de edad del grupo de pacientes fallecidos fue de 48,8 años (rango: 8-78 años). Veinte (76,9%) ingresaron en coma (escala de coma de Glasgow < 9). En cinco casos (19,2%), el sangrado se debió a un aneurisma asociado. Un porcentaje muy elevado (38,5%) tenía la MAV en la fosa posterior. Tres pacientes habían recibido previamente en otros centros tratamientos no curativos de la MAV. Del total, seis (23,1%) recibieron tratamiento endovascular/quirúrgico en nuestro hospital, y hemos asumido que, por la indicación o por el momento en que se realizó, la causa de la muerte se relacionaba con el tratamiento, aunque dos pacientes jóvenes se operaron con midriasis bilateral. Un paciente falleció por un glioblastoma asociado, y el resto, 19 (76%), por el resangrado o el daño cerebral inicial. Conclusión. El conocimiento de las causas de mortalidad puede contribuir a mejorar el resultado clínico, sobre todo en los casos en que podría estar indicado un tratamiento precoz (AU)
Aim: To determine the causes of mortality in cases of brain haemorrhage among patients with arteriovenous malformations (AVM) treated in a tertiary hospital. Patients and Methds: The patients with AVM who died over the period 1990-2014 were selected from a prospective register of vascular malformations. Demographic aspects, localisation of the AVM, associated aneurysms and previous treatments were reviewed. Three main causes of death were established: initial bleeding/rebleeding, those related with the treatment of the AVM and other causes not related with AVM. Results: A total of 400 patients were treated for AVM, 216 (54%) with a ruptured AVM, of whom 26 (12.1%) died as a result of a brain haemorrhage. The mean age of the group of patients who died was 48.8 years (range: 8-78 years). Twenty (76.9%) were admitted in coma (Glasgow Coma Scale < 9). In five cases (19.2%), bleeding was due to an associated aneurysm. A very high percentage (38.5%) had the AVM in the posterior fossa. Three patients had previously received non-curative treatments for the AVM in other medical centres. Of the total number, six (23.1%) received endovascular/surgical treatment in our hospital, and we have assumed that, due to the indication or owing to the time in which it was carried out, the cause of death was treatment-related, although two young patients underwent surgery with bilateral mydriasis. One patient died due to an associated glioblastoma, and the others, 19 (76%), due to rebleeding or to the initial brain damage. CONCLUSION. Knowing the causes of mortality can help improve the clinical outcome, above all in cases in which an early treatment could be indicated (AU)
Asunto(s)
Humanos , Malformaciones Arteriovenosas Intracraneales/epidemiología , Hemorragia Cerebral/epidemiología , Accidente Cerebrovascular/epidemiología , Aneurisma Roto/epidemiología , Malformaciones Arteriovenosas Intracraneales/complicaciones , Hemorragia Cerebral/etiología , Mortalidad Hospitalaria , Estudios Prospectivos , Procedimientos EndovascularesRESUMEN
La acidosis láctica es un efecto secundario de la metformina poco frecuente, que es más probable que se produzca en pacientes con ciertas condiciones predisponentes. Presentamos el caso de un paciente con hipertensión arterial tratada con indapamida y captopril y diabetes mellitus tipo 2 tratada con insulina y metformina con función renal previa normal, que tras toma de antiinflamatorios no esteroideos presenta cuadro de vómitos, dolor abdominal, diarrea, oliguria y acidosis láctica. En la analítica al ingreso, se objetivó urea a 227 mg/dl, creatinina a 13,2 mg/dl, pH 6,98, bicarbonato a 7,1 mmol/l y ácido láctico a 105,4 mg/dl (normal hasta 19,8 mg/dl). Tras tratamiento con dos sesiones de hemodiálisis, el paciente evoluciona favorablemente, aunque al alta persiste la insuficiencia renal. La acidosis láctica es una seria complicación del tratamiento con metformina que es más frecuente en casos de insuficiencia renal y otros procesos intercurrentes (AU)
Lactic acidosis is an uncommon side effect of metformin use, which is more likely to arise in patients with certain predisposing factors. We present the case of a patient with hypertension treated with indapamide and captopril and type 2 diabetes mellitus treated with insulin and metformin. Previous renal function was normal. After taking non-steroidal anti-inflammatory drugs, the patient developed vomiting, abdominal pain, diarrhea, oliguria, and lactic acidosis. Tests on admission showed urea 227 mg/dl, creatinine 13.2 mg/dl, pH 6.98, bicarbonate 7.1 mmol/l, and lactic acid 105.4 mg/dl (normal below 19.8 mg/dl). After two hemodialysis sessions, the patient improved, although kidney failure persisted after discharge. Lactic acidosis is a serious complication of metformin therapy and is more frequent in patients with kidney failure and other intercurrent complaints (AU)