RESUMEN
This was a prospective study comparing two groups: personalized and non-personalized treatment with P2Y12 receptor blockers during a 12-month follow-up. We aimed to investigate whether personalized antiplatelet treatment in patients with high on-treatment platelet reactivity (HTPR) improves clinical outcome. Platelet reactivity was assessed by adenosine diphosphate induced aggregation using a multiple electrode aggregometry (MEA) in 798 patients with coronary artery disease undergoing percutaneous coronary intervention (PCI). Patients with HTPR received up to four repeated loading doses of clopidogrel or prasugrel in the personalized treatment group (n=403), whereas no change in the treatment strategy was undertaken in patients with HTPR in the non-personalized treatment group (n=395). There were fewer major adverse cardiac events (MACE) in the personalized treatment group than in the non-personalized treatment group (7.4% compared with 15.3% respectively; P<0.001). The multivariate Cox regression analysis showed that the relative risk to develop MACE was 51% lower in the personalized treatment group as compared with the non-personalized treatment group [hazard ratio (HR)=0.49; 95% confidence interval (CI): 0.31-0.77; P<0.001]. Similarly, there was a clear net benefit of the personalized antiplatelet treatment over the non-personalized treatment (ischemic and bleedings events: 8.2% versus 18.7% respectively; HR=0.46; 95%CI: 0.29-0.70; P<0.001). Further analysis indicated that patients with aggregation values within the therapeutic window (21-49 units) experienced the lowest event rates (stent thrombosis and major bleeding: 2.5%) as compared with poor responders (≥50 units: 5.4%) or ultra-responders (0-20 units: 5.2%). In conclusion, personalized antiplatelet treatment might improve patients' outcome without increasing bleeding complications compared with the non-personalized treatment during a 12-month follow-up.
Asunto(s)
Enfermedad de la Arteria Coronaria/cirugía , Intervención Coronaria Percutánea/efectos adversos , Piperazinas/farmacología , Inhibidores de Agregación Plaquetaria/farmacología , Antagonistas del Receptor Purinérgico P2Y/farmacología , Tiofenos/farmacología , Ticlopidina/análogos & derivados , Anciano , Clopidogrel , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Piperazinas/efectos adversos , Agregación Plaquetaria , Inhibidores de Agregación Plaquetaria/efectos adversos , Clorhidrato de Prasugrel , Medicina de Precisión , Estudios Prospectivos , Análisis de Regresión , Tiofenos/efectos adversos , Ticlopidina/efectos adversos , Ticlopidina/farmacologíaRESUMEN
BACKGROUND: Obesity is associated with left ventricular hypertrophy and dysfunction, but little is known about the structural remodeling of cardiomyocytes, capillaries, and nerve fibers in this state. We hypothesized that all three compartments should show quantitative structural alterations. METHODS: Ten C57Bl6 mice were randomly assigned to a control or obesity group. Lean mice received standard chow, whereas obese mice received a high-fat Western diet. After 28 weeks, the mice were sacrificed, and the hearts were prepared for design-based stereology using light and electron microscopy. RESULTS: Body mass and left ventricular mass were significantly elevated in obese vs. control mice. The left ventricular hypertrophy was accompanied by a significant increase in cardiomyocyte lipid droplets and total myocyte volume. The volume fractions of myofibrils, free sarcoplasm, and mitochondria did not differ between the groups. The total length of capillaries was significantly enhanced in obese vs. control mice, whereas the total length of axons ramifying between cardiomyocytes was not different. CONCLUSIONS: Obesity is associated with significant structural alterations in cardiomyocytes and capillaries, whereas no structural changes in the myocardial innervation were observed. The structural characteristics in obese mice do not provide a clear basis for functional changes observed in obesity-related cardiac hypertrophy.
Asunto(s)
Capilares/patología , Dieta Alta en Grasa , Ventrículos Cardíacos/patología , Hipertrofia Ventricular Izquierda/patología , Miocitos Cardíacos/patología , Obesidad , Animales , Sistema Nervioso Autónomo/efectos de los fármacos , Sistema Nervioso Autónomo/patología , Peso Corporal/efectos de los fármacos , Capilares/efectos de los fármacos , Corazón/efectos de los fármacos , Ventrículos Cardíacos/efectos de los fármacos , Ventrículos Cardíacos/inervación , Hipertrofia Ventricular Izquierda/inducido químicamente , Hipertrofia Ventricular Izquierda/metabolismo , Metabolismo de los Lípidos/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Obesos , Miocardio/patología , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Obesidad/genética , Tamaño de los Órganos/efectos de los fármacosRESUMEN
Changes in body weight due to changes in food intake are reflected by corresponding changes in the cardiac phenotype. Despite a growing body of literature on cardiac hypertrophy associated with obesity, little is known on the atrophic remodelling of the heart associated with calorie restriction. We hypothesized that, besides the cardiomyocyte compartment, capillaries and nerve fibres are involved in the atrophic process. C57Bl6 mice were kept on normal diet (control group) or at a calorie-restricted diet for 3 or 7 days (n = 5 each). At the end of the protocol, mice were killed and the hearts were processed for light and electron microscopic stereological analysis of cardiomyocytes, capillaries and nerve fibres. Body, heart and left ventricular weight were significantly reduced in the calorie-restricted animals at 7 days. Most morphological parameters were not significantly different at 3 days compared with the control group, but at 7 days most of them were significantly reduced. Specifically, the total length of capillaries, the volume of cardiomyocytes as well as their subcellular compartments and the interstitium were proportionally reduced during caloric restriction. No differences were observed in the total length or the mean diameter of axons between the cardiomyocytes. Our data indicate that diet-induced left ventricular atrophy leads to a proportional atrophic process of cardiomyocytes and capillaries. The innervation is not involved in the atrophic process.