RESUMEN
OBJECTIVE: The use of low-dose aspirin (acetylsalicylic acid [ASA]) has been suggested to attenuate growth of abdominal aortic aneurysms (AAAs), yet solid clinical evidence of this hypothesis is still missing. This study aimed to investigate whether preadmission ASA use influenced the risk of presenting with rupture of AAA (rAAA) on hospital admission and subsequent 30-day case fatality. METHODS: There were 4010 patients with an incident diagnosis of rAAA and 4010 age- and sex-matched AAA patients identified in the Danish National Registry of Patients. Data on comorbidity, concomitant drug use, primary health care utilization, socioeconomic status, and vital status were obtained from nationwide health care and administrative registries. RESULTS: Preadmission ASA use was identified for 1815 (45.3%) rAAA patients and 2111 (52.6%) AAA patients, corresponding to a crude odds ratio for rAAA in ASA users of 0.72 (95% confidence interval [CI], 0.66-0.79) compared with nonusers. However, after adjustment for possible confounders, no association between ASA use and the risk of rAAA was found (adjusted odds ratio, 0.97; 95% CI, 0.86-1.08). The aggregated 30-day rAAA case-fatality rate for users of ASA was 66.0% compared with 56.9% for nonusers, corresponding to an adjusted mortality rate ratio of 1.16 (95% CI, 1.06-1.27). CONCLUSIONS: Preadmission ASA use is not associated with an altered risk of AAA rupture but seems to be associated with a worse prognosis after rupture of AAA.
Asunto(s)
Aneurisma de la Aorta Abdominal/epidemiología , Rotura de la Aorta/epidemiología , Aspirina/efectos adversos , Anciano , Anciano de 80 o más Años , Aneurisma de la Aorta Abdominal/diagnóstico por imagen , Aneurisma de la Aorta Abdominal/mortalidad , Rotura de la Aorta/diagnóstico por imagen , Rotura de la Aorta/mortalidad , Aspirina/administración & dosificación , Estudios de Casos y Controles , Dinamarca/epidemiología , Progresión de la Enfermedad , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Pronóstico , Modelos de Riesgos Proporcionales , Sistema de Registros , Medición de Riesgo , Factores de Riesgo , Factores de TiempoRESUMEN
OBJECTIVE: Asthma and abdominal aortic aneurysms (AAA) both involve inflammation. Patients with asthma have an increased risk of developing AAA or experiencing aortic rupture. This study tests the development of one disease on the progression of the other. APPROACH AND RESULTS: Ovalbumin sensitization and challenge in mice led to the development of allergic lung inflammation (ALI). Subcutaneous infusion of angiotensin II into mice produced AAA. Simultaneous production of ALI in AAA mice doubled abdominal aortic diameter and increased macrophage and mast cell content, arterial media smooth muscle cell loss, cell proliferation, and angiogenesis in AAA lesions. ALI also increased plasma IgE, reduced plasma interleukin-5, and increased bronchioalveolar total inflammatory cell and eosinophil accumulation. Intraperitoneal administration of an anti-IgE antibody suppressed AAA lesion formation and reduced lesion inflammation, plasma IgE, and bronchioalveolar inflammation. Pre-establishment of ALI also increased AAA lesion size, lesion accumulation of macrophages and mast cells, media smooth muscle cell loss, and plasma IgE, reduced plasma interleukin-5, interleukin-13, and transforming growth factor-ß, and increased bronchioalveolar inflammation. Consequent production of ALI also doubled lesion size of pre-established AAA and increased lesion mast cell and T-cell accumulation, media smooth muscle cell loss, lesion cell proliferation and apoptosis, plasma IgE, and bronchioalveolar inflammation. In periaortic CaCl2 injury-induced AAA in mice, production of ALI also increased AAA formation, lesion inflammation, plasma IgE, and bronchioalveolar inflammatory cell accumulation. CONCLUSIONS: This study suggests a pathological link between airway allergic disease and AAA. Production of one disease aggravates the progression of the other.
Asunto(s)
Angiotensina II , Aorta Abdominal/patología , Aneurisma de la Aorta Abdominal/inducido químicamente , Neumonía/complicaciones , Hipersensibilidad Respiratoria/complicaciones , Animales , Antialérgicos/farmacología , Anticuerpos Monoclonales/farmacología , Aorta Abdominal/efectos de los fármacos , Aorta Abdominal/inmunología , Aorta Abdominal/metabolismo , Aneurisma de la Aorta Abdominal/inmunología , Aneurisma de la Aorta Abdominal/metabolismo , Aneurisma de la Aorta Abdominal/patología , Aneurisma de la Aorta Abdominal/prevención & control , Apolipoproteínas E/deficiencia , Apolipoproteínas E/genética , Cloruro de Calcio , Dilatación Patológica , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Inmunoglobulina E/sangre , Inmunoglobulina E/inmunología , Mediadores de Inflamación/inmunología , Mediadores de Inflamación/metabolismo , Pulmón/inmunología , Pulmón/metabolismo , Macrófagos/inmunología , Macrófagos/metabolismo , Masculino , Mastocitos/inmunología , Mastocitos/metabolismo , Ratones Endogámicos C57BL , Ratones Noqueados , Ovalbúmina , Neumonía/inducido químicamente , Neumonía/inmunología , Neumonía/metabolismo , Neumonía/prevención & control , Hipersensibilidad Respiratoria/inducido químicamente , Hipersensibilidad Respiratoria/inmunología , Hipersensibilidad Respiratoria/metabolismo , Hipersensibilidad Respiratoria/prevención & control , Factores de Riesgo , Transducción de Señal , Remodelación VascularRESUMEN
OBJECTIVE: Both asthma and abdominal aortic aneurysms (AAA) involve inflammation. It remains unknown whether these diseases interact. APPROACH AND RESULTS: Databases analyzed included Danish National Registry of Patients, a population-based nationwide case-control study included all patients with ruptured AAA and age- and sex-matched AAA controls without rupture in Denmark from 1996 to 2012; Viborg vascular trial, subgroup study of participants from the population-based randomized Viborg vascular screening trial. Patients with asthma were categorized by hospital diagnosis, bronchodilator use, and the recorded use of other anti-asthma prescription medications. Logistic regression models were fitted to determine whether asthma associated with the risk of ruptured AAA in Danish National Registry of Patients and an independent risk of having an AAA at screening in the Viborg vascular trial. From the Danish National Registry of Patients study, asthma diagnosed <1 year or 6 months before the index date increased the risk of AAA rupture before (odds ratio [OR]=1.60-2.12) and after (OR=1.51-2.06) adjusting for AAA comorbidities. Use of bronchodilators elevated the risk of AAA rupture from ever use to within 90 days from the index date, before (OR=1.10-1.37) and after (OR=1.10-1.31) adjustment. Patients prescribed anti-asthma drugs also showed an increased risk of rupture before (OR=1.12-1.79) and after (OR=1.09-1.48) the same adjustment. In Viborg vascular trial, anti-asthmatic medication use associated with increased risk of AAA before (OR=1.45) or after adjustment for smoking (OR=1.45) or other risk factors (OR=1.46). CONCLUSIONS: Recent active asthma increased risk of AAA and ruptured AAA. These findings document and furnish novel links between airway disease and AAA, 2 common diseases that share inflammatory aspects.
Asunto(s)
Aneurisma de la Aorta Abdominal/epidemiología , Rotura de la Aorta/epidemiología , Asma/epidemiología , Anciano , Anciano de 80 o más Años , Antiasmáticos/uso terapéutico , Aneurisma de la Aorta Abdominal/diagnóstico , Rotura de la Aorta/diagnóstico , Asma/diagnóstico , Asma/tratamiento farmacológico , Broncodilatadores/uso terapéutico , Bases de Datos Factuales , Dinamarca/epidemiología , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Sistema de Registros , Medición de Riesgo , Factores de Riesgo , Factores de TiempoRESUMEN
PURPOSE: Rupture of abdominal aortic aneurysms (rAAA) is associated with high mortality. Use of angiotensin converting enzyme inhibitors (ACE-inhibitors) and angiotensin receptor blockers (ARBs) has been suggested to reduce the risk of rAAA. This nationwide, combined case-control and follow-up study aims to examine the possible impact of preadmission renin-angiotensin system blockade on the risk of rAAA and case fatality following rAAA. METHODS: Using Danish healthcare registries, a combined case-control and follow-up study was conducted among all patients with a first-time hospital admission for rAAA and AAA controls without rupture in Denmark from 1996 to 2012. Individual-level data were obtained on preadmission drug use, comorbidity, socioeconomic factors, healthcare services use, and death. RESULTS: The adjusted age-matched and sex-matched odds ratios (adj. OR) were 0.96 (95% confidence interval (CI): 0.85; 1.07) for rAAA for current ACE-inhibitor users and 0.93 (95%CI: 0.79; 1.09) for current ARB users compared with never users. Propensity score-matched analyses yielded similar results for current ACE-inhibitor users (adj. OR: 1.02, 95%CI: 0.88; 1.19) and current ARB users (adj. OR: 1.02, 95%CI: 0.83; 1.26). The total 30-day mortality rate after hospital admission was 61.0% in current ACE-inhibitor users compared with 59.4% in non-ACE-inhibitor users (adjusted mortality rate ratio (adj. MRR) 1.06, 95%CI: 0.94; 1.20) and 58.6% in current ARB users compared with 59.9% in non-ARB users (adj. MRR: 0.96, 95%CI: 0.82; 1.14). CONCLUSION: Use of renin-angiotensin system blockade was not associated with a lower risk of rAAA or lower case fatality following rAAA.
Asunto(s)
Antagonistas de Receptores de Angiotensina/efectos adversos , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Aneurisma de la Aorta Abdominal/inducido químicamente , Aneurisma de la Aorta Abdominal/epidemiología , Rotura de la Aorta/inducido químicamente , Rotura de la Aorta/epidemiología , Admisión del Paciente , Anciano , Anciano de 80 o más Años , Aneurisma de la Aorta Abdominal/diagnóstico , Rotura de la Aorta/diagnóstico , Estudios de Casos y Controles , Dinamarca/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Vigilancia de la Población/métodos , Sistema de Registros , Sistema Renina-Angiotensina/efectos de los fármacos , Sistema Renina-Angiotensina/fisiologíaRESUMEN
An abdominal aortic aneurysm (AAA) is an enlargement of the abdominal aorta. It is a common disease in the elderly, with a prevalence of 1-5%. An AAA is normally asymptomatic, and the diagnosis is often incidental, identified when a patient is examined for other conditions. The major risk of having an AAA is sudden rupture and death caused by massive hemorrhaging. As rupture risk increases with increasing AAA diameter, the current management strategies include regular imaging surveillance and elective repair before rupture occurs. Ruptured AAA (rAAA) carries high mortality, and an identification of a drug or compound with the potential to halt the growth of an AAA and/or reduce the risk of a rAAA is needed. Thus, the aims of this thesis were to examine the clinical impact of treatment with statins (Study I), reninangiotensin system (RAS) blockers (Study II), and low-dose aspirin (ASA)(Study III) on the risk of rAAA and case fatality following rAAA. The thesis is based on three nation-wide, combined case-control and follow-up studies using data from Danish population-based health-care and administrative registries. In Study I (1996-2008), we included 3,691 patients with an incident diagnosis of rAAA (cases). For the risk analyses, we matched 3,584 rAAA cases to 3,584 age- and sex-matched patients with an incident diagnosis of AAA (controls). Current statin use was associated with a lower risk of rAAA, adjusted odds ratio (OR): 0.73 (95% CI: 0.61;0.86), compared to never use of statins. Furthermore, current statin use was associated with a lower 30-day case fatality following rAAA, adjusted mortality rate ratio (MRR): 0.80 (95% CI: 0.68;0.95). In Study II (1996-2012), we identified 4,052 rAAA cases and 10,549 AAA controls. We were unable to demonstrate any association between the current use of either angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers and the risk of rAAA, adjusted ORs: 0.96 (95% CI: 0.85;1.07) and 0.93 (95% CI: 0.79;1.09), respectively. The results were robust in supplemental propensity score matched analyses. Likewise, no association between current use of RAS-blockers and 30-day case fatality was found. In Study III (1996-2012), 4,055 rAAA cases were included. The adjusted OR for the risk of rAAA in ASA users compared to non-users was 0.97 (95% CI: 0.86;1.08). However, ASA use was associated with an unfavorable 30-day case fatality, adjusted MRR 1.17 (95% CI: 1.06;1.28), corresponding to an excessive rAAA case fatality in ASA users of nearly 20%. In conclusion, we found an approximately 25% lower risk of rAAA and 20% lower 30-day case fatality in statin-treated patients. Furthermore, we found an almost 20% higher 30-day case fatality following rAAA in ASA treated patients. No association between the use of RAS-blockers and the risk of rAAA or case fatality following rAAA was found. Similarly, we found no association between the use of ASA and the risk of rAAA.