RESUMEN
OBJECTIVES: Aortic valvular sclerosis (AS) is an inflammatory process and not a result of normal ageing. The sclerotic process is accelerated by risk factors such as smoking and high cholesterol levels. The genetic factors for the development of AS are however unknown. Therefore the purpose of the present study was to investigate whether polymorphisms in the oestrogen receptor alpha (ORalpha) gene and in the transforming growth factor beta (TGF-beta1) gene were related to the presence of AS in postmenopausal women. DESIGN: Case-control study. SUBJECTS AND METHODS: Relationships were tested between polymorphisms in the ORalpha gene defined by the restriction enzymes PvuII and XbaI, and in the TGF-beta1 gene defined by AocI, and AS, lipid levels, and lipoprotein(a) [Lp(a)] in 41 postmenopausal female patients and 41 age- and sex-matched controls. These polymorphisms were also tested in relation to lipid levels and Lp(a), in 99 healthy Caucasian girls, aged 16.9 +/- 1.2 years. RESULTS: In the postmenopausal patients and age-matched controls, the PvuII polymorphism was independently associated with an increased risk of AS [odds ratio (OR) = 3.38; 95% confidence interval (CI) 1.13-10.09). A genotype defined by at least one restriction site in the PvuII polymorphism and two restriction sites in the TGF-beta1 polymorphism was related to a highly significantly increased risk of AS (OR = 4.58; 95% CI 1.68-12.51). In the adolescent female cohort, presence of two restriction sites in the PvuII polymorphism was associated with higher levels of total cholesterol (TC) (P = 0.02), and low-density lipoprotein cholesterol (LDL) (P = 0.04). CONCLUSIONS: We have demonstrated that the PvuII polymorphism in the ORalpha gene is related to both the presence of AS in postmenopausal women and to lipid levels in adolescent females, suggesting that this polymorphism may influence the risk of AS partly by affecting lipid levels.
Asunto(s)
Estenosis de la Válvula Aórtica/genética , Polimorfismo Genético/genética , Posmenopausia , Receptores de Estrógenos/genética , Adolescente , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Estudios de Casos y Controles , Receptor alfa de Estrógeno , Femenino , Genotipo , Humanos , Persona de Mediana Edad , Mapeo Restrictivo/métodos , Factores de RiesgoRESUMEN
AIMS: The aim of the present study was to identify risk markers for the development of valvular aortic stenosis (AS). Lipoprotein(a) (Lp(a)) and Chlamydia pneumoniae IgG antibody titres in plasma and in circulating immune complexes as well as leptin and tissue plasminogen activator (t-PA) in plasma were studied. METHODS AND RESULTS: One hundred and one patients (41 women and 60 men, mean age 71+/-8 years) with significant AS and 101 age- and sex-matched controls were included in this study. All patients underwent aortic valve replacement at the University Hospital in Umeå, Sweden. The controls had no symptoms of cardiovascular disease and they were examined echocardiographically. An Lp(a) level >or=480 mg x l(-1), a C. pneumoniae-specific IgG titre >or=1/128, a high leptin level and a high t-PA mass concentration in plasma were identified as risk markers for AS. A strong synergism between Lp(a) and C. pneumoniae IgG antibodies in circulating immune complexes was found. CONCLUSION: Our data indicate that a chronic C. pneumoniae infection and a high plasma Lp(a) level might influence and aggravate aortic heart valve sclerosis via the formation of circulating immune complexes. The present study also strongly suggests an association between high plasma leptin, t-PA mass concentration and AS.
Asunto(s)
Estenosis de la Válvula Aórtica/etiología , Infecciones por Chlamydophila/complicaciones , Leptina/sangre , Lipoproteína(a)/sangre , Activador de Tejido Plasminógeno/sangre , Anciano , Estenosis de la Válvula Aórtica/sangre , Chlamydophila pneumoniae , Femenino , Humanos , Inmunoglobulina A/sangre , Inmunoglobulina G/sangre , Masculino , Análisis de Regresión , Factores de RiesgoRESUMEN
AIMS: To investigate a possible relationship between the atherogenic properties of lipoprotein(a) (Lp(a)) and Chlamydia pneumoniae infections. METHODS AND RESULTS: The study population was nested within the Västerbotten Intervention Program or the WHO MONICA project. In this incident case-control study, 78 patients who had suffered acute myocardial infarction and 156 matched controls were included. The contents of circulating immune complexes were analysed for C. pneumoniae IgG antibodies and Lp(a). A significantly larger proportion of cases than controls had >/=13 mg. l(-1)Lp(a) and a C. pneumoniae specific IgG antibody titre >/=1/2 in circulating immune complexes (odds ratio=3.8). CONCLUSION: The proatherogenic effects of Lp(a) may be enhanced and/or partly mediated through the formation of circulating immune complexes containing C. pneumoniae -specific IgG antibodies. The connection between chronic C. pneumoniae infections and atherosclerosis may, at least in part, be explained by an interaction with Lp(a) through the formation of circulating immune complexes.
Asunto(s)
Anticuerpos Antibacterianos/sangre , Complejo Antígeno-Anticuerpo/sangre , Arteriosclerosis/sangre , Infecciones por Chlamydia/sangre , Chlamydophila pneumoniae/inmunología , Lipoproteína(a)/sangre , Infarto del Miocardio/sangre , Arteriosclerosis/complicaciones , Arteriosclerosis/inmunología , Estudios de Casos y Controles , Infecciones por Chlamydia/complicaciones , Infecciones por Chlamydia/inmunología , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inmunoglobulina G/sangre , Modelos Logísticos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/complicaciones , Infarto del Miocardio/inmunologíaRESUMEN
BACKGROUND AND PURPOSE: An association between high lipoprotein(a) [Lp(a)] levels and positive Chlamydia pneumoniae IgG titers in coronary artery disease has been described. The possibility of predicting ischemic stroke by measurements of plasma Lp(a) and C pneumoniae antibodies was investigated. METHODS: This incident case-control study included 101 case subjects (cases) who had suffered ischemic cerebral infarctions and 201 matched control subjects (controls). The study population was nested within the Västerbotten Intervention Program or the WHO MONICA project. Plasma samples were measured for C pneumoniae-specific IgG and IgA antibodies and Lp(a). RESULTS: A significantly higher mean Lp(a) level was found in female cases than in female controls. However, plasma Lp(a) was unable to predict ischemic cerebral infarctions in either women or men. The proportion of individuals with positive C pneumoniae-specific IgG or IgA titers did not differ between cases and controls. Antibody titers were unable to predict a future stroke. The proportion of individuals with a positive C pneumoniae IgG titer in combination with a high Lp(a) level did not differ significantly between cases and controls. CONCLUSIONS: These data suggest that there is no association between baseline plasma Lp(a) levels, presence of C pneumoniae antibodies, and future ischemic cerebral infarctions. Furthermore, no evidence of an interactive effect between high Lp(a) levels and C pneumoniae IgG titers was found. However, selection bias and a recent C pneumoniae epidemic may have influenced the results.