ABSTRACT
OBJECTIVES: The main aim of this study was to determine whether CYP2C9 and VKORC1 polymorphisms influence warfarin dose variability during initial dose-finding phase and during maintenance treatment after 360 days. METHODS: Two hundred and six consecutive patients who were beginning warfarin therapy were selected. They were assessed for general and clinical characteristics; prescribed warfarin dose; response to therapy on days 7-10, 30, 60, 180, and 360; adverse events; and CYP2C9 2, 3, 5, 6, 8, 11, and VKORC1 1639G >A assays. RESULTS: During the first 30 days of anticoagulation, the relative variability of warfarin dose was significantly associated with CYP2C9*2 and CYP2C9*3 polymorphisms (p = 0.02) and with VKORC1 1639G >A genotypes (p = 0.04). Warfarin variability was also statistically different according to predicted metabolic phenotype and to VKORC1 genotypes after 360 days of treatment, and in the phase between 180 and 360 days (long-term dose variability). Both CYP2C9 and VKORC1 polymorphisms were associated with the international normalized ratio (INR) made between 7 and 10 days/initial dose ratio, adjusted for covariates (p < 0.01 and p = 0.02, respectively). Patients carrying VKORC1 and CYP2C9 variants presented lower required dose (at the end of follow-up of 360 days) compared to patients carrying wild-type genotypes (p = 0.04 and p = 0.03, respectively). CONCLUSIONS: Genetic information on CYP2C9 and VKORC1 is important both for the initial dose-finding phase and during maintenance treatment with warfarin.
Subject(s)
Anticoagulants/administration & dosage , Aryl Hydrocarbon Hydroxylases/genetics , Blood Coagulation/drug effects , Mixed Function Oxygenases/genetics , Polymorphism, Genetic , Warfarin/administration & dosage , Anticoagulants/adverse effects , Anticoagulants/pharmacokinetics , Anticoagulants/pharmacology , Cytochrome P-450 CYP2C9 , Dose-Response Relationship, Drug , Female , Follow-Up Studies , Gene Frequency , Genotype , Humans , Male , Middle Aged , Prospective Studies , Time Factors , Vitamin K Epoxide Reductases , Warfarin/adverse effects , Warfarin/pharmacokinetics , Warfarin/pharmacologyABSTRACT
FUNDAMENTO: A fibrilação atrial é um fator de risco controverso para demência. OBJETIVO: O objetivo deste estudo é avaliar a associação entre fibrilação atrial e demência em participantes do São Paulo Ageing & Health. MÉTODOS: O São Paulo Ageing & Health é um estudo transversal, de base populacional, de idosos residentes em um uma região de baixa renda da cidade de São Paulo, Brasil. Diagnóstico de demência foi realizado de acordo com o protocolo do grupo 10/66, com base em critérios do Manual de Diagnóstico e Estatística das Perturbações Mentais (DSM-IV). O diagnóstico de fibrilação atrial foi feito por eletrocardiograma de 12 derivações, avaliado por dois cardiologistas. Dados demográficos e de fatores de risco cardiovasculares também foram obtidos. RESULTADOS: A demência foi diagnosticada em 66 (4,3%) e fibrilação atrial em 36 (2,4%) de 1.524 participantes com um eletrocardiograma válido. A razão de chances bruta para demência em participantes com fibrilação atrial foi 2,8 (intervalo de confiança [IC] 95%: 1,0-8,1; p = 0,06) em comparação com indivíduos sem fibrilação atrial. Relação positiva foi encontrada em mulheres (RC 4,2; IC 95%: 1,2-15,1; p = 0,03). Após ajuste para idade, no entanto, essa associação tornou-se não significativa (RC 2,2, IC 95%: 0,6-8,9; p = 0,26). CONCLUSÃO: Não houve associação independente entre a fibrilação atrial e demência nessa amostra. A prevalência da fibrilação atrial pode ser baixa nesta população em virtude da mortalidade cardiovascular prematura.
BACKGROUND: Atrial fibrillation (AF) is a controversial risk factor for dementia. OBJECTIVE: The objective of this study was to assess the association between AF and dementia in the "Sao Paulo Ageing & Health" (SPAH) study participants. METHODS: SPAH is a cross-sectional, population-based study of elderly people living in a deprived neighborhood in Sao Paulo, Brazil. Dementia diagnosis was performed according to the 10/66 study group protocol based on Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria. Diagnosis of AF was made using a 12-lead electrocardiogram (ECG) recording, which was assessed by two cardiologists. Data on demographics and cardiovascular risk factors were also obtained. RESULTS: Dementia was diagnosed in 66 (4.3%) and AF in 36 (2.4%) of 1,524 participants with a valid ECG. The crude odds ratio (OR) for dementia in participants with AF was 2.8 (95% confidence interval [CI]: 1.0-8.1; p=0.06) compared with individuals without AF. When analyzing data according to sex, a positive relationship was found in women (OR 4.2; 95% CI: 1.24-15.1; p=0.03). After age-adjustment, however, this association was no longer significant (OR 2.2; 95% CI: 0.6-8.9; p=0.26). CONCLUSION: There was no independent association between AF and dementia in this sample. The prevalence of AF may be low in this population owing to premature cardiovascular death.
Subject(s)
Aged , Aged, 80 and over , Female , Humans , Male , Atrial Fibrillation/complications , Dementia/etiology , Age Factors , Atrial Fibrillation/drug therapy , Brazil , Chi-Square Distribution , Cross-Sectional Studies , Risk Factors , Sex Factors , Socioeconomic FactorsABSTRACT
BACKGROUND: Atrial fibrillation (AF) is a controversial risk factor for dementia. OBJECTIVE: The objective of this study was to assess the association between AF and dementia in the "Sao Paulo Ageing & Health" (SPAH) study participants. METHODS: SPAH is a cross-sectional, population-based study of elderly people living in a deprived neighborhood in Sao Paulo, Brazil. Dementia diagnosis was performed according to the 10/66 study group protocol based on Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria. Diagnosis of AF was made using a 12-lead electrocardiogram (ECG) recording, which was assessed by two cardiologists. Data on demographics and cardiovascular risk factors were also obtained. RESULTS: Dementia was diagnosed in 66 (4.3%) and AF in 36 (2.4%) of 1,524 participants with a valid ECG. The crude odds ratio (OR) for dementia in participants with AF was 2.8 (95% confidence interval [CI]: 1.0-8.1; p=0.06) compared with individuals without AF. When analyzing data according to sex, a positive relationship was found in women (OR 4.2; 95% CI: 1.24-15.1; p=0.03). After age-adjustment, however, this association was no longer significant (OR 2.2; 95% CI: 0.6-8.9; p=0.26). CONCLUSION: There was no independent association between AF and dementia in this sample. The prevalence of AF may be low in this population owing to premature cardiovascular death.
Subject(s)
Atrial Fibrillation/complications , Dementia/etiology , Age Factors , Aged , Aged, 80 and over , Atrial Fibrillation/drug therapy , Brazil , Chi-Square Distribution , Cross-Sectional Studies , Female , Humans , Male , Risk Factors , Sex Factors , Socioeconomic FactorsABSTRACT
Fundamento: A determinação da prevalência de alterações eletrocardiográficas nas faixas etárias mais velhas da população brasileira representa importante informação com finalidade clínica e epidemiológica. Objetivo: Verificar as taxas de prevalência de fibrilação atrial, ondas alargadas Q/QS (código de Minnesota 1.1-1.2) e bloqueio de ramo esquerdo. Métodos: Em estudo de base populacional, 1.524 participantes (921 mulheres e 603 homens) com idade acima de 65 anos moradores de São Paulo, Brasil foram submetidos a exame eletrocardiográfico em repouso, a medidas antropométricas e de pressão arterial, além de coleta de sangue em jejum para dosagem de glicose, colesterol total e frações. Resultados: Prevalência ajustada por idade para ondas alargadas Q/QS foi 12,1 por cento (homens, 17,2 por cento; mulheres, 9,6 por cento), para fibrilação atrial foi de 2,4 por cento (homens 3,9 por cento; mulheres, 2,0 por cento), e, para bloqueio de ramo esquerdo foi de 3,1 por cento (homens, 3,1 por cento; mulheres, 3,8 por cento). Para fibrilação atrial (ambos os sexos), ondas alargadas Q/QS (homens) e bloqueio de ramo esquerdo (mulheres) houve aumento de frequência de acordo com a faixa etária. Após ajustes para idade, sexo, diabetes e dislipidemia, a razão de chances entre as frequências de ondas alargadas Q/QS e hipertensão arterial foi 2,4 (intervalo de confiança 95 por cento [IC 95 por centoCI] 1,4 -3,9) sendo de 5,1 (IC 95 por cento 1,8 -14,4) para mulheres e 1,7 (95 por centoCI, 0,95-3,1] para homens. Conclusão: A comparação desses dados com outros estudos revelou prevalência elevada de alargamento de ondas Q/QS nessa população com associação direta com a prevalência de hipertensão arterial.
Background: The determination of the prevalence of electrocardiographic alterations in the older age strata of the Brazilian population represents important information with clinical and epidemiological purpose. Objective: To verify the prevalence rates of atrial fibrillation, enlarged Q/QS waves (Minnesota code 1.1-1.2) and left bundle branch block. Methods: In a population-based study, 1,524 participants (921 women and 603 men) aged > 65 years and living in Sao Paulo, Brazil, were submitted to electrocardiographic assessment at rest as well as anthropometric and blood pressure measurements, in addition to fasting blood collection for the measurement of glycemia, total cholesterol and fractions. Results: The age-adjusted prevalence for enlarged Q/QS waves was12.1 percent (men, 17.2 percent; women, 9.6 percent), 2.4 percent for atrial fibrillation (men 3.9 percent; women, 2.0 percent); and 3.1 percent for left bundle branch block (men, 3.1 percent; women, 3.8 percent). For atrial fibrillation (both sexes), enlarged Q/QS waves (men) and left bundle branch block (women) there was an increase in frequency according to the age stratum. After adjusted for age, sex, diabetes mellitus and dyslipidemia, the odds ratio among the frequencies of enlarged Q/QS waves; arterial hypertension was 2.4 (95 percent CI: 1.4 -3.9) being 5.1 (95 percentCI: 1.8 -14.4) for women and 1.7 (95 percentCI: 0.95-3.1] for men. Conclusion: The comparison of these data with those from other studies showed a high prevalence of enlarged Q/QS waves in this population, with a direct association with the prevalence of arterial hypertension.
Fundamento: la determinación de la prevalencia de alteraciones electrocardiográficas en las franjas etarias más viejas en la población brasileña representa importante información con finalidad clínica y epidemiológica. Objetivo: Verificar las tasas de prevalencia de fibrilación auricular, ondas alargadas Q/QS (código de Minnesota 1.1-1.2) y bloqueo de rama izquierda. Métodos: en estudio de base poblacional, 1.524 participantes (921 mujeres y 603 hombres) con edad superior a 65 años habitantes de São Paulo, Brasil fueron sometidos a examen electrocardiográfico en reposo, a medidas antropométricas y de presión arterial, además de la extracción de sangre en ayunas para dosaje de glucemia, colesterol total y fracciones. Resultados: la prevalencia ajustada por edad para ondas alargadas Q/QS fue el 12,1 por ciento (hombres, el 17,2 por ciento; mujeres, el 9,6 por ciento), para fibrilación auricular fue del 2,4 por ciento (hombres el 3,9 por ciento; mujeres, el 2,0 por ciento), y, para bloqueo de rama izquierda fue del 3,1 por ciento (hombres, el 3,1 por ciento; mujeres, el 3,8 por ciento). Para fibrilación auricular (ambos sexos), ondas alargadas Q/QS (hombres) y bloqueo de rama izquierda (mujeres) se observó un aumento de frecuencia de acuerdo a la franja etaria. Tras los ajustes para edad, sexo, diabetes y dislipidemia, la razón de chances entre las frecuencias de ondas alargadas Q/QS e hipertensión arterial fue 2,4 (intervalo de confianza 95 por ciento [IC 95 por cientoCI] 1,4 -3,9) siendo de 5,1 (IC 95 por ciento 1,8 -14,4) para mujeres y de 1,7 (95 por cientoCI, 0,95-3,1] para hombres. Conclusión: la comparación de esos datos con otros estudios reveló prevalencia elevada de prolongación de ondas Q/QS en esa población con asociación directa con la prevalencia de hipertensión arterial.
Subject(s)
Aged , Aged, 80 and over , Female , Humans , Male , Atrial Fibrillation/epidemiology , Bundle-Branch Block/epidemiology , Age Distribution , Aging , Atrial Fibrillation/diagnosis , Brazil/epidemiology , Bundle-Branch Block/diagnosis , Cross-Sectional Studies , Electrocardiography , Hypertension/diagnosis , Hypertension/epidemiology , Prevalence , Sex DistributionABSTRACT
BACKGROUND: The determination of the prevalence of electrocardiographic alterations in the older age strata of the Brazilian population represents important information with clinical and epidemiological purpose. OBJECTIVE: To verify the prevalence rates of atrial fibrillation, enlarged Q/QS waves (Minnesota code 1.1-1.2) and left bundle branch block. METHODS: In a population-based study, 1,524 participants (921 women and 603 men) aged > 65 years and living in Sao Paulo, Brazil, were submitted to electrocardiographic assessment at rest as well as anthropometric and blood pressure measurements, in addition to fasting blood collection for the measurement of glycemia, total cholesterol and fractions. RESULTS: The age-adjusted prevalence for enlarged Q/QS waves was 12.1% (men, 17.2%; women, 9.6%), 2.4% for atrial fibrillation (men 3.9%; women, 2.0%); and 3.1% for left bundle branch block (men, 3.1%; women, 3.8%). For atrial fibrillation (both sexes), enlarged Q/QS waves (men) and left bundle branch block (women) there was an increase in frequency according to the age stratum. After adjusted for age, sex, diabetes mellitus and dyslipidemia, the odds ratio among the frequencies of enlarged Q/QS waves; arterial hypertension was 2.4 (95% CI: 1.4 -3.9) being 5.1 (95%CI: 1.8 -14.4) for women and 1.7 (95%CI: 0.95-3.1] for men. CONCLUSION: The comparison of these data with those from other studies showed a high prevalence of enlarged Q/QS waves in this population, with a direct association with the prevalence of arterial hypertension.
