RESUMEN
BACKGROUND AND PURPOSE: The aim of this study was to explore the joint effect of the APOE epsilon4 allele and midlife systolic blood pressure (SBP) on the risk for poor cognitive function in late life. METHODS: The study includes 3605 surviving members of the cohort of the Japanese-American men followed prospectively over 26 years (1965-1991) as a part of the Honolulu Heart Program. In 1965 men were aged 45 to 68 years and were living in the island of Oahu, Hawaii. For this study the sample was divided into 4 categories: normal SBP (<160 mm Hg)/No epsilon4, as the reference category; normal SBP/epsilon4; high SBP/no epsilon4; high SBP/epsilon4. The relative risk (RR) of late-life intermediate and poor cognitive function relative to good function was measured by the Cognitive Abilities Screening Instrument (CASI) test. RESULTS: After adjusting for age, education, smoking, alcohol use, and body mass index, the RR for poor cognitive function (CASI <74) compared with good cognitive function (CASI >/=82) in never-treated subjects was 1.3 (95% CI 0.9 to 1.9) for the normal SBP/epsilon4 category, 2.6 (0.7 to 10.0) for the high SBP/no epsilon4, and 13.0 (1.9 to 83.8) for the high SBP/epsilon4. Adjustment for diabetes, prevalent stroke, coronary disease, and ankle-brachial index reduced the RR of poor cognition by 25.5% (RR 13.0 to 10.8) in those with both risk factors. In the treated group, the RR was 1.9 (0.7 to 4.5) for those with both risk factors. CONCLUSIONS: The results suggest that midlife high SBP has a stronger adverse effect on cognitive function in persons with higher genetic susceptibility, but this effect may be modified by antihypertensive treatment.
Asunto(s)
Envejecimiento , Apolipoproteínas E/genética , Presión Sanguínea/genética , Trastornos del Conocimiento/genética , Hipertensión/genética , Anciano , Alelos , Antihipertensivos/uso terapéutico , Apolipoproteína E4 , Presión Sanguínea/efectos de los fármacos , Trastornos del Conocimiento/epidemiología , Estudios de Cohortes , Comorbilidad , Demografía , Estudios de Seguimiento , Predisposición Genética a la Enfermedad , Pruebas Genéticas , Hawaii/epidemiología , Humanos , Hipertensión/tratamiento farmacológico , Hipertensión/epidemiología , Japón/etnología , Masculino , Riesgo , Medición de Riesgo , Factores de RiesgoRESUMEN
Employing a double-masked, prospective design, bone loss at three skeletal sites has been monitored among 113 postmenopausal women participating in a placebo-controlled trial of the thiazide-like diuretic chlorthalidone for treatment of systolic hypertension. The mean duration of chlorthalidone use was 2.6 years, at doses of 12.5-25 mg/day. Compared with placebo use, chlorthalidone use was associated with significant reductions in annual bone loss rates. Non-use of chlorthalidone was associated with bone loss at the calcaneus (-0.56% per year) and the proximal radius (-0.91% per year); borderline bone gain was observed at the distal radius (+0.39%). In contrast, chlorthalidone use was associated with bone gain at the calcaneus (+0.44% per year) and the distal radius (+1.51% per year); proximal radius bone loss was significantly reduced to -0.32% per year. The average increment for three appendicular sites was +0.9% per year. These data support a causal relationship between chlorthalidone use and reduced bone loss.