RESUMEN
BACKGROUND: Both elevated and low resting heart rates are associated with atrial fibrillation (AF), suggesting a U-shaped relationship. However, evidence for a U-shaped causal association between genetically-determined resting heart rate and incident AF is limited. We investigated potential directional changes of the causal association between genetically-determined resting heart rate and incident AF. METHOD AND RESULTS: Seven cohorts of the AFGen consortium contributed data to this meta-analysis. All participants were of European ancestry with known AF status, genotype information, and a heart rate measurement from a baseline electrocardiogram (ECG). Three strata of instrumental variable-free resting heart rate were used to assess possible non-linear associations between genetically-determined resting heart rate and the logarithm of the incident AF hazard rate: <65; 65-75; and >75 beats per minute (bpm). Mendelian randomization analyses using a weighted resting heart rate polygenic risk score were performed for each stratum. We studied 38,981 individuals (mean age 59±10 years, 54% women) with a mean resting heart rate of 67±11 bpm. During a mean follow-up of 13±5 years, 4,779 (12%) individuals developed AF. A U-shaped association between the resting heart rate and the incident AF-hazard ratio was observed. Genetically-determined resting heart rate was inversely associated with incident AF for instrumental variable-free resting heart rates below 65 bpm (hazard ratio for genetically-determined resting heart rate, 0.96; 95% confidence interval, 0.94-0.99; p = 0.01). Genetically-determined resting heart rate was not associated with incident AF in the other two strata. CONCLUSIONS: For resting heart rates below 65 bpm, our results support an inverse causal association between genetically-determined resting heart rate and incident AF.
Asunto(s)
Fibrilación Atrial , Anciano , Electrocardiografía , Femenino , Frecuencia Cardíaca/genética , Humanos , Masculino , Análisis de la Aleatorización Mendeliana , Persona de Mediana Edad , Distribución Aleatoria , Factores de RiesgoRESUMEN
Recently, Lyn et al. (Analyst, 2007, 132, 1231) compared two ways of estimating the standard uncertainty of sampling pistachio nuts for aflatoxins--a modelling method and an empirical method. Their case study used robust analysis of variance (RANOVA) to derive the uncertainty estimates, highlighting a substantial difference between the two: the estimate of sampling uncertainty derived from the modelling method was six-fold greater than that using the empirical approach (cf. 136% and 22.5%, respectively, when expressed as relative standard deviations (RSDs) at 68% confidence). A further analysis of this case study is reported here and suggests that the estimation uncertainty during RANOVA in the empirical approach could account for this difference.
