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Drs. Ji and Sen raise the interesting possibility as to whether uric acid may be a potential link between fatty liver and hypertension. If this were the case, uric acid may mediate or confound the relationship between fatty liver and hypertension. We explored this question in a subsample of 1286 participants in the Framingham Heart Study that have both a measure of fatty liver and uric acid. The correlation between continuous fatty liver (decreased liver phantom ratio [LPR]) with uric acid levels was 0.21. To test the possibility that uric acid may account for the relationship between fatty liver and hypertension, we computed a logistic regression model where hypertension was the dependent (outcome) variable and continuous fatty liver measured with LPR was the independent (predictor) variable, with age, sex, alcoholic drinks per week, menopausal status, hormone replacement therapy, and smoking as covariates. The odds ratio per 1 standard deviation decrease in LPR (increased fatty liver) was 1.52 (95% confidence interval = 1.33-1.69; P < 0.001). We then recomputed this same model with uric acid also included as a covariate; the odds ratio per 1 standard deviation decrease in LPR was 1.41 (95% confidence interval = 1.25-1.59; P < 0.001). The odds ratios for fatty liver were not materially different with uric acid in the model versus without it in the model. These data are not consistent with uric acid fully accounting for the association between fatty liver and hypertension. However, we cannot rule out that uric acid may account for some small part of the observed association of fatty liver with hypertension, at least in our cross-sectional, observational data.

Elizabeth K. Speliotes M.D., Ph.D. M.P.H.* ‡ §, Joseph M. Massaro Ph.D.§ ¶, Christopher J. O'Donnell M.D., M.P.H.† §, Caroline S. Fox M.D., M.P.H.§ **, * Department of Gastroenterology, Massachusetts General Hospital, Boston MA, † Department of Cardiology, Massachusetts General Hospital, Boston MA, ‡ Department of Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge MA, § National Heart, Lung and Blood Institute and Boston University's The Framingham Heart Study, Framingham, MA, ¶ Department of Biostatistics, Boston University, Boston MA, ** Departments of Medicine and Endocrinology, Brigham and Women's Hospital, Boston MA.