Chapter 5 98 accurately reflects the kidney 11β-HSD type 2 enzyme activity 14. A-ring reductases, including 5α- and 5β-reductase, can be inferred by the ratio of THF/allo-THF (combined 5α- and 5β- reductase activity), allo-THF/cortisol (5α-reductase activity), THF/cortisol (5β-reductase activity), and THE/cortisone (5β-reductase activity). The ratios are summarized in Table 1. Table 1. Summary of ratios Ratio Index Cortisol/cortisone 11β-HSD type 2 activity THFs/THE 11β-HSD overall activity THF/allo-THF 5α- and 5β-reductase activity allo-THF/cortisol 5α-reductase activity THF/cortisol 5β-reductase activity THE/cortisone 5β-reductase activity Abbreviations: 11β-HSD, 11β-hydroxysteroid dehydrogenase; THFs, tetrahydrocortisol and allotetrahydrocortisol; THE, tetrahydrocortisone. Statistical analyses The studywas powered on the primary endpoint (carotid-to-femoral pulse wave velocity) of the intervention trial. A detailed power calculation can be found in our previous paper 2. An intention-to-treat analysis (using the last observation carried forward approach) was performed. Normality of data was assessed by the Kolmogorov-Smirnov test. Data are presented as means ± standard deviations or percentages. Differences in responses between magnesium and placebo treatments were calculated using a singlefactor ANCOVA, with inclusion of the baseline measurements of the outcome variable as covariate. Sex was considered as a potential confounder and therefore, the analyses were adjusted for sex. Changes were calculated as the difference between the values at the end and the start of the trial. In a sensitivity analysis, we performed a singlefactor ANCOVA with log-transformed data, because the variables 24-h urinary cortisol, cortisone and their metabolites as well as the ratios reflecting A-ring reductase activity followed a skewed distribution. Skewed data are presented as geometric means with 95% confidence intervals. A P-value of <0.05 was considered statistically significant. We did not adjust for multiple testing, as the post-hoc analyses we performed are exploratory and hypothesis generating. Analyses were performed using SPSS version 23.0 for Windows.
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