CONTEXT: Emerging evidence suggests a role for cortisol in essential hypertension, and preliminary reports indicate that urinary free cortisol (UFC) may be an intermediate phenotype. OBJECTIVES: The objectives of this study were: 1) confirm bimodality of UFC, 2) assess whether UFC variations aggregate in hypertensive families, and 3) compare low-mode and high-mode UFC groups for distinguishing features. SUBJECTS/ SETTING: Subjects included 390 hypertensives and 166 normotensives from the general community. DESIGN/ INTERVENTIONS: Subjects had blood pressure and laboratory measurements on high- and low-salt diets. Familial aggregation was evaluated in 250 hypertensive siblings from 117 families. RESULTS: Hypertensives had higher UFC than normotensives (P<0.001) and bimodal distribution of UFC (P<0.0001). Analyses were controlled for gender and dietary sodium, which are confounding determinants of UFC. Mean low-mode UFC (33.8+/-10.6 microg per 24 h) was similar to that of normotensives. The high mode, comprising 31.3% of hypertensives, had less change in mean arterial pressure between diets than the low mode (P=0.01) without any other significant differences. Observed proportions of concordance and discordance for UFC mode differed significantly from that expected (P<0.001). Observed concordance for the high mode was twice that expected, whereas for the low mode, it was similar to that expected by chance. Family membership explained a significant proportion of variance in UFC classification (P=0.027). UFC mode of one sibling was a significant predictor of the UFC mode of the other sibling [odds ratio 6.6, 95% confidence interval (2.4-18.0), P<0.001]. CONCLUSION: High-mode UFC is an intermediate phenotype of hypertension associated with salt resistance and a strong familial component supporting heritability.
CONTEXT: Emerging evidence suggests a role for cortisol in essential hypertension, and preliminary reports indicate that urinary free cortisol (UFC) may be an intermediate phenotype. OBJECTIVES: The objectives of this study were: 1) confirm bimodality of UFC, 2) assess whether UFC variations aggregate in hypertensive families, and 3) compare low-mode and high-mode UFC groups for distinguishing features. SUBJECTS/ SETTING: Subjects included 390 hypertensives and 166 normotensives from the general community. DESIGN/ INTERVENTIONS: Subjects had blood pressure and laboratory measurements on high- and low-salt diets. Familial aggregation was evaluated in 250 hypertensive siblings from 117 families. RESULTS:Hypertensives had higher UFC than normotensives (P<0.001) and bimodal distribution of UFC (P<0.0001). Analyses were controlled for gender and dietary sodium, which are confounding determinants of UFC. Mean low-mode UFC (33.8+/-10.6 microg per 24 h) was similar to that of normotensives. The high mode, comprising 31.3% of hypertensives, had less change in mean arterial pressure between diets than the low mode (P=0.01) without any other significant differences. Observed proportions of concordance and discordance for UFC mode differed significantly from that expected (P<0.001). Observed concordance for the high mode was twice that expected, whereas for the low mode, it was similar to that expected by chance. Family membership explained a significant proportion of variance in UFC classification (P=0.027). UFC mode of one sibling was a significant predictor of the UFC mode of the other sibling [odds ratio 6.6, 95% confidence interval (2.4-18.0), P<0.001]. CONCLUSION: High-mode UFC is an intermediate phenotype of hypertension associated with salt resistance and a strong familial component supporting heritability.
Authors: Bei Sun; Bindu Chamarthi; Jonathan S Williams; Alexander W Krug; Jessica Lasky-Su; Benjamin A Raby; Paul N Hopkins; Xavier Jeunemaitre; Claudio Ferri; Gordon H Williams Journal: J Clin Endocrinol Metab Date: 2012-06-20 Impact factor: 5.958
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Authors: Rene Baudrand; Mark O Goodarzi; Anand Vaidya; Patricia C Underwood; Jonathan S Williams; Xavier Jeunemaitre; Paul N Hopkins; Nancy Brown; Benjamin A Raby; Jessica Lasky-Su; Gail K Adler; Jinrui Cui; Xiuqing Guo; Kent D Taylor; Yii-Der I Chen; Anny Xiang; Leslie J Raffel; Thomas A Buchanan; Jerome I Rotter; Gordon H Williams; Luminita H Pojoga Journal: Metabolism Date: 2015-09-12 Impact factor: 8.694
Authors: Bindu Chamarthi; Gordon H Williams; Vincent Ricchiuti; Nadarajah Srikumar; Paul N Hopkins; James M Luther; Xavier Jeunemaitre; Abraham Thomas Journal: Am J Hypertens Date: 2011-06-30 Impact factor: 2.689
Authors: Patricia C Underwood; Bei Sun; Jonathan S Williams; Luminita H Pojoga; Benjamin Raby; Jessica Lasky-Su; Steven Hunt; Paul N Hopkins; Xavier Jeunemaitre; Gail K Adler; Gordon H Williams Journal: Metabolism Date: 2011-02-08 Impact factor: 8.694
Authors: Patricia C Underwood; Bei Sun; Jonathan S Williams; Luminita H Pojoga; Bindu Chamarthi; Jessica Lasky-Su; Benjamin A Raby; Paul N Hopkins; Xavier Jeunemaitre; Nancy J Brown; Gail K Adler; Gordon H Williams Journal: J Clin Endocrinol Metab Date: 2010-07-14 Impact factor: 5.958
Authors: Andrea V Haas; Paul N Hopkins; Nancy J Brown; Luminita H Pojoga; Jonathan S Williams; Gail K Adler; Gordon H Williams Journal: Endocr Connect Date: 2019-06-01 Impact factor: 3.335