Urinary free cortisol: An intermediate phenotype and a potential genetic marker for a salt-resistant subset of essential hypertension

Bindu Chamarthi, Nikheel S. Kolatkar, Steven Hunt, Jonathan S. Williams, Ellen W. Seely, Nancy J. Brown, Laine J. Murphey, Xavier Jeunemaitre, Gordon H. Williams

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

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 μg 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.

Original languageEnglish
Pages (from-to)1340-1346
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume92
Issue number4
DOIs
Publication statusPublished - Apr 2007
Externally publishedYes

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Genetic Markers
Hydrocortisone
Salts
Phenotype
Nutrition
Essential Hypertension
Dietary Sodium
Sodium-Restricted Diet
Blood pressure
Arterial Pressure
Agglomeration
Sodium
Odds Ratio
Confidence Intervals

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Urinary free cortisol : An intermediate phenotype and a potential genetic marker for a salt-resistant subset of essential hypertension. / Chamarthi, Bindu; Kolatkar, Nikheel S.; Hunt, Steven; Williams, Jonathan S.; Seely, Ellen W.; Brown, Nancy J.; Murphey, Laine J.; Jeunemaitre, Xavier; Williams, Gordon H.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 92, No. 4, 04.2007, p. 1340-1346.

Research output: Contribution to journalArticle

Chamarthi, Bindu ; Kolatkar, Nikheel S. ; Hunt, Steven ; Williams, Jonathan S. ; Seely, Ellen W. ; Brown, Nancy J. ; Murphey, Laine J. ; Jeunemaitre, Xavier ; Williams, Gordon H. / Urinary free cortisol : An intermediate phenotype and a potential genetic marker for a salt-resistant subset of essential hypertension. In: Journal of Clinical Endocrinology and Metabolism. 2007 ; Vol. 92, No. 4. pp. 1340-1346.
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abstract = "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 μg 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.",
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AU - Seely, Ellen W.

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N2 - 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 μg 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.

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