title: Urinary free cortisol: an intermediate phenotype and a potential genetic marker for a salt-resistant subset of essential hypertension.
abstract: BACKGROUND
  Emerging evidence suggests a role for cortisol in essential hypertension, and preliminary reports indicate that urinary free cortisol (UFC) may be an intermediate phenotype.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  Subjects included 390 hypertensives and 166 normotensives from the general community.
  
  
  METHODS
  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].
  
  
  CONCLUSIONS
  High-mode UFC is an intermediate phenotype of hypertension associated with salt resistance and a strong familial component supporting heritability.
authors.affiliation: Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital and Harvard Medical School, 221 Longwood Avenue, Boston, Massachusetts 02115, USA.
authors.forename: Bindu
authors.initials: B
authors.lastname: Chamarthi
authors.forename: Nikheel S
authors.initials: NS
authors.lastname: Kolatkar
authors.forename: Steven C
authors.initials: SC
authors.lastname: Hunt
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Williams
authors.forename: Ellen W
authors.initials: EW
authors.lastname: Seely
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Brown
authors.forename: Laine J
authors.initials: LJ
authors.lastname: Murphey
authors.forename: Xavier
authors.initials: X
authors.lastname: Jeunemaitre
authors.forename: Gordon H
authors.initials: GH
authors.lastname: Williams
mesh_terms: D000328:Adult; D001794:Blood Pressure; D002648:Child; D015331:Cohort Studies; D004032:Diet; D004039:Diet, Sodium-Restricted; D005260:Female; D005819:Genetic Markers; D006801:Humans; D006854:Hydrocortisone / Q000652:urine*; D006973:Hypertension / Q000145:classification / Q000503:physiopathology / Q000652:urine*; D008875:Middle Aged; D012982:Sodium, Dietary
chemical_list: D005819:Genetic Markers; D012982:Sodium, Dietary; D006854:Hydrocortisone