title: Cortisol/cortisone ratio and matrix metalloproteinase-9 activity are associated with pediatric primary hypertension.
abstract: To identify novel biomarkers associated with pediatric primary hypertension.
  
  
  
  We recruited 350 participants (4-16 years). Anthropometric parameters and aldosterone, plasma renin activity, cortisol, cortisone, Homeostasis Model Assessment Insulin Resistance (HOMA-IR), high-sensitivity C-reactive protein, adiponectin, IL-6, plasminogen activator inhibitor type 1 levels and matrix metalloproteinase-9 and matrix metalloproteinase-2 (MMP-9 and MMP-2) activities were measured. Genomic DNA was isolated. Patients with altered glucose metabolism, severe obesity [BMI-SD score (BMI-SDS) > 2.5], renovascular disease, primary aldosteronism and apparent mineralocorticoid excess syndrome were excluded.
  
  
  
  In selected participants (n = 320), SBP was positively correlated with BMI-SDS (r = 0.382, P < 0.001), HOMA-IR (r = 0.211, P < 0.001), MMP-9 activity (r = 0.215, P < 0.001) and the cortisol/cortisone ratio (r = 0.231, P < 0.001). DBP showed similar correlations with these variables. No correlation was observed with aldosterone or plasma renin activity. Participants were categorized as hypertensive (n = 59) or nonhypertensive (n = 261). In the univariate analysis, hypertensive patients had higher BMI-SDS (P < 0.001), HOMA-IR (P < 0.001), high-sensitivity C-reactive protein (P < 0.001), MMP-9 activity (P < 0.001), plasminogen activator inhibitor type 1 (P < 0.001) and cortisol/cortisone ratio (P < 0.001) than nonhypertensive patients. Multiple regression analysis showed that the variables that remained associated with hypertension were higher BMI-SDS [odds ratio (OR) = 3.74; 95% confidence interval (CI) = 1.84-7.58], a higher cortisol/cortisone ratio (OR = 3.92; 95% CI = 1.98-7.71) and increased MMP-9 activity (OR = 4.23; 95% CI = 2.15-8.32).
  
  
  
  We report that MMP-9 activity and the cortisol/cortisone ratio were higher in pediatric primary hypertensive patients, and these associations were independent of the effect of obesity. The potential role of these novel biomarkers in predicting hypertension risk and blood pressure regulation warrants further investigation.
authors.affiliation: aDivision of Pediatrics bDepartment of Endocrinology cMillennium Institute on Immunology and Immunotherapy, Department of Molecular Genetics and Microbiology, Pontificia Universidad Católica de Chile dAdvanced Center for Chronic Diseases (ACCDiS), Faculty of Chemical and Pharmaceutical Sciences, Department of Biochemistry and Molecular Biology, University of Chile eStudent, School of Medicine, Pontificia Universidad Católica de Chile fFacultad de Ciencia, Universidad San Sebastián gDepartment of Clinical Laboratories, Facultad de Medicina hDepartment of Celular and Molecular Biology, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile *Alejandro Martinez-Aguayo and Carmen Campino contributed equally to this work.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Martinez-Aguayo
authors.forename: Carmen
authors.initials: C
authors.lastname: Campino
authors.forename: Rene
authors.initials: R
authors.lastname: Baudrand
authors.forename: Cristian A
authors.initials: CA
authors.lastname: Carvajal
authors.forename: Hernán
authors.initials: H
authors.lastname: García
authors.forename: Marlene
authors.initials: M
authors.lastname: Aglony
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Bancalari
authors.forename: Lorena
authors.initials: L
authors.lastname: García
authors.forename: Carolina
authors.initials: C
authors.lastname: Loureiro
authors.forename: Andrea
authors.initials: A
authors.lastname: Vecchiola
authors.forename: Alejandra
authors.initials: A
authors.lastname: Tapia-Castillo
authors.forename: Carolina
authors.initials: C
authors.lastname: Valdivia
authors.forename: Sebastian
authors.initials: S
authors.lastname: Sanhueza
authors.forename: Cristobal A
authors.initials: CA
authors.lastname: Fuentes
authors.forename: Carlos F
authors.initials: CF
authors.lastname: Lagos
authors.forename: Sandra
authors.initials: S
authors.lastname: Solari
authors.forename: Fidel
authors.initials: F
authors.lastname: Allende
authors.forename: Alexis M
authors.initials: AM
authors.lastname: Kalergis
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Fardella
mesh_terms: D052242:Adiponectin; D000293:Adolescent; D000450:Aldosterone / Q000097:blood; D001794:Blood Pressure; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003348:Cortisone / Q000097:blood*; D003971:Diastole; D000075222:Essential Hypertension; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D006973:Hypertension / Q000097:blood* / Q000201:enzymology; D007333:Insulin Resistance; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D009767:Obesity, Morbid / Q000503:physiopathology; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D012083:Renin / Q000097:blood; D013599:Systole
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin; D015850:Interleukin-6; D017395:Plasminogen Activator Inhibitor 1; D000450:Aldosterone; D002097:C-Reactive Protein; D012083:Renin; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D003348:Cortisone; D006854:Hydrocortisone