title: Genetic predisposition to left ventricular hypertrophy and the potential involvement of cystatin-C in untreated hypertension.
abstract: BACKGROUND
  The angiotensinogen M235T and aldosterone synthase C-344T gene polymorphisms have been associated with cardiac and structure function. However, these associations in untreated hypertension remain unknown. We examined whether these variants determined both echocardiography indices and the potential associated underlying mechanisms, including cystatin-C and vascular inflammation.
  
  
  METHODS
  The study population consisted of 319 untreated patients and 191 healthy individuals. Polymorphisms were determined by polymerase chain reaction technique. Left cardiac indices of geometry and function were assessed by echocardiography. Cystatin-C, intracellular cell adhesion molecule 1, and vascular cell adhesion molecule 1 levels were measured by enzyme-linked immunosorbent assay, whereas high sensitivity C-reactive protein levels were measured by immunonephelometry.
  
  
  RESULTS
  There was no significant interaction between the angiotensinogen genotypes on left ventricular mass index (LVMI) and diastolic function indices in all study groups. Regarding C-344T polymorphism, TT homozygous hypertensive subjects exhibited higher values of LVMI compared with C allele carriers (P = 0.02) and higher prevalence of concentric hypertrophy (P < 0.001). However, this polymorphism was not associated with variations in left atrial volume and diastolic dysfunction. Cystatin-C levels were correlated with LVMI values (r = 0.22; P = 0.002) and mean E/A ratio (r = -0.24; P < 0.001). Interestingly, a linear increase of LVMI with cyctatin-C quartiles has been revealed (F = 5.01; P < 0.001). Moreover, post hoc tests showed that increased levels of cystatin-C (above 75th percentile) were significantly different between both the first (P = 0.009) and the second quartile (P = 0.02).
  
  
  CONCLUSIONS
  We have shown that C-344T potentially predicts higher values of LVMI and concentric hypertrophy in untreated hypertension, independently of renal function and subclinical inflammation. Increased levels of cystatin-C were correlated with higher LVMI values.
authors.affiliation: First Cardiology Department, Athens University Medical School, Athens, Greece. drtousoulis@hotmail.com
authors.forename: Dimitris
authors.initials: D
authors.lastname: Tousoulis
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Androulakis
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Papageorgiou
authors.forename: Antigoni
authors.initials: A
authors.lastname: Miliou
authors.forename: Evaggelos
authors.initials: E
authors.lastname: Chatzistamatiou
authors.forename: Evaggelos
authors.initials: E
authors.lastname: Oikonomou
authors.forename: George
authors.initials: G
authors.lastname: Moustakas
authors.forename: Ioannis
authors.initials: I
authors.lastname: Kallikazaros
authors.forename: Christodoulos
authors.initials: C
authors.lastname: Stefanadis
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D000808:Angiotensinogen / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D055316:Cystatin C / Q000097:blood / Q000502:physiology*; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics*; D004452:Echocardiography; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000150:complications* / Q000503:physiopathology*; D017379:Hypertrophy, Left Ventricular / Q000000981:diagnostic imaging / Q000235:genetics*; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood
chemical_list: D015415:Biomarkers; D055316:Cystatin C; D019010:Vascular Cell Adhesion Molecule-1; D000808:Angiotensinogen; D018799:Intercellular Adhesion Molecule-1; D002097:C-Reactive Protein; D019405:Cytochrome P-450 CYP11B2