title: Insulin resistance and LVH progression in patients with calcific aortic stenosis: a substudy of the ASTRONOMER trial.
abstract: OBJECTIVE
  The objective of this substudy of the ASTRONOMER (Aortic Stenosis Progression Observation: Measuring Effects of Rosuvastatin) trial was to examine the association between insulin resistance and progression of left ventricular hypertrophy (LVH) in patients with aortic stenosis (AS).
  
  
  BACKGROUND
  In a recent cross-sectional study, the authors reported that the metabolic syndrome was associated with an increased prevalence of concentric LVH in patients with AS. As a central feature of the metabolic syndrome, insulin resistance could be an important mediator of this association.
  
  
  METHODS
  This substudy included 250 of 269 patients enrolled in ASTRONOMER. Follow-up was 3.4 ± 1.3 years. Insulin resistance was evaluated using the homeostatic assessment model (HOMA) index, and patients were dichotomized using the median HOMA index value (1.24). The rate of LVH progression was estimated by calculating the annualized change in LV mass index (LVMi), measured on echocardiography. The presence of LVH was defined as an LVMi >47 g/m(2.7) in women and >49 g/m(2.7) in men.
  
  
  RESULTS
  There was a significant progression of LVH among the patients without LVH at baseline (n = 134; p < 0.0001) but not in those with it (n = 116; p = NS). In those without LVH at baseline, the annualized progression rate of LVMi was significantly faster in the subset with HOMA >1.24 compared to that in the subset with HOMA <1.24 (2.49 ± 4.38 g/m(2.7)/year vs. -0.03 ± 3.90 g/m(2.7)/year; p = 0.001). During follow-up, LVH developed in 46% of patients with HOMA >1.24 compared to 11% of those with HOMA <1.24 (p = 0.0005). Independent predictors of faster LVH progression identified on multivariate analysis were history of hypertension (p = 0.048), degree of aortic valve calcification (p = 0.035), and HOMA index (p = 0.02).
  
  
  CONCLUSIONS
  In this ASTRONOMER substudy, insulin resistance was a powerful independent predictor of progression to LVH in patients with AS. Visceral obesity and ensuing insulin resistance may thus present novel therapeutic targets in AS patients.
authors.affiliation: Institut Universitaire de Cardiologie et de Pneumologie de Québec/Québec Heart & Lung Institute, Laval University, Québec, Québec, Canada.
authors.forename: Romain
authors.initials: R
authors.lastname: Capoulade
authors.forename: Marie-Annick
authors.initials: MA
authors.lastname: Clavel
authors.forename: Jean G
authors.initials: JG
authors.lastname: Dumesnil
authors.forename: Kwan L
authors.initials: KL
authors.lastname: Chan
authors.forename: Koon K
authors.initials: KK
authors.lastname: Teo
authors.forename: James W
authors.initials: JW
authors.lastname: Tam
authors.forename: Nancy
authors.initials: N
authors.lastname: Côté
authors.forename: Patrick
authors.initials: P
authors.lastname: Mathieu
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Després
authors.forename: Philippe
authors.initials: P
authors.lastname: Pibarot
mesh_terms: D000328:Adult; D000368:Aged; D001021:Aortic Valve / Q000473:pathology / Q000503:physiopathology; D001024:Aortic Valve Stenosis / Q000150:complications* / Q000188:drug therapy / Q000503:physiopathology; D002114:Calcinosis / Q000150:complications* / Q000188:drug therapy / Q000503:physiopathology; D002170:Canada; D016009:Chi-Square Distribution; D018450:Disease Progression; D005260:Female; D005464:Fluorobenzenes / Q000627:therapeutic use; D006439:Hemodynamics; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D017379:Hypertrophy, Left Ventricular / Q000000981:diagnostic imaging / Q000209:etiology* / Q000503:physiopathology; D007333:Insulin Resistance; D016014:Linear Models; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011446:Prospective Studies; D011743:Pyrimidines / Q000627:therapeutic use; D018570:Risk Assessment; D012307:Risk Factors; D000068718:Rosuvastatin Calcium; D012720:Severity of Illness Index; D013449:Sulfonamides / Q000627:therapeutic use; D013997:Time Factors; D014463:Ultrasonography; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling
chemical_list: D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium