Insulin resistance and LVH progression in patients with calcific aortic stenosis: a substudy of the ASTRONOMER trial

JACC Cardiovasc Imaging. 2013 Feb;6(2):165-74. doi: 10.1016/j.jcmg.2012.11.004.

Abstract

Objectives: 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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aortic Valve / pathology
  • Aortic Valve / physiopathology
  • Aortic Valve Stenosis / complications*
  • Aortic Valve Stenosis / drug therapy
  • Aortic Valve Stenosis / physiopathology
  • Calcinosis / complications*
  • Calcinosis / drug therapy
  • Calcinosis / physiopathology
  • Canada
  • Chi-Square Distribution
  • Disease Progression
  • Female
  • Fluorobenzenes / therapeutic use
  • Hemodynamics
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Hypertrophy, Left Ventricular / diagnostic imaging
  • Hypertrophy, Left Ventricular / etiology*
  • Hypertrophy, Left Ventricular / physiopathology
  • Insulin Resistance*
  • Linear Models
  • Logistic Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Prospective Studies
  • Pyrimidines / therapeutic use
  • Risk Assessment
  • Risk Factors
  • Rosuvastatin Calcium
  • Severity of Illness Index
  • Sulfonamides / therapeutic use
  • Time Factors
  • Ultrasonography
  • Ventricular Function, Left
  • Ventricular Remodeling

Substances

  • Fluorobenzenes
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Pyrimidines
  • Sulfonamides
  • Rosuvastatin Calcium

Supplementary concepts

  • Aortic Valve, Calcification of