Author + information
- Received May 30, 2012
- Revision received November 15, 2012
- Accepted November 26, 2012
- Published online February 1, 2013.
- Romain Capoulade, MSc⁎,
- Marie-Annick Clavel, DVM, PhD⁎,
- Jean G. Dumesnil, MD⁎,
- Kwan L. Chan, MD†,
- Koon K. Teo, MBBCh, PhD‡,
- James W. Tam, MD§,
- Nancy Côté, MSc⁎,
- Patrick Mathieu, MD⁎,
- Jean-Pierre Després, PhD⁎,
- Philippe Pibarot, DVM, PhD⁎,⁎ (, )
- ASTRONOMER Investigators
- ↵⁎Reprint requests and correspondence:
Dr. Philippe Pibarot, Institut Universitaire de Cardiologie et de Pneumologie de Québec, 2725 Chemin Sainte-Foy, Québec, Québec G1V-4G5, Canada
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/m2.7 in women and >49 g/m2.7 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/m2.7/year vs. −0.03 ± 3.90 g/m2.7/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.
The ASTRONOMER study was funded by AstraZeneca and the Canadian Institutes of Health Research (CIHR), Ottawa, Canada. This substudy was also funded in part by a CIHR grant #MOP-79342. Mr. Capoulade holds a PhD scholarship from the International Chair on Cardiometabolic Risk, Québec, Québec, Canada. Dr. Clavel holds a Vanier Canada Graduate Scholarship, Canadian Institutes of Health Research, Ottawa, Ontario, Canada. Dr. Mathieu is a research scholar from the Fonds de Recherches en Santé du Québec, Montreal, Canada. Dr. Després has received honoraria as a speaker or consulting fees from Abbott, AstraZeneca, GlaxoSmithKline, Pfizer Canada Inc., Merck, Sanofi, Novartis, Theratechnologies, and Torrent Pharma Ltd; and is the Scientific Director of the International Chair on Cardiometabolic Risk based at Université Laval. Dr. Pibarot holds the Canada Research Chair in Valvular Heart Diseases, supported by CIHR. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received May 30, 2012.
- Revision received November 15, 2012.
- Accepted November 26, 2012.
- American College of Cardiology Foundation