Abstract
BackgroundTo evaluate the effect of lifestyle intervention in conjunction with rosiglitazone or placebo therapy on left ventricular (LV) mass, using cardiovascular magnetic resonance (CMR) in the metabolic syndrome.MethodsThe present study was a pre-specified substudy of a double-blind randomized controlled trial evaluating the effect of lifestyle intervention in conjunction with rosiglitazone or placebo therapy on carotid artery atherosclerosis in the metabolic syndrome. From this original study population, 10 subjects from the placebo group and 10 from the rosiglitazone group were randomly selected. At baseline and follow-up (52 weeks), clinical and laboratory measurements were assessed and a CMR-examination was performed to evaluate LV mass indexed for body surface area (LV mass-I). Subsequently, the effect of therapy (rosiglitazone vs. placebo) and clinical and laboratory variables on LV mass-I was evaluated.ResultsIn both groups, body mass index, waist circumference, systolic and diastolic blood pressure significantly decreased during follow-up. Interestingly, LV mass-I significantly decreased in the placebo group (48.9 ± 5.3 g/m2 vs. 44.3 ± 5.6 g/m2, p < 0.001) indicating reverse remodeling, whereas LV mass-I remained unchanged in the rosiglitazone group (54.7 ± 9.9 g/m2 vs. 53.7 ± 9.2 g/m2, p = 0.3). After correction for systolic and diastolic blood pressure and triglyceride, the kind of therapy (rosiglitazone vs. placebo) remained the only significant predictor of LV mass-I reduction.ConclusionsLifestyle intervention resulted in a reduction of LV mass-I in the metabolic syndrome, indicating reverse remodeling. However, rosiglitazone therapy may have inhibited this positive reverse remodeling.Trial registrationCurrent Controlled Trials ISRCTN54951661.
Highlights
To evaluate the effect of lifestyle intervention in conjunction with rosiglitazone or placebo therapy on left ventricular (LV) mass, using cardiovascular magnetic resonance (CMR) in the metabolic syndrome
The present study was a pre-specified substudy of a double-blind randomized controlled trial evaluating the effect of lifestyle in conjunction with rosiglitazone or placebo therapy on carotid artery atherosclerosis in subjects with the metabolic syndrome (Rosiglitazone versUs placeBo on the prevENtion of progression of atheroSclerosis, RUBENS trial)
Clinical and laboratory characteristics At baseline, no differences in clinical and laboratory variables were observed between subjects who were randomized for rosiglitazone or placebo therapy
Summary
To evaluate the effect of lifestyle intervention in conjunction with rosiglitazone or placebo therapy on left ventricular (LV) mass, using cardiovascular magnetic resonance (CMR) in the metabolic syndrome. The metabolic syndrome is a clustering of cardiovascular risk factors including abnormalities in glucose and lipid metabolism, abdominal obesity and hypertension [1], and is associated with increased risk of cardiovascular morbidity and mortality [2,3]. Thiazolidinediones (rosiglitazone, pioglitazone and troglitazone) represent a group of insulin sensitizing agents that can act as such ligands of the nuclear transcription factor PPAR-g [5]. PPARs undergo specific conformational changes that allow for the recruitment of coactivator proteins [8]. Ligands differ in their ability to interact with coactivators, which explains the various biologic responses observed [6,7]. Clinical studies have shown that thiazolidinediones e.g. lower blood glucose levels by enhancing hepatic and peripheral glucose uptake and increase free fatty acid uptake and storage in adipose tissue (thereby decreasing free fatty acid uptake in other tissues) [5,9]
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