Abstract 14648: The Small Dense LDL phenotype and the Progression of Aortic Stenosis : a substudy of the ASTRONOMER trial
Background: We previously reported that metabolic syndrome (MetS) which represents a cluster of metabolic abnormalities including insulin resistance, is associated with faster progression of AS. A recent study suggested that statins may worsen insulin resistance in hypercholesterolemic patients. The Objectives of this substudy from the ASTRONOMER trial (AS Progression Observation: Measuring Effects of Rosuvastatin Trial) was to determine predictors of AS progression in a large prospective multicenter study and to assess the effect of statin on the metabolic profile in this population.
Methods: Among the 269 patients randomized in ASTRONOMER, 255 had an echocardiographic follow-up (mean time: 3.4 ±1.2 years) and 230 had complete follow-up of metabolic profile. None had hypercholesterolemia, diabetes, or coronary artery disease at baseline. However, 32% had systemic hypertension and 26% met MetS. Hemodynamic progression rate of AS was evaluated by the annualized increase in peak aortic jet velocity. Evolution of metabolic profile was assessed by annualized changes (Δ) in LDL-chol, HDL-chol, triglycerides, glucose, insulin, HOMA index and proportion of small LDL particles (%Small-LDL).
Results: After adjustment for gender, hypertension, smoking history, valvulo-arterial impedance, LDL-chol, creatinin, and status of randomization, baseline factors independently predicting faster AS progression were older age (p=0.05), higher degree of valve calcification (p=0.02), higher peak jet velocity (p=0.003), and MetS (p=0.01). When adding the changes in metabolic markers into this model, Δ%Small-LDL (p=0.006) but not ΔLDL came out as an independent predictor of AS progression. At 1 year, statin treatment was associated with marked reduction in LDL-Chol (−55±2 vs. −3±2%, p<0.0001), but with significant increases in both %Small-LDL (+55±9 vs. +13±9%, p=0.005) and HOMA index (+34±6 vs. +14±6%, p=0.02).
Conclusion: These findings suggest that the presence of high %Small-LDL, a phenotype typically linked to visceral obesity and insulin resistance, may accelerate the progression of AS. The fact that statin therapy worsens insulin resistance and increases %Small-LDL may explain, at least in part, its failure to slow AS progression.
- © 2010 by American Heart Association, Inc.