Effects of Obesity on Lipid-Lowering, Anti-Inflammatory, and Antiatherosclerotic Benefits of Atorvastatin or Pravastatin in Patients With Coronary Artery Disease (from the REVERSAL Study)

The effect of obesity on atherosclerotic burden and its modulation by lipid-lowering therapy is unknown. The Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) study was analyzed to determine the influence of increasing body mass index (BMI) on plasma lipids, C-reactive protein, plaque burden as determined by intravascular ultrasound, and the serial change in these parameters with a moderate or intensive lipid-lowering strategy. Patients with a higher BMI were younger, more likely to be women, and had a greater prevalence of hypertension, diabetes, and the metabolic syndrome. Although a higher BMI was associated with a lower high-density lipoprotein level and higher triglyceride and C-reactive protein levels, there was no apparent influence of BMI on plaque burden. However, with the intensive lipid-lowering strategy, a greater BMI was associated with a lower proportionate decrease in low-density lipoprotein (49.1 ± 21.4% vs 43.0 ± 22.4%, p = 0.008) and a greater proportionate decrease in C-reactive protein (39.7% vs 33.3%, p <0.04). Further, although moderate and intensive lipid-lowering strategies halted plaque progression in subjects with a lower BMI (median progression rates +1.5% and +1.2%, respectively), a significant effect on plaque progression rates was seen only with adoption of an intensive lipid-lowering strategy in the most obese subjects (median progression rate -1.88% vs +6.5% with the moderate lipid-lowering strategy, p = 0.01). In conclusion, plaque progression in obese patients is attenuated using an intensive, but not moderate, lipid-lowering strategy. These results highlight the need for aggressive risk factor modification and a decrease in vascular inflammation in obese patients.