Effect of pravastatin on LDL particle concentration as determined by NMR spectroscopy: a substudy of a randomized placebo controlled trial

AIM: Recent data suggests that LDL particle concentration, as determined by Nuclear Magnetic Resonance (NMR) spectroscopy, may be associated with cardiovascular risk. We sought to determine the effect of randomization to pravastatin therapy on LDL particle concentration-NMR, among a primary prevention population. METHODS AND RESULTS: LDL particle concentration-NMR, LDL size-NMR, and standard chemical lipid parameters were measured at baseline and after 12 weeks among 500 individuals without overt coronary disease randomly allocated to pravastatin 40mg (n=256) or placebo (n=244). Randomization to pravastatin therapy caused a 19% reduction in median LDL particle concentration-NMR at 12 weeks, as compared to a 4.2% increase among those randomized to placebo (P<0.001 for pravastatin group compared to placebo). Pravastatin therapy caused a median 24.9% reduction in LDL cholesterol measured chemically compared to a 0.9% increase in the placebo group (P<0.001). Pravastatin therapy did not cause a significant change in median LDL size-NMR (0.5% increase in pravastatin group vs 0.0% in placebo group; P=0.25). The change in LDL particle concentration with pravastatin correlated inversely with baseline LDL size (r=-0.24; P<0.001) such that the largest reduction in LDL particle concentration-NMR was among those with the smallest LDL size-NMR at baseline (median% change =21.4% for tertile 1 of LDL size, 19.9% for tertile 2, and 16.5% for tertile 3; P=0.03). In contrast, pravastatin-induced changes in LDL cholesterol did not correlate with baseline LDL size-NMR (r=-0.05; P=0.47). CONCLUSION: Among individuals without overt hyperlipidemia or known coronary artery disease, randomized allocation to pravastatin (40mg) therapy for 12 weeks caused a reduction in LDL particle concentration-NMR, the magnitude of which was dependent on baseline LDL size-NMR.