Abstract 5087: LDL Lowering Does Not Improve Calf Muscle Perfusion or Energetics or Exercise Performance in Peripheral Arterial Disease

Abstract

Introduction. Prior studies suggest benefit of statins on walking performance in patients with peripheral arterial disease (PAD). Hypothesis. We hypothesized that LDL reduction in PAD would improve calf muscle perfusion and energetics as assessed by magnetic resonance imaging (MRI) and spectroscopy (MRS). Methods. Fifty eight patients with mild-to-moderate symptomatic PAD (mean±SD age 63±10 years, ankle brachial index (ABI) 0.70±0.14) were studied before and 1 year after therapy with simvastatin 40mg or simvastatin 40mg/ezetimibe 10mg (R,n=31) if statin-naive or ezetimbibe 10mg (Z,n=27) if on a statin. Calf muscle phosphocreatine recovery time constant (PCr) was measured using 31 phosphorus MRS immediately after symptom-limited exercise on a 1.5T scanner. Calf muscle perfusion was measured using first-pass contrast-enhanced MRI with 0.1 mM/kg gadolinium infused at peak exercise, (n=44 after excluding those with renal dysfunction). Time intensity curves in calf muscle were normalized to nearby proton density and the upslope was used to assess perfusion. Gadolinium-enhanced MRA was graded for number and degree of stenoses. Patients performed a 6 minute walk and Skinner-Gardner treadmill test with VO 2 measurement. Changes in parameters between groups were analyzed with F-test and between time point with paired t-test. Results. LDL at baseline was higher in R than Z (118±36 verus 103±25 mg/dl), p=0.07 and decreased more in R than Z (−42±35 versus −21±32), p=0.02 resulting in similar final LDL. There were no differences in any of the MRI or exercise parameters between treatment groups. See table for changes in parameters for the study as a whole. Conclusion. LDL lowering therapy over 1 year in PAD did not improve calf muscle perfusion, cellular metabolism, or exercise parameters. Statins are known to decrease risk of myocardial infarction, stroke, and death in PAD, but LDL lowering per se does not improve exercise calf muscle physiology or exercise performance.