Abstract P073: Higher LDL and Lesser LDL-Drop Linked to More Muscle Problems in Men on Statins
Background: Muscle adverse effects (MAEs) on statins of fatigue, pain and weakness are well recognized. The relationship of MAEs to LDL and testosterone (levels and change) have not been well-characterized.
Goal: To assess the relation of MAE development to baseline LDL and testosterone in men, and to change-on-statins in these.
Method: 692 men without diabetes or CVD and with LDL 115-190mg/dL underwent (sex-stratified) double-blind randomization equally to pravastatin 40mg, simvastatin 20mg or placebo for 6 months. Outcomes of muscle pain, muscle weakness and energy (to address fatigue) were self-rated at baseline from 0-10, and on follow-up from -2 much less to +2 much more than at baseline. Final 6-month (on-treatment) minus baseline values defined LDL-change (mg/dL) and testosterone-change (ng/mL). Ordinal logit examined the change in each MAE on treatment, as a function of baseline and change-in LDL and testosterone (adjusted for baseline rating of the MAE), separately on statins and placebo.
Results: Less LDL drop with treatment (and higher baseline LDL) were linked to greater worsening in muscle-related outcomes on statins (Table). In contrast, greater testosterone drop predicted greater worsening in pain and (trend) weakness on statins. The sign and magnitude was similar for LDL-findings across outcomes; and for testosterone-findings for pain and weakness. Neither LDL nor testosterone relations approached significance on placebo (Table legend). Discussion: These findings comport with evidence connecting genetic markers that produce lesser LDL-drop-on-statins, to higher MAE-risk-on-statins (SEARCH trial). Prooxidant predominance of statins has been linked to statin MAEs (Sinzinger et al 2001), and LDL helps transport fat soluble antioxidants. We speculate that LDL may be upregulated, prior to and on statins, when needs for its antioxidant transport are greater - and risks associated with its reduction increased.
- © 2013 by American Heart Association, Inc.