Patients with familial hypercholesterolemia (FH) may be at increased risk for 
statin-associated muscle symptoms because they require long-term treatment with 
high-intensity statin therapy. We sought to determine (1) whether other 
predisposing factors, including the well-known genetic variant associated with 
statin-associated muscle symptoms-solute carrier organic anion transporter 
family, member 1B1 (SLCO1B1) rs4149056-also increase the risk of 
statin-associated muscle symptoms in FH patients, and (2) the natural history 
and management for FH patients with statin-associated muscle symptoms.
METHODS: We queried electronic records (2004-2014) of 278 genetically screened 
FH patients (113 men, 165 women; mean [SD] pretreatment low-density lipoprotein 
cholesterol [LDL-C] 259 [72] mg/dL) recruited from lipid clinics in the Dallas, 
TX, area from 2004 to 2014. Statin-associated muscle symptoms were defined as 
muscle symptoms arising while taking a statin and interrupting therapy.
RESULTS: The risk of muscle symptoms was associated with age (odds ratio 1.6 
[95% CI 1.2-2.2]), body mass index in non-African Americans (0.90 [0.83-0.97]), 
and hypertension (0.4 [0.2-0.9]). Simvastatin was the most commonly used statin, 
and it was the statin most associated with muscle symptoms. Among FH patients 
with muscle symptoms, 41% (n = 40) reestablished statin therapy ("eventually 
tolerant") and 29% (n = 28) never reestablished statin therapy ("never 
tolerant"). Rosuvastatin (43%) and pravastatin (30%) were the most common 
eventually tolerated statins, and eventually tolerant patients achieved lower 
treated LDL-C levels (eventually tolerant 127 vs never tolerant 192 mg/dL, P < 
.001). Never tolerant patients also developed muscle symptoms on nonstatins (16% 
vs 50%, P = .003). SLCO1B1 rs4149056 genotyping revealed 224 wild-type patients 
(TT) and 49 heterozygotes (TC). SLCO1B1 genotype was not associated with the 
risk of statin-associated muscle symptoms (odds ratio 1.40 [95% CI 0.74-2.64]).
CONCLUSION: Age, not SLCO1B1 rs4149056 genotype, was the strongest risk factor 
for statin-associated muscle symptoms in FH patients. After developing muscle 
symptoms, many patients reestablished statin therapy and achieved significant 
LDL-C reductions. Overall, 10% of all FH patients had statin-associated muscle 
symptoms and never reestablished statin therapy. Such patients developed muscle 
symptoms even on nonstatin lipid-lowering drugs and continued to have elevations 
in LDL-C. Further insight is needed into the relationship between FH and 
statin-associated muscle symptoms so all FH patients can be adequately treated.