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FH is an inherited condition resulting in markedly elevated LDL-c leading to early mid life CAD.The aims of the study were to evaluate the effectiveness of long term lipid lowering therapy on LDL-c levels, and on the natural history of FH.The charts of 327 adults and 89 children and adolescents of approximately 1,000 heterozygous (He) FH patients, treated at the Cholesterol Treatment Center, Cincinnati, OH between 1974 and 2008 were randomly reviewed.Mean initial untreated, most recent treated LDL-c levels (mg/dL) and percent changes were: 256±60, 116±46,-55%, for the adults and 250±50, 142±49,-43% for the children and adolescents.Of all adults 24% were treated with statin monotherapy, 55% with statin plus one other agent (mainly Ezetimibe), the rest were on 3 or more lipid lowering medications.For the adults, the interval between recurrent CVD events prior to referral to the clinic was 5.3±4.8 compared to 7.4±6.7 years since.For the children and adolescents, 47% were treated with statin mono therapy mainly Atorvastatin or Rosuvastatin, 53% with combination therapy (mainly Vytorin or Rosuvastain Ezetimibe).At the end of the study period 15 patients of the children and adolescents subjects were >30 years old.None of them had developed any symptomatic CVD or needed any revascularization procedure.In conclusion, Long term statin based combination therapy provides the opportunity to achieve substantial changes in LDL-c levels in the majority of HeFH patients and appears to alter their CVD risk significantly.