Long Term Treatment of Heterozygous Familial Hypercholesterolemia with the Statin/Ezetimibe Combination Prevents Heart Disease

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 723-739-Lipids: Therapeutics & Case Reports
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-724
Vorawan Ummaritchot*1, Eliana Polisecki2 and Ernst John Schaefer3
1Tufts Medical Center, Boston, MA, 2Boston Heart Diagnostics, Framingham, MA, 3Tufts Univ, Boston, MA
Introduction: Heterozygous familial hypercholesterolemia (FH) is associated with marked increases in low density lipoprotein (LDL) cholesterol (C), premature coronary heart disease (CHD), tendinous xanthomas, and usually defects in the LDL receptor. Limited information is available about long term follow-up of these cases since the introduction of statins and ezetimibe.

Clinical Case:  A 76 year old woman has been followed for the past 30 years because of significantly elevated baseline LDL-C levels of 410 mg/dL, Tendinous xanthomas, and arcus senilis were first noted when she was in her teens. She quit smoking more than 30 years ago. She had no diabetes, but was diagnosed with hypertension in her 30s. In the past she had been tried on both cholestyramine, colestipol, and niacin, but was unable to take these medications because of gastro-intestinal side effects. When statin therapy (inhibits cholesterol synthesis) became available 25 years ago she was placed on maximal doses of lovastatin, then simvastatin, then atorvastatin, and most recently rosuvastatin  40 mg/day. In addition when ezetimibe (inhibits cholesterol absorption) became available 13 years ago she was placed on 10 mg/day of this medication.  She has never developed any chest pain on exertion, and has had a normal stress test, and echocardiogram. In addition on physical examination she has very significant arcus senilis and very modest tendon xanthomas on her hands, but no detectable bruits over her carotid arteries, her heart, her abdomen, or her femoral arteries. Her most recent lipid profile on blood drawn after an overnight fast revealed: total cholesterol 231 mg/dl, triglycerides 56 mg/dl, direct LDL-C 120 mg/dl (about 70% lower than baseline), small dense LDL-C 38 mg/dl, high density lipoprotein (HDL) -C 89 mg/dl, Analysis of her plasma sterols revealed suppressed markers of both cholesterol synthesis (lathosterol) and  absorption (beta-sitosterol and campesterol). Sequencing of her LDL receptor gene revealed a novel heterozygous mutation at nucleotide 654 (ctgg654del) resulting in a deletion of a glycine at residue 219 in the amino acid sequence of the LDL receptor. Her mother also had heterozygous FH and died at age 80 years of CHD. Her sister also has heterozygous FH and required quadruple bypass at age 80 years. At that time she was only receiving simvastatin. One daughter also has heterozygous FH and is also receiving statin and ezetimibe treatment, and is doing well at age 54 years.

Conclusions: Statins have been shown to markedly decrease CHD risk in a variety of populations. In our view the combination of an effective statin and ezetimibe is ideal for normalizing LDL cholesterol and CHD risk in heterozygous familial hypercholesterolemia.

Disclosure: EP: Employee, Boston Heart Diagnostics. EJS: Employee, Boston Heart Diagnostics. Nothing to Disclose: VU

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm