Circ J 2009; 73: 963 -966 amilial hypercholesterolemia (FH) is frequently associated with premature coronary artery disease (CAD), because of the marked hypercholesterolemia, the most major cause of which is attributed to a lowdensity lipoprotein (LDL) receptor gene mutation. 1 We previously reported that CAD starts to occur after 26 years of age for men, and after 50 years of age for women in Japanese cases of heterozygous FH without effective cholesterol-lowering therapy. 2 Although aortic valve stenosis (AVS), which is also known as an atherosclerotic degenerative disease, has often been reported in homozygous FH, it seems to be rare in heterozygous FH. 3 Many clinical trials in the past decade have shown the efficacy of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) for the primary and secondary prevention of CAD. 4-6 FH is highly resistant to conventional drug therapy and high-dose statin combined with other cholesterol-lowering drugs, such as cholesterol-sequestering resin, is frequently needed. 7 Although 2 prospective studies of the prevention of progression of AVS by aggressive cholesterol-lowering therapy using high-dose statin have been reported, 8,9 the results are conflicting.We report a female heterozygous FH patient with marked progression of AVS requiring surgical replacement, despite her LDL-cholesterol level having been controlled by LDL apheresis combined with drug therapy, and her coronary atherosclerosis and saphenous vein graft (SVG) disease have progressed minimally over 20 years.
Case ReportA 49-year-old woman was referred to Kanazawa University Hospital in 1982 for further investigation of her hypercholesterolemia. She had no diabetes mellitus, hypertension, or smoking habit. Her serum total cholesterol, triglyceride, and high-density lipoprotein (HDL)-cholesterol levels were 489, 174, and 43 mg/dl, respectively. She had xanthelasma palpebrarum and bilateral Achilles tendon xanthomas (13 mm), and her younger brother, younger sister, and her 2 sons also presented with primary hypercholesterolemia. A diagnosis of heterozygous FH was later confirmed by gene analysis of a splice site mutation in the intron 15 (IVS15-3 C>A) of the LDL receptor gene. 10 Coronary angiography showed severe stenosis in the proximal (Received February 18, 2008; revised manuscript received June 4, 2008; accepted June 11, 2008; released online December 16, 2008 In 1982, a 49-year-old Japanese woman had been referred to our hospital for further investigation of her hypercholesterolemia. She was diagnosed as heterozygous familial hypercholesterolemia, because of Achilles tendon xanthoma and a family history of primary hypercholesterolemia. Three years later, she had chest pain on effort and angina pectoris was diagnosed by coronary angiography. At that time, she underwent coronary artery bypass grafting surgery with 2 saphenous vein grafts (SVG). Because more aggressive cholesterol-lowering therapy was needed for secondary prevention of coronary artery disease (CAD), weekly low-density lipop...