Difference in the Risk Factors for Coronary, Renal and Other Peripheral Arteriosclerosis in Heterozygous Familial Hypercholesterolemia

Abstract

therosclerotic lesions in an individual do not progress at a same rate, 1 despite the systemic atherosclerosis risk factors affecting all arteries uniformly. The severity and extent of lesions differ throughout the body 2 and although the topographic distribution of atherosclerotic lesions in rabbits fed a low-level cholesterol diet has been shown, 3 no studies of humans have been conducted to date.Familial hypercholesterolemia (FH) is characterized by accelerated atherosclerotic lesions, and because the prevalence of heterozygous FH is not rare (1 in 500 in general population), 4-6 it provides a good opportunity to examine the variance in the development of peripheral arteriosclerosis.Of the peripheral arteriosclerotic diseases, the clinical significance of renal arteriosclerosis (RAS) has been underestimated despite its clinical importance in progressing to renovascular hypertension (RVHT) and nephrosclerosis. Therefore, we investigated the distribution of the atherosclerotic lesions in heterozygous FH, including RAS, abdominal aortic sclerosis (AOS) and iliac arteriosclerosis Circulation Journal Vol. 68, July 2004 (IAS) and coronary artery disease (CAD), by performing coronary and abdominal aortic angiography (AAA) and then analyzing in detail the possible contributing factors. Methods SubjectsSubjects were 117 consecutive heterozygous FH patients who underwent coronary angiography (CAG) in 4 hospitals (Kanazawa University Hospital, Kanazawa Cardiovascular Hospital, Fukui Cardiovascular Hospital, Komatsu Municipal Hospital) from April 1994 to March 1997 (These 4 hospitals are in the Hokuriku district (north central) of Japan, where approximately 3% of the Japanese population resides). The diagnosis of FH was based on the criteria we previously reported. 6 The subjects consisted of 79 men and 38 women aged 22-76 years (mean, 53 years). None had undergone any angioplastic or vascular surgeries, such as coronary artery bypass graft (CABG) surgery, percutaneous transluminal coronary angioplasty (PTCA), stenting or percutaneous transluminal angioplasty (PTA), or lipidlowering therapies before this study. Smokers and habitual alcohol consumers were identified by the information obtained in a patient questionnaire. Subjects who smoked at least 10 cigarettes per day were classified as current smokers. Subjects who habitually consumed more than 1 unit of alcohol (633 ml of beer or 180 ml of wine or 180 ml of sake or 70 ml of hard liquor) every week were classified as current drinkers. Measurement of Achilles tendon thickness was based on the method we previously described.

Characteristics and Vascular Complications of Familial Hypercholesterolemia in Korea

“…In other studies, the risk of this complication was 5 to 10 times greater than that in controls 36) . The prevalence of iliac artery disease (more than minimal) in FH patients in Japan was 56% 37) . Information on cerebrovascular or peripheral artery disease in Korean FH patients remains to be evaluated.…”

Efficacy of Colestimide Coadministered With Atorvastatin in Japanese Patients With Heterozygous Familial Hypercholesterolemia (FH)

“…In the current study, FH was diagnosed by our clinical criterion 2,18,19 and confirmed by genetic method in 14 of the 15 enrolled patients. 18,19 We failed to find the LDL receptor gene mutation in 1 patient, whose baseline LDL-C concentration was almost the average for heterozygous FH, namely 262 mg/dl.…”

“…18,19 We failed to find the LDL receptor gene mutation in 1 patient, whose baseline LDL-C concentration was almost the average for heterozygous FH, namely 262 mg/dl. Because no patient with familial defective apolipoprotein B has been reported in Japan, 32 it is possible that perhaps this particular patient might be another case of autosomal dominant hypercholesterolemia, such as PCSK9 gene mutation.…”

“…All of the patients fulfilled our diagnostic criteria for FH: 2,18,19 primary hypercholesterolemia (>230 mg/dl) with tendon xanthomas, or first generation relatives of previously diagnosed heterozygous FH patients showing primary hypercholesterolemia (>230 mg/dl). All except for 1 participant had the mutation of the LDL receptor gene.…”

A case of homozygous familial hypercholesterolemia with focal segmental glomerulosclerosis

“…Of the peripheral arteriosclerotic diseases, the clinical significance of renal arteriosclerosis (RAS) may have been underestimated despite its causal relationship with renovascular hypertension and nephrosclerosis. Yagi et al [8] reported atherosclerotic changes in coronary arteries, abdominal aorta, and iliac and renal arteries in adult FH patients, and most cases of RAS (64%) presented with <25% stenosis. Yokoyama et al [9] also angiographically demonstrated that atheromatous lesions regressed in the aortic valve region and in the left renal artery in a patient with homozygous FH who was treated with long-term, repetitive LDL-C apheresis.…”