disease. Sprecher et al., characterized the residual LDL receptor activity in fibroblasts of 14 
FH patients and attempted to correlate this with several clinical indices (41). They 
demonstrated a statistically significant inverse correlation between residual LDL receptor 
activity and 1) pretreatment cholesterol and LDL levels, and 2) age of onset of angina pectoris. 
They also noted an association between LDL receptor activity and cholesterol reduction in 
response to conventional pharmacological therapy. In another study, Goldstein and Brown 
analyzed 57 homozygous deficient patients for residual LDL receptor activity in fibroblasts and 
classified them as receptor-negative (<2% of control, N=31) and receptor-defective (>2% of 
control, N=26) (42). Receptor status was correlated with age of onset and severity of coronary 
artery disease. Manifestations of coronary artery disease developed before the age of 10 in 32% 
(10/31) of receptor-negative patients and in only 4% (1/26) of the receptor-defective 
patients. Furthermore, 25% (8/31) of the receptor-negative patients died of the sequelae of 
coronary artery disease before the age of 25 (mean = 11 years old), whereas only 4% (1/26) 
of receptor-defective patients died during this time interval. This observation was confirmed 
in a study by Sprecher et al. that characterized a group of 16 unrelated FH homozygotes with 
respect to the presence or absence of overt CAD (43). Patients with symptomatic CAD had 
extremely high total serum cholesterols (862 +/- 62 mg/dl) and were primarily receptor 
negative. Four of seven symptomatic patients died of CAD; the average age death was 12 years of 
age. The asymptomatic group had lower serum cholesterols (629 +/- 75 mg/dl) and were 
primarily receptor defective. No deaths were reported in this group. Haitas et al. studied a 
population of White Afrikaners that have a high incidence of receptor defective FH (44). A 
group of 49 patients, symptomatic with CAD, had an average serum cholesterol equal to 744 
mg/dl; and 11 patients eventually died at an average age of 18 years old. Additional studies in 
various ethnic groups including Lebanese (45), Japanese (46, 47), and French Canadians (48) 
confirm these findings. A table of the population studies reviewed above are summarized in 
Table 1. 
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