Evaluation of coronary risk factors in patients with heterozygous familialhypercholesterolemia

at onset of clinically manifested coronary artery disease (CAD) varies wide ly among patients with familial hypercholesterolemia (FH). A number of fact ors in addition to high low-density lipoprotein cholesterol (LDL) have been suggested as predictors of risk among patients with FH, but a comprehensiv e examination of their utility is lacking. We therefore measured plasma lip ids, carotid intima-medial thickness, and a variety of coronary risk factor s in 262 patients with FH greater than or equal to 30 years old (68 of whom had premature CAD). Age (p <0.0001) and gender were the most important det erminants of premature CAD risk, with men having 5.64 times the risk of wom en (p <0.0001). In addition, cigarette smoking (odds ratio [OR] 2.71, p = 0 .026), smaller LDL as determined by the LDL cholesterol/LDL apolipoprotein B ratio (OR 2.60, p = 0.014), and white blood cell count (p = 0.014) were a lso statistically significant risk factors. Lipoprotein(a) and the presence of xanthoma were associated with risk only in very early coronary cases. A fter correction for age, carotid intima-media thickness was not associated with CAD risk. Insulin, fibrinogen, homocysteine, plasma C-reactive protein , and the angiotensin-converting enzyme insertion/deletion polymorphism wer e unrelated to risk in this cohort. These results provide little justificat ion for extensive investigation of risk factors among patients with FH, at least for the risk factors examined here. Rather, the inherent high LDL cho lesterol of these patients should be the focus of preventive efforts. The n ovel finding of increased risk with smaller LDL may prove useful but needs further confirmation. (C) 2001 by Excerpta Medico, Inc.