Evaluation of coronary risk factors in patients with heterozygous familial hypercholesterolemia.
Age at onset of clinically manifested coronary artery disease (CAD) varies widely among patients with familial hypercholesterolemia (FH). A number of factors in addition to high low-density lipoprotein cholesterol (LDL) have been suggested as predictors of risk among patients with FH, but a comprehensive examination of their utility is lacking. We therefore measured plasma lipids, carotid intima-medial thickness, and a variety of coronary risk factors in 262 patients with FH > or = 30 years old (68 of whom had premature CAD). Age (p < 0.0001) and gender were the most important determinants of premature CAD risk, with men having 5.64 times the risk of women (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 also statistically significant risk factors. Lipoprotein(a) and the presence of xanthoma were associated with risk only in very early coronary cases. After 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 were unrelated to risk in this cohort. These results provide little justification for extensive investigation of risk factors among patients with FH, at least for the risk factors examined here. Rather, the inherent high LDL cholesterol of these patients should be the focus of preventive efforts. The novel finding of increased risk with smaller LDL may prove useful but needs further confirmation.
Department of Pathology, University of Utah School of Medicine, Salt Lake City, USA. paul@ucvg.med.utah.edu
P N
PN
Hopkins
S
S
Stephenson
L L
LL
Wu
W A
WA
Riley
Y
Y
Xin
S C
SC
Hunt
D000328:Adult; D000367:Age Factors; D000368:Aged; D001055:Apolipoproteins B / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003327:Coronary Disease / Q000097:blood / Q000235:genetics* / Q000517:prevention & control; D005260:Female; D006580:Genetic Carrier Screening; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000235:genetics* / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D012737:Sex Factors
D001055:Apolipoproteins B; D008078:Cholesterol, LDL