Association of heterozygous familial hypercholesterolemia with smaller HDL particle size.
Small, dense HDL particles have been associated with factors known to increase the risk of cardiovascular disease, such as obesity, hypertriglyceridemia, small dense LDL particles, decreased HDL-cholesterol levels and increased apoA-I fractional catabolic rate from plasma. In order to assess the potential contribution of HDL particle size to atherosclerosis in heterozygous familial hypercholesterolemia (FH), we examined the electrophoretic characteristics of HDL particles in a large cohort of well defined FH heterozygotes and controls. A total of 259 FH heterozygotes and 208 controls participated in the study. FH subjects were carriers of one of the nine French Canadian mutations in the LDL receptor gene. All subjects were apoE3 homozygotes. HDL particles were characterized by non-denaturing polyacrylamide gradient gel electrophoresis following a 6-week lipid-lowering drug-free baseline period. The integrated HDL size was significantly smaller in the FH group compared to controls (FH=87.3+/-5.2 Angstroms versus controls=91.6+/-4.9 Angstroms, P<0.0001). In each groups, men had smaller HDL particles than women. Multiple regression linear analyses showed that the FH/Control status accounted for 20.3% of the variance in the integrated HDL size. These results suggest that the FH/control status was independently associated with variations in HDL particle size and that these variations could contribute to the development of premature atherosclerosis in these patients.
Hogue
Jean-Charles
JC
Lipid Research Center (S-102), CHUL Research Center, Laval University, Que, Canada.
Lamarche
Benoît
B
Gaudet
Daniel
D
Tremblay
André J
AJ
Després
Jean-Pierre
JP
Bergeron
Jean
J
Gagné
Claude
C
Couture
Patrick
P
D000328:Adult; D015992:Body Mass Index; D005260:Female; D006580:Genetic Carrier Screening; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D008075:Lipoproteins, HDL / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011792:Quebec / Q000453:epidemiology; D011973:Receptors, LDL / Q000097:blood; D012016:Reference Values; D014280:Triglycerides / Q000097:blood
D000960:Hypolipidemic Agents; D008075:Lipoproteins, HDL; D011973:Receptors, LDL; D014280:Triglycerides