The relation of lipoprotein[a] concentrations and apolipoprotein[a] phenotypes with asymptomatic atherosclerosis in subjects of the Atherosclerosis Risk in Communities (ARIC) Study.
Plasma levels of lipoprotein[a] (Lp[a]) are associated with increased risk of coronary artery disease and show an inverse correlation with apolipoprotein[a] (apo[a]) molecular weight. We determined Lp[a] levels and apo[a] phenotypes in 171 cases with preclinical extracranial carotid atherosclerosis as ascertained by B-mode ultrasound and in 274 control subjects free of carotid atherosclerosis. Lp[a] protein levels measured by enzyme-linked immunosorbent assay ranged from 4 to 361 micrograms/mL in cases and from 2 to 392 micrograms/mL in controls, but median levels of Lp[a] were higher in cases than in controls (51 micrograms/mL versus 33 micrograms/mL, P < .003). In both groups, all 11 apo[a] polymorphs that are resolved by the procedure used were present, resulting in 43 and 39 different apo[a] phenotypes in cases and controls, respectively. An inverse relation between apo[a] polymorph size and Lp[a] level was observed in both cases (r = -0.49, P < .001) and controls (r = -0.34, P < .001). Apo[a] phenotype distributions were similar in cases and controls. However, in 17 phenotypes with three or more subjects per group, the difference of mean Lp[a] concentrations between cases and controls was 32 +/- 36 micrograms/mL (mean +/- SD). Thus, the higher Lp[a] levels in cases were not associated with a greater prevalence of small apo[a] polymorphs. Stepwise logistic regression analyses of known risk factors for coronary heart disease showed that plasma Lp[a] concentration was an independent predictor of case-control status, while Lp[a] phenotype was not, irrespective of the presence or absence of Lp[a] concentration in the model.(ABSTRACT TRUNCATED AT 250 WORDS)
Brown
S A
SA
Department of Medicine, Baylor College of Medicine, Houston, TX 77030.
Morrisett
J D
JD
Boerwinkle
E
E
Hutchinson
R
R
Patsch
W
W
D000483:Alleles; D001054:Apolipoproteins A / Q000235:genetics* / Q000378:metabolism; D001055:Apolipoproteins B / Q000378:metabolism; D001161:Arteriosclerosis / Q000097:blood*; D002340:Carotid Artery Diseases / Q000097:blood; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000097:blood; D015914:Estrogen Replacement Therapy; D005260:Female; D006801:Humans; D017270:Lipoprotein(a) / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic; D012307:Risk Factors
D001054:Apolipoproteins A; D001055:Apolipoproteins B; D008076:Cholesterol, HDL; D017270:Lipoprotein(a)