SIGNIFICANT ASSOCIATION BETWEEN LOW-MOLECULAR-WEIGHT APOLIPOPROTEIN(A) ISOFORMS AND INTERMITTENT CLAUDICATION

The role of lipoprotein(a) (Lp[a]) and apolipoprotein(a) (apo[a]) isoforms in symptomatic peripheral atherosclerosis was studied in 100 randomly selected middle-aged (45-69 years) men with intermittent claudication (IC) and 100 randomly selected healthy control (C) subjects. IC and C subjects were matched pairwise for sex, age, and smoking habits. Plasma Lp(a) concentrations were significantly higher in IC subjects, with a median value of 20.12 mg/dl, compared with 11.11 mg/dl in C subjects (p<0.0009). The elevated Lp(a) concentration was to a great extent due to a significant difference in the frequency distribution of apo(a) isoforms between IC and C subjects (p<0.029). Low-molecular-weight apo(a) isoforms were more prevalent in IC than C subjects. Also, IC subjects with apo(a) S2 and S3 phenotypes had higher Lp(a) concentrations than control subjects with the same phenotypes: S2: 60.70 mg/dl (IC) and 48.69 mg/dl (C), p<0.038; and S3: 30.18 mg/dl (IC) and 12.01 mg/dl (C), p <0.042, so other still-unknown factors, genetic or nongenetic, may be important. Stepwise logistic regression analysis demonstrated that Lp(a) concentration contributed significantly (p<0.0002) to IC, independent of age, smoking, hypertension, diabetes mellitus, plasma total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, apo B, and plasma total triglycerides. Apo(a) isoforms grouped according to molecular weight were also independent of the above risk factors associated (p=0.016) with the occurrence of IC because of their low-molecular-weight but were not independent of Lp(a) concentrations. Because IC and C subjects had similar smoking habits, the study also suggests that elevated Lp(a) levels due to a preponderance of low-molecular-weight apo(a) isoforms may be an explanation for the difference in risk that smokers have for developing IC.