An application of apo(a) isoforms for the clinical assessment of Lp(a)

To examine whether or not Lp(a) is applicable as a diagnostic marker for atherosclerosis, we studied the correlation between Lp(a) levels and molecular weights of apo(a) isoforms in sera from both normal healthy adults and diabetic patients. Serum Lp(a) level was measured by turbidimetric immunoassay (TIA) and the molecular weight of apo(a) isoform was determined by Western blotting analysis. The serum Lp(a) levels of the diabetic patients (25.0 mg/dl +/- 2.2 [mean +/- SE], n = 54) were significantly higher than those of the normal subjects (14.4 mg/dl +/- 0.57, n = 500). With respect to the correlation between serum Lp(a) levels and the molecular weights of apo(a) isoforms, there was an inverse correlation in sera from normal subjects (n = 298), whereas there was no correlation in sera from the diabetic patients. Statistical significant inverse correlation (r = -0.91, y = 224.25 - 3.07x) was especially observed in 50 representative apo(a) isotypes from the normal subjects. By applying a standardized curve based on the significant inverse correlation to serum Lp(a) levels, 40.7% (22/54) of the diabetic patients were revealed to have an abnormally high value of serum Lp(a). Moreover, it was found that the significantly higher mean value of serum Lp(a) in the diabetic group was caused by the 22 patients with higher value of Lp(a). The present findings suggest that determination of apo(a) isoform size provides estimation of the serum Lp(a) value and that the inverse correlation curve between serum Lp(a) level and the molecular weight of apo(a) isoform may be applicable to the clinical use of Lp(a).