Combined effects of small apolipoprotein (a) isoforms and small, dense LDL on coronary artery disease risk

Lipoprotein (a) [Lp(a)] consists of low-density lipoprotein (LDL) and apolipoprotein (a) [apo(a)]. Both Lp(a) constituents are well-recognized risk factors for coronary artery disease (CAD). This study investigates the interrelationship of apo(a) and LDL size, as well as their possible synergistic effect on the increase of CAD risk.

One hundred nine CAD patients and 102 apparently healthy subjects were included in the study. Lp(a) concentration was measured using immunoturbidimetry. The sizes of apo(a) isoforms were determined by SDS-agarose gel electrophoresis followed by immunoblotting. LDL particle size was determined by gradient gel electrophoresis.

We found an inverse correlation between apo(a) size and Lp(a) concentration (r(2) = 31%, p <0.001 in the control group and r(2) = 35%, p <0.001 in the CAD group). Individuals with smaller apo(a) isoforms and small, dense LDL (sdLDL) >50% had the highest risk of CAD development (OR = 4.23, p = 0.017). The synergy index (SIM) for the combination of smaller apo(a) isoforms and sdLDL >50% was 1.2. Adjustment for Lp(a) and triacylglycerol concentrations eliminated smaller apo(a)/sdLDL >50% related risk (p = 0.233 and p = 0.09, respectively).

Smaller apo(a) isoforms appear to be superior to sdLDL for the assessment of CAD risk. Their combined effect is synergistic.