Association of Apo(a)isoform size with dyslipoproteinemia in male venous thrombosis patients.

Background: Lp(a) is a proatherogenic lipoprotein that may also be prothrombotic. Apo(a) size isoforms have differential effects on fibrinolysis. Whereas Lp(a) concentrations have been linked to venous thromboembolic disease (VTE) risk, apo(a) polymorphisms in VTE have not been studied.

Methods: We used a standardized high resolution agarose gel electrophoresis technique to determine apo(a) isoform size, and a Lp(a) immunoassay insensitive to apo(a) size to measure Lp(a) concentration in 46 men with VTE and 46 age-matched healthy controls.

Results: Apo(a) isoform distribution in VTE cases and controls was bimodal and VTE patients tended to have more medium-sized isoforms K(4)-(19-27) (54.3% vs. 34.8%, p=0.06). Cases and controls had the same median predominant apo(a) size isoform (23.5 K(4) repeats) and comparable Lp(a) concentrations. However, subgroup analysis based on apo(a) isoform size (K(4)< or =23 or K(4)> or =24) revealed that cases in the K(4)> or =24 subgroup had higher Lp(a) concentrations than the controls in this isofrom subgroup (14.5 mmol vs. 6.6 mmol, p=0.029). Also, dyslipoproteinemia (smaller LDL and HDL particles, higher LDL and lower HDL parameters) was strongly associated with VTE only in this larger apo(a) isoform group.

Conclusions: These observations provide the first evidence that determination of apo(a) isoforms may provide useful novel insights into VTE risk.