Lipoprotein(a): a not-so-well-known risk factor for the development of cardiovascular disease in patients with type 2 diabetes mellitus

Lipoprotein(a) (Lp(a)), first discovered by Kare Berg in 1963, is an independent risk factor for the development of atherosclerotic cardiovascular disease (CVD) [1]. The structure of Lp(a) is similar to that of low density lipopro-tein; both complexes contain a lipid core surrounded by apolipoprotein B (apoB), but in Lp(a), a unique apolipo-protein, apolipoprotein A (apo(a)), is covalently bound to apoB via a disul-fide bond [1]. Apo(a) shares high sequence homology with plasminogen but has no fibrinolytic activity. Rather , apo(a) enhances coagulation and compromises clot lysis [2]. The plasma concentrations of Lp(a) are (principally) determined genetically and differ according to ethnicity [3]. Caucasians have lower median plasma levels than do Africans, and Chinese and Asian populations have lower levels than do Caucasians [4,5]. In this issue of the Korean Journal of Internal Medicine, Lim et al. [6] report that an elevated Lp(a) level is an independent predictor of the development of CVD in Korean patients with type 2 diabetes mellitus (T2DM). This has high importance, as very limited information is available on the range of Lp(a) levels and the association of Lp(a) with CVD in Koreans. The study is particularly meaningful because the cited authors prospectively followed up a relatively large patient cohort for over 10 years. New CVDs developed in 24.2% of patients during the 11.1 years of follow up. This confirms that patients with T2DM are at a very high risk of CVD. However, the incidence of CVD in the cited study seems to be much higher than those in other recent studies. This may be because all patients were enrolled in 2003 to 2004, the proportion treated with statins was only 11.6%, and the baseline mean glycated hemoglobin (HbA1c) level was relatively high (8.9%). CVD was much more prevalent among patients with mean HbA1c levels > 9.0% than among those with mean HbA1c levels < 7.0% over the study period. The work confirms that strict glycemic control can reduce the CVD risk in patients with T2DM of relatively long duration. A high Lp(a) level increases the CVD risk, particularly that in high-risk groups. However, it is very difficult to determine the Lp(a) level indicative of risk. Some studies use 30 or 50 mg/dL as the cutoff value; others define high-risk patients as those in the highest quartile or quintile. Lp(a) plasma concentrations differ according to ethnic-ity [3]; thus, more research is required