Lipoprotein(a) and Cardiometabolic Diseases: The Mystery Continues

Lipoprotein(a) [Lp(a)]2 is a structurally and functionally unique lipoprotein consisting of the glycoprotein apolipoprotein(a) [Apo(a)] covalently linked to LDL (1). Soon after its discovery in 1963 by Berg, Lp(a) was shown in case-control studies to be associated with coronary heart disease (CHD) (2). Since then, it has received widespread interest, and a large database has been accumulated concerning its potential role as a predictor of cardiovascular risk. Recently, a metaanalysis, summarizing results of 36 prospective long-term studies with a total of 126 634 participants, was reported by the Emerging Risk Factors Collaboration (3). It confirmed a significant and independent association between increased Lp(a) concentrations and risk of CHD, resulting in a summary odds ratio (OR) of 1.13 (95% CI 1.09–1.18) for each SD increase after adjustment for conventional cardiovascular risk factors. The corresponding adjusted risk ratio for ischemic stroke was 1.10 (95% CI 1.02–1.18).In this issue of Clinical Chemistry , Mora et al. (4) report prospective data from healthy US women [Women's Health Study (WHS)] on Lp(a) concentration and risk of type 2 diabetes and replicate their findings in a cohort of Danish men and women [Copenhagen City Heart Study (CCHS)] with prevalent diabetes. In WHS participants, incident type 2 diabetes was ascertained primarily by self-report on annual follow-up questionnaires but was extensively validated by supplemental questionnaires and review of medical records. In the CCHS, prevalent type 2 diabetes was ascertained by self-report, the use of hypoglycemic drugs, or a nonfasting plasma glucose >200 mg/dL. Surprisingly, Lp(a) concentrations in the WHS and CCHS were significantly lower in diabetes cases compared with noncases, although the medians differed clearly by study population (WHS 9.5 vs 10.7 mg/dL, P < 0.001; CCHS 15.7 vs 17.4 mg/dL, P = 0.006). Pearson correlation coefficients showed a low correlation of Lp(a) with other risk …