Risk estimation for coronary heart disease (CHD) at the population level was not enhanced by correcting LDL-C for its content of lipoprotein(a) (Lp[a]), according to a study published July 1 in JACC.

Using data from eight European-based cohorts within the BiomarCaRE project, Natalie Arnold, MD, et al., investigated the effect of the Lp(a)-C contribution to CHD risk attributable to LDL-C. Because of their overlapping densities, conventional quantification of LDL-C includes cholesterol that is attributable to Lp(a). The investigators used established estimations of either 30% or 17.3% of total Lp(a) mass for correcting LDL-C, as well as categorized Lp(a) mass as high (≥90th percentile) or low/moderate (<90th percentile).

In their analysis with 68,748 participants (48.4% men) without CHD at baseline, results showed a similar risk estimate for incident CHD for LDL-C and for LDL-C corrected at 30% and 17% (subdistribution hazard ratio (sHR), 2.73 vs. 2.51 vs. 2.64, respectively). Among participants in the high vs. low/moderate Lp(a) group, the sHR was higher for uncorrected LDL-C and incident CHD (4.38 vs. 2.60), while apoB risk estimates were lower in those with high vs. low LP(a) mass (2.43 vs. 3.34).

Over the median 9.72 years of follow-up, 3,536 participants experienced a CHD event, defined as fatal or nonfatal myocardial infarction, coronary death, unstable angina, coronary revascularization or unclassifiable death.

Noting that to their knowledge this is the largest study to date to investigate the impact of concomitant Lp(a) level in this setting, the researchers write that their findings "highlight the need not only of understanding the underlying pathophysiological mechanisms of the role of Lp(a) in LDL-C- or apoB-related risk of future CHD, but also the necessity to establish a more practical solution of how to deal with such complex and variable relationships between these entities."

In an accompanying editorial comment, Sotirios Tsimikas, MD, FACC; Calvin Yang, MD, PhD; and Florian Kronenberg, MD, write that "the need for accurately determining LDL-C, specifically in patients with elevated Lp(a), continues to be an important area to optimize clinical care in an era of therapeutics targeted to specific lipoproteins." They also caution that the study findings should be considered "hypothesis-generating pending future studies that quantitate Lp(a)-C empirically and similar analyses are performed using corrected LDL-C."

Clinical Topics: Dyslipidemia, Advanced Lipid Testing, Lipid Metabolism, Nonstatins

Keywords: Cholesterol, LDL, Coronary Disease, Myocardial Infarction, Lipoprotein(a), Angina, Unstable, Apolipoproteins B