Physicians' Academy for Cardiovascular Education

CVD risk associated with high Lp(a) reduced at low LDL-c in primary prevention setting

Cardiovascular disease risk associated with elevated lipoprotein(a) attenuates at low low-density lipoprotein cholesterol levels in a primary prevention setting

Literature - Verbeek R, Hoogeveen RM, Langsted A, et al. - Eur Heart J 2018; published online ahead of print

Introduction and methods

Elevated lipoprotein(a) [Lp(a)] is an independent risk factor for CVD and a causal association has been shown in Mendelian randomization studies [1-4]. It has been suggested that elevated Lp(a) predominantly causes CVD together with high levels of LDL-c [5 -6]. However, the question remains whether CVD risk associated with high Lp(a) levels is reduced in individuals with low LDL-c levels.

To test the association of Lp(a) and LDL-c with the risk of CVD incidence and mortality, data of two large prospective cohort studies were used.

Participants in the European Prospective Investigation of Cancer (EPIC)-Norfolk prospective population study enrolled between 1993 and 1997 and participants of the Copenhagen City Heart Study (CCHS) prospective population study examined from 1991 to 1994 and 2001 to 2003 were included in this study.

Those with myocardial infarction, stroke or lipid-lowering therapy at baseline, missing LDL-c or Lp(a) levels, and non-Caucasian individuals were excluded, leaving a study population of 16,654 participants from EPIC-Norfolk and 9448 participants from the CCHS.

Individuals were divided in groups by Lp(a) and LDL-c cut-offs. Low Lp(a) was defined as <80th cohort percentile in both cohorts based on the EAS proposed threshold for Lp(a) [7]. LDL-c was corrected for Lp(a)-derived LDL-c (LDL-ccorr) [8] and groups were created for LDL-ccorr levels <2.5, 2.5-3.49, 3.5-4.49, 4.5-5.49 and ≥5.5 mmol/L.

Atherosclerotic CVD events in this study included coronary heart disease, non-fatal myocardial infarction, and fatal- or non-fatal stroke.

Main results


This study confirmed that Lp(a) and LDL-c are independently associated with CVD risk in a primary prevention setting. The increased CVD risk at high Lp(a) concentrations is reduced at low LDL-c levels, however, no interaction was observed between Lp(a) and LDL-ccorr levels on CVD risk.


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