Physicians' Academy for Cardiovascular Education

How much LDL-c lowering is needed to overcome the increased ASCVD risk caused by high Lp(a)?

News - May 25, 2022

Estimating the magnitude of LDL-c reduction needed to overcome the increased risk of atherosclerotic cardiovascular events caused by Lp(a) – to guide clinical management

Presented at EAS 2022 by Brian Ference (Cambridge, UK)

Introduction and methods

Unfortunately, diet and exercise do not reduce Lp(a) levels, and there is no effective therapy to reduce Lp(a) at the moment. Therefore, guidelines recommend intensive risk factor modification among individuals with increased risk due to elevated Lp(a) levels. But this guidance is not specific enough, resulting in clinical inertia on measuring Lp(a) levels among clinicians.

Aim of the study

The primary objective was to quantify the amount of LDL-c lowering needed to overcome the increased risk caused by Lp(a) – depending on the age at which LDL-c lowering is initiated. The secondary objective was to provide clinical guidance about how elevated Lp(a) levels can be used to guide individual treatment decisions to reduce the risk of ASCVD events until potent Lp(a) lowering therapies will become available.


The study was designed as a naturally randomized trial of 445,765 participants that were enrolled in the UK Biobank. Each individual was naturally randomized to either average Lp(a), higher Lp(a), or both higher Lp(a) and lower LDL using genetic instruments.

Primary outcome

The primary outcome was lifetime risk of major coronary events (MCE – first occurrence of fatal or nonfatal MI or coronary revascularization) from 30-80 years.

Main results


In this study, the quantification of additional LDL-c lowering that is needed to overcome the increased ASCVD risk caused by elevated Lp(a) levels was demonstrated. This provides a clear and directly actionable clinical guidance for how to use Lp(a) to individualize the prevention of ASCVD. The intensity of additional LDL-c lowering depends both on a individual’s absolute Lp(a) level and the age at which LDL-c lowering is started.

– Our coverage of EAS 2022 is based on the information provided during the congress –

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