Physicians' Academy for Cardiovascular Education
Combining a polygenic score with lifetime exposure to LDL-c and BP more accurately predicts lifetime CV risk

Combining a polygenic score with lifetime exposure to LDL-c and BP more accurately predicts lifetime CV risk

News - Mar. 29, 2020

Integrating The Effect Of Polygenic Scores, Low Density Lipoproteins And Systolic Blood Pressure On The Lifetime Risk Of Cardiovascular Disease

Presented at ACC.20 by Brian A Ference (Cambridge, UK)

Introduction and methods

There is a great interest in polygenic scores (PGS) to predict CVD. However, recent studies suggest that adding PGS to short term risk estimation equation may not provide meaningful information. PGS have may potential clinical value in that they predict lifetime risk early in life, before the onset of disease and identify persons with high lifetime CV risk, who will benefit from early intervention. Recent evidence suggest that effects of high LDL-c levels and blood pressure (BP) accumulate over time. Use of PGS may identify those with high lifetime CV risk and these high-risk patients may benefit from early intervention by minimizing lifetime exposure to high LDL-c and BP. This personalized strategy of screening and treatment decisions could have an important clinical impact.

This study examined lifetime CV risk at all levels of a PGS for coronary artery disease (CAD) depending on difference in lifetime exposure to LDL-c and systolic BP (SBP) using Mendelian randomization in order to make inferences about how a PGS for CAD can be combined with information on LDL-c and SBP. 445,566 Participants in the UK Biobank were enrolled in this study (54% female, mean age: 57.2 years). Primary outcome was major coronary events, a composite of first occurrence of fatal or non-fatal myocardial infarction or coronary vascularization. Using all participants in the UK Biobank, a polygenic score with 4,051,820 variants was deconstructed into an LDL score and an SBP score from Mendelian randomization, and a residual PGS representing all other pathways (variants significantly associated with LDL-c or SBP were excluded from constructing PGS).

Main results


Combining PGS for CAD with information on lifetime exposure to LDL-c and SBP more accurately estimates lifetime risk of CVD, more accurately identifies subjects who benefit from early intervention, and better estimates potential benefit from early interventions. This strategy may help in personalizing CV risk and prevention.

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