Malene Højgaard Andersen - PhD Scholarship 2023

Project summary:
Low-density lipoprotein cholesterol, coronary artery disease severity and cardiovascular disease events across the age-spectrum

Are untreated LDL-C levels associated with higher risk for future ASCVD events in all age-groups due to more severe CAD on CTA?

Key questions remain regarding LDL-C’s role in CAD and ASCVD events across all ages. We will assess LDL-C’s link to severe CAD and risk for future ASCVD events in 85,000 patients who underwent CTA between 2008 and 2021, collecting data on risk factors, coronary atherosclerosis, and ASCVD events. Additionally, we will perform advanced plaque imaging in 2,000 patients using new software for deeper insights into LDL-C’s association with atherosclerosis development.

Project Title

Low-density lipoprotein cholesterol, coronary artery disease severity and cardiovascular disease events across the age-spectrum: Novel insights from 85,000 individuals undergoing computed tomography angiography from the Western Denmark Heart Registry

Background

LDL cholesterol (LDL-C) is a well-known central driving force for development of atherosclerosis. Yet, important questions remain regarding the role of LDL-C as a risk factor for coronary artery disease (CAD) and atherosclerotic cardiovascular disease (ASCVD) events in all ages, including whether LDL-C is associated with CAD severity, whether on-treatment LDL-C is associated with future ASCVD events and whether the magnitude of changes in LDL-C is associated with future ASCVD events.

Aim

To assess if LDL-C levels are associated with more severe CAD and higher risk for developing future ASCVD events in all ages. Further, to assess the role of on-treatment LDL-C levels and absolute changes in LDL-C levels during statin treatment for future ASCVD events. Further, provide deep insights into the association of LDL-C with CAD severity, by performing advanced coronary plaque analyses to obtain unprecedented information on coronary atherosclerosis phenotypes.

Methods

We include 85.000 patients undergoing CTA between 2008 and 2021 from Western Denmark Heart Registry (WDHR). CTA provides information on the coronary atherosclerosis burden and presence of stenoses. Information on cholesterol values, medication use and development of ASCVD events are collected using Danish Registries.

Further, we will perform advanced plaque imaging in 2000 patients using new imaging software to provide deep insights into the association of LDL-C with atherosclerosis development.

Preliminary results

Preliminary analyses performed January 2023 have shown that untreated LDL cholesterol levels obtained before CTA are strongly associated with coronary artery disease severity as assessed by both presence of coronary calcification, degree of coronary calcification (i.e 90th percentile) and coronary stenoses across all age-groups, including those age 75-95 years. Further, preliminary results show that LDL cholesterol is associated with future myocardial infarction events across the age-spectrum.