High-risk coronary artery plaque in asymptomatic patients with type 2 diabetes mellitus: Assessment using serial coronary computed tomography angiography and relation to triglycerides and glucagon-like peptide 1 receptor agonists

Laurits Heinsen

Research output: ThesisPh.D. thesis


This PhD thesis is based on three original manuscripts, and the studies were carried out at the Cardiovascular Research Unit at OUH Svendborg.

Ischemic heart disease remains the leading cause of mortality in type 2 diabetes mellitus (T2D). Despite a significant risk reduction in the last decades, T2D remains associated with twice the risk of all-cause mortality, mainly due to coronary artery disease (CAD). Coronary computed tomography angiography(CCTA) allows the characterization of coronary artery plaque and disease progression, and several studies have demonstrated that high-risk plaque (HRP) is associated with acute coronary syndrome (ACS). Risk stratification of asymptomatic diabetes is challenging and a better understanding of the extent and progression of coronary atherosclerosis in relation to patient characteristics and risk factors is of interest. The overall aim of this PhD study was to assess plaque characteristics and predictions of plaque progression in a cohort of asymptomatic patients with diabetes without CAD. 

Study objective:
1) To assess the prevalence of HRP in asymptomatic T2D and the relationship between HRP and cardiovascular disease (CVD) risk factors, diabetes profile, and the coronary artery calcium score(CACS).
2) To assess the association of changes in lipoproteins and glycated hemoglobin (HbA1c) in relation to changes in HRP volumes.
3) To assess changes in the total atheroma (TAV) and composition from baseline to follow-up stratified by liraglutide treatment

This PhD thesis is based on data from a prospective observational study performed between March 2016and September 2017 at Odense University Hospital Svendborg. Patients were asymptomatic and without a history of CAD. Serial CCTA was performed to assess total atheroma volume (TAV) and plaque composition at baseline and one-year follow-up. In addition, CACS was assessed from non-enhanced images. A clinical assessment including blood pressure, electrocardiogram, current medication, diabetic complications, and blood test was performed at baseline and at follow-up. 

The main findings of this PhD thesis were:
1) HRP was identified in 37% of patients and was associated with higher HbA1c, greater tobacco exposure, and male gender. HRP was detected in all groups of CACS, and the absence of coronary artery calcium (CACS = 0) could not rule out HRP.
2) An increase in triglycerides was associated with the progression of HRP as well as an overall plaque progression. Changes in triglycerides were closely associated with weight gain, stagnant HbA1c, and evidence of increased hepatic fat accumulation. Furthermore, there was a strong association between the increase in triglyceride and the increase in remnant cholesterol.
3) We found no association between changes in TAV and liraglutide treatment. The secondary endpoint, changes in plaque composition stratified by liraglutide treatment was positive, and a significant increase in the fibrous plaque volume was detected in the liraglutide treated patients.

In conclusion, CCTA is a non-invasive examination that allows the characterization of plaque composition and changes over time. HRP was detected in 37% of the patients and was associated with higher HbA1c,tobacco exposure, and male gender. Our results warrant caution for use of calcium scoring in this patient group as the absence of coronary artery calcium could not rule out CAD. We found a significant association between an increase in triglyceride levels and HRP progression. The data suggested that this finding was mediated by an increase in remnant cholesterol driven by a worsening in glucometabolic control. Finally, liraglutide was associated with an increase in fibrous plaque which could indicate plaque stabilization. To the best of our knowledge, this study is the first study to assess the association between liraglutide treatment and coronary atherosclerosis in humans.
Original languageEnglish
Awarding Institution
  • University of Southern Denmark
  • Egstrup, Kenneth, Principal supervisor
  • Lambrechtsen, Jess, Co-supervisor
  • Auscher, Søren, Co-supervisor
Date of defence23. Jun 2022
Publication statusPublished - 30. May 2022

Note re. dissertation

Print copy of the thesis is restricted to reference use in the Library.


Dive into the research topics of 'High-risk coronary artery plaque in asymptomatic patients with type 2 diabetes mellitus: Assessment using serial coronary computed tomography angiography and relation to triglycerides and glucagon-like peptide 1 receptor agonists'. Together they form a unique fingerprint.

Cite this