Rationale, Design, and Methodological Aspects of the BUDAPEST-GLOBAL Study (Burden of Atherosclerotic Plaques Study in Twins-Genetic Loci and the Burden of Atherosclerotic Lesions)

Abstract

The heritability of coronary atherosclerotic plaque burden, coronary geometry, and phenotypes associated with increased cardiometabolic risk are largely unknown. The primary aim of the Burden of Atherosclerotic Plaques Study in Twins-Genetic Loci and the Burden of Atherosclerotic Lesions (BUDAPEST-GLOBAL) study is to evaluate the influence of genetic and environmental factors on the burden of coronary artery disease. By design this is a prospective, single-center, classical twin study. In total, 202 twins (61 monozygotic pairs, 40 dizygotic same-sex pairs) were enrolled from the Hungarian Twin Registry database. All twins underwent non-contrast-enhanced computed tomography (CT) for the detection and quantification of coronary artery calcium and for the measurement of epicardial fat volumes. In addition, a single non-contrast-enhanced image slice was acquired at the level of L3-L4 to assess abdominal fat distribution. Coronary CT angiography was used for the detection and quantification of plaque, stenosis, and overall coronary artery disease burden. For the primary analysis, we will assess the presence and volume of atherosclerotic plaques. Furthermore, the 3-dimensional coronary geometry will be assessed based on the coronary CT angiography datasets. Additional phenotypic analyses will include per-patient epicardial and abdominal fat quantity measurements. Measurements obtained from monozygotic and dizygotic twin pairs will be compared to evaluate the genetic or environmental effects of the given phenotype. The BUDAPEST-GLOBAL study provides a unique framework to shed some light on the genetic and environmental influences of cardiometabolic disorders.

Figure 1

Coronary CTA images of a 58‐year‐old female monozygotic twin pair. Volume rendered reformations of the heart (A, D) of twin A and twin B, respectively. Curved multiplanar reconstructions (B, E). The blue arrows indicate coronary atherosclerotic plaques. The graphs on (C) and (F) illustrate the areas of different plaque components of twin A and twin B, respectively. The lipid‐rich (low‐CT attenuation) plaque components are shown in red. Fibro‐fatty tissue is shown in light green. Fibrous tissue is shown in dark green. Calcium is shown in white. The blue arrows indicate the corresponding plaques to panels B and E, whereas the green arrows indicate plaques that are not visible on panels B and E due to the viewing direction on the vessel. Abbreviations: CT, computed tomography; CTA, computed tomography angiography; LAD, left anterior descending artery.

Figure 2

Coronary centerlines (A, B) of a monozygotic 46‐year‐old female twin pair. The distance between the superimposed coronary trees is indicated by the red cords on (C). Abbreviations: LAD, left anterior descending artery; LCx, left circumflex coronary artery; RCA, right coronary artery.

Figure 3

Volume rendered non–contrast‐enhanced native CT images of the chest of a 67‐year‐old male monozygotic twin pair (A, B). The yellow volume represents the epicardial adipose tissue compartment. The panels C and D are axial CT images of the same twin pair. The blue areas represent the epicardial adipose tissue compartments. Abbreviations: CT, computed tomography.