Genetic ancestry impacts atherosclerotic plaques

The study summary

Genetically determined ancestry correlates with specific plaque morphological and molecular features

Cardiovascular disease (CVD), mainly driven by atherosclerosis, is correlated to a plethora of factors: age, sex, diabetes, smoking, hypertension, genetics, socio-economic status. Yet these alone can’t fully explain why ethnic disparities in CVD exist. For example, coronary artery calcification, a marker of atherosclerosis, is more prevalent in individuals of European descent despite occurring universally with age.

To better understand these disparities, we turned to genetic ancestry - a more precise indicator than self-reported ethnicity. Using data from the Athero-Express Biobank Study, a Dutch cohort with details atherosclerotic plaque analyses from nearly 2,000 patients, we identified two ancestry groups: European (1,866 patients) and non-European (51 patients), reflecting the Nethderlands’ diverse population and migratory history.

Our findings showed that non-European ancestry correlates with increased plaque vulnerability, meaning plaques were more prone to rupture and cause cardiovascular events (OR=1.67, p=0.045). Gene expression analyses highlighted specific genes, like NLGN4X and SERPINF1, related to inflammation and vascular health. Pathway analyses further confirmed a heightened inflammatory signature in plaques from non-European individuals.

These results emphasize that genetic ancestry matters in the biology of atherosclerosis. Including more diverse populations in cardiovascular research is vital to uncover differences in disease mechanisms and develop personalized, equitable therapies.