Sex-Differences in Atherosclerosis

Cardiovascular disease accounts for 51% of deaths in women and 42% in men in Europe. A major underlying cause is atherosclerosis, a chronic condition in which fatty substances such as cholesterol accumulate in the vessel wall over many years, forming plaques. These plaques narrow the arteries and reduce blood flow. If a plaque becomes unstable and disrupts, a blood clot can form and suddenly block the vessel. When this occurs in the heart or brain, it leads to a heart attack or stroke. 

Importantly, atherosclerosis does not affect women and men in the same way. Although cardiovascular disease has long been perceived as a “man’s disease,” it is the leading cause of death in both sexes. Women, however, are more likely to experience missed or delayed diagnoses. This reflects fundamental differences in disease biology, as well as the historical underrepresentation of women in clinical trials and biobank studies. 

Men more often develop focal, rupture-prone plaques associated with accelerated atherosclerosis, whereas women more frequently present with diffuse disease and plaque erosion, a distinct pathological process that can also lead to acute cardiovascular events. Despite its clinical importance, plaque erosion remains poorly understood, limiting our ability to predict and prevent these events in women. 

Our research focuses on uncovering the mechanisms underlying these sex differences in atherosclerosis. By identifying sex-specific plaque characteristics and molecular pathways, we aim to address critical knowledge gaps and enable more accurate diagnosis and prevention strategies. This work is essential to improving outcomes and advancing health equity for both women and men with cardiovascular disease. 

Funded by the 2022 Leducq AtheroGEN consortium