Cardiovascular disease (CVD) remains the leading cause of death worldwide and prevention of key modifiable CVD risk factors such as smoking are still a global public health priority. Striking sex differences in CVD risk exist throughout life but the aetiology of these differences is not well understood. In adults, modifiable risk factors have different associations with CVD risk in females and males. For example, smoking is a stronger risk factor for CVD in females compared with males. Whether these differences are due to true sex differences in the causal effects of risk factors because of biology or arise due to biases in research is not understood. In addition, there is limited study of the contribution of modifiable risk factors through childhood and adolescence (when many risk factors start) to CVD risk in females and males. The study of the sex-specific aetiology of CVD risk is an exciting and growing area of research, that offers opportunities for more effective CVD prevention efforts. Using sophisticated life course and causal inference epidemiology in world-renowned cohort studies, I will improve understanding of the sex-specific aetiology of CVD across the life course. I will use different methods for causal inference to better understand the strength of the causal effects of modifiable risk factors in each sex. From childhood, I will study the contribution of life course trajectories of risk factors to sex-specific CVD risk, informing the timing of prevention in each sex. I will also identify mediators of modifiable risk factors and CVD risk to gain a greater understanding of the specific steps linking cause and effect in females and males. Taken together, the findings of this work will provide new opportunities to inform sex-and life stage-specific prevention of established CVD risk factors which still drive the majority of contemporary CVD burden.
