Coronary artery disease burden in women poorly explained by traditional risk factors: Sex disaggregated analyses from the BioHEART-CT study

Background and aims: Targeting the modifiable risk factors for coronary artery disease (CAD) has substantial impact at the community level. However, it is not uncommon for individuals to present with atherosclerosis related events without identified risk factors. We examined sex differences in the association of risk factors and atherosclerotic burden assessed by CT coronary angiography (CTCA).

Methods: We analysed clinical and imaging data in 1002 individuals in the BioHEART cohort.

Results: 45% were female, 35% had no CAD identified. Median coronary calcium score was 9.9 Agatston units (IQR: 0-146), and median Gensini Score was 3.5 (IQR: 0-11.5). 26% had a calcified plaque predominant phenotype, and 18% had a non-calcified plaque predominant phenotype. There were no sex differences in the prevalence of risk factors. However, there were notable sex differences in the adjusted associations of risk factors with CAD. Age and hypercholesterolaemia (OR 1.56, 95% CI 1.03-2.36, p = 0.04 in males, and OR 1.75, 95% CI 1.09-2.78, p = 0.02 in females) were associated with the presence of CAD in both genders (p < 0.05). Diabetes and smoking were associated with presence of CAD, calcified CAD, and non-calcified plaque in males (p < 0.05) but not females. In women, none of the standard modifiable risk factors were associated with the amount of plaque present when adjusted for age, BMI, and family history of premature CAD.

Conclusions: CTCA provides an important opportunity for improving the stratification of cohorts to assess underlying biology and risk. We demonstrate sex-specific differences in associations of risk factors with atherosclerosis burden.