Abstract
Cardiovascular disease (CVD) accounts for over $300 billion in direct healthcare costs and is expected to rise over time, worsening the economic burden. To close the gap in CVD outcomes between men and women, sex-specific study designs and druggable targets are essential. Sex differences driven by sex hormones are well established in CVD, particularly the cardioprotective effects of testosterone in men and estradiol in women; however, the role of sex chromosomes, particularly X-linked genes, is not yet fully understood. Sexual dimorphism in CVD shows that women are protected compared to men, which diminishes with age. The low awareness and understanding of CVD risk in women contribute to delays in treatment. Oxidative stress is a key player in CVD. In this review, we briefly introduce reactive oxygen species (ROS) and sex chromosomes. Next, we examine X-linked escapee genes, which provide a unique perspective on sex differences in biology. Thereafter, we discuss the role of oxidative stress in CVD and risk factors, including hypertension and atherosclerosis, identify knowledge gaps, and potential research opportunities to address CVD disparity among women. In closing, we highlight the clinical trial outcomes in CVD and antioxidant treatments.