WHEP Scholar Priya Ramachandrula
Drexel University College of Medicine, Class of 2021
Coronary artery disease (CAD) is the leading cause of death worldwide and as a result has garnered much attention in the form of research, clinical care and pharmaceutical trials. However, amidst all of this research lie several misconceptions and disparities in understanding the disease’s differences in men and women. For quite some time, sex and its role in coronary artery disease was not explored and was often clouded by the misconception that CAD affected males more than females. For the duration of this paper, sex is defined as the assigned sex at birth. There seem to be many contributors to this misunderstanding that females are not affected as much by CAD. Research in this field has uncovered sex-based differences in the risk factors, clinical presentation, pathogenesis, and the clinical outcomes and treatment of CAD. But this data has also revealed gaps in our understanding of these sex-based differences and current management of CAD.
With regard to risk factors, research reveals factors common to both women and men like smoking, hypercholesterolemia, and diabetes, which were found to increase the risk of developing CAD more in women than men. Furthermore, female-specific factors like menopausal status and hypertension related to pregnancy were also found to impact the risk of CAD. These are not risk factors that are taken into account in standardized risk calculators such as the ASCVD. Studies have demonstrated that sex-based differences may be overshadowed by the limitations and large overestimations of the ASCVD. As a result, a complete history and evaluation of risk factors become increasingly important in the evaluation of a patient at risk for CAD. Also, an understanding of why these risk factors played a greater role in women regarding the development of CAD needs to be further explored.
The pathogenesis of CAD is also suggested to be different by sex. These differences have been limited as studies exploring the pathogenesis have been conducted in largely male populations. Research suggests that these differences in pathogenesis are largely driven by estrogen. The clinical presentation of CAD in women is also characterized by atypical symptoms including abdominal pain and vague fatigue, leading to under-recognition and delayed treatment. These differences in pathogenesis and clinical presentation reveal that our understanding of CAD still has many gaps with respect to sex.
Finally, treatment outcomes are also different for women when compared to men. Women with CAD seem to be treated less aggressively than men with a smaller proportion recommended to undergo invasive procedures like CABG. There are several contributing factors for this. One challenge in our limitation of this understanding has to do with the limited landscape of available trial data representing women. Till 2006, trials funded by the NHLBI had only a 38% representation of women. Additionally, studies have revealed that implicit bias may play a role in the increased rates of conservative medical management of women with CAD. Retrospective studies and surveys have shown increased conservative management for women. Physicians reported rationale for these decisions was due to atypical presentations and studies that demonstrated higher dosing errors in antithrombin and antiplatelet therapy in women. This finding opens an interesting question regarding the role of implicit bias in CAD therapy in women versus men.
Ultimately, the data shows that sex-based differences exist in all aspects of CAD from pathogenesis to treatment exist. Now more than ever, in a world of data-driven medicine, we are exploring the effects of these differences on the outcomes and our physiological understanding of CAD. With cardiac disease being the leading cause of death in women, incorporating these differences into medical management and further exploring their impact in clinical trials become the imperative next step in beginning to advance the medical treatment of CAD.