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Sex and (the) CAD

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Dr. Tara Sedlak and team

Heart disease and stroke is a leading cause of death for women in Canada; however, two-thirds of all research focuses on men. This lack of research can lead to underdiagnosis and, subsequently, undertreatment. At CHÉOS, a number of scientists are working to close this gap, including Dr. Tara Sedlak, one of only a few Women’s Heart Health Cardiologists in Canada.

Dr. Sedlak is a cardiology expert who practices across Vancouver. In addition to being a Scientist at CHÉOS, she is also a Clinical Associate Professor of the Division of Cardiology at UBC, Cardiologist at Vancouver General and BC Women’s Hospitals, and Director of the Leslie Diamond Women’s Heart Health Clinic.

In addition to her clinic work, Dr. Sedlak is conducting important research analyzing the sex differences in coronary artery disease (CAD) and the usefulness of the risk predicting calculators currently available.

Case study

Let’s begin by looking at two cases. John is a 75-year-old male who has a history of hypertension and dyslipidemia. He takes Ramipril and Crestor and has noticed exertional typical chest pain for 6 months. Sarah is a 75-year-old female who has identical health issues, takes the same medications, and experiences the same chest pain for the same duration. While these brief histories are identical, the risk calculators used (Diamond Forrester and CAD2) showed that CAD was more likely the cause of the John’s chest pain than Sarah’s, highlighting that sex appears to impact the accuracy of these calculators.

Sex-specific differences in CAD

A number of factors can increase the risk of CAD in females compared to males, including pregnancy events like gestational diabetes, pre-eclampsia, and maternal placenta syndromes, and hormonal influences like premature menopause, PCOS, and HRT. Diabetes, smoking, and psychosocial stress are also deemed more important risk factors for CAD in females than in males.

Sex doesn’t just affect the risk of CAD. Females may also describe chest pain differently; rather than the typical ‘elephant on the chest’ or gripping pain, they may experience more tightness in the chest, radiation to the jaw, dizziness, etc. The etiology of chest pain may also vary; for example, instead of large blood vessel disease, they could have small blood vessel disease.

Finally, CAD testing accuracy differs between males and females; for example, stress testing is less accurate in females. This is important as, in addition to being a health burden to the individual, CAD has a huge financial cost to Canada’s health care system, as testing can be expensive.

CAD risk prediction

Dr. Sedlak presents her research in front of a full house at a CHÉOS WiP Seminar

Currently, three main risk prediction models can be used to determine the likelihood of chest pain being caused by CAD: Diamond Forrester, Confirm Risk Score (CRS), and CAD2 score. Of these, Diamond Forrester is usually recommended in guidelines and textbooks. However, following a systematic review, Dr. Sedlak and her team highlighted that, while Diamond Forrester works reasonably well in males, it is inaccurate in females. The newer risk scores, CRS and CAD2, include more elements than Diamond Forrester and, while the review deemed these tools as better, they still carry a relatively low predictive value in females.

Now, Dr. Sedlak hopes to create a fourth, more accurate risk assessment tool.

Pilot study

The first step in creating a new risk assessment tool was the conduct of a pilot study.

Using the available literature, Dr. Sedlak and her team created a comprehensive checklist of the elements they thought would be useful predictors for both males and females. As all previous studies in the field were retrospective, the team decided to conduct this study prospectively, meaning the causes of the participants’ chest pain were still unknown. This allowed them to follow up with the participants and find out their diagnosis, subsequently helping them identify which candidate elements were associated with CAD for each sex and develop a predictive model.

Although the numbers were small (183 participants), the results of this study helped the team begin to understand which of differences the participants were asked about were potentially predictive of CAD.

The future

With promising results from her pilot study, Dr. Sedlak has submitted a grant proposal for a larger prospective study. The main objective of this study is to continue her work developing an improved algorithm for the prediction of obstructive CAD for both males and females using information available from a routine office visit.

If successful, the resulting sex-specific algorithm could be published for clinical use, allowing more accurate detection of underlying CAD. This has the potential to benefit both males and females, and reduce the overall costs associated with CAD.

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