Exploring Cardiovascular Risk in Transgender Patients

Transgender individuals face numerous health disparities compared to the general population, including elevated rates of HIV, mental illness, and substance use disorder.¹ Additionally, various research findings have demonstrated an increased risk for cardiovascular disease (CVD) among transgender patients, although results have been mixed across studies.

In a retrospective single-center study published in September 2021 in the American Journal of Preventive Cardiology, Mahowald et al examined CVD prevalence rates and associated comorbidities in transgender women referred to a women’s heart clinic for management of CVD or cardiac risk factors or for preoperative risk assessment in preparation for gender-affirming surgery.² Of the 52 patients (aged mean, 57±10 years) comprising the sample, 92% were receiving gender-affirming hormone therapy.

The pooled cohort equation demonstrated that the 10-year risk for atherosclerotic CVD was 9.4±7.7% when using a risk calculation for cisgender men, compared with 5.2±5.1% when using a risk calculation for cisgender women (P <.001).

“Older transgender women may have an underestimated prevalence of CVD and its risk factors,” the authors wrote.² “More research is needed to identify cardiovascular health profiles, improve practice consistency, and establish normative values for transgender patients.”

In a 2019 study using data from the Behavioral Risk Factor Surveillance System (BRFSS), Caseres et al found higher rates of any CVD condition (adjusted odd ratio [AOR], 2.98; 95% CI, 1.65-3.06) as well as diabetes (AOR, 1.45; 95% CI, 1.05-1.99), angina and coronary heart disease (AOR, 1.90; 95% CI, 1.34-2.68), stroke (AOR, 1.88; 95% CI, 1.16-3.03), and myocardial infarction (AOR, 2.98; 95% CI, 2.14-4.17) among transgender women compared with cisgender women.³

The results further showed higher rates of myocardial infarction among gender nonconforming individuals compared to cisgender women (AOR, 2.68; 95% CI, 1.14-6.30). Comparisons between transgender women and transgender men yielded no differences in CVD rates.³

In another 2019 study that used BRFSS data, the rate of myocardial infarction was substantially higher in transgender men compared with cisgender men (OR, 2.53; 95% CI, 1.14–5.63; P =.02) and cisgender women (OR, 4.90; 95% CI, 2.21–10.90; P <.01), after adjustment for CVD risk factors such as age, presence of hypertension, exercise, and smoking.⁴ Among transgender women, the rate of myocardial infarction was higher compared to cisgender women (OR, 2.56; 95% CI, 1.78–3.68; P <.01) but not in comparison to cisgender men.⁴

Research published in August 2021 in Transgender Health also used data from the BRFSS to investigate the odds of CVD among transgender individuals compared with cisgender individuals.⁵ Analyses revealed that the odds of CVD were 2.66 times greater (95% CI, 1.60–4.41) among participants assigned female at birth (AFAB) who identify as transgender vs cisgender, while no significant difference in the odds of CVD was noted between transgender vs cisgender participants among those assigned male at birth (AMAB).

In a comparison between gender nonconforming and cisgender participants, the odds of CVD were 2.21 times higher (95% CI, 1.04–4.70) among the gender nonconforming individuals.⁵

Noting a possible link between estrogen-based hormone therapy and CVD in transgender individuals, Getahun et al explored this association in a 2018 cohort study based on electronic medical records of 2,842 transgender women and 2,118 transgender men matched to 48,686 cisgender men and 48,775 cisgender women, respectively.⁶ The results showed a higher incidence of venous thromboembolism (VTE) among transgender women, with more pronounced differences found among those who initiated hormone therapy during the follow-up period.

The differences in VTE risk at 2 and 8 years were 4.1 (95% CI, 1.6-6.7) and 16.7 (95% CI, 6.4-27.5) per 1000 persons compared with cisgender men, and 3.4 (95% CI, 1.1-5.6) and 13.7 (95% CI, 4.1-22.7) compared with cisgender women. There was insufficient evidence to draw conclusions regarding comparative VTE risk among transgender men.⁶

A systematic review published in 2021 in the Journal of Sex Medicine reported a greater incidence of VTE in AMAB patients compared with AFAB patients (42.8 vs 10.8 VTE per 10,000 patient years; P =.02) and a “similar or higher” incidence in AMAB patients compared with cisgender women on hormone replacement therapy.⁷

The key question regarding these findings is, “How important is the impact of exogenous estrogen on VTE risk?” according to study co-author Dr Joshua D. Safer, MD, FACP, FACE, executive director of the Mount Sinai Center for Transgender Medicine and Surgery and professor of medicine at the Icahn School of Medicine at Mount Sinai in New York, and co-author of the 2018 study and other articles on the topic.^6,1,8 “It may be that standard approaches to otherwise high-risk patients – like deep vein thrombosis prophylaxis in surgery – essentially erase the very modest increased risk of VTE suggested in cross-sectional studies.”

The higher body weight and lower frequency of exercise observed in transgender populations may further contribute to an elevated CVD risk, he noted.⁹ Such factors may be attributable to the discomfort these individuals experience in a hostile environment such as the typical fitness center. “It may be that the stigma and discrimination experienced by transgender people are the greatest concerns for CV health, contributing to decreased exercise, more obesity, and delayed medical care,” Dr Safer said.

In addition, psychosocial stressors related to other forms of structural violence including reduced access to affordable housing and health care may contribute to excess CVD and associated mortality in this population, as described in a scientific statement published in 2021 by the American Heart Association.⁹

“At the population level, the largest benefit for transgender people may be to remove stigma in order to better integrate them in exercise programs and athletics and appropriate health care,” Dr Safer stated. On the clinician level, “Physician and medical staff education is important to create safe spaces for transgender people to receive timely care.” These efforts may include the use of medical forms with inclusive language such as questions about the patient’s current gender identity as well as their gender assigned at birth if this information is needed, and use of the term “relationship status” rather than “marital status,” for example.¹⁰

For clinicians who are unsure of how to address the increased CV risk observed among transgender patients, “A major point is not to rush to overemphasize the likely small – if any – contribution from exogenous hormone treatment and to approach transgender people like anyone else,” Dr Safer advises.

References

1. Safer JD, Coleman E, Feldman J, et al. Barriers to healthcare for transgender individuals. Curr Opin Endocrinol Diabetes Obes. 2016;23(2):168-71. doi:10.1097/MED.0000000000000227
2. Mahowald MK, Maheshwari AK, Lara-Breitinger KM, et al. Characteristics of transgender women referred to women’s heart clinic. Am J Prev Cardiol. Published online July 10, 2021. doi: 10.1016/j.ajpc.2021.100223.
3. Caceres BA, Jackman KB, Edmondson D, Bockting WO. Assessing gender identity differences in cardiovascular disease in US adults: an analysis of data from the 2014-2017 BRFSS. J Behav Med. 2020;43(2):329-338. doi:10.1007/s10865-019-00102-8
4. Alzahrani T, Nguyen T, Ryan A, et al. Cardiovascular disease risk factors and myocardial infarction in the transgender population. Circ Cardiovasc Qual Outcomes. Published online April 5, 2019. doi:10.1161/CIRCOUTCOMES.119.005597
5. Howerton I, Harris JK. Transgender identity and cardiovascular disease. Transgender Health. Published online 19, 2021. doi:10.1089/trgh.2020.0188
6. Getahun D, Nash R, Flanders WD, et al. Cross-sex hormones and acute cardiovascular events in transgender persons: A cohort study. Ann Intern Med. Published online August 21, 2018. doi:10.7326/M17-2785
7. Kotamarti VS, Greige N, Heiman AJ, Patel A, Ricci JA. Risk for venous thromboembolism in transgender patients undergoing cross-sex hormone treatment: A systematic review. J Sex Med. Published online June 14, 2021. doi:10.1016/j.jsxm.2021.04.006
8. Slack DJ, Safer JD. Cardiovascular health maintenance in aging individuals: The implications for transgender men and women on hormone therapy. Endocr Pract. Published online December 12, 2021. doi:10.1016/j.eprac.2020.11.001
9. Streed CG Jr, Beach LB, Caceres BA, et al; American Heart Association Council on Peripheral Vascular Disease; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular and Stroke Nursing; Council on Cardiovascular Radiology and Intervention; Council on Hypertension; and Stroke Council. Assessing and addressing cardiovascular health in people who are transgender and gender diverse: A Scientific statement from the American Heart Association Circulation. Published online July 8, 2021. doi:10.1161/CIR.0000000000001003
10. Schultz G. Making medical forms and doctor visits more inclusive: Creating safe appointments for transgender, nonbinary, and gender diverse individuals. INvisible Project. Accessed online July 1, 2022.

This article originally appeared on The Cardiology Advisor