CAP TODAY Pathology/Laboratory Medicine/Laboratory Management
Charna Albert
February 2023—Sex hormones, rather than sex assigned at birth, may be a stronger driver of the observed concentration differences between healthy men and women for biomarkers of cardiac disease, say the authors of a study published in JAMA Cardiology (Greene DN, et al. JAMA Cardiol. 2022;7[11]:1170–1174).
Dr. Greene
The aim of their cross-sectional prospective study was to determine the distribution of high-sensitivity cardiac troponin (hs-cTn) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in healthy transgender people who were prescribed testosterone or estradiol for 12 months or more. Seventy-nine transgender men and 93 transgender women were recruited for the study between late 2017 and mid-2018 from internal medicine and primary care clinics that specialize in transgender medical care.
The study found that concentrations of hs-cTn were higher in transgender men than in transgender women. For Abbott hs-cTnI, the authors report, the median concentration observed in transgender men and women was 0.9 (0.6–1.7) ng/L and 0.6 (0.3–1.0) ng/L, respectively. Results were consistent across two additional hs-cTn assays from Beckman Coulter (hs-cTnI) and Roche (hs-cTnT). The median NT-proBNP concentration was significantly higher in transgender women (49 [32–86] ng/L) than in transgender men (17 [13–27] ng/L).
“Seeing the distribution of relative results in the cohort of transgender men and women be so consistent between the three [troponin] assays was surprising to me,” says study coauthor Dina N. Greene, PhD, D(ABCC), clinical associate professor, University of Washington, and associate laboratory director, LetsGetChecked. These results were particularly unusual for a study measuring low concentrations of cardiac troponin in healthy people, Dr. Greene says, noting that lack of standardization or harmonization of cardiac troponin assays usually has an effect. “That’s not to say the cohorts are perfect and this is the be-all, end-all, but it was an encouraging way for me to feel comfortable presenting the data as it is.”
Study participants were a range of ages, used different methods of hormone administration, and had been on gender-affirming hormone therapy for varying lengths of time (mean of 4.8 years for transgender men and 3.5 for transgender women). “The heart doesn’t remodel as quickly as you might think. That’s a couple years of hormone therapy. But clearly there is cardiac restructuring happening,” she says. The duration needed to show changes in hs-cTn and NT-proBNP concentrations remains unknown, the study says.
Dr. Greene and coauthors note in the study that systematic reviews indicate that the hs-cTn concentration differences observed between the sexes lead to differing 99th percentile upper reference limits, and that some clinical guidelines stress the importance of using sex-specific decision points. Though the study was a pilot only—“these were cardiac healthy people,” Dr. Greene says, “and we weren’t powered strongly enough to have 99th percentiles derived from this study”—the initial data suggest that when sex-specific 99th percentiles are used, the numeric value associated with affirmed gender, rather than sex assigned at birth, may be the appropriate upper reference limit.
These results, she says, highlight the importance of serial troponin measurements. Any patient with an initial measurement below the male-specific 99th percentile but above the female-specific 99th percentile should have a second measurement taken, she says, “but for a transgender man it’s even more important that you get that serial measurement, because you don’t know which 99th percentile is appropriate. Should you have used the female or the male? In transgender people it’s even more important to follow the standards of care for getting a serial troponin measurement when trying to distinguish between acute myocardial infarction and other reasons for chest pain, or other symptoms that often are associated with acute myocardial infarction.”