Study highlights need for increased awareness of cardiovascular risk in transgender women
Transgender women have modified profiles of biomarkers that correlate with with systemic inflammation and cardiovascular disease that are seemingly affected by feminizing hormonal therapy and HIV, according to findings from CROI.
“I initially had the idea for this study while working at the University of California, Los Angeles, and caring for transgender women there,” Jordan E. Lake, MD, MSc, associate professor in the division of infectious diseases, director of the HIV medicine fellowship and co-director of the South American Program in HIV/STI Prevention Research at UT Health/McGovern Medical School, told Healio. “Several transgender women I knew had major cardiovascular events at young ages. I began looking into the literature and realized this area was underresearched as a whole; almost no data existed, specifically on transgender women living with HIV.”
Lake and colleagues assessed transgender women who were enrolled in the study from community-based organizations and clinics in Los Angeles and Houston. Patients were frequency matched to cisgender male controls in the Multicenter AIDS Cohort Study according to age, race, substance use and ART type. Serum biomarker concentrations were evaluated using enzyme-linked immunosorbent assays. Multivariable linear regression analyses were used to evaluate factors that correlated with log10-transformed biomarker concentrations.
The study included 122 transgender women, 75 of whom were HIV-positive, and 80 cisgender men, 40 of whom were HIV-positive. Transgender women had a mean age of 43 years, while the mean age of cisgender men was 45 years. Almost all participants in both groups – 90% of transgender women and 91% of cisgender men – were non-Hispanic black, Hispanic or multiracial. The median CD4+ count among people with HIV was 609 cells/uL. Nearly three-quarters of transgender women (67%) were on feminizing hormonal therapy (FHT), including 68% of those with HIV and 66% of those without HIV.
According to Lake, the study showed that, compared with matched, cisgender men, “transgender women have altered profiles of biomarkers associated with systemic inflammation and cardiovascular disease that seem to be influenced by both FHT and HIV, even after adjusting for key risk factors.”
Among people with HIV, extracellular newly identified receptor for advanced glycation end-products (ENRAGE), oxidized LDL (oxLDL) and soluble tumor necrosis factor receptor type (sTNFRI) concentrations were higher, and von Willebrand factor (vWF) and endothelin-1 were lower, moving from cisgender men to transgender women not on FHT (n = 24) to transgender women on FHT (n = 51). For those without HIV, ENRAGE, oxLDL and plasminogen activator inhibitor-1 (PAI-1) were higher moving from cisgender men to transgender women not on FHT (n = 16) to transgender women on FHT (n =31).
Additionally, in a multivariate analysis limited to persons with undetectable HIV-1 RNA that adjusted for HIV serostatus, gender, age, race/ethnicity, BMI and smoking, being a transwoman (but not HIV status) correlated with higher EN-RAGE, interleukin-6, interleukin-8, P selectin, PAI-1, oxLDL and sTNFRI/II concentrations and lower vWF, whereas both being a transgender woman and a person with HIV correlated with lower endothelin -1.
While it is know that estradiol can decrease the levels of some ART, with no known impact on ART efficacy, it is not clear whether ART affects hormone efficacy or if these relationships are altered at very high hormone doses, Lake told Healio.
“The take-home message is to have heightened awareness of cardiovascular risk in transgender women, especially those living with HIV and taking FHT,” she concluded. “Right now, we do not fully understand the ramifications of the findings, or how HIV and FHT interact to affect cardiovascular risk, but practitioners can work to minimize modifiable cardiovascular risk factors in their patients.” – by Caitlyn Stulpin
Lake JE, et al. Abstract 645. Presented at: Conference on Retroviruses and Opportunistic Infections; March 8-11, 2020; Boston.
Disclosure: Lake reports receiving a research grant from Gilead Sciences.