Abstract
We sought to characterize the cardiovascular disease (CVD) risk factor profile of transgender women with HIV identified through a U.S. healthcare database. Compared with age- and race-matched cisgender men with HIV, transgender women with HIV had an increased prevalence of anemia and lower absolute hemoglobin levels. HIV control was sub-optimal and prevalence of HCV co-infection was high among transgender women. Further study of non-traditional CVD risk factors/immune activation among transgender women with HIV is warranted.
Keywords: HIV, transgender, women, cardiovascular disease risk
RESEARCH LETTER
Nearly a third of transgender women in the U.S. test positive for HIV infection, according to a meta-analysis from the Centers of Disease Control.1 U.S. epidemiologic studies suggest HIV infection confers a heightened risk of myocardial infarction (MI)2 and heart failure (HF).3 Parameters influencing increased cardiovascular disease (CVD) risk among people living with HIV (PLHIV) include traditional and non-traditional risk factors,4 as well as preventive care delivery patterns.5 In parallel, observational studies conducted among broad groups of transgender women (HIV serostatus not reported) signal increased CVD risk in this population.6,7 CVD risk research among transgender women has primarily focused on metabolic effects of gender-affirming hormonal therapies. No prior studies have systematically examined CVD risk factors among transgender women with HIV in the U.S.
We sought to characterize the CVD risk factor profile of transgender women with HIV identified through the Partners HIV Cohort - an observational virtual cohort of PLHIV receiving care through the Partners Healthcare System (PHS) in Boston, Massachusetts and diagnosed with HIV through November 2013 (n=5502). Partners HIV Cohort data elements derive from the PHS Research Patient Data Registry, which features complete PHS clinical information.8 As part of this study, transgender women in the Partners HIV Cohort were identified through electronic data mining employing the search terms “transgender,” “transsexual,” and “gender dysphoria”. Next, a control group from within the Partners HIV Cohort was developed matched to the group of transgender women on sex-at-birth, age/birth year, and race (4:1 ratio; transgender women n=23; cisgender men n=92). Cisgender men were selected as the comparator group to address the following question: For PLHIV with male sex at birth, how does gender identification influence parameters relevant to CVD risk? Electronic medical records were manually reviewed to confirm HIV status and gender identity, and to ascertain the most recent available data on traditional and non-traditional CVD risk factors. Normally distributed data are presented as mean ± standard deviation (SD) and non-normally distributed data are presented as median, interquartile range (IQR). Comparisons of CVD risk parameters between transgender women and cisgender men with HIV were made using the chi-square test, the Student’s two-tailed t-test, or the Wilcoxon test, as appropriate. JMP Pro software (version 12.0, SAS Institute, Cary, North Carolina, U.S.A) was used for analyses, with statistical significance set at P ≤ 0.05.
The CVD risk factor profiles of transgender women with HIV and age- and race-matched cisgender men with HIV are presented in Table 1. Median age in both groups was 51 years. Within each group, approximately half identified as Black/African-American while nearly one fifth identified as Hispanic. Among transgender women with HIV, estrogen was prescribed to 83% while suppression of endogenous testosterone production (surgical or pharmacologic) was documented among 30%. Compared with cisgender men with HIV, transgender women with HIV had lower hemoglobin levels (13.0 (11.2, 14.3) vs. 13.8 (12.4, 15.0) g/dL, p=0.04), and thereby higher rates of anemia (65% vs. 38%, p=0.02). With respect to traditional CVD risk factors, there were no significant between-group differences in prevalence of hyperlipidemia or hypertension. Diabetes prevalence was 22% among transgender women with HIV and 14% among cisgender men with HIV. With respect to non-traditional CVD risk factors, depression prevalence tended to be higher among transgender women with HIV, though this finding did not reach statistical significance. Notably, only 68% of transgender women with HIV were on ART as compared to 83% of cisgender men with HIV (p=0.14). There was a non-significant trend toward a lower CD4 count and nadir CD4 count among transgender women with HIV. Additionally, there tended to be higher rates of hepatitis C virus (HCV) co-infection among transgender women with HIV vs. cisgender men with HIV (43% vs. 26%, p=0.11).
Table 1.
Baseline Characteristics Among Transgender Women and Cisgender Men with HIV
| Parameter | Transgender Women with HIV (N=23) |
Cisgender Men with HIV (N=92) |
P value |
|---|---|---|---|
| Non-HIV-specific Parameters | |||
|
| |||
| Age (years) | 51 (40, 63) | 51 (41, 62) | 0.93 |
| Race/ethnicity | |||
| White | 9% (2/23) | 11% (10/89) | 0.49 |
| Black/African American | 52% (12/23) | 51% (45/89) | |
| Hispanic | 17% (4/23) | 19% (17/89) | |
| Other | 13% (3/23) | 18% (16/89) | |
| Unknown | 9% (2/23) | 1% (1/89) | |
| Hyperlipidemia | 26% (6/23) | 29% (26/91) | 0.81 |
| Current statin use | 13% (3/23) | 20% (18/91) | 0.44 |
| Total cholesterol (mg/dL) | 170 (145, 224) | 171 (145, 211) | 0.80 |
| LDL-c (mg/dL) | 97 ± 36 | 98 ± 36 | 0.89 |
| HDL-c (mg/dL) | 54 (32, 62) | 44 (35, 55) | 0.52 |
| Triglycerides (mg/dL) | 138 (88, 242) | 123 (88, 213) | 0.52 |
| HTN | 27% (6/22) | 33% (30/90) | 0.58 |
| Systolic blood pressure (mmHg) | 112 (110, 140) | 128 (117, 137) | 0.11 |
| Diastolic blood pressure (mmHg) | 73 ± 14 | 78 ± 12 | 0.12 |
| DM | 22% (5/23) | 14% (13/91) | 0.40 |
| Current cigarette smoking | 29% (6/21) | 35% (29/84) | 0.60 |
| Current cocaine use | 10% (2/21) | 6% (5/86) | 0.56 |
| Current alcohol use | 5% (1/21) | 3% (3/86) | 0.79 |
| Depression | 48% (11/23) | 32% (29/90) | 0.17 |
| Anxiety | 17% (4/23) | 25% (22/89) | 0.45 |
| Creatinine (mg/dL) | 1.0 (0.9, 1.2) | 1.0 (0.9, 1.2) | 0.88 |
| Anemia* | 65% (15/23) | 38% (35/91) | 0.02 |
| Hemoglobin (g/dL) | 13.0 (11.2, 14.3) | 13.8 (12.4, 15.0) | 0.04 |
|
| |||
| HIV-specific Parameters | |||
|
| |||
| Duration since HIV diagnosis (years) | 17 ± 7 | 15 ± 8 | 0.38 |
| Currently on ART | 68% (15/22) | 83% (73/88) | 0.14 |
| CD4 count (cells/mm3) | 374 (111, 610) | 502 (276, 683) | 0.19 |
| Nadir CD4 (cells/mm3) | 102 (26, 356) | 223 (72, 370) | 0.19 |
| CD4 to CD8 ratio | 0.5 (0.3, 0.9) | 0.6 (0.3, 1.1) | 0.42 |
| Undetectable viral load | 63% (10/16) | 61% (43/71) | 0.89 |
| HCV co-infection | 43% (10/23) | 26% (23/88) | 0.11 |
Abbreviations: ART, antiretroviral therapy; CVD, cardiovascular disease; DM, diabetes mellitus; HCV, hepatitis C virus; HDL-c, high density lipoprotein cholesterol; HIV, human immunodeficiency virus; HTN, hypertension; and LDL-c, low density lipoprotein cholesterol. All available data points were incorporated into the summative presentation above, although a significant number of missing data points were noted for lipid parameters. Normally distributed variables are presented as mean ± standard deviation; non-normally distributed data are presented as median (interquartile range).
Anemia was defined using a hemoglobin threshold of < 13.5 g/dL.
Through this study, we discovered an increased prevalence of anemia and lower hemoglobin levels among transgender women with HIV vs. cisgender men with HIV. In the general population, anemia has been characterized as a risk factor for MI and HF.9,10 Among PLHIV, anemia also has been shown to relate to accelerated HIV disease progression and increased systemic immune activation/inflammation,11,12,13 of relevance to HIV-associated CVD. Suppression of endogenous testosterone production may contribute to anemia among transgender women with HIV. Indeed, studies of individuals with testosterone-dependent malignancies have shown that androgen depletion induces anemia, and leads to loss of lean muscle mass and insulin resistance.14
Our study also reveals suboptimal HIV control and a high prevalence of HCV co-infection among transgender women with HIV. Baguso et al. previously demonstrated that transgender women with HIV had lower rates of viral suppression (by self-report through an AIDS Clinical Trials Group Adherence Questionnaire) as compared to a mixed control group of cisgender men and women.15 Suboptimal HIV control (low CD4/high viral load) and HCV co-infection have been associated with CVD events among PLHIV.16,3,17 Propagation of heightened systemic immune activation may represent a common mechanism through which suboptimal HIV control and HCV-co-infection predispose to MI and HF.
Our characterization of the CVD risk factor profile among transgender women with HIV (vs. cisgender men with HIV) in a U.S. healthcare system reveals several key findings: increased prevalence of anemia, as well as suboptimal HIV control and a high prevalence of HCV co-infection. Anemia, poor HIV control, and HCV co-infection may all represent modifiable non-traditional CVD risk factors among transgender women with HIV. Limitations of our study include the relatively small sample size of transgender women with HIV and incomplete data capture on gender affirming hormonal therapy (including hormone therapy pursued outside PHS). To maximize our sample size, we systematically identified all transgender women with HIV receiving care at PHS across a wide date range. However, duration of HIV was similar between our group of transgender women and cisgender men, suggesting both groups may have had parallel exposure to older HIV treatment and CVD prevention strategies. Additional research is warranted on CVD risk (MI, HF, thromboembolism) and traditional / non-traditional risk-mechanisms among transgender women with HIV.18
Acknowledgments
Financial Support: LTF received support from NIHT32DK007028. VAT received support from NIH R01HL132786. TGN received support from the Kohlberg Foundation, the American Heart Association Fellow to Faculty Award 12FTF12060588, NIH 1R01HL130539, NIH 1R01HL137562, and NIH/Harvard Center for AIDS Research P30AI060354. MVZ received support from NIH 1R01AI123001, 1R01HL137562, and NIH/Harvard Center for AIDS Research P30AI060354.
MVZ has participated in a Scientific Advisory Board Meeting for Roche Diagnostics and has received research funding for an investigator-initiated study from Gilead to her institution.
Footnotes
Disclosures: All disclosures are unrelated to this manuscript.
References
- 1.Herbst JH, Jacobs ED, Finlayson TJ, McKleroy VS, Neumann MS, Crepaz N. Estimating HIV prevalence and risk behaviors of transgender persons in the United States: a systematic review. AIDS Behav. 2008 Jan;12(1):1–17. doi: 10.1007/s10461-007-9299-3. [DOI] [PubMed] [Google Scholar]
- 2.Freiberg MS, Chang CC, Kuller LH, et al. HIV infection and the risk of acute myocardial infarction. JAMA Intern Med. 2013 Apr 22;173(8):614–622. doi: 10.1001/jamainternmed.2013.3728. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Freiberg MS, Chang CH, Skanderson M, et al. Association Between HIV Infection and the Risk of Heart Failure With Reduced Ejection Fraction and Preserved Ejection Fraction in the Antiretroviral Therapy Era: Results From the Veterans Aging Cohort Study. JAMA Cardiol. 2017 May 01;2(5):536–546. doi: 10.1001/jamacardio.2017.0264. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Nou E, Lo J, Hadigan C, Grinspoon SK. Pathophysiology and management of cardiovascular disease in patients with HIV. Lancet Diabetes Endocrinol. 2016 Jul;4(7):598–610. doi: 10.1016/S2213-8587(15)00388-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Ladapo JA, Richards AK, DeWitt CM, et al. Disparities in the Quality of Cardiovascular Care Between HIV-Infected Versus HIV-Uninfected Adults in the United States: A Cross-Sectional Study. J Am Heart Assoc. 2017 Nov 14;6(11) doi: 10.1161/JAHA.117.007107. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Wierckx K, Elaut E, Declercq E, et al. Prevalence of cardiovascular disease and cancer during cross-sex hormone therapy in a large cohort of trans persons: a case-control study. Eur J Endocrinol. 2013 Oct;169(4):471–478. doi: 10.1530/EJE-13-0493. [DOI] [PubMed] [Google Scholar]
- 7.Gooren LJ, Wierckx K, Giltay EJ. Cardiovascular disease in transsexual persons treated with cross-sex hormones: reversal of the traditional sex difference in cardiovascular disease pattern. Eur J Endocrinol. 2014 Jun;170(6):809–819. doi: 10.1530/EJE-14-0011. [DOI] [PubMed] [Google Scholar]
- 8.Triant VA, Perez J, Regan S, et al. Cardiovascular Risk Prediction Functions Underestimate Risk in HIV Infection. Circulation. 2018 Feb 14; doi: 10.1161/CIRCULATIONAHA.117.028975. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Grote Beverborg N, van Veldhuisen DJ, van der Meer P. Anemia in Heart Failure: Still Relevant? JACC Heart Fail. 2018 Mar;6(3):201–208. doi: 10.1016/j.jchf.2017.08.023. [DOI] [PubMed] [Google Scholar]
- 10.Kaiafa G, Kanellos I, Savopoulos C, Kakaletsis N, Giannakoulas G, Hatzitolios AI. Is anemia a new cardiovascular risk factor? Int J Cardiol. 2015;186:117–124. doi: 10.1016/j.ijcard.2015.03.159. [DOI] [PubMed] [Google Scholar]
- 11.O'Brien ME, Kupka R, Msamanga GI, Saathoff E, Hunter DJ, Fawzi WW. Anemia is an independent predictor of mortality and immunologic progression of disease among women with HIV in Tanzania. J Acquir Immune Defic Syndr. 2005 Oct 1;40(2):219–225. doi: 10.1097/01.qai.0000166374.16222.a2. [DOI] [PubMed] [Google Scholar]
- 12.Borges AH, Weitz JI, Collins G, et al. Markers of inflammation and activation of coagulation are associated with anaemia in antiretroviral-treated HIV disease. AIDS. 2014 Jul 31;28(12):1791–1796. doi: 10.1097/QAD.0000000000000344. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Lipshultz HM, Hileman CO, Ahuja S, Funderburg NT, McComsey GA. Anaemia is associated with monocyte activation in HIV-infected adults on antiretroviral therapy. Antivir Ther. 2015;20(5):521–527. doi: 10.3851/IMP2940. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Tzortzis V, Samarinas M, Zachos I, Oeconomou A, Pisters LL, Bargiota A. Adverse effects of androgen deprivation therapy in patients with prostate cancer: focus on metabolic complications. Hormones (Athens) 2017 Apr;16(2):115–123. doi: 10.14310/horm.2002.1727. [DOI] [PubMed] [Google Scholar]
- 15.Baguso GN, Gay CL, Lee KA. Medication adherence among transgender women living with HIV. AIDS Care. 2016 Aug;28(8):976–981. doi: 10.1080/09540121.2016.1146401. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Triant VA, Regan S, Lee H, Sax PE, Meigs JB, Grinspoon SK. Association of immunologic and virologic factors with myocardial infarction rates in a US healthcare system. J Acquir Immune Defic Syndr. 2010 Dec 15;55(5):615–619. doi: 10.1097/QAI.0b013e3181f4b752. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Osibogun O, Ogunmoroti O, Michos ED, et al. HIV/HCV coinfection and the risk of cardiovascular disease: A meta-analysis. J Viral Hepat. 2017 Nov;24(11):998–1004. doi: 10.1111/jvh.12725. [DOI] [PubMed] [Google Scholar]
- 18.Gianella S, Haw JS, Blumenthal J, Sullivan B, Smith DM. The Importance of HIV Research for Transgender and Gender Non-Binary Individuals. Clin Infect Dis. 2017 Nov 8; doi: 10.1093/cid/cix990. [DOI] [PMC free article] [PubMed] [Google Scholar]