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HIV and Cardiac End-Organ Damage in Women: Findings from an Echocardiographic Study Across the United States
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in WIHS - This study suggests that WWH have a higher risk of LVSD compared to sociodemographically similar WWOH, but their risk for isolated LVDD, LAE, LVH, and high TRV is increased only with reduced CD4 + count.
The findings also underscore the importance of HIV control and preservation of immune competence for prevention.
In this study of U.S. women, we found that those with HIV had a near-significant 1.7-fold higher risk of echocardiographic LVSD, but similar risk of isolated LVDD, LAE, LVH and elevated TRV, compared with WWOH after adjustment for potential confounders. The burden of RVSD, valve disease and pericardial disease was low in this cohort, and did not differ by HIV serostatus. We found no relationship between meaures of HIV disease control or severity and LVSD, but such associations were present for the other adverse cardiac phenotypes. Specifically, there was a gradient of increasing risk for the remaining phenotypes with lower CD4+ count. Among WWH, declining CD4+ counts were or tended to be associated with increased risk for isolated LVDD, LAE and LVH. WWH and CD4+ count in the lowest category had significantly higher LAE, LVH and elevated TRV compared to WWOH. There was a positive association15
between duration of INSTI use and isolated LVDD, but otherwise no relationship between16
cumulative ART use and cardiac phenotypes.
Introduction
Antiretroviral therapy (ART) has afforded marked gains in life expectancy for people with HIV (PWH), but this has been counterbalanced by a high burden of chronic diseases (1).
Various studies have documented that, compared to people without HIV, PWH exhibit an elevated risk of cardiovascular disease (2-8). As assessed in cohorts with less intensive ART use than in contemporary practice, such risks have been shown to be more pronounced in the setting of high viremic load or immunosuppression (3, 5, 6, 8).
Imaging studies have likewise reported a high frequency of cardiac functional abnormalities (9) and pulmonary hypertension (PH) (10) in PWH. A meta-analysis of echocardiographic studies of PWH from high- and low-income countries conducted pre- and post-ART reported on various cardiac phenotypes, documenting marked prevalences of left ventricular systolic dysfunction (LVSD), LV diastolic dysfunction (LVDD), right ventricular systolic dysfunction (RVSD), and PH (11). There was substantial heterogeneity in the findings, but after accounting for geographic region, LVSD was less common in more recent studies (11).
As with assessments of cardiovascular events, investigations of HIV-associated cardiac dysfunction have largely focused on men. Further, a common limitation of existing studies of HIV-related heart disease is that they have included as controls HIV-negative individuals who lack the same high-risk behavior profiles overrepresented in PWH (12). This makes unclear to what extent the associated risk is attributable to HIV itself or relates instead to associated cardiovascular risk factors. This limitation has been a particular feature of imaging studies of HIV, many of which have been uncontrolled or selected age- and sex-matched healthy volunteers as comparators. While women account for half of HIV-positive cases worldwide, and one- quarter in the U.S., available data on adverse cardiac phenotypes in women remain sparse (13).
To address these gaps, we undertook an echocardiographic study within the Women’s Interagency HIV Study (WIHS) to test the hypothesis that among women with (WWH) and without HIV (WWOH) having similar risk factor profiles, HIV and HIV-specific factors are associated with various forms of cardiac end-organ damage.
Clinical Infectious Diseases 03 October 2022
Abstract
Background
People with HIV have been reported to have increased risk of clinical and subclinical cardiovascular disease. Existing studies have focused on men and often have been uncontrolled or lacked adequate HIV-negative comparators.
Methods
We performed echocardiography in participants with, or at risk for, HIV from the Women’s Interagency HIV Study. We evaluated associations of HIV and HIV-related factors with cardiac phenotypes, including left ventricular systolic dysfunction (LVSD), isolated LV diastolic dysfunction (LVDD), left atrial enlargement (LAE), LV hypertrophy (LVH), and increased tricuspid regurgitation velocity (TRV).
Results
Of 1654 participants (age 51 ± 9), 70% were HIV-positive. Sixty-three (5.4%) women with HIV (WWH) had LVSD; 71 (6.5%) had isolated LVDD. Compared to women without HIV (WWOH), WWH had a near-significantly increased risk of LVSD (adjusted RR = 1.69 [95% CI = 1.00, 2.86], p = 0.051). No significant association was noted for HIV seropositivity with other phenotypes, but there was a risk gradient for decreasing CD4 + count among WWH that approached or reached significance for isolated LVDD (ptrend = 0.069), LAE (ptrend = 0.002) and LVH (ptrend = 0.003). WWH with CD4 + count < 200 cells/mm3 had significantly higher prevalence of LAE, LVH and high TRV than WWOH (p < 0.05). There were no consistent associations for viral suppression or antiretroviral-drug exposure.
Conclusions
This study suggests that WWH have a higher risk of LVSD compared to sociodemographically smilar WWOH, but their risk for isolated LVDD, LAE, LVH, and high TRV is increased only with reduced CD4 + count. Although these findings warrant replication, they support the importance of cardiovascular risk-factor and HIV-disease control for heart disease prevention in this population.
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