Sex modifies the association between HIV and coronary artery disease among older adults in Uganda

Abstract

Introduction Little is known about the epidemiology of coronary artery disease (CAD) in sub‐Saharan Africa, where the majority of people living with HIV (PLHIV) live. We assessed the association of HIV with CAD and explored relationships with monocyte activation in sex‐stratified analyses of older PLHIV and people without HIV (PWOH) in Uganda. Methods The Ugandan Study of HIV effects on the Myocardium and Atherosclerosis (mUTIMA) follows 100 PLHIV on antiretroviral therapy (ART) and 100 age‐ and sex‐matched PWOH controls in Kampala, Uganda; all >45 years of age with >1 cardiovascular disease risk factor. At the year 2 exam (2017–2019), 189 participants had available coronary calcium score and 165 had coronary CT angiography (CCTA) for this analysis. A subset of participants ( n = 107) had both CCTA and fresh whole blood flow cytometry for monocyte phenotyping. Results Median age was 57.8 years and 63% were females. Overall, 88% had hypertension, 37% had diabetes and 4% were smokers. Atherosclerotic cardiovascular disease (ASCVD) risk was modestly higher for PWOH, but not statistically significant (median 10‐year ASCVD risk 7.2% for PLHIV vs. 8.6% for PWOH, p = 0.09). Median duration of ART was 12.7 years and 86% had suppressed viral load. Despite a high prevalence of risk factors, only 34/165 (21%, 95% CI 15–28%) had any coronary plaque. After adjustment for ASCVD risk score, HIV status was not associated with CAD (OR 0.55, 95% CI 0.23–1.30) but was associated with more severe CAD (segment severity score>3) among those with disease (OR 10.9, 95% CI 1.67–70.45). Females had a trend towards higher odds of CAD among PLHIV (OR 4.1, 95% CI 0.4–44.9), but a trend towards lower odds of CAD among PWOH (OR 0.30; 95% CI 0.07–1.3; HIV*sex interaction p = 0.019). CAD was positively correlated with classical monocytes ( r = 0.3, p = 0.012) and negatively correlated with CX3CR1 expression ( r = –0.31, p = 0.011) in PLHIV and negatively correlated with patrolling monocytes ( r = –0.36, p = 0.031) and tissue factor expression ( r = –0.39, p = 0.017) in PWOH. Conclusions Our results suggest that HIV may be associated more with severity rather than the presence of CAD in Uganda. Sex differences in the HIV effect suggest that tailored CAD prevention strategies may be required in this setting.

Statin protects men but not women with HIV against loss of muscle mass, strength, and physical function: a pilot study

“…Interestingly, differences were not observed among women of the same age, BMI, race, time living with HIV, and time of ART use on and not on statins. Sex-based differences are observed in HIV pathogenesis 38 , 39 , HIV related comorbidities such as cardiovascular disease 40 , 41 , and muscle strength among PLWH 42 . Scully 38 demonstrated that female sex is associated with better control of HIV through heightened levels of immune activation, but this may be maladaptive over time as it may predispose to cardiovascular disease and other non-AIDS comorbidities.…”

“…Scully 38 demonstrated that female sex is associated with better control of HIV through heightened levels of immune activation, but this may be maladaptive over time as it may predispose to cardiovascular disease and other non-AIDS comorbidities. Indeed, women may have a higher burden of HIV related coronary artery disease and are more likely to have HIV-related heart failure 40 , 43 . Additionally, the cholesterol-lowering effects of atorvastatin are greater in women 44 , and it is suggested that women may be at greater risk for statin-related myotoxicity compared with men 45 .…”

Latent tuberculosis is associated with heightened levels of pro-and anti-inflammatory cytokines among Kenyan men and women living with HIV on long-term antiretroviral therapy

“…We also recently demonstrated an association between IL-4 with carotid plaque burden in PWH, suggesting a direct role of type 2 type response in atherosclerosis plaque development [ 42 ]. Our observation that the cytokine response was significantly increased in women is concerning and could explain the higher risk of CVD observed among the HIV-positive women with HIV in the SSA compared to the men [ 43 , 44 ]. Our results are particularly relevant in the context of Kenya and other TB-endemic settings and provides support for LTBI treatment to reduce inflammation in persons with HIV infection.…”

Cardiovascular disease risk in women living with HIV

“…In these studies, neither HIV nor sex was a predictor of CIMT progression over 4 years in Uganda [80]. In a CCTA study of coronary disease in Uganda, WLWH had 4× higher odds of plaque compared with MLWH, whereas men without HIV had 3× higher odds of plaque than women without HIV in models that adjusted for ASCVD risk and age ( P for interaction 0.02) [79 ▪ ]. Why sex effects may vary across different countries and contexts has not been studied in detail.…”

“…Two recent studies from sub-Saharan Africa, where more than two of three of all WLWH reside, provide a broader picture of subclinical atherosclerosis in PLWH outside of high-income countries [79 ▪ ,80]. In these studies, neither HIV nor sex was a predictor of CIMT progression over 4 years in Uganda [80].…”