Inflammatory biomarkers and prevalent coronary atherosclerosis among Ugandan adults with and without HIV

Abstract Background Chronic inflammation is implicated in coronary atherosclerosis, particularly among people with HIV, who may experience persistent immune activation despite antiretroviral therapy. However, most evidence linking inflammatory biomarkers to coronary artery disease (CAD) comes from populations outside sub-Saharan Africa. We assessed associations between inflammatory biomarkers and CAD among older adults with and without HIV in southwestern Uganda. Methods We analyzed adults aged ≥ 40 years in a community-based cohort in rural southwestern Uganda. CAD was assessed using coronary artery calcium scanning and contrast-enhanced coronary computed tomography angiography. Biomarkers included indicators of macrophage activation (sCD163), hypercoagulability (D-dimer), systemic inflammation (C-reactive protein), gut epithelial integrity (fatty acid binding protein 2), and hematologic inflammatory indices derived from complete blood counts. We fitted Firth penalized logistic regression models to estimate crude, HIV-stratified, and multivariable-adjusted associations. Receiver-operating-characteristic analyses assessed whether select biomarkers improved discrimination beyond the atherosclerotic cardiovascular disease (ASCVD) risk score. Results Among 585 participants, mean age was 57.7 years, 287 (49.1%) had HIV, and 45 (7.7%) had CAD. Most biomarkers, including C-reactive protein, D-dimer, fatty acid–binding protein 2, and complete blood count–derived inflammatory indices, were not associated with CAD after multivariable adjustment and false-discovery-rate correction. Higher sCD163 was inversely associated with CAD in the adjusted overall model (odds ratio per 1-standard-deviation increase, 0.63; 95% confidence interval, 0.47–0.87; q = 0.048), but this finding was not consistent across HIV strata. Adding sCD163 to the ASCVD risk score did not improve discrimination for CAD. Conclusions In this cohort of older adults in rural Uganda, inflammatory biomarkers showed limited associations with CAD and did not improve discrimination beyond conventional risk assessment. These findings support emphasis on established cardiovascular risk assessment among older Ugandans, and further investigation into the pathogenesis of CVD risk in this population.

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Publication Details

Journal
Research Square
Published
2026-11-10
DOI
https://doi.org/10.21203/rs.3.rs-11473007/v1
Primary Topic
HIV-related health complications and treatments
Type
preprint
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preprint

Inflammatory biomarkers and prevalent coronary atherosclerosis among Ugandan adults with and without HIV

Angelo K. Takigami, Mark Jacob Siedner, Samson Okello, Geoffrey Erem et al.
Research Square
HIV-related health complications and treatments
preprint

Inflammatory biomarkers and prevalent coronary atherosclerosis among Ugandan adults with and without HIV

Angelo K. Takigami, Mark Jacob Siedner, Samson Okello, Geoffrey Erem, Moses Acan, Prossy Bibangambah, Godfrey Masette, Vikas Thondapu, Andrew Ochieng, Richard Migisha, Pauline Byakika‐Kibwika, Edna Tindimwebwa, Peter Kangwagye, Zahra Reynolds, Brian Burns Ghoshhajra, Rebecca F. Gilbert, Eliza J. Passell, Rita Nassanga, Flavia Atwiine, Mangun Randhawa, Stephen B. Asiimwe, Christopher T. Longenecker, Abraham Muhwezi
preprint en

Abstract

Abstract Background Chronic inflammation is implicated in coronary atherosclerosis, particularly among people with HIV, who may experience persistent immune activation despite antiretroviral therapy. However, most evidence linking inflammatory biomarkers to coronary artery disease (CAD) comes from populations outside sub-Saharan Africa. We assessed associations between inflammatory biomarkers and CAD among older adults with and without HIV in southwestern Uganda. Methods We analyzed adults aged ≥ 40 years in a community-based cohort in rural southwestern Uganda. CAD was assessed using coronary artery calcium scanning and contrast-enhanced coronary computed tomography angiography. Biomarkers included indicators of macrophage activation (sCD163), hypercoagulability (D-dimer), systemic inflammation (C-reactive protein), gut epithelial integrity (fatty acid binding protein 2), and hematologic inflammatory indices derived from complete blood counts. We fitted Firth penalized logistic regression models to estimate crude, HIV-stratified, and multivariable-adjusted associations. Receiver-operating-characteristic analyses assessed whether select biomarkers improved discrimination beyond the atherosclerotic cardiovascular disease (ASCVD) risk score. Results Among 585 participants, mean age was 57.7 years, 287 (49.1%) had HIV, and 45 (7.7%) had CAD. Most biomarkers, including C-reactive protein, D-dimer, fatty acid–binding protein 2, and complete blood count–derived inflammatory indices, were not associated with CAD after multivariable adjustment and false-discovery-rate correction. Higher sCD163 was inversely associated with CAD in the adjusted overall model (odds ratio per 1-standard-deviation increase, 0.63; 95% confidence interval, 0.47–0.87; q = 0.048), but this finding was not consistent across HIV strata. Adding sCD163 to the ASCVD risk score did not improve discrimination for CAD. Conclusions In this cohort of older adults in rural Uganda, inflammatory biomarkers showed limited associations with CAD and did not improve discrimination beyond conventional risk assessment. These findings support emphasis on established cardiovascular risk assessment among older Ugandans, and further investigation into the pathogenesis of CVD risk in this population.

Research Square
University of North Carolina at Chapel Hill (US), Mbarara University of Science and Technology (UG), University of Washington (US), Nsambya Hospital (UG), Yale University (US), Massachusetts General Hospital (US), Makerere University (UG)
HIV-related health complications and treatments
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