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

Q: What is the clinical evidence from this study?

Study design: Cross-Sectional. Population: Coronary artery disease among adults with and without HIV (n=585). Intervention: Circulating inflammatory biomarkers (specifically soluble CD163 per 1-SD increase, alongside hs-CRP, D-dimer, FABP2, and CBC-derived indices) vs. Lower biomarker levels (per 1-SD decrease in natural-log transformed biomarker). Primary outcome: Prevalent coronary artery disease (Agatston calcium score >0 or any plaque on contrast-enhanced coronary CT angiography) (OR 0.63, 95% CI 0.47-0.87, p=0.004 (q=0.048)).

Q: What does this research mean for the field?

Circulating inflammatory biomarkers are largely unassociated with prevalent coronary artery disease and do not improve cardiovascular risk discrimination in older Ugandan adults with and without HIV. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

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

doi:10.21203/rs.3.rs-11473007/v1

Key result

Circulating inflammatory biomarkers were mostly unassociated with coronary artery disease in older Ugandans, though higher sCD163 showed an inverse association.

Why the study?

Chronic inflammation is implicated in coronary atherosclerosis, especially in people with HIV on antiretroviral therapy, yet most evidence linking inflammatory biomarkers to CAD comes from populations outside sub-Saharan Africa.

Do circulating and hematologic inflammatory biomarkers associate with and improve discrimination for prevalent coronary artery disease beyond conventional ASCVD risk assessment in older Ugandan adults with and without HIV?

Key Points

To assess associations between circulating inflammatory biomarkers and coronary artery disease among older adults with and without HIV in rural southwestern Uganda.
Analyzed 585 participants aged ≥ 40 years from a community-based cohort in rural southwestern Uganda (287 with HIV, 298 without HIV).
Assessed coronary artery disease (CAD) via coronary artery calcium scanning and contrast-enhanced coronary computed tomography angiography.
Evaluated biomarkers of inflammation (sCD163, D-dimer, CRP, FABP2, and complete blood count indices) using Firth penalized logistic regression adjusted for cardiovascular risk factors.
Among 585 participants, 45 (7.7%) had imaging-defined CAD, with CAD prevalence not differing significantly by HIV status (P=0.288).
In multivariable-adjusted models, higher sCD163 was inversely associated with CAD (OR per 1-SD increase, 0.63; 95% CI, 0.47–0.87; p=0.004; q=0.048), but was not consistent across HIV strata.

Study Design

Type

Cross-Sectional (n=585)

Blinding

Blinded imaging readers

Multicenter

Yes

Structured PICO

Do circulating and hematologic inflammatory biomarkers associate with and improve discrimination for prevalent coronary artery disease beyond conventional ASCVD risk assessment in older Ugandan adults with and without HIV?

P

Population

585 community-dwelling older adults (mean age 57.7 years, 48.7% female, 49.1% with HIV on ART ≥3 years) in rural southwestern Uganda evaluated cross-sectionally with coronary CT imaging.

E

Exposure

Circulating and derived inflammatory biomarkers: soluble CD163 (sCD163), D-dimer, high-sensitivity C-reactive protein (hs-CRP), fatty acid-binding protein 2 (FABP2), and complete blood count-derived hematologic inflammatory indices (NLR, PLR, LMR, SII, SIRI, PIV, MHR)

C

Comparator

Conventional atherosclerotic cardiovascular disease (ASCVD) 10-year risk score alone (in discrimination analyses); comparison across HIV status (people with HIV vs. people without HIV)

O

Outcome

Prevalent coronary artery disease (CAD), defined as a composite of an Agatston calcium score >0 on non-contrast ECG-gated CT or any evidence of plaque on contrast-enhanced coronary CT angiography (CCTA), interpreted by blinded cardiovascular radiologistssurrogate

Main Result

Odds Ratio: 0.63 (95% CI 0.47–0.87)

p-value: p=0.004 (q=0.048)

In older rural Ugandan adults with and without HIV, systemic and hematologic inflammatory biomarkers showed minimal association with prevalent CT-defined coronary artery disease and did not improve risk discrimination beyond the conventional ASCVD risk score.

Limitations

Cross-sectional design precludes conclusions about temporality or causal relationships
Relatively small number of CAD events (n=45) reduced statistical power, particularly in HIV- and sex-stratified analyses
Biomarker-specific missingness reduced analytic sample sizes for some models
Circulating biomarkers were measured at a single time point and may not reflect cumulative inflammatory exposure
Focus on imaging-defined subclinical CAD rather than clinical cardiovascular events may limit generalizability to hard clinical outcomes
Limited statistical power afforded by the low prevalence of CAD in the cohort (n=45, 7.7%)
Assessed prevalent CAD on imaging, but not incident cardiovascular events or mortality
Small number of CAD events within HIV strata precluded multivariable adjustment in stratified models

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Implication

Most inflammatory biomarkers should not inform CAD assessment in older Ugandans; leaves open the inconsistent inverse sCD163 association for validation.

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.

Discussion

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Cite This Study

Migisha et al. (2026) conducted a cross-sectional in Coronary artery disease among adults with and without HIV (n=585). Circulating inflammatory biomarkers (specifically soluble CD163 per 1-SD increase, alongside hs-CRP, D-dimer, FABP2, and CBC-derived indices) vs. Lower biomarker levels (per 1-SD decrease in natural-log transformed biomarker) was evaluated on Prevalent coronary artery disease (Agatston calcium score >0 or any plaque on contrast-enhanced coronary CT angiography) (OR 0.63, 95% CI 0.47-0.87, p=0.004 (q=0.048)). Circulating inflammatory biomarkers were mostly unassociated with coronary artery disease in older Ugandans, though higher sCD163 showed an inverse association.

synapsesocial.com/papers/6af46da27bb3da179b850289 https://doi.org/10.21203/rs.3.rs-11473007/v1

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

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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