Elevated levels of monocyte activation markers are associated with subclinical atherosclerosis in men with and those without HIV infection

Abstract

Background: Heightened immune activation among human immunodeficiency virus (HIV)-infected persons may contribute to atherosclerosis. We assessed associations of serologic markers of monocyte activation, soluble CD163 (sCD163) and soluble CD14 (sCD14), and monocyte chemoattractant protein 1 (CCL2) with subclinical atherosclerosis among men with and those without HIV infection in the Multicenter AIDS Cohort Study.

Methods: We performed noncontrast computed tomography on 906 men (566 HIV-infected men and 340 HIV-uninfected men), 709 of whom also underwent coronary computed tomographic angiography. Associations between each biomarker and the prevalence of coronary plaque, the prevalence of stenosis of ≥50%, and the extent of plaque were assessed by logistic and linear regression, adjusting for age, race, HIV serostatus, and cardiovascular risk factors.

Results: Levels of all biomarkers were higher among HIV-infected men, of whom 81% had undetectable HIV RNA, and were associated with lower CD4(+) T-cell counts. In the entire population and among HIV-infected men, higher biomarker levels were associated with a greater prevalence of coronary artery stenosis of ≥50%. Higher sCD163 levels were also associated with greater prevalences of coronary artery calcium, mixed plaque, and calcified plaque; higher CCL2 levels were associated with a greater extent of noncalcified plaque.

Conclusions: sCD163, sCD14, and CCL2 levels were elevated in treated HIV-infected men and associated with atherosclerosis. Monocyte activation may increase the risk for cardiovascular disease in individuals with HIV infection.

Keywords: atherosclerosis; human immunodeficiency virus; inflammation; monocyte activation; plaque.

Figure 1.

Estimated odds ratios (circles) and 95% confidence intervals (vertical lines) for the associations between the soluble CD163 level (sCD163; quintile 5, compared with quintile 1) and the prevalence of coronary plaque (defined as a plaque score of >0, as defined in “Methods” section) among the combined cohort (n = 906 for coronary artery calcium; n = 709 for coronary plaque subtypes). Models were adjusted for age, race, human immunodeficiency virus serostatus, and cardiovascular disease risk factors (body mass index; cumulative pack-years of smoking; use of hypertension, diabetes, or lipid-lowering medication; systolic blood pressure; fasting glucose level; and total cholesterol and high-density lipoprotein cholesterol levels for those not receiving hypertension, diabetes, or lipid-lowering medications). Red lines indicate P values of < .05. *P < .05 and **P < .01 for trends across biomarker quintiles.

Figure 2.

Estimated odds ratios (circles) and 95% confidence intervals (vertical lines) for the associations between biomarkers (quintile 5, compared with quintile 1) and prevalence of coronary artery stenosis of ≥50% for the combined cohort (n = 709). See the Figure 1 legend for definitions of models and symbols. Abbreviations: sCD14, soluble CD14; sCD163, soluble CD163.

Figure 3.

Estimated odds ratios (circles) and 95% confidence intervals (vertical lines) for the associations between biomarkers (quintile 5, compared with quintile 1) and prevalence of coronary plaque, including coronary stenosis of ≥50%, among human immunodeficiency virus-infected men (n = 566 for coronary artery calcium; n = 426 for coronary plaque subtypes). See the Figure 1 legend for definitions of models and symbols. Abbreviations: sCD14, soluble CD14; sCD163, soluble CD163.