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Higher Levels of Interleukin-6 and Soluble Tumor Necrosis Factor-Alpha Receptor I are Associated with Increased Coronary Atherosclerotic Plaque in the Multicenter AIDS Cohort Study (MACS)
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Reported by Jules Levin
CROI 2012 March 5-8 Seattle WA
KERUNNE KETLOGETSWE1, LISA JACOBSON1, XIUHONG LI1, FRANK PALELLA2, LAWRENCE A. KINGSLEY3, MALLORY D. WITT4, RICHARD T. GEORGE1, JOSEPH MARGOLICK1, MATTHEW BUDOFF4, WENDY S POST1
1JOHNS HOPKINS UNIVERSITY, BALTIMORE MD; 2NORTHWESTERN UNIVERSITY, CHICAGO, IL; 3UNIVERSITY OF PITTSBURGH, PITTSBURGH, PA; 4HARBOR-UCLA MEDICAL CENTER, LOS ANGELES, CA
Background: Elevated serum levels of inflammatory biomarkers are seen in HIV+ individuals and may reflect increased risk for coronary heart disease (CHD). We assessed the relationship between several biomarkers and coronary artery atherosclerosis.
Methods: Men who have sex with men (MSM), aged 45 to 70, 258 HIV+ and 121 HIV-, underwent coronary CT angiography. Total plaque score (TPS) was calculated as the sum of plaque scores in coronary segments. Serum levels of C-reactive protein (CRP), D-dimer, fibrinogen, interleukin 6 (IL-6), soluble tumor necrosis factor-α receptors 1 and 2 (TNF-αR1 and R2), intracellular adhesion molecule 1 (ICAM-1), and monocyte chemoattractant protein 1 (MCP-1) were measured. Logistic regression was performed to evaluate associations between biomarkers and the top quartile of TPS (>6) compared with the lower quartiles combined (0 to 6), first adjusted for age, race, and HIV serostatus, then adjusting for CHD risk factors, and then testing for an interaction by HIV status.
Results: Coronary plaque was present in 84% of the men. There was no difference in TPS based on HIV serostatus. Higher IL-6 levels were associated with a TPS >6 after adjustment for age, race, and HIV serostatus (OR 1.46, 95%CI 1.08 to 1.99) and when adjusted for CHD risk factors (OR 1.48, 95%CI 1.01 to 2.17). There was a trend toward higher IL-6 in HIV+ men (p = 0.07), but no differences in IL-6 based on HIV serostatus after adjusting for CHD risk factors (p = 0.16). Among HIV+, IL-6 was associated with plasma HIV RNA levels (p <0.0001) and a history of AIDS (p <0.02). Higher TNF-αR1 also was associated with TPS >6, adjusted for age, race and HIV serostatus (OR 2.50, 95%CI 1.06 to 5.92) and adjusted for CHD risk factors (OR 3.28, 95%CI 1.01 to 10.67). TNF-αR1 was higher in HIV+ men than HIV- men, even after adjusting for CHD risk factors (p = 0.02), and was associated with a history of AIDS, nadir CD4 cell count/mm3 (CD4, both p = 0.001), most recent CD4 and HIV RNA, and peak HIV RNA (all p <0.05). There was a modest correlation between IL-6 and TNF-αR1 (r = 0.29, p <0.0001). There was no interaction by HIV serostatus for IL-6 or TNF-αR1. The remaining biomarkers were not associated with TPS.
Conclusions: Higher plasma levels of IL-6 and TNF-αR1 were associated with both markers of later-stage HIV disease and increased subclinical coronary atherosclerotic plaque, independent of CHD risk factors. These findings are consistent with the hypothesis that greater systemic inflammation is associated with atherosclerosis.
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