Biomarkers and Electrocardiographic Evidence of Myocardial Ischemia in Patients With Human Immunodeficiency Virus Infection

Study Questions:

What is the relation of inflammatory and coagulation biomarkers among patients with human immunodeficiency virus (HIV) with electrocardiographic (ECG) evidence of myocardial ischemia?

Methods:

High-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and D-dimer levels were measured at study entry for 3,085 HIV-infected participants (mean age 44 years; 26.4% women; 24.6% black) in the Strategies for Management of Antiretroviral Therapy trial. Logistic regression models were used to examine the associations of these biomarkers with prevalent and incident myocardial ischemia. The latter analyses were performed for 1,411 participants who were randomly assigned to receive continuous antiretroviral therapy during follow-up to suppress the HIV viral load and had ≥1 ECG reading during the follow-up period.

Results:

The median hs-CRP, IL-6, and D-dimer levels were 1.65 μg/ml (interquartile range, 0.69-4.11), 1.60 pg/ml (interquartile range, 1.00-2.75), and 0.18 μg/ml (interquartile range, 0.11-0.32), respectively. At baseline, the prevalence of major or minor Q-QS or ST-T ECG abnormalities was 18.6%. The biomarker levels were associated with prevalent major or minor ischemic abnormalities on the univariate analyses; however, adjustment for traditional risk factors attenuated these associations. The adjusted odds ratio for major or minor ischemic abnormalities and 95% confidence intervals for the greatest versus lowest quartiles were 1.3 (0.9-1.7) for hs-CRP, 1.0 (0.7-1.3) for IL-6, and 1.1 (0.9-1.5) for D-dimer. During a median follow-up of 2.3 years, new definite or probable ischemic ECG abnormalities developed in 11.7% of participants receiving continuous antiretroviral therapy. Biomarker levels were not associated with incident abnormalities on unadjusted or adjusted analyses.

Conclusions:

The authors concluded that higher levels of hs-CRP, IL-6, and D-dimer were not associated with ischemic ECG abnormalities.

Perspective:

This study reported that the prevalence of baseline ECG abnormalities indicative of cardiac ischemia increased with greater biomarker levels; however, after adjustment for age and other risk factors, none of the associations remained significant. Similarly, those who developed incident ECG abnormalities had greater baseline biomarker levels than those who did not, but associations were not significant on either unadjusted or adjusted analysis. It appears that elevated biomarker levels and ECG abnormalities indicating myocardial ischemia might reflect different risk pathways for cardiovascular disease.

Keywords: Myocardial Ischemia, C-Reactive Protein, Biological Markers, Fibrin Fibrinogen Degradation Products, Interleukin-6, Electrocardiography


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