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Biomarkers and electrocardiographic evidence of myocardial ischemia in patients with human immunodeficiency virus infection.

ABSTRACT: We assessed the relation of inflammatory and coagulation biomarkers with electrocardiographic (ECG) evidence of myocardial ischemia. High-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and D-dimer levels were measured at study entry for 3,085 human immunodeficiency virus-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 human immunodeficiency virus viral load and had ?1 ECG reading during the follow-up period. The median hsCRP, IL-6, and D-dimer level was 1.65 ?g/ml (interquartile range 0.69 to 4.11), 1.60 pg/ml (interquartile range 1.00 to 2.75), and 0.18 ?g/ml (interquartile range 0.11 to 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 was 1.3 (95% confidence interval 0.9 to 1.7) for hsCRP, 1.0 (95% confidence interval 0.7 to 1.3) for IL-6, and 1.1 (95% confidence interval 0.9 to 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. In conclusion, higher levels of hsCRP, IL-6, and D-dimer were not associated with ischemic ECG abnormalities. Elevated biomarker levels and ECG abnormalities indicating myocardial ischemia might reflect different risk pathways for cardiovascular disease.

SUBMITTER: Gupta M

PROVIDER: S-EPMC3619189 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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Biomarkers and electrocardiographic evidence of myocardial ischemia in patients with human immunodeficiency virus infection.

Gupta Mihir M Miller Christopher J CJ Baker Jason V JV Lazar Jason J Bogner Johannes R JR Calmy Alexandra A Soliman Elsayed Z EZ Neaton James D JD

The American journal of cardiology 20121229 5

We assessed the relation of inflammatory and coagulation biomarkers with electrocardiographic (ECG) evidence of myocardial ischemia. High-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and D-dimer levels were measured at study entry for 3,085 human immunodeficiency virus-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 bioma ...[more]

PMID: 23276469

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Project description:BackgroundDespite advances in antiretroviral therapy (ART), people living with human immunodeficiency virus (HIV) continue to be at increased risk of cardiometabolic complications compared to HIV-uninfected individuals. Advanced glycation end products (AGEs) are implicated in the development and progression of cardiometabolic complications in the general population. Their role in HIV remains unclear.MethodsACTG A5260s is a prospective open-label randomized trial in which ART-naive people living with HIV were randomized to tenofovir disoproxil fumarate /emtricitabine plus atazanavir/ritonavir, darunavir/ritonavir, or raltegravir over 96 weeks. Changes in circulating AGEs with ART initiation were assessed, and linear regression was used to examine the associations between serum AGEs with carotid intima-media thickness (cIMT), visceral and subcutaneous adipose tissue, total fat, lean mass, body mass index, insulin resistance, leptin, and adiponectin.ResultsOverall, 214 participants were included. Ninety percent were male, 48% were White, the median age was 36 years, median HIV-1 RNA was 4.58 log10 copies/mL, and median CD4 count was 338 cells/µL. Most AGEs remained relatively unchanged following 96 weeks of ART initiation, except for methylglyoxal-derived hydroimidazolone 1 (MG-H1), which increased following 96 weeks of ART (mean fold change, 1.15 [95% confidence interval, 1.02-1.30]). No differences were detected across ART regimens. Increases in AGE levels over time were associated with worsening body fat composition measures, insulin resistance, and cIMT, even after adjusting for clinically relevant factors.ConclusionsAGE levels did not decrease following ART initiation. Most AGE levels remained stable, except for MG-H1, which increased. In people with HIV on ART, the accumulation of circulating AGEs over time appears to be independently associated with worsening cardiometabolic biomarkers.Summary: Antiretroviral therapy (ART) does not appear to be effective in reducing advanced glycation end product (AGE) levels. On the contrary, AGE levels seem to increase following ART initiation. Accumulation of AGEs was found to be independently associated with cardiometabolic complications in treated people living with HIV.

Project description:BackgroundCardiotoxicity induced by 5-fluorouracil (5-FU) is well known but poorly understood. In this study, we undertook ECG recording (Holter) and analyses of the biomarkers troponin and copeptin in patients receiving 5-FU to increase our understanding of the cardiotoxicity.Subjects, materials, and methodsPatients with colorectal or anal cancer that received first-time treatment with 5-FU-based chemotherapy were prospectively included. Holter recording, clinical evaluation, 12-lead electrocardiogram, and assessment of plasma concentrations of troponin I and copeptin were performed before (control) and during 5-FU treatment (intervention).ResultsA total of 108 patients were included, 82 with colorectal and 26 with anal cancer. The proportion of patients with myocardial ischemia on Holter recording was significantly higher during the first 5-FU infusion (14.1%) than before (3.7%; p = .001). The ischemic burden per day (p = .001), the number of ST depression episodes per day (p = .003), and the total duration of ischemic episodes per day (p = .003) were higher during the first 5-FU infusion than before, as was plasma copeptin (p < .001), whereas plasma troponin I was similar (p > 0.999). Six patients (5.6%) developed acute coronary syndromes and two (1.8%) developed symptomatic arrhythmias during 5-FU treatment.Conclusion5-FU infusion is associated with an increase in the number of patients with myocardial ischemia on Holter recording. According to biomarker analyses, 5-FU is associated with an increase in copeptin, but rarely with increases in cardiac troponin I. However, 5%-6% of the patients developed acute coronary syndromes during treatment with 5-FU.Implications for practiceSymptomatic 5-fluorouracil (5-FU) cardiotoxicity occurs in 0.6%-19% of patients treated with this drug, but a small electrocardiographic (Holter) study has revealed silent myocardial ischemia in asymptomatic patients, suggesting a more prevalent subclinical cardiac influence. This study demonstrated a significant increase in the number of patients with myocardial ischemia on Holter recording during 5-FU treatment and an increase in ischemic burden. Cardiac biomarker analyses suggested that 5-FU infusion results in endogenous stress (increased copeptin) but rarely induces myocyte injury (no change in troponin). These findings suggest a more prevalent cardiac influence from 5-FU and that Holter recording is an important tool in the evaluation of patients with suspected cardiotoxicity from 5-FU.

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Biomarkers and electrocardiographic evidence of myocardial ischemia in patients with human immunodeficiency virus infection.

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Biomarkers and electrocardiographic evidence of myocardial ischemia in patients with human immunodeficiency virus infection.

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