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Anticytokine Immune Therapy and Atherothrombotic Cardiovascular Risk.

ABSTRACT: Accumulating observations in humans and animals indicate that inflammation plays a key role in atherosclerosis development and subsequent complications. Moreover, the use of loss- or gain-of-function genetically modified, atherosclerosis-prone mice has provided strong experimental evidence for a causal role of innate and adaptive immunity in atherosclerosis and has revealed the pathogenic activity of proinflammatory cytokines, including TNF (tumor necrosis factor)-?, IL (interleukin)-1?, IL-6, and IL-18, and the atheroprotective effect of anti-inflammatory cytokines, including IL-10 and TGF-?. For the past 15 years, treatments using monoclonal antibodies specifically targeting cytokines, commonly referred as biological therapies, have transformed the treatment of chronic inflammatory diseases, such as rheumatoid arthritis or psoriasis, both conditions associated with increased cardiovascular risk. Analyzing the impact of anticytokine therapies on the cardiovascular outcomes of patients with chronic inflammatory diseases provides insight into the clinical relevance of experimental data on the role of inflammation in atherothrombotic cardiovascular diseases. CANTOS (Canakinumab Antiinflammatory Thrombosis Outcome Study) provided the first evidence that targeting inflammation in humans with atherosclerosis could improve clinical outcomes. Treatment with the anti-IL-1? antibody canakinumab significantly reduced recurrent cardiovascular events in individuals with stable coronary artery disease well-treated with standard-of-care measures. Other clinical studies support the protective effects of treatment with anti-TNF-? and anti-IL-6 receptor monoclonal antibodies on cardiovascular risk. Blockade of the IL-23/IL-17 axis, however, warrants caution as a cardiovascular intervention. Targeting this pathway has improved psoriasis but may augment cardiovascular risk in certain patients. Thus, careful consideration of the cardiovascular risk profile may influence the choice of the most appropriate treatment for patients with chronic inflammatory diseases.Visual Overview: An online visual overview is available for this article.

SUBMITTER: Ait-Oufella H

PROVIDER: S-EPMC6681658 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Anticytokine Immune Therapy and Atherothrombotic Cardiovascular Risk.

Ait-Oufella Hafid H Libby Peter P Tedgui Alain A

Arteriosclerosis, thrombosis, and vascular biology 20190711 8

Accumulating observations in humans and animals indicate that inflammation plays a key role in atherosclerosis development and subsequent complications. Moreover, the use of loss- or gain-of-function genetically modified, atherosclerosis-prone mice has provided strong experimental evidence for a causal role of innate and adaptive immunity in atherosclerosis and has revealed the pathogenic activity of proinflammatory cytokines, including TNF (tumor necrosis factor)-α, IL (interleukin)-1β, IL-6, a ...[more]

PMID: 31294625

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Project description:Background Patients with stable atherothrombotic disease vary in their risk of developing heart failure (HF). Circulating cardiovascular biomarkers may improve HF risk assessment and identify patients who may benefit from emerging HF preventive therapies. Methods and Results We measured high-sensitivity cardiac troponin I and BNP (B-type natriuretic peptide) in 15 833 patients with prior myocardial infarction, ischemic stroke, or peripheral artery disease from the TRA 2°P-TIMI 50 (Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events-Thrombolysis in Myocardial Infarction 50) trial, excluding patients with recent myocardial infarction (<30 days). Biomarkers were categorized using a priori cut points. Hospitalization for HF (HHF) end points were adjudicated with blinded structured review of serious adverse events. Associations between biomarkers and HHF outcomes were adjusted for sex and independent clinical risk predictors of HHF in our cohort (age ≥75, prior HF, type 2 diabetes mellitus, polyvascular disease, body mass index, anemia, chronic kidney disease, hypertension). Baseline high-sensitivity cardiac troponin I and BNP each identified a significant graded risk of HHF independent of clinical risk predictors, including in the subgroups of patients with and without type 2 diabetes mellitus and with and without prior HF. Patients with both high-sensitivity cardiac troponin I ≥5 ng/L and BNP ≥100 pg/mL had the highest HHF event rates. When added to a multivariable Cox regression model with clinical risk predictors (C-index 0.88; 95% CI, 0.85-0.90), BNP (C -index 0.92; 95% CI, 0.90-0.93), and high-sensitivity cardiac troponin I (C-index 0.90; 95% CI, 0.88-0.92) each significantly improved the prognostic performance of the model (both PLRT<0.001). Conclusions Biomarkers of myocardial injury and hemodynamic stress are independent predictors of HHF risk in patients with stable atherothrombotic disease, with and without prior HF and/or type 2 diabetes mellitus. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00526474.

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Anticytokine Immune Therapy and Atherothrombotic Cardiovascular Risk.

Publications

Anticytokine Immune Therapy and Atherothrombotic Cardiovascular Risk.

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