Increased serum IL-6 is predictive of long-term cardiovascular events in high-risk patients submitted to coronary angiography: an observational study

Márcio Mossmann; Marco Vugman Wainstein; Stéfani Mariani; Guilherme Pinheiro Machado; Gustavo Neves de Araújo; Michael Andrades; Sandro Cadaval Gonçalves; Marcello Casaccia Bertoluci

doi:10.1186/s13098-022-00891-0

Increased serum IL-6 is predictive of long-term cardiovascular events in high-risk patients submitted to coronary angiography: an observational study

Diabetol Metab Syndr. 2022 Aug 26;14(1):125. doi: 10.1186/s13098-022-00891-0.

Authors

Affiliations

¹ Post-Graduate Program in Medical Sciences: Cardiology and Cardiovascular Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
² Cardiology Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
³ Internal Medicine Department, School of Medicine, UFRGS, Porto Alegre, Rio Grande do Sul, Brazil.
⁴ Unidade de Análises Moleculares e de Proteínas (UAMP), Hospital de Clinicas de 17 Porto Alegre, Porto Alegre, Brazil.
⁵ Endocrinology Division, Hospital de Clínicas de Porto Alegre (HCPA), Universidade Federal Do Rio Grande Do Sul (UFRGS), Ramiro Barcelos 2350, Porto Alegre, Rio Grande do Sul, 90035-003, Brazil. mbertoluci@hcpa.edu.br.
⁶ Internal Medicine Department, School of Medicine, UFRGS, Porto Alegre, Rio Grande do Sul, Brazil. mbertoluci@hcpa.edu.br.

Abstract

Background: Interleukin-6 (IL-6) is an inflammation-related cytokine associated with an elevated risk of cardiovascular events. In a previous study, we demonstrated that increased IL-6 was predictive of sub-clinical atherosclerotic coronary disease in intermediate-risk patients undergoing coronary angiography. In the present study, we investigated whether increased serum IL-6 is predictive of cardiovascular events in high-risk patients.

Methods: In this observational study, consecutive patients referred for elective coronary angiography due to stable chest pain/myocardial ischemia had IL-6 measured immediately before the procedure. Long-term follow-up was performed by phone call or e-mail, and their clinical registries were revised. The primary outcome was a composite of new myocardial infarction, new ischemic stroke, hospitalization due to heart failure, new coronary revascularization, cardiovascular death, and death due to all causes.

Results: From 141 patients submitted to coronary angiography and IL-6 analysis, 100 had complete follow-up data for a mean of 5.7 years. The median age was 61.1 years, 44% were men, and 61% had type-2 diabetes. The median overall time-to-event for the primary outcome was 297 weeks (95% confidence interval [CI] 266.95-327.16). A receiver operator characteristic curve defined the best cut-off value of baseline serum IL-6 (0.44 pg/mL) with sensitivity (84.37%) and specificity (38.24%) to define two groups. High (> 0.44 pg/mL) IL-6 levels were predictive of cardiovascular events. (p for interaction = 0.015) (hazard ratio = 2.81; 95% CI 1.38-5.72, p = 0.01). Subgroup analysis did not find interactions between patients with or without diabetes, obesity, or hypertension.

Conclusion: In conclusion, an interleukin-6 level higher than 0.44 pg/mL, obtained just before elective coronary angiography, was associated with a poorer prognosis after a mean of 5,7-year. A pre-procedure IL-6 below 0.44 pg/mL, on the other hand, has a very good negative predictive value, suggesting a good prognosis, and may be useful to better indicate coronary angiography in high-risk patients. .

Keywords: Coronary artery disease; Diabetes; High-sensitive C-reactive protein; Inflammation; Interleukin-6.