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Assessment of Vascular Function in Patients With Chronic Kidney Disease
Published on: June 16, 2014
Interleukin 6 and Cardiovascular Outcomes in Patients With Chronic Kidney Disease and Chronic Coronary Syndrome
Gorav Batra1,2, Tatevik Ghukasyan Lakic1, Johan Lindbäck1
1Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
Insights
Elevated interleukin-6 (IL-6) levels increase the risk of major adverse cardiovascular events (MACE) in patients with chronic coronary syndrome, regardless of chronic kidney disease (CKD) stage. This highlights IL-6 as a potential biomarker for identifying high-risk individuals.
Area of Science:
- Cardiovascular Medicine
- Nephrology
- Inflammation Research
Background:
- Inflammation is a known driver of cardiovascular disease (CVD).
- Anti-inflammatory therapies reduce cardiovascular events in chronic coronary syndrome (CCS).
- Chronic kidney disease (CKD) is an independent risk factor for CVD, but the role of inflammation, specifically interleukin-6 (IL-6), in this context remains unclear.
Purpose of the Study:
- To investigate the association between IL-6 levels and cardiovascular outcomes in patients with CCS.
- To examine how kidney function, assessed by estimated glomerular filtration rate (eGFR), modifies the relationship between IL-6 and cardiovascular events.
Main Methods:
- A substudy of the multicenter STABILITY trial, including 14,611 patients with CCS and available baseline IL-6 levels.
- Patients were stratified by eGFR levels: normal (≥90 mL/min/1.73 m2), mild CKD (60-90 mL/min/1.73 m2), and moderate to severe CKD (<60 mL/min/1.73 m2).
- Associations between IL-6 levels (continuous and categorical [<2.0 ng/L vs ≥2.0 ng/L]) and major adverse cardiovascular events (MACE) were analyzed.
Main Results:
- Higher IL-6 levels were independently associated with an increased risk of MACE across all CKD strata (P < .001).
- Elevated IL-6 (≥2.0 ng/L) was linked to a significantly higher risk of MACE in patients with normal kidney function (HR, 1.35), mild CKD (HR, 1.57), and moderate to severe CKD (HR, 1.60).
- The risk of MACE associated with elevated IL-6 increased with decreasing eGFR levels.
Conclusions:
- In patients with CCS, elevated IL-6 levels are consistently associated with an increased risk of MACE, irrespective of the stage of CKD.
- IL-6 levels, in conjunction with CKD stage, may serve as valuable biomarkers for identifying CCS patients who could benefit from anti-inflammatory therapies.
- These findings underscore the critical role of inflammation in CVD pathogenesis, particularly in the presence of impaired kidney function.
Importance:
Inflammation promotes cardiovascular disease and anti-inflammatory treatment reduces cardiovascular events in patients with chronic coronary syndrome. Chronic kidney disease (CKD) is a risk factor for cardiovascular disease. It is unclear how inflammation mediated by interleukin 6 (IL-6) in patients with CKD is linked to cardiovascular disease.
Objective:
To investigate associations between IL-6 and cardiovascular outcomes in patients with chronic coronary syndrome in association with kidney function.
Design, Setting, And Participants:
This multicenter cohort study included patients enrolled at 663 centers in 39 countries with chronic coronary syndrome who were included in the Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy (STABILITY) trial. Patients were enrolled between December 2008 and April 2010 and were followed up for a median length of 3.7 years. Analysis in this substudy began September 2020.
Exposures:
Exposures were IL-6 and creatinine estimated glomerular filtration rates (eGFR), which were collected at baseline. Associations between continuous and categorical levels (<2.0 ng/L vs ≥2.0 ng/L) of IL-6 and cardiovascular outcomes were tested in association with eGFR cutoffs (normal eGFR level [≥90 mL/min/1.73 m2], mildly decreased eGFR level [60-90 mL/min/1.73 m2], and moderately to severely decreased eGFR level [<60 mL/min/1.73 m2]).
Main Outcomes And Measures:
Main outcome was major adverse cardiovascular events (MACE), a composite of cardiovascular death, myocardial infarction, and stroke.
Results:
This substudy of the STABILITY trial included 14 611 patients with available IL-6 levels at baseline. The median (interquartile range) age was 65 (59-71) years, and 2700 (18.5%) were female. During follow-up, MACE occurred in 1459 individuals (10.0%). Higher levels of IL-6 were in continuous models independently associated with risk of MACE (P < .001) in all CKD strata. Using predefined strata, elevated IL-6 level (≥2.0 vs <2.0 ng/L) was associated with increased risk of MACE at normal kidney function (2.9% vs 1.9% events/y [hazard ratio, 1.35; 95% CI, 1.02-1.78]), mild CKD (3.3% vs 1.9% [hazard ratio, 1.57; 95% CI, 1.35-1.83]), and moderate to severe CKD (5.0% vs 2.9% [hazard ratio, 1.60; 95% CI, 1.28-1.99]).
Conclusions And Relevance:
In patients with chronic coronary syndrome, elevated levels of IL-6 were associated with risk of MACE in all CKD strata. Thus, IL-6 and CKD stage may help when identifying patients with chronic coronary syndrome for anti-inflammatory treatment.
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