Interleukin 6 and Cardiovascular Outcomes in Patients With Chronic Kidney Disease and Chronic Coronary Syndrome

Question What are the associations between interleukin 6 (IL-6) and cardiovascular outcomes in patients with chronic coronary syndrome in association with kidney function? Findings In this cohort study of 14 611 patients with chronic coronary syndrome, IL-6 and estimated glomerular filtration rates were obtained. Elevated IL-6 was in continuous models associated with higher risk of major adverse cardiovascular events in all chronic kidney disease strata and in categorical analysis (IL-6 >= 2.0 ng/L vs <2.0 ng/L) associated with major adverse cardiovascular events in all chronic kidney disease strata. Meaning IL-6 and chronic kidney disease stage may help to identify patients with chronic coronary syndrome for anti-inflammatory treatment. 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 m(2)], mildly decreased eGFR level [60-90 mL/min/1.73 m(2)], and moderately to severely decreased eGFR level [<60 mL/min/1.73 m(2)]). 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. This cohort study outlines the associations and interactions between interleukin 6, chronic kidney disease, and the risk of major cardiovascular outcomes in patients with chronic coronary syndrome.