Association of interleukin-6 and interleukin-18 with cardiovascular disease in older adults: Atherosclerosis Risk in Communities study

Interleukin-6 (IL-6) and interleukin-18 (IL-18), important cytokines implicated in atherosclerosis and inflammaging, were assessed for associations with global cardiovascular disease (CVD), atrial fibrillation (AF), and death in older adults.Participants from Atherosclerosis Risk in Communities study Visit 5 (mean age 75.4 ± 5.1 years) with IL-6 and IL-18 measurements were included (n = 5672). Cox regression models were used to assess associations of IL-6 and IL-18 with coronary heart disease (CHD), ischaemic stroke, heart failure (HF) hospitalization, global CVD (composite of CHD, stroke, and HF), AF, and all-cause death. Over a median follow-up of 7.2 years, there were 1235 global CVD events, 530 AF events, and 1173 deaths. Higher IL-6 [hazard ratio (HR) 1.57, 95% confidence interval (CI) 1.44-1.72 per log unit increase] and IL-18 (HR 1.13, 95% CI 1.01-1.26) were significantly associated with global CVD after adjustment for cardiovascular risk factors. Association between IL-6 and global CVD remained significant after further adjustment for high-sensitivity C-reactive protein (hs-CRP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high-sensitivity troponin T (hs-TnT) but was no longer significant for IL-18 after further adjustments. Interleukin-6 was also associated with increased risk for CHD, HF, and AF after adjustment for covariates. Both IL-6 and IL-18 were associated with increased risk for all-cause death independent of cardiovascular risk factors and other biomarkers.Among older adults, both IL-6 and IL-18 were associated with global CVD and death. The association between IL-6 with CVD appears to be more robust and was independent of hs-CRP, NT-proBNP, and hs-TnT.In older adults in the Atherosclerosis Risk in Communities study (average age 75 years), higher levels of interleukin-6 and interleukin-18, two proteins implicated in atherosclerosis and increased inflammation that occurs with ageing, significantly increased risk for global cardiovascular disease (including coronary heart disease, stroke, and heart failure) during the next ∼7 years; interleukin-6 also increased risk for global cardiovascular disease, coronary heart disease, heart failure, and atrial fibrillation even after adjustment for other biomarkers of inflammation and subclinical myocardial injury, and both interleukin-6 and interleukin-18 were associated with increased risk for all-cause death independent of cardiovascular risk factors and other biomarkers. In older adults, higher levels of interleukin-6 and interleukin-18 were both associated with increased risk for global cardiovascular disease (including coronary heart disease, stroke, and heart failure) and death.The association between interleukin-6 and global cardiovascular disease appeared to be stronger than that for interleukin-18 and remained significant after adjustment for other biomarkers of inflammation and subclinical myocardial injury.