Abstract
We sought to examine the relationship between circulating interleukin-6 (IL-6) level and regional left-ventricular (LV) function among apparently healthy individuals free of cardiovascular disease. Using magnetic resonance myocardial tagging, we determined peak systolic circumferential strain (Ecc) as a measure of regional systolic function in 894 asymptomatic participants in the Multi-Ethnic Study of Atherosclerosis. Ecc was analysed by harmonic phase imaging separately in the LV anterior wall, septum, lateral wall, and inferior wall. Global Ecc was calculated as the average of Ecc in all myocardial segments. We performed multivariable linear regression to evaluate the independent associations between log IL-6 and Ecc, after adjusting for demographic features, cardiovascular risk factors, and markers of subclinical atherosclerosis. The inverse relationships between IL-6 and absolute Ecc were similar in both genders. In multivariable analysis, higher IL-6 level was independently associated with reduced systolic function (less negative Ecc) in the septum [regression coefficient = 1.03 per unit higher log IL-6, 95% confidence interval (CI) 0.26-1.79, P = 0.008] and inferior wall (regression coefficient = 1.65, 95% CI 0.74-2.56, P < 0.001), but not in the anterior wall (P = 0.27) or lateral wall (P = 0.52). Overall, there was an independent inverse association between IL-6 and global Ecc (regression coefficient = 0.94, 95% CI 0.37-1.51, P = 0.001). Compared with C-reactive protein, higher IL-6 level demonstrates a stronger independent association with reduced regional systolic function. In asymptomatic men and women without documented cardiovascular disease, there is a strong, independent, inverse relationship between IL-6 and regional LV systolic function. These findings suggest that IL-6 may underlie the pathogenetic link between inflammation, LV dysfunction and incipient heart failure. The observed variable relationships between IL-6 and systolic function across different LV regions warrant further investigations.
Highlights
The pivotal role of inflammation in cardiovascular disease has been increasingly recognized.[1]
Higher IL-6 level was independently associated with reduced systolic function in the septum [regression coefficient 1⁄4 1.03 per unit higher log IL-6, 95% confidence interval (CI) 0.26–1.79, P 1⁄4 0.008] and inferior wall, but not in the anterior wall (P 1⁄4 0.27) or lateral wall (P 1⁄4 0.52)
In asymptomatic men and women without documented cardiovascular disease, there is a strong, independent, inverse relationship between IL-6 and regional LV systolic function. These findings suggest that IL-6 may underlie the pathogenetic link between inflammation, LV dysfunction and incipient heart failure
Summary
The pivotal role of inflammation in cardiovascular disease has been increasingly recognized.[1]. Accumulating clinical evidence suggests that IL-6 may promote the development and progression of left-ventricular (LV) dysfunction leading to HF.[9,10,11] Because coronary artery disease is a major cause of HF, myocardial ischaemia or infarction from atherosclerotic plaque rupture may be the causal link between inflammation and HF.[10]. Inflammation may exert a more direct and detrimental effect on myocardial function.[2,3] several epidemiological studies have demonstrated an association between inflammation and incident HF,9,11 – 13 the precise pathogenetic mechanisms remain to be elucidated. Cardiac magnetic resonance imaging (MRI) is considered a reference standard for assessment of LV structure and function,[14] and may provide valuable insights into the intriguing link between inflammation and HF. Magnetic resonance tagging detects subtle changes in regional myocardial function, which may afford unique pathophysiologic insights.[14,15]
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