P6352The antimicrobial protein Azurocidin-1 is associated with prevalent diastolic dysfunction and incident congestive heart failure in a Swedish population cohort

Abstract

Abstract Background Although Azurocidin-1 (Azu-1), also known as heparin binding protein, has been associated with myocardial infarction, possible associations of Azu-1 with congestive heart failure (CHF) remains unknown. Here we tested the possible association of Azu-1 with prevalent diastolic dysfunction and/or incident CHF in a large Swedish prospective population based cohort. Methods Azu-1 was analyzed using the Proseek Multiplex CVD III panel in 1737 participants from a subsample of the population (mean age 67 years, 29% women) who underwent a complete echocardiographic examination. All biomarkers were logarithmized and standardized prior to statistical analysis. Logistic and linear regression were adjusted for age, sex, BMI, diabetes, systolic and diastolic blood, anti-hypertensive treatment and subjects with an ejection fraction below 50% were excluded for the analysis of prevalent diastolic dysfunction and Azu-1. For the linear regression model, we used E/é ratio as a key functional variable in assessing diastolic function according to ESC 2016 Guidelines for Acute and Chronic Heart Failure. Furthermore, we dichotomized the E/é ratio at >13 in another logistic regression model. Finally, in line with ESC Guidelines 2016, we combined the key functional (E/é >13) and key structural (left ventricular mass index (LVMI) ≥115 g/m2 for males and ≥95 g/m2 for females) alterations for diastolic dysfunction and used this variable in both logistic regression for association with Azu-1 and for Cox regression analysis of incident CHF. 1439 subjects (938 cases with some degree of diastolic dysfunction and 501 controls) remained for the analysis. For the analysis of incident CHF, Cox regression was used excluding subjects with ejection fraction below 50% and prevalent CHF and further adjusted for prevalent coronary disease on top of age, sex, BMI, diabetes, systolic and diastolic blood and anti-hypertensive treatment. 1,511 subjects (64 incident cases of CHF vs 1447 controls; median follow up time 8.9 years) remained. Results After adjustment for above mentioned risk factors, each 1 standard deviation (SD) of increase in Azu-1 was associated with any degree of prevalent diastolic dysfunction (odds ratio (OR) 1.13, p=0.048), E/é >13 OR 1.21, p=0.028 and for combined LVMI and E/é OR 1.17, p=0.015. In fully adjusted linear regression Azu-1 was associated with E/é with a β-coefficient of 0.056, p=0.018. In a fully adjusted Cox regression models Azu-1 was associated with incident CHF (hazard ratio (HR) 1.32, p=0.025). As expected and as proof of concept E/é >13 and combined LVMI with E/é were also associated with incident CHF; HR 2.84, p<0.001 and HR 2.12, p=0.006, respectively. Conclusion An inflammatory mediator, Azurocidin-1, is associated with prevalent diastolic dysfunction, E/é, E/é combined with LVMI as well as incident congestive heart failure in a population-based cohort.