May 19, 2017Open Access
Inflammatory biomarkers as predictors of heart failure in women without obstructive coronary artery disease: A report from the NHLBI-sponsored Women’s Ischemia Syndrome Evaluation (WISE)
Key Result
In women with ischemia, non-obstructive CAD, and preserved EF, elevated IL-6 predicted heart failure hospitalization (AHR 2.5; 95% CI 1.2-5.0; p=0.02) and all-cause mortality.
Study Design
Type
Cross-Sectional (n=390)
Structured PICO
Do elevated inflammatory biomarkers predict heart failure hospitalization and all-cause mortality in women with signs and symptoms of ischemia, non-obstructive CAD, and preserved EF?
P
Population
390 women with signs and symptoms of ischemia, non-obstructive coronary artery disease (>50% diameter stenosis excluded), and preserved left ventricular ejection fraction. Mean age 56 ± 11 years. Major exclusion criteria included cardiomyopathy, NYHA class IV congestive heart failure, recent myocardial infarction, and significant valvular heart disease.
I
Intervention
Baseline measurement of inflammatory biomarkers (serum interleukin-6 [IL-6], high-sensitivity C-reactive protein [hs-CRP], and serum amyloid A [SAA])
C
Comparator
Lower levels of the respective inflammatory biomarkers (e.g., lowest quartile vs highest quartile, or continuous comparison)
O
Outcome
First occurrence of all-cause mortality and heart failure hospitalization at a median follow-up of 6 yearshard clinical
In women with signs of ischemia but no obstructive coronary artery disease and preserved ejection fraction, elevated baseline IL-6 is strongly associated with future heart failure hospitalization and all-cause mortality.
Main Result
Effect estimate: AHR 2.5 (95% CI 1.2-5.0)
p-value: p=0.02
Abstract
BACKGROUND: Women with signs and symptoms of ischemia, no obstructive coronary artery disease (CAD) and preserved left ventricular ejection fraction (EF) often have diastolic dysfunction and experience elevated rates of major adverse cardiac events (MACE), including heart failure (HF) hospitalization with preserved ejection fraction (HFpEF). We evaluated the predictive value of inflammatory biomarkers for long-term HF hospitalization and all-cause mortality in these women. METHODS: We performed a cross-sectional analysis to investigate the relationships between inflammatory biomarkers serum interleukin-6 (IL-6), C-reactive protein (hs-CRP) and serum amyloid A (SAA) and median of 6 years follow-up for all-cause mortality and HF hospitalization among women with signs and symptoms of ischemia, non-obstructive CAD and preserved EF. Multivariable Cox regression analysis tested associations between biomarker levels and adverse outcomes. RESULTS: Among 390 women, mean age 56 ± 11 years, median follow up of 6 years, we observed that there is continuous association between IL-6 level and HF hospitalization (adjusted hazard ratio AHR 2.5 1.2-5.0, p = 0.02). In addition, we found significant association between IL-6, SAA levels and all-cause mortality AHR (1.8 1.1-3.0, p = 0.01) (1.5 1.0-2.1, p = 0.04), respectively. CONCLUSION: In women with signs and symptoms of ischemia, non-obstructive CAD and preserved EF, elevated IL-6 predicted HF hospitalization and all-cause mortality, while SAA level was only associated with all-cause mortality. These results suggest that inflammation plays a role in the pathogenesis of development of HFpEF, as well all-cause mortality.