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. 2017 May 19;12(5):e0177684.
doi: 10.1371/journal.pone.0177684. eCollection 2017.

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)

Ahmed AlBadri  1 , Kha Lai  1 , Janet Wei  1 , Sofy Landes  1 , Puja K Mehta  1 , Quanlin Li  2 , Delia Johnson  3 , Steven E Reis  3 , Sheryl F Kelsey  3 , Vera Bittner  4 , George Sopko  5 , Leslee J Shaw  6 , Carl J Pepine  7 , C Noel Bairey Merz  1
Affiliations

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)

Ahmed AlBadri et al. PLoS One. .

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.

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Conflict of interest statement

Competing Interests: Dr. AlBadri, Dr. Lai, Dr Wei, Dr. Landes, Dr. Mehta, Mr. Quanlin, Dr. Johnson, Dr. Reis, Dr. Kelsey, Dr. Bittner, Dr. Sopko, Dr. Shaw, and Dr. Pepine have nothing to disclose. Dr. Bairey Merz reports consulting revenue paid to CSMC from Gilead, Medscape, Research Triangle Institute, research money from Gilead, Erika Glazer, payments for lectures from Beaumont Hospital, European Horizon, Florida Hospital, INOVA, Korean Cardiology Society, Practice Point Communications, Pri-Med, University of Chicago, VBWG, University of Colorado, University of Utah, WomenHeart, Harold Buchwald Heart-Health, Tufts. Dr. Mehta received a significant research support from Gilead and General Electric. Dr. Anderson is a consultant for BioSense Webster and subsidiary of Johnson and Johnson. Dr. Samuels is a consultant for Abbot Vascular and Volcano Corporation. Dr. Handberg reports unrestricted educational grants from Amarin, Amgen, AstraZeneca, Baxter, Boehringer Ingleheim, Catadasis, Cytori, Daiichi Sankyo, Esperion, Genentech, Gilead, ISIS Pharmaceuticals, Mesoblast, Neostem, Sanofi/Aventis, and Unified Therapeutics, outside the submitted work. Mrs. Minissian reports receiving grants from NIH/NHLBI, AHA, National Lipid Foundation, Gilead, Cover Letter honorarium from Preventative Cardiovascular Nurses Association and WebMD and consultant for Sanofi Aventis-Regeneron. Dr. Pepine reports grants from NIH/NHLBI, during the conduct of the study; grants from Amarin, Amgen, AstraZeneca, Baxter, Boehringer Ingleheim, Catadasis, Cytori, Daiichi Sankyo, Esperion, Genentech, ISIS Pharmaceuticals, Neostem, Sanofi/Aventis, and Unified Therapeutics, outside the submitted work. QMED, Inc. donated digital ambulatory ECG monitors used in a subgroup of WISE cohort. There were no other relevant declaration relating to employment, consultancy, patents, products in development, marketed products. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. All-cause survival curves by IL-6 level (N = 390).
The black line indicates IL-6 level <4.79 pg/mL and the red line is when IL-6 ≥4.79 pg/mL among women with signs and symptoms of ischemia, no obstructive CAD and preserved EF (median follow up of 6 years).
Fig 2
Fig 2. HF hospitalization by IL-6 level (N = 390).
The black line indicates IL-6 level <4.79 pg/mL and the red line is when IL-6 ≥4.79 pg/mL among women with signs and symptoms of ischemia, no obstructive CAD and preserved EF (median follow up of 6 years).
See this image and copyright information in PMC

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