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)

Abstract

BackgroundWomen 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.MethodsWe 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.ResultsAmong 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.ConclusionIn 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.

Sex differences in heart failure

“…The interpretation of cardiac biomarkers should vary between genders. In a recent study, high‐sensitivity troponin I was shown to significantly increase the diagnosis of acute myocardial infarction in women (11%–22%) but not men (19%–22%) . The role of B‐type natriuretic peptide (BNP) and N‐terminal prohormone of brain natriuretic peptide (NT‐proBNP) has been well validated for both diagnostic and therapeutic assessment of HF .…”

“…In a recent study, high-sensitivity troponin I was shown to significantly increase the diagnosis of acute myocardial infarction in women (11%-22%) but not men (19%-22%). 10 The role of B-type natriuretic peptide (BNP) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) has been well validated for both diagnostic and therapeutic assessment of HF. 11,12 Although the clinical correlations of these measurements are similar, the baseline values have significant gender differences.…”

Do most patients with obesity or type 2 diabetes, and atrial fibrillation, also have undiagnosed heart failure? A critical conceptual framework for understanding mechanisms and improving diagnosis and treatment

“…Importantly, systemic inflammation precedes and predicts both HFpEF and AF in the community . Biomarkers of systemic inflammation and collagen turnover are elevated in both AF and HFpEF and are associated with exercise intolerance and abnormalities in diastolic filling .…”

“…Importantly, systemic inflammation precedes and predicts both HFpEF and AF in the community. 41,42 Biomarkers of systemic inflammation and collagen turnover are elevated in both AF and HFpEF and are associated with exercise intolerance and abnormalities in diastolic filling. [43][44][45] Proteomic analyses suggest a strong link between HFpEF and biomarkers of inflammation and extracellular matrix reorganization 46 and have shown that AF parallels the metabolic and inflammatory comorbidities in HFpEF.…”

Novel heart failure biomarkers: why do we fail to exploit their potential?

“…Also, in humans, inhibition of IL-6 has been tested, but it was not able to improve coronary flow reserve in patients post-myocardial infarction [114]. Nevertheless, because IL-6 has been shown to be involved in HF development, and because levels of this inflammatory marker are increased in HF and are able to predict HF outcome in various types of HF [5,[115][116][117][118][119], it could serve as an HF biomarker. The use of IL-6 in a multi-biomarker model has been suggested [120], but circulating IL-6 levels are also affected by factors like stress, physical exercise, gender and age [119].…”