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.
Highlights
Signs and symptoms of ischemia in the absence of obstructive coronary artery disease (CAD) is highly prevalent in women and frequently associated with recurrent symptoms, repeated testing and coronary microvascular dysfunction (CMD) [1]
Women with signs and symptoms of ischemia and no obstructive CAD are at elevated risk for major adverse cardiac events (MACE), dominantly heart failure (HF) hospitalization [3] which we have documented to be heart failure with preserved ejection fraction (HFpEF) [4], and diastolic dysfunction [5, 6]
Given the unexpected predominance of HFpEF hospitalization at 6-year follow-up in WISE [3, 4], we investigated the relationships between inflammatory markers [interleukin-6 (IL-6), C-reactive protein, and serum amyloid A (SAA)] and longer-term adverse outcomes in this unique population of patients with signs and symptoms of ischemia with non-obstructive CAD and preserved EF as part of the Women’s Ischemia Syndrome Evaluation (WISE) study sponsored by the National Heart, Lung, and Blood Institute (NHLBI)
Summary
Signs and symptoms of ischemia in the absence of obstructive coronary artery disease (CAD) is highly prevalent in women and frequently associated with recurrent symptoms, repeated testing and coronary microvascular dysfunction (CMD) [1]. Women with signs and symptoms of ischemia and no obstructive CAD are at elevated risk for major adverse cardiac events (MACE), dominantly heart failure (HF) hospitalization [3] which we have documented to be heart failure with preserved ejection fraction (HFpEF) [4], and diastolic dysfunction [5, 6]. Others have reported that elevated C-reactive protein levels correlate with symptoms and markers of myocardial ischemia in patients with chest pain and non-obstructive CAD [9] While these observations suggest that systemic inflammation may be linked with CMD, relations to development of HFpEF have not been investigated. 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
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