Fabian Hammer1, Timo Deutschbein2, Almuth Marx3, Gülmisal Güder4, Roman Michalski4, Georg Ertl4, Bruno Allolio5, Christiane E Angermann4, Stefan Störk4, Martin Fassnacht6. 1. Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany; Department of Internal Medicine I, Cardiology, University Hospital Würzburg, Würzburg, Germany; Department of Internal Medicine B, University Medicine Greifswald, Greifswald, Germany. Electronic address: fabian.hammer@uni-greifswald.de. 2. Department of Internal Medicine I, Endocrine and Diabetes Unit, University Hospital Würzburg, Würzburg, Germany. 3. Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany. 4. Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany; Department of Internal Medicine I, Cardiology, University Hospital Würzburg, Würzburg, Germany. 5. Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany; Department of Internal Medicine I, Endocrine and Diabetes Unit, University Hospital Würzburg, Würzburg, Germany. 6. Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany; Department of Internal Medicine I, Endocrine and Diabetes Unit, University Hospital Würzburg, Würzburg, Germany; Central Laboratory, Research Unit, University Hospital Würzburg, Würzburg, Germany.
Abstract
AIMS: Serum cortisol independently predicts mortality risk in patients with systolic heart failure. Salivary cortisol may provide advantages as it better reflects the biologically active free compound. Furthermore, sampling is non-invasive and may easily be performed in outpatients. We comparatively evaluated associations of morning (MSC) vs. evening salivary cortisol (ESC) and all-cause mortality risk. METHODS AND RESULTS: MSC (8 am) and ESC (9 pm) were determined in 229 patients with heart failure participating in the Interdisciplinary Network for Heart Failure program (66 ± 13 years; 21% female; 37% New York Heart Association (NYHA) class III/IV, median left ventricular ejection fraction 33%). The association of cortisol with mortality risk was determined by univariate and Cox multivariable regression analyses adjusting for age, sex, NYHA class, and N-terminal pro-hormone B-type natriuretic peptide. Compared to ESC, MSC was significantly higher and exhibited a higher variance: median 0.59 ng/ml (interquartile range 0.41-0.93) vs. 0.25 ng/ml (0.15-0.48), p<0.001. During 18 months of follow-up, 25 (11%) patients died. In univariate and multivariable models mortality risk was not increased in the highest MSC quartile: crude hazard ratio (HR) 1.81 (95% confidence interval 0.79-4.14, p=0.160), adjusted HR 1.26 (0.51-3.13, p=0.616). However, patients in the highest ESC quartile had a significantly increased mortality risk, suggesting that associations of high ESC and increased mortality were independent of disease severity: crude HR 3.33 (1.50-7.42, p=0.003), adjusted HR 2.49 (1.01-6.14, p=0.047). ESC alone proved the best predictor of mortality. CONCLUSION: High ESC but not MSC levels independently predict increased mortality risk in heart failure.
AIMS: Serum cortisol independently predicts mortality risk in patients with systolic heart failure. Salivary cortisol may provide advantages as it better reflects the biologically active free compound. Furthermore, sampling is non-invasive and may easily be performed in outpatients. We comparatively evaluated associations of morning (MSC) vs. evening salivary cortisol (ESC) and all-cause mortality risk. METHODS AND RESULTS: MSC (8 am) and ESC (9 pm) were determined in 229 patients with heart failure participating in the Interdisciplinary Network for Heart Failure program (66 ± 13 years; 21% female; 37% New York Heart Association (NYHA) class III/IV, median left ventricular ejection fraction 33%). The association of cortisol with mortality risk was determined by univariate and Cox multivariable regression analyses adjusting for age, sex, NYHA class, and N-terminal pro-hormone B-type natriuretic peptide. Compared to ESC, MSC was significantly higher and exhibited a higher variance: median 0.59 ng/ml (interquartile range 0.41-0.93) vs. 0.25 ng/ml (0.15-0.48), p<0.001. During 18 months of follow-up, 25 (11%) patients died. In univariate and multivariable models mortality risk was not increased in the highest MSC quartile: crude hazard ratio (HR) 1.81 (95% confidence interval 0.79-4.14, p=0.160), adjusted HR 1.26 (0.51-3.13, p=0.616). However, patients in the highest ESC quartile had a significantly increased mortality risk, suggesting that associations of high ESC and increased mortality were independent of disease severity: crude HR 3.33 (1.50-7.42, p=0.003), adjusted HR 2.49 (1.01-6.14, p=0.047). ESC alone proved the best predictor of mortality. CONCLUSION: High ESC but not MSC levels independently predict increased mortality risk in heart failure.