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Original Articles

Serum Cortisol as a Useful Predictor of Cardiac Events in Patients With Chronic Heart Failure

The Impact of Oxidative Stress

Masayuki Yamaji, MD; Takayoshi Tsutamoto, MD; Chiho Kawahara, MD; Keizo Nishiyama, MD; Takashi Yamamoto, MD; Masanori Fujii, MD and Minoru Horie, MD

From the Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Tsukinowa, Seta, Otsu, Japan.

Correspondence to Takayoshi Tsutamoto, MD, Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science Tsukinowa, Seta, Otsu 520-2192, Japan. E-mail tutamoto{at}belle.shiga-med.ac.jp

Received March 27, 2009; accepted September 10, 2009.

Background— The pathophysiological role of cortisol, which binds to the mineralocorticoid receptor with an affinity equal to that of aldosterone (ALD), may be influenced by oxidative stress in patients with chronic heart failure. We evaluated cardiac event prediction using cortisol levels in chronic heart failure, in comparison with ALD, adrenocorticotropic hormone, and brain natriuretic peptide (BNP), and the impact of oxidative stress.

Methods and Results— We measured the plasma levels of biomarkers such as BNP, ALD, adrenocorticotropic hormone, serum cortisol, and oxidized low-density lipoprotein (oxLDL), a biomarker of oxidative stress, in 319 consecutive symptomatic patients with chronic heart failure, and we followed these patients for a mean period of 33 months. During the follow-up period, 29 patients had cardiac events (death or hospitalization). Plasma levels of BNP, ALD, adrenocorticotropic hormone, oxLDL, and serum cortisol (16.8±1.8 µg/dL versus 12.4±0.3 µg/dL, P=0.01) were significantly higher in patients with cardiac events than in those without cardiac events. On stepwise multivariate analyses, high levels of BNP (P=0.0003), renin (P=0.002), cortisol (P=0.02), and oxLDL (P=0.002) were independent predictors of cardiac events, but ALD and adrenocorticotropic hormone levels were not. In patients with serum cortisol 12.5 µg/dL, the hazard ratio of cardiac events in patients with oxLDL 12 U/mL was 3.5 compared with that in patients with oxLDL <12 U/mL (P=0.008).

Conclusions— These findings indicate that serum cortisol levels were a complementary and incremental cardiac event risk predictor in combination with BNP in patients with chronic heart failure and that cardiac event prediction based on cortisol levels was influenced by oxidative stress.

Key Words: cortisol • aldosterone • BNP • oxidative stress • cardiac events • prognosis • heart failure

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