Neurohormonal determinants of peak oxygen uptake in patients with chronic heart failure.
Chronic heart failure (CHF) is characterized by the activation of neurohormones and cytokines. This study determined whether peak oxygen uptake (VO2) can be predicted by the degree of neurohormonal and cytokine activations in CHF. Plasma norepinephrine. epinephrine, renin-angiotensin system activity, ANP, BNP, and serum interleukin-6 (IL-6) and tumor necrosis factor (TNF)-alpha were measured in 84 CHF patients (age, 59 +/- 1 years, LVEF, 36 +/- 1%) and 34 controls. Maximal cardiopulmonary exercise testing was performed. Peak VO2 (Controls vs CHF: 27.8 +/- 1.3 vs 18.2 +/- 0.5 mL/min/kg, P < 0.0001) was lower in CHF. Patients with CHF had increased plasma norepinephrine (211 +/- 11 vs 315 +/- 24 pg/mL), renin activity (1.2 +/- 0.2 vs 6.2 +/- 1.1 ng/mL/hr), ANP (22 +/- 3 vs 72 +/- 7 pg/mL), and BNP levels (18 +/- 3 vs 200 +/- 25 pg/mL) (all P < 0.01). Serum IL-6 (1.1 0.1 vs 2.4 +/- 0.3 pg/mL) and TNF-alpha (2.7 +/- 0.2 vs 4.0 +/- 0.3 pg/mL) levels were higher in CHF (both P < 0.001). Univariate analysis revealed that age (P < 0.001), cardiothoracic ratio (P < 0.001), norepinephrine (P < 0.0001), ANP (P < 0.001), BNP (P < 0.01), and log IL-6 (P < 0.05) were significantly related with peak VO2. Stepwise regression analysis indicated that plasma norepinephrine and ANP emerged as significant determinants of peak VO2, independent of patient age (overall R = 0.61, P < 0.0001). In summary, patients with CHF exhibited activation of neurohormones and proinflammatory cytokines. Among the elevated hormonal and cytokine markers, plasma norepinephrine and ANP levels were independent predictors of exercise capacity.
Division of Cardiovascular Medicine, Department of Internal Medicine, Tottori University, Faculty of Medicine, Yonago, Japan.
Toru
T
Kinugawa
Masahiko
M
Kato
Kazuhide
K
Ogino
Osamu
O
Igawa
Ichiro
I
Hisatome
Chiaki
C
Shigemasa
Ryuji
R
Nohara
D009320:Atrial Natriuretic Factor / Q000097:blood; D002908:Chronic Disease; D016207:Cytokines / Q000378:metabolism*; D005080:Exercise Test; D005260:Female; D006333:Heart Failure / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020097:Natriuretic Peptide, Brain / Q000097:blood; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009638:Norepinephrine / Q000097:blood; D010101:Oxygen Consumption; D012084:Renin-Angiotensin System / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D015850:Interleukin-6; D018377:Neurotransmitter Agents; D014409:Tumor Necrosis Factor-alpha; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; D009638:Norepinephrine