Adiponectin is an anti-inflammatory, antiatherogenic
adipokine elevated in
heart failure (HF) that may protect against endothelial dysfunction by influencing underlying
nitric oxide bioavailability. In this study, we examine the relationship between plasma
adiponectin levels and measures of
nitric oxide bioavailability and myocardial performance in patients with chronic systolic HF. In 139 ambulatory patients with stable, chronic systolic HF (left ventricular [LV] ejection fraction ≤40%, New York Heart Association class I to IV), we measured plasma levels of
adiponectin,
asymmetric dimethylarginine (ADMA), and global
arginine bioavailability (GABR), and performed comprehensive echocardiography with assessment of cardiac structure and performance. Adverse events (all-cause mortality or
cardiac transplantation) were prospectively tracked for a median of 39 months. Plasma
adiponectin levels directly correlated with plasma ADMA levels (Spearman's r = 0.41, P < 0.001) and
aminoterminal pro-B-type natriuretic peptide (
NT-proBNP) levels (r = 0.55, P < 0.001), inversely correlated with GABR (r = -0.39, P < 0.001), and were not associated with
high-sensitivity C-reactive protein (P = 0.81) or
myeloperoxidase (P = 0.07). Interestingly, increased plasma
adiponectin levels remained positively correlated with plasma ADMA levels only in patients with elevated
NT-proBNP levels (r = 0.33, P = 0.009). Higher plasma
adiponectin levels were associated with worse
LV diastolic dysfunction (rank sums P = 0.002), right ventricular (RV) systolic dysfunction (rank sums P = 0.002), and RV diastolic dysfunction (rank sums P = 0.011), but not after adjustment for plasma ADMA and
NT-proBNP levels. Plasma
adiponectin levels predicted increased risk of adverse clinical events (hazard ratio, 95% confidence interval 1.45 [1.02-2.07], P = 0.038) but not after adjustment for plasma ADMA and
NT-proBNP levels, or echocardiographic indices of diastolic or RV systolic dysfunction. In patients with chronic systolic HF,
adiponectin production is more closely linked with
nitric oxide bioavailability than
inflammation, and appears to be more robust in the setting of cardiac dysfunction or elevated
natriuretic peptide levels.