Abstract 19301: Lymphocyte G-Protein Coupled Receptor Kinase-2 (grk2) Levels Predict Cardiac Mortality in Patients With Advanced Heart Failure.
Aims: Increased cardiac G-protein coupled receptor kinase-2 (GRK2) expression and activity are pivotal events in the pathogenesis of HF in part causing β-adrenergic receptor (βAR) dysfunction in myocardium. Exercise training exerts several beneficial effects on cardiovascular system, included reduction of GRK2 expression and resensitization of βAR signaling and function in the failing heart. Importantly, abnormalities of βAR signaling in the heart can be mirrored in circulating lymphocytes of heart failure (HF) patients and lymphocyte GRK2 has been shown to correlate with disease severity, as increased levels tracking with more severe LV dysfunction . In the present study, we aimed to evaluate whether lymphocyte GRK2 levels can predict long-term mortality in HF patients.
Methods and Results: We prospectively studied 141 patients with advanced post-ischemic HF who underwent 3-month of exercise training program. Lymphocyte GRK2 protein and mRNA levels, plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) and norepinephrine were measured at baseline and after training along with clinical and functional parameters (left ventricular ejection fraction, NYHA class, and peak VO2). Cardiac-related mortality was evaluated during a mean follow up period of 26±12 months. Baseline NT-proBNP, norepinephrine, and peak VO2 were all strong predictors of cardiac death. Interestingly, lymphocyte GRK2 protein expression also showed an independent prognostic value. Exercise-induced changes (expressed as delta%) of blood and functional parameters indicated that delta lymphocyte GRK2 (post versus pre exercise levels) was the strongest predictor of cardiac mortality. The lack of any significant effect of exercise to reduce lymphocyte GRK2 protein levels identified those HF patients with the poorest outcome.
Conclusion: Our data offer the first demonstration that lymphocyte GRK2 can be an independent predictor of cardiac mortality in patients with advanced HF. Larger studies are needed for a definitive determination of the ultimate usefulness of GRK2 levels serving as blood-measured biomarker in the HF clinic.
- © 2010 by American Heart Association, Inc.