Effects of beta-blocker therapy on hs-CRP levels in elderly patients with ischemic and non-ischemic heart failure: Results from the CIBIS-ELD trail

C reactive protein (CRP) is a biomarker indicating systemic inflammation. Elevated levels of this biomarker are associated with increased rates of cardiovascular disease, including chronic heart failure (HF). High‐sensitivity CRP assays were developed in order to measure lower levels of CRP, down to 0.3mg/l (hs‐CRP). Up to now, very little is known about the effects of beta‐blocker titration on hs‐CRP levels in ischemic and non‐ischemic HF patients. Also, little is known if this effect differs between selective and unselective blockers. Purpose: This research explored the trajectories of hs‐CRP before and after beta‐blocker (carvedilol vs bisoprolol) titration in elderly HF patients depending on the type of beta‐blocker used and the etiology of the disease (ischemic vs non‐ischemic). Methods: We measured plasma levels of hs‐CRP and NT‐proBNP in 520 HF patients ≥ 65 years (72.06±5.24 years, 38%f, LVEF 41.8±13.8%; ischemic n=243; nonischemic n=277) of the Cardiac Insufficiency Bisoprolol Study in ELDerly (CIBIS‐ELD). In this trial, patients were randomized to bisoprolol vs. carvedilol and doses were uptitrated to the target or maximally tolerated dose. hs‐CRP and NT‐proBNP levels were assessed at baseline (BL) and at follow‐up (FU), after 12 weeks. Results: In patients with ischemic HF, hs‐CRP levels decreased in the bisoprolol group (BL=0.60±0.94 mg/ dl, n=166; FU=0.43±0.694mg/dl, n=131; p=0.010), and were without a change in the carvedilol group (BL=0.60±1.69mg/dl, n=181; FU=0.57±0.982mg/ dl, n=136; p=0.731). There was also no change of hs‐CRP levels in non‐ischemic HF patients in both groups (bisoprolol: BL=0.64±1.175 mg/dl, n=197; FU=0.470±0.81mg/dl, n=152, p=0.069; carvedilol: BL=0.45±0.78mg/dl, n=198; FU=0.41±0.701 mg/ dl, n=152, p=0.420). Plasma levels of NT‐proBNP decreased in ischemic patients treated with bisoprolol, (BL=1594±2146 pg/ml, n=169; FU=1468±2110pg/ ml, n=133, p=0.04), while changes in the carvedilol group were not significant (BL=1648±1991 pg/ml, n=188; FU=1567±2119pg/ml, n=135, p=0.556). In the non‐ischemic group NT‐pro levels did not change significantly in the carvedilol group, while there was an increase in non‐ischemic patients in the bisoprolol group (BL=1427±3113 pg/ml, n=208; FU=1533±5385 pg/ml, n=166, p=0.017). Conclusion: Results indicate that bisoprolol might be associated with a decrease of hs‐CRP and NT‐proBNP levels only in ischemic HF patients, while in nonischemic HF patients there was no change of hs‐CRP and an increase of NT‐proBNP levels. In carvedilol treated patients no significant changes were shown in neither group