β-blockade: benefits beyond blood pressure reduction?

Abstract

Hypertension is a major cardiovascular (CV) risk factor, but several other common conditions, including chronic obstructive pulmonary disease (COPD), osteoporosis, and peripheral arterial disease (PAD), have been shown to independently increase the risk of CV events and death. The physiological basis for an increased CV risk in those conditions probably lies in the augmentations of oxidative stress, endothelial dysfunction, systemic inflammation, and arterial stiffness, which all are also hallmarks of hypertension. β-Blockers have been used for the treatment of hypertension for more than 40 years, but a number of meta-analyses have demonstrated that treatment with these agents may be associated with an increased risk of CV events and mortality. However, the majority of primary prevention β-blocker trials employed atenolol, an earlier-generation β(1) -selective blocker whose mechanism of action is based on a reduction of cardiac output. Available evidence suggests that vasodilatory β-blockers may be free of the deleterious effects of atenolol. The purpose of this review is to summarize pathophysiologic mechanisms thought to be responsible for the increased CV risk associated with COPD, osteoporosis, and PAD, and examine the possible benefits of vasodilatory β-blockade in those conditions. Our examination focused on nebivolol, a β(1) -selective agent with vasodilatory effects most likely mediated via β(3) activation.

Figure 1

The use of β‐blockers in patients with chronic obstructive pulmonary disease (COPD) is associated with a higher survival rate than non‐use. The symbols “+” and “o” denote time points at which individuals who were (“o”) and were not (“+”) taking β‐blockers either died or dropped out of the study (ie, were “censored”). Adapted with permission from Rutten and colleagues. ⁷⁴

Figure 2

Steady low‐level rise in nitric oxide (NO) concentration induced by nebivolol treatment may facilitate bone formation. The symbols (+) and (−) denote positive and negative modulation, respectively: “↑” and “↓” indicate increase and decrease, respectively; eNOS, endothelial NO synthase; iNOS, inducible NO synthase. Adapted with permission from Wimalawansa. ¹⁰⁰