Statin therapy in heart failure: is it time for a second look?

C ongestive heart failure (CHF) is a common end-stage clinical presentation of coronary artery disease or 2 of its major risk factors, hypertension and diabetes mellitus. Because of this, patients with CHF are often prescribed 3-hydroxy-3-methylglutaryl coenzyme-A inhibitors (statins) that not only prevent cardiovascular events such as myocardial infarction, but also reduce the risk of incident heart failure. In concept, statin therapy could benefit patients with CHF by multiple mechanisms, including reduction in further ischemic events, decreased sympathetic activity, or improved endothelial function. However, once heart failure has developed, from either ischemic or nonischemic heart disease, the benefit of statin therapy is more controversial. In the present issue of the Journal, Haack et al 1 present a well-executed series of experiments showing that simvastatin treatment significantly improved respiratory variability and arrhythmia observed in a postinfarction rat CHF model. This improvement was associated with amelioration of enhanced peripheral arterial chemosensitivity, a major mechanism mediating periodic breathing and central sleep apnea (CSA) in CHF. 2,3 Rats with CHF exhibited increased respiratory variability with reduced tidal volume and augmented ventilatory responses to hypoxia but not hypercapnia. Simvastatin mediated downregulation of the exaggerated hypoxic ventilatory response and carotid nerve discharge. These changes were associated with upregulation of Kruppel-like factor 2 and endothelial NO synthase within the carotid body and nucleus tractus solitarii, a group of respiratory neurons within the dorsal respiratory group that receive afferent input from the peripheral chemoreceptors. In essence, these findings demonstrate that the increased carotid body chemosensitivity, respiratory instability, and cardiac arrhythmias observed in CHF are ameliorated by simvastatin treatment in rats. In CHF, periodic breathing and CSA are prevalent comor-bidities 4 associated with increased mortality. One mechanism mediating CSA in patients with CHF is the enhanced sensitivity of the peripheral and central chemoreceptors, resulting in augmented ventilatory responses to hypoxia and hypercapnia. Furthermore, the severity of CSA correlates with the degree of sensitivity to CO 2. 7 Therefore, it is surprising that in the present study, CO 2 chemosensitivity remained unchanged. Given the increased morbidity and mortality associated with CSA in CHF, could statins represent a pharmacological therapy in CHF that would be of clinical benefit? Indeed, effective treatment of CSA improves survival of patients with heart failure. 6 In 1 study, patients with the highest burden of CSA 9 were the least likely to have their CSA suppressed with continuous positive airway pressure therapy. If statins dampen chemosensitivity, …