T he development and clinical application of statins has been one of the most significant advances in health care over the past quarter of a century. Statins have been shown to prevent heart failure (HF), reduce the risk of myocardial infarction and stroke, as well as reduce mortality in patients with and without coronary artery disease, independent of serum cholesterol. 1 Their role in patients with established HF is, however, controversial. Although their use in patients with HF is supported by observational studies and meta-analyses, 2,3 their use has not been supported by the results of the pivotal large-scale prospective randomized trials in patients with HF and a reduced ejection fraction (HFrEF), GISSI-HF (Gruppo Italiano per la Sperimentazione della Streptochinasi nell'Infarto Miocardico-Heart Failure), and Controlled Rosuvastatin Multinational Trial in HF (CORONA). 4,5 There is, however, a suggestion from the CORONA trial and other studies that patients with mild HF as evidenced by a relatively low level of NT-pro BNP may benefit. 6 Current guidelines do not therefore recommend the use of a statin in patients with established HF without other indications such as hypercholesterolemia, diabetes, or atherosclerotic cardiovascular disease. 7 The trial data suggest that statins can be continued in patients with established HF who are already on treatment. 7 Given the relatively large number of patients with hypercholesterolemia, the proven benefit of statins in patients without HF as well as the suggestion that they may be of benefit in patients with mild HF an increasing number of patients with established HF, both those with HFrEF and HF with a preserved ejection fraction are currently being treated with a statin. Thus, it is important to understand whether these patients will benefit or be at increased risk from the use of a statin. The explanation as to why statins have been shown to have a clear beneficial effect in patients with hypercholesterolemia and/or coronary artery disease without established HF, although their use in patients with established HF has not been clearly proven, remains uncertain.In this issue of the journal, Ahmad et al 8 compared the physical performance of 172 patients diagnosed with chronic HF, both HFrEF and HF with a preserved ejection fraction (50 treated with and 122 without a statin) to 59 control patients. They measured handgrip strength, gait speed, and a short physical performance battery as well as plasma biomarkers including the sarcopenia marker C-terminal agrin fragment 222 (CAF22), the intestinal barrier integrity marker zonulin, and C-reactive protein (CRP) and correlated these biomarkers with the markers of physical performance. Not surprisingly, they found that the patients with HF had a reduction in physical performance as compared to their control patients without HF. Of interest was their finding that patients with HF, irrespective of etiology, had a significant elevation in CAF22 and zonulin and that there was a strong inverse correlation between CAF22 and mar...