A Study Of The Usage Of Statins In A Community Heart Failure Population: The Impact of HMG Co-Enzyme A Reductase Inhibitors on Heart Structural Parameters, Brain Naturetic Peptide, Markers of Inflammation and Fibrosis

Heart Failure (HF) remains a major public health problem. Despite significant advances in the pharmacological management of this condition, the high mortality associated with heart failure remains a concern with annual figures ranging from 10 - 15% in mildly symptomatic patients to 50 - 60% in patients with severe heart failure.1

The major aetiological cause of HF is ischemic heart disease (IHD). While guidelines on the treatment of IHD recommend the use of lipid lowering therapy with hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) to improve prognosis, recent surveys from the UK and have shown that these effective therapies are being under-utilised.2 The reasons appear to be multifactorial but include issues related to efficacy, safety, potential for adverse drug reactions, failure to prescribe appropriate medication or dose and noncompliance with therapy.3

Some data from the large trials of statins are suggestive of benefit. In the 4S study 412 patients (9.2% of the study population) developed chronic heart failure requiring treatment, i.e. 228 (10.3%) in the placebo group and 184 (8.3%) patients in the group treated with simvastatin (p < 0.015). However, several questions remain, not least how statins might be beneficial in the setting of symptomatic heart failure.4 Treatment of heart failure has been targeted to a certain extent at the cause - and in the case of the majority of heart failure patients, the cause is related to ischemic heart disease and, perhaps, atherosclerosis. Furthermore, it is believed that the non-lipid lowering effects of statins, including neoangiogenesis, inhibition of proinflammatory cytokine activity, anti-fibrotic effects and favorable modulation of the autonomic nervous system, could play a positive role in the medical management of HF.5,6

However, there are several specific concerns, which clinicians may have in relation to the use of statins in heart failure. The average age of a community heart failure population is generally above 70 years and observational data from Framingham have suggested an inverse relationship between total cholesterol levels and all-cause mortality in older patients.5 There is an association between a total cholesterol level less than 5.2 mmol/L and impaired one-year event free survival in a large group of patients with heart failure.6 Statins can have a deleterious effect on myocardial function and thus have adverse effects on skeletal or cardiac muscles due to the inhibition of the synthesis of mevalonate, a precursor of ubiquinone.7

Elevated levels of markers such as C-reactive protein, TNF alpha and other inflammatory cytokines have been associated with poorer outcome in patients with HF, but excluding those with clear sources of infection or other inflammatory disorder, elevated C-reactive protein correlates with NYHA functional class and is associated with higher levels of morbidity.9 Several therapies in HF, notably ACE inhibition and AII Receptor Blockade have been shown to have anti-cytokine effects.10 Statins have been shown to reduce levels of circulating inflammatory cytokines in IHD. Recent data using atorvastatin has suggested that significant reductions in C-reactive protein levels are only seen in the patients with the highest pre-existing levels.11