Physicians' Academy for Cardiovascular Education

Lower muscle sympathetic nerve activity in HFpEF with lipophilic, but not hydrophilic statin

Differential effects of lipophilic and hydrophilic statins on muscle sympathetic nerve activity in heart failure with preserved left ventricular ejection fraction

Literature - Tokuhisa H, Murai H, Okabe Y, et al. - Autonomic Neuroscience: Basic and Clinical 213 (2018) 8–14

Introduction and methods

Sympathetic nerve activity is increased in patients with HF with preserved ejection fraction (HFpEF) and may contribute to poor prognosis [1,2]. Some data suggesting that lipophilic statins, which reduce sympathetic nerve activity in patients with hypertension HF with reduced ejection fraction (HFrEF) beyond their cholesterol-lowering activity, may also improve diastolic dysfunction and reduce mortality rates in HFpEF patients [3,4]. It was therefore hypothesized that lipophilic statin treatment reduces sympathetic nerve activity in patients with HFpEF.

In this prospective study, the effect of lipophilic and hydrophilic statins on muscle sympathetic nerve activity (MSNA) was evaluated in HFpEF patients, by means of direct recording of MSNA. The outcome of interest was MSNA burst frequency and burst incidence. Moreover, echocardiographic parameters, plasma brain natriuretic peptide (BNP) levels and baroreflex sensitivity were evaluated. Patients with diabetes, CKD, atrial fibrillation, >10% ventricular and/or atrial premature contractions, pacemaker, secondary hypertension, glycated hemoglobin >6.5%, eGFR <60 ml/min/1.73m2, acute decompensated HF, and acute CVD, were excluded from the study, leaving a sample of ten HFpEF patients.

HFpEF was defined as left ventricular ejection fraction (LVEF) ≥45% according to the guidelines of the Japanese Society of Cardiology [5]. Patients were randomly assigned to receive either 10 mg atorvastatin daily, which is a lipophilic statin, or 2.5 mg rosuvastatin daily, a hydrophilic statin, for eight weeks. After a one-week washout period, patients were crossed over to treatment with the other statin for eight additional weeks.

Main results


In a prospective cross-over study of ten HFpEF patients, atorvastatin treatment was associated with reduced MSNA without affecting baroreflex sensitivity, while rosuvastatin was not. The authors suggest that only lipophilic statins have a favorable effect on sympathetic nerve activity independent of their LDL-C lowering activity in these patients.


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