Statin therapy improves locomotor muscle microvascular reactivity in patients with heart failure with preserved ejection fraction

Am J Physiol Heart Circ Physiol. 2024 Oct 1;327(4):H859-H865. doi: 10.1152/ajpheart.00427.2024. Epub 2024 Aug 9.

Abstract

Peripheral microvascular dysfunction has been documented in patients with heart failure with preserved ejection fraction (HFpEF), which may be related to elevated levels of inflammation and oxidative stress. Unfortunately, few strategies have been identified to effectively ameliorate this disease-related derangement. Thus, using a parallel, double-blind, placebo-controlled design, this study evaluated the efficacy of 30-day atorvastatin administration (10 mg daily) on lower limb microvascular reactivity, functional capacity, and biomarkers of inflammation and oxidative stress in patients with HFpEF (statin, n = 8, 76 ± 6 yr; placebo, n = 8, 68 ± 9 yr). The passive limb movement (PLM)-induced hyperemic response and 6-min walk test (6MWT) distance were evaluated to assess ambulatory muscle microvascular function and functional capacity, respectively. Circulating biomarkers were also measured to assess the contribution of changes in inflammation and redox balance to these outcomes. The total hyperemic response to PLM, assessed as leg blood flow area under the curve (LBFAUC), increased following the statin intervention (pre, 60 ± 68 mL; post, 164 ± 90 mL; P < 0.01), whereas these variables were unchanged in the placebo group (P = 0.99). There were no significant differences in 6MWT distance following statin or placebo intervention. Malondialdehyde (MDA), a marker of lipid peroxidation, was significantly reduced following the statin intervention (pre, 0.68 ± 0.10; post, 0.51 ± 0.11; P < 0.01) while other circulating biomarkers were unchanged. Together, these data provide new evidence for the efficacy of low-dose statin administration to improve locomotor muscle microvascular reactivity in patients with HFpEF, which may be due, in part, to a diminution in oxidative stress.NEW & NOTEWORTHY This was the first study to investigate the impact of statin administration on locomotor muscle microvascular function in patients with HFpEF. In support of our hypothesis, the total hyperemic response to PLM, assessed as leg blood flow area under the curve, increased, and malondialdehyde, a marker of oxidative damage, was reduced following the statin intervention. Together, these data provide new evidence for the efficacy of statin administration to improve locomotor muscle microvascular reactivity in patients with HFpEF, which may be due, in part, to reduced oxidative stress.

Keywords: heart failure; leg blood flow; microvascular; passive limb movement; statin.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Aged, 80 and over
  • Atorvastatin* / administration & dosage
  • Atorvastatin* / therapeutic use
  • Biomarkers / blood
  • Double-Blind Method
  • Exercise Tolerance / drug effects
  • Female
  • Heart Failure* / blood
  • Heart Failure* / drug therapy
  • Heart Failure* / physiopathology
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors* / administration & dosage
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors* / therapeutic use
  • Hyperemia / physiopathology
  • Lower Extremity / blood supply
  • Male
  • Microcirculation* / drug effects
  • Microvessels / drug effects
  • Microvessels / physiopathology
  • Middle Aged
  • Muscle, Skeletal* / blood supply
  • Muscle, Skeletal* / drug effects
  • Muscle, Skeletal* / physiopathology
  • Oxidative Stress* / drug effects
  • Regional Blood Flow / drug effects
  • Stroke Volume* / drug effects
  • Treatment Outcome
  • Ventricular Function, Left / drug effects
  • Walk Test

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Atorvastatin
  • Biomarkers