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Potential Impact of Statins on Neuronal Stress Responses in Patients at Risk for Cardiovascular Disease

2021; Multidisciplinary Digital Publishing Institute; Volume: 11; Issue: 4 Linguagem: Inglês

10.3390/jpm11040261

2075-4426

Flavia Diggelmann, Susan Bengs, Ahmed Haider, Gioia Epprecht, Anna Luisa Beeler, Dominik Etter, Winandus J. Wijnen, Angela Portmann, Geoffrey Warnock, Valérie Treyer, Muriel Grämer, Atanas Todorov, Nidaa Mikaïl, Alexia Rossi, Tobias A. Fuchs, Aju P. Pazhenkottil, Ronny R. Buechel, Felix C. Tanner, Philipp A. Kaufmann, Cathérine Gebhard, Michael Fiechter,

Computational Drug Discovery Methods

Background: Recent studies indicate that enhanced neuronal stress responses are associated with adverse cardiovascular outcomes. A chronic inflammatory state seems to mediate this detrimental neuro-cardiac communication. Statins are among the most widely prescribed medications in primary and secondary cardiovascular disease (CVD) prevention and not only lower lipid levels but also exhibit strong anti-inflammatory and neuroprotective effects. We therefore sought to investigate the influence of statins on neuronal stress responses in a patient cohort at risk for CVD. Methods: 563 patients (61.5 ± 14.0 years) who underwent echocardiography and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) were retrospectively identified. Metabolic activity of the amygdala, a part of the brain’s salience network, was quantified by 18F-FDG uptake, while normal cardiac morphology and function were assured by echocardiography. Vertebral bone marrow metabolism, a marker of inflammatory activity, was measured by 18F-FDG PET. Results: Increased neuronal stress responses were associated with an increased inflammatory activity in the bone marrow (r = 0.152, p = 0.015) as well as with a subclinical reduction in left ventricular ejection fraction (LVEF, r = −0.138, p = 0.025). In a fully-adjusted linear regression model, statin treatment was identified as an independent, negative predictor of amygdalar metabolic activity (B-coefficient −0.171, p = 0.043). Conclusions: Our hypothesis-generating investigation suggests a potential link between the anti-inflammatory actions of statins and reduced neuronal stress responses which could lead to improved cardiovascular outcomes. The latter warrants further studies in a larger and prospective population.