scholarly journals Short-Term Treatment with Alirocumab, Flow-Dependent Dilatation of the Brachial Artery and Use of Magnetic Resonance Diffusion Tensor Imaging to Evaluate Vascular Structure: An Exploratory Pilot Study

Biomedicines ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 152
Author(s):  
Thomas Metzner ◽  
Deborah R. Leitner ◽  
Gudrun Dimsity ◽  
Felix Gunzer ◽  
Peter Opriessnig ◽  
...  

Background: Short-term effects of alirocumab on vascular function have hardly been investigated. Moreover, there is a scarce of reliable non-invasive methods to evaluate atherosclerotic changes of the vasculature. The ALIROCKS trial was performed to address these issues using standard ultrasound-based procedures and a completely novel magnetic resonance-based imaging technique. Methods: A total of 24 patients with an indication for treatment with PCSK9 antibodies were recruited. There were 2 visits to the study site, the first before initiation of treatment with alirocumab and the second after 10 weeks of treatment. The key outcome measures included the change of carotid vessel wall fractional anisotropy, a novel magnetic resonance-based measure of vascular integrity, and the changes of carotid intima-media thickness and flow-dependent dilatation of the brachial artery measured with ultrasound. Results: A total of 19 patients completed the trial, 2 patients stopped treatment, 3 patients did not undergo the second visit due to the COVID pandemic. All of them had atherosclerotic vascular disease. Their mean (standard deviation) LDL-cholesterol concentration was 154 (85) mg/dL at baseline and was reduced by 76 (44) mg/dL in response to alirocumab treatment (p < 0.001, n = 19). P-selectin and vascular endothelial growth factors remained unchanged. Flow-dependent dilatation of the brachial artery (+41%, p = 0.241, n = 18), carotid intima-media thickness (p = 0.914, n = 18), and fractional anisotropy of the carotid artery (p = 0.358, n = 13) also did not significantly change. Conclusion: Despite a nominal amelioration for flow-dependent dilatation, significant effects of short-term treatment with alirocumab on vascular function were not detectable. More work would be needed to evaluate, whether fractional anisotropy may be useful in clinical atherosclerosis research.

2014 ◽  
Vol 19 (5) ◽  
pp. 288-293 ◽  
Author(s):  
Efstathios Manios ◽  
Fotios Michas ◽  
Kimon Stamatelopoulos ◽  
Gerasimos Barlas ◽  
Eleni Koroboki ◽  
...  

2016 ◽  
Vol 27 (3) ◽  
pp. 488-497 ◽  
Author(s):  
Fátima F. Pinto ◽  
Inês Gomes ◽  
Petra Loureiro ◽  
Sérgio Laranjo ◽  
Ana T. Timóteo ◽  
...  

AbstractBackgroundKawasaki disease is an acute systemic vasculitis. Cardiac complications are frequent and include endothelial dysfunction in patients with coronary anomalies. Thus far, endothelial dysfunction in patients with no coronary lesions is poorly understood. Our aim was to access the vascular function in adolescents and young adults long term after Kawasaki disease, but without coronary aneurysms or any other cardiac risk factors.MethodsWe carried out a single-centre prospective study in a Portuguese population. We evaluated two groups of subjects: (1) Kawasaki disease patients over 11 years of age, diagnosed >5 years ago, with no coronary lesions or any other risk factors for cardiovascular disease; (2) control group of individuals without cardiovascular risk factors. Patients and controls were clinically assessed. Endo-PAT and carotid intima-media thickness assessment were performed to determine vascular function.ResultsIn total, 43 Kawasaki disease patients were assessed and compared with 43 controls. Kawasaki disease patients presented a decreased reactive hyperaemia index compared with controls (1.59±0.45 versus 1.98±0.41; p<0.001). Augmentation index was similar in both groups (−4.5±7 versus −5±9%; p 0.6). The mean carotid intima-media thickness was not significantly increased in the Kawasaki disease group. There were no statistically significant changes with regard to laboratory data.ConclusionsChildren with Kawasaki disease may have long-term sequelae, even when there is no discernible coronary artery involvement in the acute stage of the disease. Further research is needed to assess whether known strategies to improve endothelial function would bring potential benefits to Kawasaki disease patients.


2010 ◽  
Vol 17 (5) ◽  
pp. 541-549 ◽  
Author(s):  
Maria Pia Sormani ◽  
Bettina Stubinski ◽  
Peter Cornelisse ◽  
Sanda Rocak ◽  
David Li ◽  
...  

Background: Use of quantitative magnetic resonance imaging (MRI) metrics as surrogates for clinical outcomes in multiple sclerosis (MS) trials is controversial. Objectives: We sought to validate, at the individual-patient level, the number of MRI active lesions, as a surrogate marker for relapses in MS. Methods: Individual-patient data from two large, placebo-controlled clinical trials of subcutaneous interferon β-1a in patients with relapsing–remitting or secondary progressive (SP) MS were analysed separately and as pooled data. The four Prentice criteria were applied to assess surrogacy for the number of new T2 MRI lesions. The predictive value of short-term treatment effects on this MRI marker for longer-term clinical relapses was also assessed. Results: All Prentice criteria were satisfied. The number of new T2 MRI lesions correlated with the number of relapses over the follow-up period. The proportion of treatment effect on relapses accounted for by the effect of treatment on new T2 MRI lesions over 2 years was 53% in patients with relapsing–remitting MS, 67% in patients with secondary progressive MS, and 62% in pooled data. In the pooled data, treatment effects on new lesions over 1 year mediated a good proportion (70%) of effects on relapses over the subsequent year. Conclusions: This study provides evidence that new T2 MRI lesion count is a surrogate for relapses in patients with MS treated with interferon or drugs with a similar mechanism of action. Short-term treatment effects on this MRI measure can predict longer-term effects on relapses.


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