Endothelial function improvement in patients with familial hypercholesterolemia receiving PCSK-9 inhibitors on top of maximally tolerated lipid lowering therapy

Minno, Alessandro Di; Gentile, Marco; Iannuzzo, Gabriella; Calcaterra, Ilenia; Tripaldella, Maria; Porro, Benedetta; Cavalca, Viviana; Taranto, Maria Donata Di; Tremoli, Elena; Fortunato, Giuliana; Rubba, P.; Minno, Matteo Nicola Dario Di

doi:10.1016/j.thromres.2020.07.049

Cited by 33 publications

(34 citation statements)

References 56 publications

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“…The main outcome measure was FMD, representing the percent (%) change in BAD from baseline to the maximum value registered during reactive hyperaemia induced by forearm ischemia [31]. Post-ischemic reactive hyperemia was measured as the total area under the curve (AUC) of the shear rate after deflation [32,33], with shear rate being calculated as 4 × blood velocity/BAD [34]. Given the rest period before starting the test and the initial preparation procedures, the overall assessment took ≈ 20 min per patient.…”

Section: Brachial Artery Flow-mediated Dilation (Fmd)mentioning

confidence: 99%

Persistent Endothelial Dysfunction in Post-Acute COVID-19 Syndrome: A Case-Control Study

et al. 2021

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Background: Endothelial dysfunction has a key role in the pathogenesis of coronavirus disease 2019 (COVID-19) and its disabling complications. We designed a case-control study to assess the alterations of endothelium-dependent flow-mediated dilation (FMD) among convalescent COVID-19 patients. Methods: COVID-19 patients referred to a Pulmonary Rehabilitation Unit within 2 months from swab test negativization were consecutively evaluated for inclusion and compared to controls matched for age, gender, and cardiovascular risk factors. Results: A total of 133 convalescent COVID-19 patients (81.2% males, mean age 61.6 years) and 133 matched controls (80.5% males, mean age 60.4 years) were included. A significantly lower FMD was documented in convalescent COVID-19 patients as compared to controls (3.2% ± 2.6 vs. 6.4% ± 4.1 p < 0.001), confirmed when stratifying the study population according to age and major clinical variables. Among cases, females exhibited significantly higher FMD values as compared to males (6.1% ± 2.9 vs. 2.5% ± 1.9, p < 0.001). Thus, no significant difference was observed between cases and controls in the subgroup analysis on females (6.1% ± 2.9 vs. 5.3% ± 3.4, p = 0.362). Among convalescent COVID-19 patients, FMD showed a direct correlation with arterial oxygen tension (rho = 0.247, p = 0.004), forced expiratory volume in 1 s (rho = 0.436, p < 0.001), forced vital capacity (rho = 0.406, p < 0.001), and diffusing capacity for carbon monoxide (rho = 0.280, p = 0.008). Overall, after adjusting for major confounders, a recent COVID-19 was a major and independent predictor of FMD values (β = −0.427, p < 0.001). Conclusions: Post-acute COVID-19 syndrome is associated with a persistent and sex-biased endothelial dysfunction, directly correlated with the severity of pulmonary impairment.

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Section: Brachial Artery Flow-mediated Dilation (Fmd)mentioning

confidence: 99%

Persistent Endothelial Dysfunction in Post-Acute COVID-19 Syndrome: A Case-Control Study

et al. 2021

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“…Normalized FMD was calculated as (FMD/SR AUC ) × 10 4 (arbitrary units) to minimize individual variability in the hyperemic stimulus [35]. The full post-occlusive RH during 240 s after deflation was defined by total share rate area under the curve (SR AUC-TOT ) as well as by the ratio of average flow velocity after cuff deflation/flow velocity measured at baseline [36,37]. Considering the initial rest period and preliminary procedures, the entire exam lasted an average of 20 min per patient.…”

Section: Brachial Artery Flow-mediated Dilation (Fmd)mentioning

confidence: 99%

“…Finally, we have to consider that our study population consisted of patients with a relatively high prevalence of concomitant CV risk factors, potentially affecting vascular reactivity [37]. To evaluate sources of heterogeneity, we performed a sensitivity analysis after stratifying patients according to the presence/absence of any traditional CV risk factor.…”

Section: Limitationsmentioning

confidence: 99%

Clinical Assessment of Endothelial Function in Convalescent COVID-19 Patients Undergoing Multidisciplinary Pulmonary Rehabilitation

et al. 2021

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Background: Growing evidence points to a key role of endothelial dysfunction in the pathogenesis of COVID-19. In this study, we evaluated changes in endothelium-dependent flow-mediated dilation (FMD) in a cohort of convalescent COVID-19 patients undergoing pulmonary rehabilitation (PR). Methods: After swab test negativization, convalescent COVID-19 patients referring to a post-acute care facility for PR were consecutively screened for inclusion. Study procedures were performed at the time of hospitalization and discharge. Results: We enrolled 82 convalescent COVID-19 patients (85.4% males, mean age 60.4 years). After PR, a significant improvement in most pulmonary function tests and exercise capacity was documented. FMD changed from 2.48% ± 2.01 to 4.24% ± 2.81 (p < 0.001), corresponding to a 70.9% increase. Significantly higher changes in FMD were found in patients without a history of vascular events as compared to those with (+2.04% ± 2.30 vs. +0.61% ± 1.83, p = 0.013). Values of forced expiratory volume in 1 s (FEV1%), forced vital capacity (FVC%) and diffusion capacity for carbon monoxide (DLCO%) significantly and directly correlated with FMD both at baseline and after PR. Patients with normal FEV1% (≥80% predicted) during the overall study period or those normalizing FEV1% after PR showed a more significant FMD change as compared to patients with persistently impaired FEV1% (<80% predicted) (p for trend = 0.029). This finding was confirmed in a multivariate analysis. Conclusions: Clinically evaluated endothelial function improves after PR in convalescent COVID-19 patients. A direct and persistent association between the severity of pulmonary and vascular disease can be hypothesized. Endothelial function testing may be useful in the follow-up of convalescent COVID-19 patients.

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“…FMD and RHI of the brachial artery were evaluated according to a standardized ultrasound protocol [ 25 ] using an automatic edge detection software (Cardiovascular Suite ® , FMD studio, QUIPU Srl, Pisa, Italy) as described in Supplemental Materials and in a previous work [ 26 ].…”

Section: Methodsmentioning

confidence: 99%

Vascular Effects of the Polyphenolic Nutraceutical Supplement Taurisolo®: Focus on the Protection of the Endothelial Function

et al. 2021

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Preservation of vascular endothelium integrity and functionality represents an unmet medical need. Indeed, endothelial dysfunction leads to decreased nitric oxide biosynthesis, which is prodromic of hypertension and hypercoagulability. In this panorama, the nutraceutical supplement Taurisolo®, a polyphenolic extract from Aglianico cultivar grape, rich in catechin and procyanidins, was evaluated as a vasoprotective, vasorelaxing, anti-hypertensive and anti-coagulant agent in: cell lines, isolated vessels, in vivo models of chronic hypertension and hypercoagulability, and in clinical tests of endothelial reactivity. Taurisolo® demonstrated to fully protect vascular cell viability from oxidative stimulus at 100 µg/mL and evoke vasorelaxing effects (Emax = 80.6% ± 1.9 and pEC50 = 1.19 ± 0.03) by activation of the Sirtuins-AMPK-pathway. Moreover, Taurisolo®, chronically administered at 20 mg/Kg/die in in vivo experiments, inhibited the onset of cardiac hypertrophy (heart weight/rat weight = 3.96 ± 0.09 vs. 4.30 ± 0.03), hypercoagulability (decrease of fibrinogen vs. control: p < 0.01) and hypertension (mean of Psys: 200 ± 2 vs. control 234 ± 2 mmHg) and improved endothelial function (Emax = 88.9% ± 1.5 vs. control 59.6% ± 3.6; flow-mediated dilation in healthy volunteers after 400 mg twice daily for 8 weeks vs. baseline: p = 0.019). In conclusion, Taurisolo® preserves the vascular function against ox-inflamm-ageing process and the consequent cardiovascular accidents.

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Endothelial function improvement in patients with familial hypercholesterolemia receiving PCSK-9 inhibitors on top of maximally tolerated lipid lowering therapy

Cited by 33 publications

References 56 publications

Persistent Endothelial Dysfunction in Post-Acute COVID-19 Syndrome: A Case-Control Study

Persistent Endothelial Dysfunction in Post-Acute COVID-19 Syndrome: A Case-Control Study

Clinical Assessment of Endothelial Function in Convalescent COVID-19 Patients Undergoing Multidisciplinary Pulmonary Rehabilitation

Vascular Effects of the Polyphenolic Nutraceutical Supplement Taurisolo®: Focus on the Protection of the Endothelial Function

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