Increased nocturnal heart rate and wave reflection are early markers of cardiovascular disease in Williams–Beuren syndrome children

Maloberti, Alessandro; Cesana, Francesca; Hametner, Bernhard; Dozio, D.; Villa, Paolo; Hulpke-Wette, Martin; Schwarz, Achim; Selicorni, Angelo; Wassertheurer, Siegfried; Mancia, Giuseppe; Giannattasio, Cristina

doi:10.1097/hjh.0000000000000454

Cited by 12 publications

(6 citation statements)

References 33 publications

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“…Given the importance of the α1-adrenergic control of vascular tone, the lower response to phenylephrine could represent an adaptive mechanism to counteract luminal stenosis. Although there is little information about the functioning of the autonomic nervous system in WBS patients, a previous study reported that WBS children show increases in both heart rate and wave reflection values during the night, which may suggest abnormal sympathetic nervous system hyperactivity in WBS 48 . The results of the present study suggest that this hyperactivity might be counteracted by a lower response to aortic α1-adrenoceptor activation.…”

Section: Discussionmentioning

confidence: 98%

Stenosis coexists with compromised α1-adrenergic contractions in the ascending aorta of a mouse model of Williams-Beuren syndrome

Jiménez‐Altayó

Ortiz‐Romero

Puertas-Umbert

et al. 2020

Sci Rep

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Williams-Beuren syndrome (WBS) is a rare disorder caused by a heterozygous deletion of 26-28 contiguous genes that affects the brain and cardiovascular system. Here, we investigated whether WBS affects aortic structure and function in the complete deletion (CD) mouse model harbouring the most common deletion found in WBS patients. Thoracic aortas from 3-4 months-old male CD mice and wild-type littermates were mounted in wire myographs or were processed for histomorphometrical analysis. Nitric oxide synthase (NOS) isoforms and oxidative stress levels were assessed. Ascending aortas from young adult CD mice showed moderate (50%) luminal stenosis, whereas endothelial function and oxidative stress were comparable to wild-type. CD mice showed greater contractions to KCl. However, α1-adrenergic contractions to phenylephrine, but not with a thromboxane analogue, were compromised. Decreased phenylephrine responses were not affected by selective inducible NOS blockade with 1400 W, but were prevented by the non-selective NOS inhibitor L-NAME and the selective neuronal NOS inhibitor SMTC. Consistently, CD mice showed increased neuronal NOS expression in aortas. Overall, aortic stenosis in CD mice coexists with excessive nNOS-derived NO signaling that compromises ascending aorta α1-adrenergic contractions. We suggest that increased neuronal NOS signaling may act as a physiological 'brake' against the detrimental effects of stenosis. Williams-Beuren syndrome (WBS) [OMIM 194050] is a rare congenital multisystem disorder caused by a recurrent heterozygous deletion of 26-28 contiguous genes on chromosome band 7q11.23 1. This syndrome affects males and females equally with a prevalence that is estimated to range between 1/7,500 and 1/10,000 2. Mainly due to elastin (ELN) haploinsufficiency, this condition is commonly characterized by cardiovascular alterations that can occur early in life 3 , can evolve into potentially serious complications, and are the main cause of death in WBS patients 1,4. Supravalvular aortic stenosis is the most frequent cardiovascular anomaly, affecting approximately 70% of patients 1,5 , and it is a potentially life-threatening condition 6,7. Surgery may be required and drug treatments for this disorder and other cardiovascular manifestations in WBS generally not differ from that in the general population 8. Therefore, a thorough analysis of the pathophysiological mechanisms of aortic disease in WBS is needed to define more safe and effective personalized therapies. Mouse models of elastin deficiency have provided valuable insights into the mechanisms responsible for the development of aortic anomalies in WBS. Thus, partial rescue of Eln −/− by transgenic expression of human ELN 9,10 is sufficient to cause a similar aortic phenotype to typical WBS patients 11-15. However, there is increasing evidence that other genes besides Eln may be relevant in modulating the WBS cardiovascular phenotype. Various

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Section: Discussionmentioning

confidence: 98%

Stenosis coexists with compromised α1-adrenergic contractions in the ascending aorta of a mouse model of Williams-Beuren syndrome

Jiménez‐Altayó

Ortiz‐Romero

Puertas-Umbert

et al. 2020

Sci Rep

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“…Common carotid artery stiffness was evaluated by cfPWV and AIx using the Complior SP System (Alam Medical, Vincennes, France) [14,15], with participants in a supine position.…”

Section: Arterial Stiffness Measurementmentioning

confidence: 99%

High Neutrophil-to-Lymphocyte Ratio is a Significant Predictor of Cardiovascular and All-Cause Mortality in Patients Undergoing Peritoneal Dialysis

Wang

Zhang

et al. 2018

Kidney Blood Press Res

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Background/Aims: Chronic inflammation is associated with increased risk of cardiovascular death in patients with end-stage renal disease (ESRD). Although elevated neutrophil-tolymphocyte ratio (NLR), a novel inflammatory marker, has been shown to predict cardiovascular disease and all-cause mortality in the general population, limited evidence is available for its role in ESRD. Methods: We enrolled 86 patients undergoing peritoneal dialysis (PD) for a 36-month follow-up to investigate the association between the NLR and arterial stiffness markers, namely, carotid-femoral pulse wave velocity (cfPWV) and carotid augmentation index (AIx), and mortality in PD patients. The primary endpoints were cardiovascular mortality and all-cause mortality. Kaplan-Meier curves were used to show the cumulative incidence of cardiovascular mortality and all-cause mortality. Results: High NLR was found to be a predictor of increased cfPWV (β = 1.150; P < 0.001) and AIx (β = 3.945; P < 0.001) in patients on PD. Patients with higher NLR had lower survival during follow-up. Kaplan-Meier curves showed that the cumulative incidences of both cardiovascular mortality and all-cause mortality were significantly higher in patients with NLR ≥ 4.5 (both P < 0.01). Conclusion: Our results suggest that high NLR is independently associated with arterial stiffness and predicts cardiovascular and all-cause mortality in PD patients.

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“…Within our cohort only low doses of beta blockers have been prescribed which may also explain the observed heart rates in our study. In a recent study of children with Williams-Beuren syndrome who had borderline hypertensive peripheral blood pressures without prescription of beta blockers increased heart rates at nighttime as an early hallmark of cardiovascular changes have been reported [ 30 ]. With respect to the diurnal heart rate patterns Fig.…”

Section: Discussionmentioning

confidence: 99%

Ambulatory (24 h) blood pressure and arterial stiffness measurement in Marfan syndrome patients: a case control feasibility and pilot study

Hillebrand

Nouri

Hametner

et al. 2016

BMC Cardiovasc Disord

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BackgroundThe aim of this work is the investigation of measures of ambulatory brachial and aortic blood pressure and indices of arterial stiffness and aortic wave reflection in Marfan patients.MethodsA case-control study was conducted including patients with diagnosed Marfan syndrome following Ghent2 nosology and healthy controls matched for sex, age and daytime brachial systolic blood pressure. For each subject a 24 h ambulatory blood pressure and 24 h pulse wave analysis measurement was performed.ResultsAll parameters showed a circadian pattern whereby pressure dipping was more pronounced in Marfan patients. During daytime only Marfan patients with aortic root surgery showed increased pulse wave velocity. In contrast, various nighttime measurements, wave reflection determinants and circadian patterns showed a significant difference.ConclusionsThe findings of our study provide evidence that ambulatory measurement of arterial stiffness parameters is feasible and that these determinants are significantly different in Marfan syndrome patients compared to controls in particular at nighttime. Further investigation is therefore indicated.

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Increased nocturnal heart rate and wave reflection are early markers of cardiovascular disease in Williams–Beuren syndrome children

Cited by 12 publications

References 33 publications

Stenosis coexists with compromised α1-adrenergic contractions in the ascending aorta of a mouse model of Williams-Beuren syndrome

Stenosis coexists with compromised α1-adrenergic contractions in the ascending aorta of a mouse model of Williams-Beuren syndrome

High Neutrophil-to-Lymphocyte Ratio is a Significant Predictor of Cardiovascular and All-Cause Mortality in Patients Undergoing Peritoneal Dialysis

Ambulatory (24 h) blood pressure and arterial stiffness measurement in Marfan syndrome patients: a case control feasibility and pilot study

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