Down's syndrome and atherosclerosis

doi:10.1016/0021-9150(89)90110-X

Atherosclerosis

Volume 76, Issues 2–3, April 1989, Pages 269-272

https://doi.org/10.1016/0021-9150(89)90110-X Get rights and content

Abstract

Necropsy findings in patients with Down's syndrome have suggested an absence of atherosclerosis throughout the cardiovascular system, but there are also contradictory results. We compared the left coronary arteries of 15 institutionalised Down's syndrome patients (5 males, 10 females, mean age 51 years) with those of 6 other institutionalised mentally retarded patients (4 males, 2 females, mean age 49) and 20 normal, free-living subjects (10 males, 10 females, mean age 48) by macroscopic inspection of the opened coronary arteries and by biochemical analysis of their intima-media. The arteries of Down patients contained a lower percentage of raised lesions and less calcium than the arteries of the control groups. Thus, even though the coronary arteries of mongoloids were not completely free of atherosclerosis, it was milder than in other mental patients and free-living subjects of the same age.

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Cited by (87)

Gene-dosage imbalance due to trisomic HSA21 and genotype–phenotype association in Down syndrome
2022, Genetics and Neurobiology of Down Syndrome
Gene-dosage imbalance appears central causing phenotypic expression in individuals with Down syndrome (DS), their facial and cognitive differences, and early onset of Alzheimer disease (AD) and/or aging compared to the euploid population. Besides, the impact of the triplicated HSA21 genes and the cooperating effects of the disomic genes further complicate the genotype–phenotype basis of phenotypic variability in DS. Molecular understanding has tagged some of the HSA21 genes with DS phenotypes; however, disrupted genomic homeostasis is yet to be delineated with DS features aiming at therapeutic developments. Altogether, a cocktail of overexpressed, underexpressed, and compensated genic expression has indicated interaction of genic and nongenic complements, including epigenetic and environmental components. The situation is more complex for mosaic or translocated DS. Nonetheless, research on DS pathomechanism is primarily concentrated on primates and/or cell lines developed from DS patients. Specific link of triplicated DSCR1, DYRK1A, APP, SOD, RCAN1, RUNX1, ETS2, ERG, etc. with DS phenotypes, AD, cardiac defects, leukemia, and others has often been contradicted in studies involving reduction of trisomy to disomy through cross-breeding of DS mouse models. Thus, collective effects of gene-dosage imbalance, allelic variations, and contribution of modifier genes of the global genome and coincidental small effects confer phenotypes in DS individuals. Moreover, gene expression in different trisomic tissues at different developmental stages and also altered transcription to proteomic translation render variable clinical phenotypes in individuals with DS. This chapter has summarized the gene-dosage imbalance, interaction of genes, transcriptomes, and proteomics in trisomic condition, with a view to understanding the factors of phenotypic variability in DS patients.
Co-occurring medical conditions in aging adults with Down syndrome
2021, The Neurobiology of Aging and Alzheimer Disease in Down Syndrome
Longevity has increased rapidly in the population with Down syndrome (DS) since around 1970 with many individuals surviving into the late 50s and 60s (born 1960–1985). There has been a notable increase in the number of aging adults between 35 and 60 years (born 1947–1972) who now require expert medical care. By the time individuals with DS reach their 40s, several age-related medical conditions are usually evident and may be expected to progress over time. As aging and medical complexity increases, this places further demands on aging caretakers and family members. In elderly adults who are experiencing sudden changes in behavior or adaptive status, it is essential to consider the contributory role of several high-impact medical conditions including sensory (hearing, vision) impairment, sleep apnea, seizures, hypothyroidism, chronic pain, or congestive heart failure. Deterioration in gait and motor function can have multiple causes unrelated to dementia including cervical spondylosis with neural canal stenosis, cervical spine subluxation, lumbar disc herniation, osteoarthritis of the hip or knee, and stroke. A high level of medical vigilance, close monitoring, and timely evaluation is required to detect and treat occult medical conditions early in their course.
Peripheral blood flow regulation in response to sympathetic stimulation in individuals with down syndrome
2018, Artery Research
Individuals with Down syndrome (DS) experience autonomic dysfunction, with reduced sympathetic and parasympathetic control. This results in alterations in resting heart rate and blood pressure and attenuated responses to sympathoexcitatory stimuli. It is unknown to what extent this impacts the regulation of peripheral blood flow in response to sympathetic stimuli, which is an important prerequisite to exercise and perform work. Therefore, we aimed to investigate differences in peripheral blood flow regulation in response to lower body negative pressure (LBNP) between individuals with and without DS
Participants (n = 10 males with DS and n = 11 male controls, mean age 23.7 years ± 3.2) underwent 5 min of LBNP stimulations (−20 mmHg), after resting supine for 10 min. One minute steady state blood pressure and blood flow at baseline and during LBNP were obtained for analysis. Mean flow velocity and arterial diameters were recorded with ultrasonography; foreram blood flow (FBF), shear rate and forearm vascular conductance (FVC) were calculated using brachial blood pressure measured right before ultrasound recordings
Participants with DS responded differently (consistent with reduced vasoconstrictive control) to the LBNP stimulus (significant ConditionxGroup interaction effect) for mean velocity (p = 0.02), FBF (p = 0.04), shear rate (p = 0.02) and FVC (p = 0.03), compared to participants without DS.
Young males with DS exhibit reduced peripheral blood flow regulation in response to LBNP compared to controls, indicating a blunted sympathetic control of blood flow. Further research is necessary to explore the impact of these findings on exercise and work capacity.
Cerebrovascular contributions to aging and Alzheimer's disease in Down syndrome
2016, Biochimica et Biophysica Acta - Molecular Basis of Disease
Citation Excerpt :
Other studies also report much lower frequency of atheroma [13,109]. Although less frequent in DS, atherosclerosis has been observed in two middle aged adults who had strokes [73] but it tends to be milder in adults with DS [110]. Indeed, death from atherosclerosis in adults with DS in a Swedish population was rare but may be more frequent than previously thought [26].
Down syndrome (DS) is a common cause of intellectual disability and is also associated with early age of onset of Alzheimer's disease (AD). Due to an extra copy of chromosome 21, most adults over 40 years old with DS have beta-amyloid plaques as a result of overexpression of the amyloid precursor protein. Cerebrovascular pathology may also be a significant contributor to neuropathology observed in the brains of adults with DS. This review describes the features of cardiovascular dysfunction and cerebrovascular pathology in DS that may be modifiable risk factors and thus targets for interventions. We will describe cerebrovascular pathology, the role of co-morbidities, imaging studies indicating vascular pathology and the possible consequences. It is clear that our understanding of aging and AD in people with DS will benefit from further studies to determine the role that cerebrovascular dysfunction contributes to cognitive health. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock.
Haemodynamic profile of Spanish adults with Down syndrome
2020, Revista Clinica Espanola
Si bien se desconocen los motivos, la prevalencia de hipertensión arterial y de eventos cardiovasculares ateroscleróticos en la población adulta con síndrome de Down (SD) es anecdótica. Para entender mejor este hallazgo evaluamos las características hemodinámicas de una cohorte de adultos con SD.
Estudio transversal en adultos con SD incluidos de modo consecutivo de las consultas externas del servicio de medicina interna entre junio y noviembre 2018. Se recogieron variables demográficas, clínicas y analíticas. Se utilizó un dispositivo de bioimpedancia torácica (HOTMAN® System) para las medidas hemodinámicas. Se realizó una monitorización ambulatoria de presión arterial en un subgrupo de sujetos.
Veintiséis sujetos de edad media 45 ± 11 años participaron en el estudio (50% varones). La presión arterial (PA) media en la muestra fue de 109/69 ± 11/9 mm Hg, con una frecuencia cardiaca media de 60 ± 12 lpm. Ningún sujeto era hipertenso. El perfil hemodinámico predominante consistió en normodinamismo (65%), normotensión (96%), hipocronotropismo (46%), normoinotropismo (50%) e hipervolemia (54%), con valores normales de resistencias vasculares periféricas (58%). Se realizó una monitorización ambulatoria de la presión sarterial a 12 sujetos (46%). Los valores medios en 24 horas de PA sistólica fueron 105 ± 11 mm Hg, PA diastólica 67 ± 11 mm Hg, PA media 80 ± 11 mm Hg y frecuencia cardiaca media 61 ± 6 lpm.
El perfil hemodinámico más frecuentemente observado en adultos con SD consistió en hipocronotropismo e hipervolemia, con valores normales de resistencias vasculares periféricas y valores medios óptimos de PA. No identificamos ningún sujeto hipertenso en nuestra muestra.
Although the reasons are unknown, the prevalence of arterial hypertension and atherosclerotic cardiovascular events in the adult population with Down syndrome (SD) is anecdotal. To better understand this finding, we evaluated the haemodynamic characteristics of a cohort of adults with SD.
We conducted a cross-sectional study of adults with SD recruited consecutively from the outpatient clinics of an internal medicine department between June and November 2018. We collected demographic, clinical and laboratory variables and employed a thoracic bioimpedance device (HOTMAN® System) for the haemodynamic measures. Outpatient blood pressure monitoring (OBPM) was conducted on a subgroup of participants.
Twenty-six participants (mean age, 45 ± 11 years) participated in the study (50% men). The sample's mean blood pressure (BP) was 109/69 ± 11/9 mm Hg, with a mean heart rate of 60 ± 12 bpm. None of the participants had hypertension. The predominant haemodynamic profile consisted of normal dynamism (65%), normal BP (96%), hypochronotropism (46%), normal inotropism (50%) and hypervolaemia (54%), with normal peripheral vascular resistance values (58%). Twelve participants underwent OBPM (46%). The mean 24-h systolic BP, diastolic BP, mean BP and mean heart rate were 105 ± 11 mm Hg, 67 ± 11 mm Hg, 80 ± 11 mm Hg and 61 ± 6 bpm, respectively.
The most common haemodynamic profile observed in adults with SD consisted of hypochronotropism and hypervolaemia, with normal values for peripheral vascular resistance and optimal mean BP values. There were no participants with hypertension in our sample.
Health in Down syndrome: creating a conceptual model
2023, Journal of Intellectual Disability Research

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^∗: Present address: Department of Medicine, M-013D, Division of Endocrinology and Metabolism, University of California, San Diego, La Jolla, CA 92093, U.S.A.

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Preliminary noteDown's syndrome and atherosclerosis

Abstract

Clin. Chim. Acta

Atherosclerosis

J. Biol. Chem.

Life Sci.

Down's syndrome: an atheroma-free model?

Br. Med. J.

Down's syndrome as a model disease

Arch. Intern. Med.

Preliminary note
Down's syndrome and atherosclerosis