Risk of Major Cardiovascular Events in People with Down Syndrome

Christopher G Sobey, Courtney P Judkins, Vijaya Sundararajan, Thanh G Phan, Grant R Drummond, Velandai K Srikanth, Christopher G Sobey, Courtney P Judkins, Vijaya Sundararajan, Thanh G Phan, Grant R Drummond, Velandai K Srikanth

Abstract

Background: Improved medical care over more than five decades has markedly increased life expectancy, from 12 years to approximately 60 years, in people with Down syndrome (DS). With increased survival into late adulthood, there is now a greater need for the medical care of people with DS to prevent and treat aging-related disorders. In the wider population, acquired cardiovascular diseases such as stroke and coronary heart disease are common with increasing age, but the risks of these diseases in people with DS are unknown. There are no population-level data on the incidence of acquired major cerebrovascular and coronary diseases in DS, and no data examining how cardiovascular comorbidities or risk factors in DS might impact on cardiovascular event incidence. Such data would be also valuable to inform health care planning for people with DS. Our objective was therefore to conduct a population-level matched cohort study to quantify the risk of incident major cardiovascular events in DS.

Methods and findings: A population-level matched cohort study compared the risk of incident cardiovascular events between hospitalized patients with and without DS, adjusting for sex, and vascular risk factors. The sample was derived from hospitalization data within the Australian state of Victoria from 1993-2010. For each DS admission, 4 exact age-matched non-DS admissions were randomly selected from all hospitalizations within a week of the relevant DS admission to form the comparison cohort. There were 4,081 people with DS and 16,324 without DS, with a total of 212,539 person-years of observation. Compared to the group without DS, there was a higher prevalence in the DS group of congenital heart disease, cardiac arrhythmia, dementia, pulmonary hypertension, diabetes and sleep apnea, and a lower prevalence of ever-smoking. DS was associated with a greater risk of incident cerebrovascular events (Risk Ratio, RR 2.70, 95% CI 2.08, 3.53) especially among females (RR 3.31, 95% CI 2.21, 4.94) and patients aged ≤ 50 years old. The association of DS with ischemic strokes was substantially attenuated on adjustment for cardioembolic risk (RR 1.93, 95% CI 1.04, 3.20), but unaffected by adjustment for atherosclerotic risk. DS was associated with a 40-70% reduced risk of any coronary event in males (RR 0.58, 95% CI 0.40, 0.84) but not in females (RR 1.14, 95% CI 0.73, 1.77).

Conclusions: DS is associated with a high risk of stroke, expressed across all ages. Ischemic stroke risk in DS appears mostly driven by cardioembolic risk. The greater risk of hemorrhagic stroke and lower risk of coronary events (in males) in DS remain unexplained.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

References

    1. Penrose LS. The incidence of mongolism in the general population. J Mental Sci 1949. 95: 685–688.
    1. Glasson EJ, Sullivan SG, Hussain R, Petterson BA, Montgomery PD, Bittles AH. The changing survival profile of people with Down's syndrome: implications for genetic counselling. 2002. Clin Gen 62: 390–393.
    1. Tyrrell J, Cosgrave M, McCarron M, McPherson J, Calvert J, Kelly A, et al. Dementia in people with Down's syndrome. Int J Geriatric Psych 2001. 16: 1168–1174.
    1. Irving CA, Chaudhari MP. Cardiovascular abnormalities in Down's syndrome: spectrum, management and survival over 22 years. Arch Dis Child 2012. 97: 326–330. 10.1136/adc.2010.210534
    1. Rodan L, McCrindle BW, Manlhiot C, MacGregor DL, Askalan R, Moharir M, et al. Stroke recurrence in children with congenital heart disease. Ann Neurol 2012. 72: 103–111. 10.1002/ana.23574
    1. Murdoch JC, Rodger JC, Rao SS, Fletcher CD, Dunnigan MG Down's syndrome: an atheroma-free model? Br Med J 1977. 2: 226–228.
    1. Brattstrom L, Englund E, Brun A. Does Down syndrome support homocysteine theory of arteriosclerosis? Lancet 1987. 1: 391–392.
    1. Yla-Herttuala S, Luoma J, Nikkari T, Kivimaki T. Down's syndrome and atherosclerosis. Atherosclerosis 1989. 76: 269–272.
    1. Barnhart RC, Connolly B. Aging and Down syndrome: implications for physical therapy. Physical Ther 2007. 87: 1399–1406.
    1. de Winter CF, Bastiaanse LP, Hilgenkamp TI, Evenhuis HM, Echteld MA. Overweight and obesity in older people with intellectual disability. Res Dev Disabil 2012. 33: 398–405. 10.1016/j.ridd.2011.09.022
    1. de Winter CF, Bastiaanse LP, Hilgenkamp TI, Evenhuis HM, Echteld MA. Cardiovascular risk factors (diabetes, hypertension, hypercholesterolemia and metabolic syndrome) in older people with intellectual disability: results of the HA-ID study. Res Dev Disabil 2012. 33: 1722–1731. 10.1016/j.ridd.2012.04.010
    1. International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Australian Modification (ICD-10-AM) 2012. Available: . Accessed 2012 March 23.
    1. State Government of Victoria, Australia. Victorian Registry of Births, Deaths and Marriages 2012. Available: . Accessed 2012 March 23.
    1. Henderson T, Shepheard J, Sundararajan V. Quality of diagnosis and procedure coding in ICD-10 administrative data. Med Care 2006. 44: 1011–1019.
    1. Vis JC, Duffels MG, Winter MM, Weijerman ME, Cobben JM, Huisman SA, et al. Down syndrome: a cardiovascular perspective. JIDR 2009. 53: 419–425. 10.1111/j.1365-2788.2009.01158.x
    1. Kainth DS, Chaudhry SA, Kainth HS, Suri FK, Qureshi AI. Prevalence and characteristics of concurrent down syndrome in patients with moyamoya disease. Neurosurgery 2013. 72: 210–215. 10.1227/NEU.0b013e31827b9beb
    1. Cramer SC, Robertson RL, Dooling EC, Scott RM. Moyamoya and Down syndrome. Clinical and radiological features. Stroke 1996. 27: 2131–2135.
    1. Down Syndrome Australia: Down syndrome population statistics. Available: . Accessed 2015 August 5.
    1. de Graaf G, Buckley F, Skotko BG. Estimates of the live births, natural losses, and elective terminations with Down syndrome in the United States. Am J Med Genet A. 2015. 167A:756–767. 10.1002/ajmg.a.37001
    1. Miettinen OS. Individual matching with multiple controls in the case of all-or-none responses. Biometrics 1969. 25: 339–355.
    1. Kokotailo RA, Hill MD. Coding of stroke and stroke risk factors using international classification of diseases, revisions 9 and 10. Stroke 2005. 36: 1776–1781.
    1. Sacco S, Pistoia F, Carolei A. Stroke tracked by administrative coding data: Is it fair? Stroke 2013. 44: 1766–1768. 10.1161/STROKEAHA.113.001742
    1. Haesebaert J, Termoz A, Polazzi S, Mouchoux C, Mechtouff L, Derex L, et al. Can hospital discharge databases be used to follow ischemic stroke incidence? Stroke 2013. 44: 1770–1774. 10.1161/STROKEAHA.113.001300
    1. Baraona F, Gurvitz M, Landzberg MJ, Opotowsky AR. Hospitalizations and mortality in the United States for adults with Down Syndrome and congenital heart disease. Am J Cardiol 2013. 111: 1046–1051. 10.1016/j.amjcard.2012.12.025

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