Recent research suggests that autistic people may have poorer healthcare quality and increased risk of co-occurring health conditions; however, health risks of autistic people remain under-researched–particularly in large, representative datasets. Since the number of adults diagnosed with autism has increased, more research is needed in order to estimate the physical health risks to this population and to design appropriate, preventative guidelines. This is particularly relevant for Covid-19-associated mortality, which significantly impacts people with a history of heart conditions, obesity, and diabetes. Using data from GP and hospital visits, we aim to calculate how often autistic people experience heart-related symptoms (e.g. angina), heart disease (e.g. heart attacks), death/hospitalization due to heart complications, or death/hospitalization due to Covid-19, and compare this to non-autistic people. To make sure our conclusion is not affected by causative factors other than autism, we will also take lifestyle conditions into account (e.g. smoking, socioeconomic status, age etc.). In addition, we will investigate if these linked to other mental health and neurodevelopmental conditions such (anxiety, depression, ADHD etc), as co-occurring mental health conditions have also been linked to cardiovascular conditions. We will further investigate if these cardiovascular and mental health condition differ by age of diagnosis and by co-occurring intellectual disability. In addition, we will conduct the same analysis in mothers of autistic people, since recent data has shown that they are also more likely to have PCOS, abnormal hormone levels during pregnancy, and increased risk of other serious conditions (e.g. cancer).
We propose to use the Clinical Practice Research Datalink (CPRD), linkages to the Hospital Episode Statistics (Admitted Patient Care data), Covid-19 linkages, and Office of National Statistics (ONS) Death data linkage to consider the cardiovascular health of autistic individuals, and its relationships to psychiatric/neurodevelopmental conditions and severe disease from Covid-19. We will use clinical, referral, therapy, and test records to determine whether individuals have increased glycosylated haemoglobin (HbA1C), HDL cholesterol, Non-HDL:HDL cholesterol ratio, BMI, use of medications, as well as whether or not individuals are more likely to exhibit severe cardiovascular or Covid-19-related outcomes. Cohort 1 will consist of autistic individuals and will be matched 5:1 with non-autistic controls on age, sex, and practice (Cohort 2). We will use Cox regression to determine risk of cardiovascular or Covid-19 outcomes (including death/hospitalization). Composite risk scores will be investigated for association to autism, via linear regression (Pearson’s coefficient). We will covary for several confounding factors, including psychiatric/neurodevelopmental conditions, as well as ethnicity and socioeconomic status via the Patient-Level Indices of Multiple Deprivation (IMD) and Ethnicity linkages. We will also use regression to investigate if both mental health and cardiovascular outcomes differ based on sex, age of autism diagnosis, and co-occurring intellectual disability. Missing data on covariates will be imputed via use of Multiple Imputation by Chain Equations (MICE). Mixed effects modelling will be utilized to account for nested data structure. Statistical significance of the results will be adjusted with the application of Benjamini-Hochberg False Discovery Rate. We will use the Mother-to-Baby link to identify non-autistic mothers of Cohort 1; they will make up Cohort 3 and will be matched on age, sex, and practice to the mothers of Cohort 2 (Cohort 4). We will use the same procedure to test the same risk factors and outcomes in this population.
Risk Score: HbA1C; HDL cholesterol; Non-HDL:HDL cholesterol ratio; BMI
Cardiovascular treatments: Prescriptions for statins, beta blockers, ACE inhibitors, diuretics, and calcium-channel blockers
Cardiovascular Signs & Symptoms: angina; hypertension; arrhythmias; transient ischaemic attack (TIA)
Cardiovascular Outcomes: ischemic stroke; myocardial infarction; heart failure, coronary revascularization procedures
Cause of Death/Hospitalization: Cardiovascular outcomes (listed above) and Covid-19
Variation among autistic people: Cardiovascular outcomes, co-occurring mental health conditions, intellectual disability, ethnicity, sex, and age of diagnosis
Simon Baron-Cohen - Chief Investigator - University of Cambridge
Elizabeth Weir - Corresponding Applicant - University of Cambridge
Adriana Cherskov - Collaborator - Yale University
Alex Tsompanidis - Collaborator - University of Cambridge
Brigid Kennedy - Collaborator - University of Cambridge
Carrie Allison - Collaborator - University of Cambridge
Fiona Matthews - Collaborator - Newcastle University
Rupert Payne - Collaborator - University of Bristol
Varun Warrier - Collaborator - University of Cambridge
Xinhe Zhang - Collaborator - University of Cambridge
CHESS (Hospitalisation in England Surveillance System);CPRD Mother-Baby Link;HES Admitted Patient Care;ICNARC (COVID-19 Intensive Care National Audit and Research Centre);ONS Death Registration Data;Patient Level Index of Multiple Deprivation;COVID-19 Linkages;CPRD GOLD Ethnicity Record