Various factors, such as blood pressure, glucose and cholesterol levels, body mass index and kidney function are well-recognised risk factors for cardiovascular diseases and death. Recently, a few studies involving people with diabetes reported that variability over time of these factors can also lead to the development of cardiovascular disease (such as heart attacks or stroke). Our proposed study aims to examine the associations between the variability of cardiovascular risk factors and the risk of developing cardiovascular and non-cardiovascular diseases in the general population. The findings from this study will improve understanding of the role of variability in cardiovascular risk factors on cardiovascular and non-cardiovascular diseases among patients managed in general practice. An improved understanding of the effect of variability of cardiovascular risk factors could improve the management of patients in primary care.
The detrimental effects of variability in cardiovascular risk factors, such as blood pressure, glucose, cholesterol concentration, body mass index and estimated glomerular filtration rate on the risk of cardiovascular and non-cardiovascular diseases remains unclear. This study aims to evaluate the association of variability of cardiovascular risk factors with the risk of cardiovascular and non-cardiovascular diseases. The retrospective cohort study will be conducted on patients aged ?18 years old at cohort entry between 2005 and 2010. Eligible patients will be followed-up to 2019. The exposure is the standard deviation, degree of change and rate of change of measurements of cardiovascular risk factors. The primary outcome is the first event of cardiovascular disease including ischaemic heart disease, stroke and CVD mortality. The secondary outcomes are the ischaemic heart disease, haemorrhagic stroke, ischaemic stroke and haemorrhagic stroke. The tertiary outcomes include atrial fibrillation, chronic kidney disease, pulmonary embolism, heart failure, deep vein thrombosis, stroke unspecified; aortic aneurysm; dementia; all-cause mortality, non-CVD-related mortality and cancer. Our proposed outcome measures will be determined from the diagnoses and mortality records, and thus CPRD will be linked with (i) ONS Death Registration Data and (ii) HES Admitted Patient Care. To deal with random errors in this variability measurement, the joint model (mixed effects submodel and time-to-event submodel simultaneously using shared random effects) will be applied to estimate the variability of cardiovascular risk factors (standard deviation) based on the mixed effect model, and then the associations between the variability of cardiovascular risk factors and risk of cardiovascular and non-cardiovascular diseases will be evaluated by Cox proportional hazards regression adjusted for patient characteristics. Subgroup analyses will be conducted, stratifying by subject baseline characteristics, including age, gender, deprivation, smoking status, blood pressure level, the type of anti-hypertensive drugs, number of types of anti-hypertensive drugs, hypertension; diabetes and Charlson comorbidity index.
Primary outcome
Incident non-fatal myocardial infarction, non-fatal stroke or cardiovascular-related mortality
Secondary outcome
Incident all-cause mortality; non-fatal myocardial infarction, non-fatal stroke, cardiovascular-related mortality; haemorrhagic stroke (outcomes individually)
Tertiary outcome
Incident: heart failure; atrial fibrillation; peripheral arterial disease; chronic kidney disease unspecified stroke; aortic aneurysm; deep vein thrombosis; pulmonary embolism; dementia; non-CVD-related mortality; cancer.
Darren Ashcroft - Chief Investigator - University of Manchester
Darren Ashcroft - Corresponding Applicant - University of Manchester
Alison Wright - Collaborator - University of Manchester
David Reeves - Collaborator - University of Manchester
Eric Yuk Fai Wan - Collaborator - University of Hong Kong
Evangelos Kontopantelis - Collaborator - University of Manchester
Ian Wong - Collaborator - University College London ( UCL )
Jessica Barrett - Collaborator - University of Cambridge
Mamas Mamas - Collaborator - Keele University
Martin Rutter - Collaborator - University of Manchester
Rosa Parisi - Collaborator - University of Manchester
HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation;Practice Level Index of Multiple Deprivation